Transmembrane Transporters

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

28 | Feb 15 2024

The MuSICAL screening strategy efficiently identified a potentially effective triple combination therapy for paediatric AML using FDA-approved compounds, showcasing promising avenues for rapid clinical translation and therapeutic advancements. [Read the Full Post]

Vestibular Testing-New Physiological Results for the Optimization of Clinical VEMP Stimuli

28 | Feb 12 2024

The review explores the intricate synaptic and receptor mechanisms of auditory and vestibular systems, proposing an "ultrafast" non-quantal transmission as the cause of rapid vestibular afferent responses, with profound implications for clinical testing and understanding neural processing in these sensory pathways. [Read the Full Post]

The role of glutamate NMDA receptors of the mediodorsal thalamus in scopolamine-induced amnesia in rats

26 | Feb 11 2024

This study demonstrates that activation of glutamate NMDA receptors in the mediodorsal thalamus mitigates scopolamine-induced memory impairment, while their blockade exacerbates this cognitive deficit, suggesting a pivotal role for the MD glutamatergic system via the NMDA receptor pathway in memory consolidation. [Read the Full Post]

Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's

18 | Feb 11 2024

The study elucidates that L-type voltage-gated calcium channels (LTCCs) govern dopamine release in a regionally and sexually divergent manner, influenced by multiple factors associated with either increased vulnerability or protection against Parkinson's disease. [Read the Full Post]

DHA and EPA Alleviate Epileptic Depression in PTZ-Treated Young Mice Model by Inhibiting Neuroinflammation through Regulating Microglial M2 Polarization and Improving Mitochondrial Metabolism

21 | Feb 07 2024

The study's findings highlight the potential of EPA and DHA supplementation as effective interventions to alleviate depressive symptoms in pediatric patients with epilepsy, with EPA demonstrating particularly favorable effects by mitigating neuronal degeneration, reducing neuroinflammation, and modulating oxidative stress through distinct molecular mechanisms. [Read the Full Post]

Content of amino acids and biogenic amines in stored meat as a result of a broiler diet supplemented with β-alanine and garlic extract

25 | Feb 07 2024

Supplementing chicken feed with garlic extract and β-alanine showed promise in increasing protein content, altering amino acid levels, and potentially reducing biogenic amine formation, improving the quality and shelf life of poultry meat during storage. [Read the Full Post]

CYP-catalysed Cycling of Clozapine and Clozapine- N-oxide Promotes the Generation of Reactive Oxygen Species in vitro

42 | Feb 06 2024

This study reveals that specific CYP isoforms, particularly CYP3A4, not only drive clozapine metabolism to its major metabolites but also link to the formation of reactive species, potentially underpinning clozapine-induced toxicity in treatment-resistant schizophrenia. [Read the Full Post]

Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology

23 | Feb 05 2024

The identification of creatine within synaptic vesicles and its demonstrated impact on neuronal function suggests its potential role as a novel neurotransmitter, marking a significant advancement in understanding brain physiology and potential implications for neurological disorders. [Read the Full Post]

Integrative Pharmacology in the Treatment of Substance Use Disorders

20 | Feb 05 2024

Navigating the intricate web of neurobiological pathways, an integrated approach targeting KYNA-NMDA-α7nAChRcentric pathophysiology presents a promising avenue for developing novel combination treatments to address substance use disorders comprehensively. [Read the Full Post]

Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis

12 | Feb 04 2024

The intricate interplay between the AAA+ ATPase Pch2, Crm1 exportin-mediated nucleocytoplasmic transport, and the identification of a specific Nuclear Export Signal within Pch2 unveils a crucial regulatory mechanism governing its cellular distribution and function during meiosis. [Read the Full Post]

Optimization of anesthetic procedure in crustaceans: Evidence for sedative and analgesic-like effect of MS-222 using a semi-automated device for exposure to noxious stimulus

18 | Feb 02 2024

This study demonstrates the efficacy of MS-222 as an anesthetic in Gammarus pulex while introducing a novel semi-automated electric shock device for assessing nociceptive responses in aquatic invertebrates, highlighting its potential for standardized research protocols in this field. [Read the Full Post]

C5 methylation confers accessibility, stability and selectivity to picrotoxinin

71 | Feb 02 2024

Exploring minor modifications in picrotoxinin analogs revealed that a C5 methyl group significantly altered channel selectivity between mammalian and insect ion channels, pioneering the first systematic structure-activity relationship studies for picrotoxinin while highlighting the impact of subtle structural changes on functional properties. [Read the Full Post]

Role of monocarboxylate transporter I/lactate dehydrogenase B-mediated lactate recycling in tamoxifen-resistant breast cancer cells

18 | Jan 31 2024

The study identifies that tamoxifen-resistant breast cancer cells depend on enhanced glycolysis, particularly lactate metabolism mediated by MCT1 and LDHB, proposing that targeting these pathways could offer a promising strategy for treating tamoxifen-resistant breast cancer. [Read the Full Post]

Tumor Microenvironment Responsive CD8+ T Cells and Myeloid-Derived Suppressor Cells to Trigger CD73 Inhibitor AB680-Based Synergistic Therapy for Pancreatic Cancer

24 | Jan 31 2024

AB680, a potent CD73 inhibitor, demonstrates significant efficacy in augmenting CD8+ T cell infiltration, prolonging survival, and when combined with PD-1 blockade while attenuating gemcitabine's effects, offering a promising immunotherapeutic strategy in pancreatic ductal adenocarcinoma. [Read the Full Post]

Identification and characterization of an ectophosphatase activity involved in Acanthamoeba castellanii adhesion to host cells

18 | Jan 31 2024

The ectophosphatase activity in Acanthamoeba castellanii, particularly stimulated by mannose residues, appears crucial for trophozoite adhesion to host cells, suggesting a pivotal role in the pathogenesis of associated infections. [Read the Full Post]

Polyamine metabolism and glutamate receptor agonists-mediated excitotoxicity in the rat brain

33 | Jan 28 2024

The study compared various glutamate receptor agonists' impact on inducing excitotoxic brain damage in rats, revealing PUT as a potential general marker of such damage due to its concurrent increase with brain injury following both ionotropic and metabotropic glutamate receptor activation. [Read the Full Post]

Role of ON and OFF Visual Pathways in Rod- and Cone-Driven Flicker Responses

34 | Jan 28 2024

The study identified distinct neurotransmitter effects on rod and cone-driven flicker responses, emphasizing the involvement of ON and OFF visual pathways, horizontal cells, and the sensitivity of low-frequency flicker in ophthalmic pathophysiological research. [Read the Full Post]

Ultra-stable MOF@MOF nanoplatform for photodynamic therapy sensitized by relieved hypoxia due to mitochondrial respiration inhibition

21 | Jan 16 2024

The innovative MOF@MOF structure, bolstering stability and effectively alleviating hypoxia in tumors via 7ACC2, represents a groundbreaking leap in enhancing photodynamic therapy, heralding a promising era for MOF-based nanomedicines. [Read the Full Post]

Fabrication and characterization of dihydromyricetin-loaded microcapsules stabilized by glyceryl monostearate and whey protein-xanthan gum

59 | Jan 02 2024

Encapsulation of dihydromyricetin using glyceryl monostearate and octyl/decyl glycerate as inner cores, whey protein, and xanthan gum as wall materials demonstrated enhanced stability, controlled release, and improved antioxidant effects, presenting a promising strategy for delivering lipophilic bioactive compounds with heightened bioavailability and stability. [Read the Full Post]

Active Components of Leontopodium alpinum Callus Culture Extract for Blue Light Damage in Human Foreskin Fibroblasts

74 | Dec 31 2023

Research on Leontopodium alpinum callus culture extract's components, particularly leontopodic acid A, reveals promising potential in protecting skin cells from blue light damage, offering avenues for future skincare and pharmaceutical developments. [Read the Full Post]

C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway

32 | Dec 30 2023

High levels of C5a accelerate vascular smooth muscle cell calcification via C5aR1, activating the PERK-eIF2α-ATF4-CREB3L1 pathway, highlighting C5 or C5aR1 as potential therapeutic targets for vascular calcification. [Read the Full Post]

Puerarin ameliorates myocardial remodeling of spontaneously hypertensive rats through inhibiting TRPC6-CaN-NFATc3 pathway

31 | Dec 25 2023

Puerarin administration in spontaneously hypertensive rats demonstrated significant improvements in cardiac function and myocardial structure, potentially mediated by its inhibition of the TRPC6-CaN-NFATc3 pathway, suggesting promise for Puerarin as a therapeutic intervention in hypertensive myocardial remodeling. [Read the Full Post]

Exercise attenuates neuronal degeneration in Parkinson's disease rat model by regulating the level of adenosine 2A receptor

84 | Dec 23 2023

Exercise appears to mitigate Parkinson's disease symptoms in rats by reducing neurodegeneration through a-synuclein aggregation reduction and adenosine 2A receptor modulation, although the co-administration of an adenosine A2A receptor agonist reverses these beneficial effects. [Read the Full Post]

Heat stress upregulates aromatases expression through nuclear DAX-1 deficiency in R2C Leydig tumor cells

23 | Dec 19 2023

Heat stress at 40 °C was found to increase aromatase expression in Leydig cells, leading to a decreased testosterone to estradiol ratio, potentially impacting spermatogenesis, with the mechanism involving interference with the DAX-1-SF-1 interaction and induction of SF-1-dependent aromatase transcription. [Read the Full Post]

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

42 | Dec 18 2023

The study demonstrates that blocking L-type Ca2+ channels attenuates cardiac arrhythmias induced by acute myocardial infarction, implicating the Ca2+/cAMP/adenosine signaling pathway as a promising therapeutic target to reduce severe and fatal arrhythmias in humans. [Read the Full Post]

An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives

32 | Dec 15 2023

The research on bufalin, a compound found in toad venom, demonstrates significant potential in overcoming drug resistance in cancer cells through its diverse mechanisms of action, chemo-sensitizing properties, derivative development, and proactive consideration of obstacles, emphasizing the need for further in-depth studies and clinical trials. [Read the Full Post]

Chaperone-mediated autophagy protects against hyperglycemic stress

30 | Dec 12 2023

The study demonstrates the existence of chaperone-mediated autophagy (CMA) in rainbow trout, revealing its activation under high-glucose conditions, mediated by the KFERQ motif, Lamp2A, mitochondrial reactive oxygen species, and the Nfe2l2/Nrf2 pathway, highlighting its crucial role in protecting against glucose-induced stress. [Read the Full Post]

Simulated microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

33 | Dec 09 2023

Microgravity-induced shortening of primary cilia triggers overexpression and hyperactivity of TRPV4 channels, leading to intracellular Ca2+ overload, oxidative stress, and loss of osteogenic potential in osteoblasts, a process preventable by protecting primary cilia. [Read the Full Post]

Dual action of Dooku1 on PIEZO1 channel in human red blood cells

20 | Dec 04 2023

In the context of Red Blood Cells (RBCs), Dooku1, previously considered a PIEZO1 antagonist, was found to behave as a lower-potency agonist, triggering calcium entry and activating PIEZO1 channels, highlighting the complex pharmacological interactions specific to RBC membranes. [Read the Full Post]

Cuminum cyminum Ameliorates Urotoxic Effects of Cyclophosphamide by Modulating Antioxidant, Inflammatory Cytokines, and Urinary Bladder Overactivity: In vivo and In Silioc investigations

20 | Dec 02 2023

The study demonstrates that the aqueous ethanol extract of Cuminum cyminum attenuates cyclophosphamide-induced bladder toxicity in rats by reducing oxidative stress, inflammation, and smooth muscle overactivity, while in silico analysis identifies potential bioactive compounds for future drug development. [Read the Full Post]

Microglia trigger the structural plasticity of GABAergic neurons in the hippocampal CA1 region of a lipopolysaccharide-induced neuroinflammation model

17 | Nov 26 2023

The study demonstrates that LPS-induced microglial activation in the hippocampal CA1 region leads to cognitive impairment through the upregulation of GABAergic inhibitory synapses, and this effect can be reversed by blocking GABA receptor activity or depleting microglia, highlighting the critical role of neuroinflammatory responses and synaptic plasticity in cognitive dysfunction. [Read the Full Post]

Revisiting matrix hydrogel composed of gelatin and hyaluronic acid and its application in cartilage regeneration

28 | Nov 25 2023

The biomacromolecule-based bioadhesive matrix hydrogel, composed of methacrylate gelatin and modified hyaluronic acid, demonstrates promising potential for cartilage repair by promoting tissue integration, supporting chondrogenesis of stem cells, and enhancing articular cartilage regeneration in knee osteoarthritis. [Read the Full Post]

Spinal cannabinoid receptor 2 activation alleviates neuropathic pain by regulating microglia and suppressing P2X7 receptor

55 | Nov 19 2023

The study demonstrates that continuous activation of cannabinoid receptor 2 (CB2R) with the specific agonist PM226 promotes a neuroprotective transition in microglia, attenuates neuropathic pain, and reduces proinflammatory P2X7 receptor content, offering a potential therapeutic avenue for managing neuropathic pain with low abuse potential. [Read the Full Post]

Atypical Acetylcholine Receptors on the Neurons of the Turkish Snail

34 | Nov 17 2023

The study on Helix lucorum snail neurons demonstrated that their nicotinic acetylcholine receptors (nAChRs) exhibit a complex and atypical pharmacological profile, responding to various nAChR ligands and muscarinic receptor ligands, with α7, muscle-type, and α9 nAChRs playing key roles in mediating acetylcholine-induced depolarization. [Read the Full Post]

ASCT2-mediated glutamine uptake promotes Th1 differentiation via ROS-EGR1-PAC1 pathway in oral lichen planus

29 | Nov 11 2023

The study reveals that glutamine uptake mediated by ASCT2 plays a pivotal role in promoting Th1 differentiation through a ROS-EGR1-PAC1 pathway in oral lichen planus, suggesting that targeting ASCT2 could be a potential therapeutic approach for T cell-mediated autoimmune diseases by restoring redox balance. [Read the Full Post]

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives

19 | Nov 01 2023

The study demonstrated that Lomerizine (Lom) and its derivatives exhibited potent anti-CHIKV activity and low cytotoxicity, particularly compounds B1 and B7, suggesting their potential as effective anti-Chikungunya drugs. [Read the Full Post]

Identification of a pharmacological approach to reduce ACE2 expression and development of an in vitro COVID-19 viral entry model

24 | Oct 31 2023

This study developed an in vitro cellular model and identified inhibitors, CK869 and EIPA, that effectively reduced ACE2 expression and inhibited ACE2-dependent viral entry, providing potential candidates for further investigation as therapeutic drugs against COVID-19. [Read the Full Post]

Role of P2X7R in eosinophilic and non‑eosinophilic chronic rhinosinusitis with nasal polyps

59 | Oct 30 2023

The study found that P2X7R is overexpressed in chronic rhinosinusitis with nasal polyps (CRSwNP), and its activation mediates NLRP3 inflammasome activation, suggesting its potential role in the pathogenesis of CRSwNP. [Read the Full Post]

Inhibition of mitochondrial VDAC1 oligomerization alleviates apoptosis and necroptosis of retinal neurons following OGD/R injury

10 | Oct 26 2023

The study found that inhibiting the oligomerization of Voltage-dependent anion channel 1 (VDAC1) rescues mitochondrial dysfunction and reduces apoptosis/necroptosis in retinal cells, offering a potential therapeutic strategy for ocular diseases caused by ischemia-reperfusion injury. [Read the Full Post]

The copper chelator ammonium tetrathiomolybdate inhibits the progression of experimental endometriosis in TNFR1-deficient mice

19 | Oct 24 2023

Treatment with ammonium tetrathiomolybdate (TM), a copper chelator, inhibits the progression of endometriosis in TNFR1-deficient mice by restoring copper and estradiol levels, reducing lesion size, inhibiting cell proliferation and angiogenesis, and modulating oxidative stress markers. [Read the Full Post]

Potential for cardiac toxicity with methylimidazolium ionic liquids

31 | Oct 21 2023

This study suggests that Methylimidazolium ionic liquids (MILs) have the potential to cause cardiotoxicity in rats, while mice may be less sensitive to MIL-induced cardiac toxicity due to higher expression and/or function of cardiac transport proteins, highlighting potential hazards of MIL exposure in humans if their use levels increase. [Read the Full Post]

Assessment of verdinexor as a canine P-glycoprotein substrate

19 | Oct 20 2023

Verdinexor has been determined to not be a substrate for canine P-gp based on cytotoxicity and competitive flow cytometry assays using a cell line overexpressing canine P-gp. [Read the Full Post]

Improvement of the functional value of green soybean (edamame) using germination and tempe fermentation: A comparative metabolomics study

46 | Oct 18 2023

This study demonstrated that tempe fermentation significantly increased the concentrations of important bioactive metabolites in green soybean, thereby highlighting its potential to improve the functionality of this legume. [Read the Full Post]

Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis

38 | Oct 11 2023

The interim findings of the STRIDE registry show that long-term treatment with ataluren plus standard of care delays disease progression milestones in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) compared to standard of care alone. [Read the Full Post]

The Heart Failure Knights

23 | Oct 08 2023

The 2021 European Society of Cardiology guidelines have introduced a four-pillar approach for optimal drug therapy in heart failure, and emerging molecules such as vericiguat, omecamtiv mecarbil, mavacamten, and aficamten show promise in improving outcomes for patients with reduced ejection fraction heart failure. [Read the Full Post]

The purinergic receptors 2X3 on spiral ganglion neurons enhance the medial olivocochlear reflex in mice after long-term moderate noise exposure

32 | Oct 07 2023

Long-term moderate noise exposure increases the expression of P2X3 receptors in spiral ganglion neurons (SGNs) and enhances the medial olivocochlear (MOC) reflex, which can be downregulated by AF-353, a specific antagonist for P2X3 receptors. [Read the Full Post]

[Therapeutic drug monitoring of antipsychotic drugs in routine psychiatric practice]

65 | Oct 01 2023

This study examined the relationship between daily doses of antipsychotic drugs, their serum concentrations, and patient characteristics in the treatment of schizophrenia, highlighting the importance of therapeutic drug monitoring and individual patient factors on drug exposure. [Read the Full Post]

HTLV-1 bZIP factor-induced reprogramming of lactate metabolism and epigenetic status promote leukemic cell expansion

80 | Sep 26 2023

The study demonstrates that the viral oncogene HBZ upregulates TAp73, which in turn promotes lactate excretion through the upregulation of lactate transporters MCT1 and MCT4, revealing a potential common mechanism underlying cancer metabolism and suggesting the therapeutic potential of targeting this pathway. [Read the Full Post]

Mechanism of action of reserpine in producing gastric haemorrhage and erosion in the mouse

26 | Sep 26 2023

Reserpine-like drugs, such as reserpine and deserpidine, induce gastric hemorrhage in mice within six hours of subcutaneous injection, likely through a mechanism involving central components and the release of 5-hydroxytryptamine. [Read the Full Post]

Monocarboxylate transporter 4 inhibition potentiates hepatocellular carcinoma immunotherapy through enhancing T cell infiltration and immune attack

19 | Sep 26 2023

The study revealed that inhibiting MCT4 in hepatocellular carcinoma improved immune responses, suppressed tumor growth, and enhanced the efficacy of immunotherapy, suggesting MCT4 as a potential therapeutic target for tailoring HCC treatment. [Read the Full Post]

Iron Chelator VLX600 Inhibits Mitochondrial Respiration and Promotes Sensitization of Neuroblastoma Cells in Nutrition-Restricted Conditions

77 | Sep 17 2023

The iron chelator VLX600 inhibits mitochondrial respiration, reduces MYCN/LMO1 expression, and induces cell death in neuroblastoma cells, regardless of MYCN status, suggesting its potential as a therapeutic agent in combination with conventional chemotherapy for the treatment of neuroblastoma. [Read the Full Post]

PPARδ inhibition blocks the induction and function of tumor-induced IL-10+ regulatory B cells and enhances cancer immunotherapy

31 | Sep 12 2023

This study demonstrates that PPARδ is crucial for the development and function of IL-10+ Bregs, and targeting PPARδ shows promise in improving antitumor immunotherapy outcomes. [Read the Full Post]

Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

25 | Sep 12 2023

The study found that infusion of apocynin before ischemia or at reperfusion protected the heart by improving cardiac hemodynamics, reducing infarct size, decreasing pro-inflammatory cytokine levels, increasing anti-inflammatory cytokine and antioxidant levels, and involving CD38, nitric oxide, and acidic stores. [Read the Full Post]

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats

26 | Sep 10 2023

The study found that blocking facilitative glucose channels with phloretin reduced glucose absorption and improved ultrafiltration efficiency in peritoneal dialysis, suggesting it as a promising approach for therapeutic interventions in this context. [Read the Full Post]

Phase II drugs under clinical investigation for the treatment of chronic constipation

106 | Sep 10 2023

New investigational drugs for the treatment of chronic constipation show promise in terms of improved effectiveness and tolerability, but further clinical trials with larger sample sizes and longer durations are needed to establish their efficacy and safety. [Read the Full Post]

Real-world outcomes and direct care cost before and after elexacaftor/tezacaftor/ivacaftor initiation in commercially insured members with cystic fibrosis

23 | Sep 02 2023

The study found that among commercially insured individuals with cystic fibrosis initiating treatment with ELX/TEZ/IVA, there was a significant increase in total cost of care, primarily driven by increased pharmacy benefit costs, despite notable reductions in healthcare resource utilization and pulmonary exacerbation events. [Read the Full Post]

Positive and negative impacts of elexacaftor/tezacaftor/ivacaftor: Healthcare providers' observations across US centers

32 | Sep 02 2023

This study found that while Elexacaftor/tezacaftor/ivacaftor (ETI) had positive physical effects in cystic fibrosis patients, it was also associated with negative side effects such as sleep difficulties and worsening psychological functioning. [Read the Full Post]

Targeting Glutaminolysis Shows Efficacy in Both Prednisolone-Sensitive and in Metabolically Rewired Prednisolone-Resistant B-Cell Chi

15 | Aug 29 2023

The study revealed that prednisolone-resistant childhood acute lymphoblastic leukemia (cALL) cells exhibit significant alterations in metabolic pathways, including oxidative phosphorylation, glycolysis, amino acid metabolism, and activation of mTORC1 and MYC signaling, highlighting the potential therapeutic target of inhibiting glutamine metabolism. [Read the Full Post]

Selective Inhibition of L-type Amino Acid Transporter 1 Suppresses Cell Proliferation in Ovarian Clear Cell Carcinoma

23 | Aug 20 2023

Selective inhibition of L-type amino acid transporter 1 (LAT1) using nanvuranlat (JPH203) effectively suppresses cell proliferation via the mTOR pathway by inhibiting leucine uptake in ovarian clear cell carcinoma (OCCC), suggesting LAT1 as a potential therapeutic target for this aggressive ovarian cancer. [Read the Full Post]

Involvement of a flavoprotein, acetohydroxyacid synthase, in growth and riboflavin production in riboflavin-overproducing Ashbya gossypii mutant

73 | Aug 16 2023

This study demonstrates that branched-chain amino acids, particularly through the regulation of acetohydroxyacid synthase, play a crucial role in enhancing riboflavin production in the Ashbya gossypii mutant strain, offering a novel approach for optimizing riboflavin production in this organism. [Read the Full Post]

Dichloroacetic acid and rapamycin synergistically inhibit tumor progression

103 | Aug 15 2023

Rapamycin treatment leads to the inactivation of the pyruvate dehydrogenase complex (PDHc) through mTOR signaling inhibition, reducing cancer cells' response to rapamycin, while reactivating PDHc with dichloroacetic acid (DCA) enhances their susceptibility to rapamycin treatment. [Read the Full Post]

Fueling the Pipeline via Innovations in Organic Synthesis

16 | Aug 10 2023

Synthetic organic chemistry, particularly through the involvement of Discovery Synthesis Groups like AbbVie's Centralized Organic Synthesis (COS), is of paramount importance in the pharmaceutical industry as it accelerates the drug discovery process, addresses synthetic accessibility challenges, and contributes to the development of advanced drug candidates in various therapeutic areas. [Read the Full Post]

Novel Correctors and Potentiators Enhance Translational Readthrough in CFTR Nonsense Mutations

33 | Aug 10 2023

The study evaluated the effectiveness of novel CFTR correctors, potentiators, and readthrough compounds in restoring CFTR function in cells with premature-termination codon (PTC) mutations, showing promising results for the potential treatment of cystic fibrosis. [Read the Full Post]

Enhanced chemotherapeutic efficacy of docetaxel in human lung cancer cell line via GLUT1 inhibitor

23 | Aug 03 2023

The study demonstrated that co-administration of a GLUT1 inhibitor and docetaxel synergistically increased cytotoxicity and apoptosis in lung cancer cells, suggesting a promising therapeutic strategy for the treatment of lung cancer patients. [Read the Full Post]

Timely expression of PGAM5 and its cleavage control mitochondrial homeostasis during neurite re-growth after traumatic brain injury

48 | Jul 27 2023

The study reveals that phosphoglycerate mutase 5 (PGAM5) acts as a mitochondrial sensor in traumatic brain injury (TBI), promoting mitophagy and subsequent cleavage by PARL, leading to increased mitochondrial transcription factor A (TFAM) expression and functional recovery. [Read the Full Post]

pH-sensitive smart indicators based on cellulose and different natural pigments for tracing kimchi ripening stages

157 | Jul 27 2023

The study found that cellulose-based pH-sensitive indicators loaded with natural pigments showed more pronounced color changes in response to lactic acid and pH variations, with alkalized indicators being particularly effective for monitoring the fermentation process of acidic foods such as kimchi. [Read the Full Post]

Melatonin promotes orofacial antinociception in adult zebrafish by modulating TRP channels

90 | Jul 20 2023

Melatonin demonstrated an orofacial antinociceptive effect in adult zebrafish, which was associated with the modulation of TRP channels, particularly TRPV1. [Read the Full Post]

Mortality trends of aortic stenosis in high-income countries from 2000 to 2020

47 | Jul 18 2023

This study investigates recent mortality trends from aortic stenosis among eight high-income countries, revealing an increase in crude mortality rates but shifts towards decreasing trends in age-standardized rates in three countries and among individuals aged ≥80 years. [Read the Full Post]

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease

57 | Jul 18 2023

The study found that sotagliflozin, at a dose of 400 mg but not 200 mg, significantly reduced HbA1c levels compared to placebo after 26 weeks in adults with type 2 diabetes and stage 3 chronic kidney disease, while both doses showed reductions in urine albumin-creatinine ratio at week 26, but not sustained at week 52, and the safety profile was similar to previous reports. [Read the Full Post]

Inhibitors of the ATPase p97/VCP: From basic research to clinical applications

77 | Jul 17 2023

The development of p97 inhibitors as UPS-targeting cancer therapies represents a promising approach for addressing protein homeostasis deficiencies underlying various cancers and neurodegenerative diseases. [Read the Full Post]

Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells

31 | Jul 13 2023

This study describes the synthesis and evaluation of hybrid molecules combining sclareol and synthetic 1,2,4-triazolo[1,5-a]pyrimidines, resulting in compounds with improved cytotoxic properties, selectivity towards glioblastoma cells, and evasion of multidrug resistance. [Read the Full Post]

MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines

18 | Jul 13 2023

This study generated doxorubicin-resistant sublines of canine prostate adenocarcinoma and urothelial cell carcinoma cell lines, identifying drug efflux via MDR1 overexpression as a common mechanism, and suggesting the use of MDR1 inhibitors and combination therapies to address acquired chemoresistance. [Read the Full Post]

Empagliflozin and sacubitril/valsartan reverse methotrexate cardiotoxicity by repressing oxidative stress and hypoxia in heart embryonic H9c2 cardiomyocytes - the role of morphology of mitochondria observed on electron microscopy

73 | Jul 12 2023

S/V and EMPA treatment demonstrated significant reductions in HIF-1α levels and oxidative stress markers, along with increased antioxidant parameters and improved mitochondria morphology in H9c2 rat embryonic cardiomyocyte cells. [Read the Full Post]

Lymphatic-draining nanoparticles deliver Bay K8644 payload to lymphatic vessels and enhance their pumping function

37 | Jul 06 2023

This study showed that formulating S-(-)-Bay K8644 (BayK) within lymph-draining nanoparticles (NPs) improved lymphatic vessel function and effectively treated lymphatic dysfunction, providing a promising therapeutic approach. [Read the Full Post]

Investigations into the Signaling Pathways Involving Glucose-Stimulated Zinc Secretion (GSZS) from Prostate Epithelial Cells In Vitro and In Vivo

21 | Jul 06 2023

Exposure of prostate cells to high glucose leads to glucose-stimulated zinc secretion (GSZS) both in vitro and in vivo, requiring glycolytic flux and involving the activation of specific signaling pathways. [Read the Full Post]

Targeting of Glucose Transport and the NAD Pathway in Neuroendocrine Tumor (NET) Cells Reveals New Treatment Options

29 | Jul 06 2023

In this study, the effectiveness of glucose transporter (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as potential treatments for neuroendocrine tumors (NET) was demonstrated through significant effects on tumor cell proliferation and survival rates. [Read the Full Post]

Prosaposin PS18 reduces dopaminergic neurodegeneration in a 6-hydroxydopamine rat model of Parkinson's disease

21 | Jul 03 2023

PS18, a peptide derived from prosaposin, exhibits neuroprotective effects by reducing dopaminergic neuronal loss, apoptosis, and endoplasmic reticulum stress in cellular and animal models of Parkinson's disease. [Read the Full Post]

Synthesis and Preclinical Positron Emission Tomography Imaging of the p38 MAPK Inhibitor [11C]Talmapimod: Effects of Drug Efflux and Sex Differences

37 | Jun 27 2023

The development of the first positron emission tomography (PET) radiotracer for imaging MAPK p38α/β, synthesized through radiolabeling the inhibitor talmapimod with carbon-11, showed promising results but faced challenges regarding its non-displaceable binding and P-gp efflux. [Read the Full Post]

Characterization of Potent ABCG2 Inhibitor Derived from Chromone: From the Mechanism of Inhibition to Human Extracellular Vesicles for Drug Delivery

42 | Jun 27 2023

This study characterizes a potent ABCG2 inhibitor, C4a, and demonstrates its selectivity and efficacy in inhibiting ABCG2-mediated drug efflux, utilizing liposomes and extracellular vesicles for improved delivery and highlighting the potential of plasma circulating EVs as a drug delivery system for hydrophobic drugs targeting membrane proteins. [Read the Full Post]

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance

79 | Jun 19 2023

The 2023 statement on homozygous familial hypercholesterolaemia (HoFH) provides updated clinical guidance, emphasizing phenotypic features over genotype, prioritizing combination LDL-C-lowering therapy, and recommending the creation of national screening programs and education initiatives to address global inequities in HoFH care. [Read the Full Post]

Identification of Piperlongumine as Potent Inhibitor of Necroptosis

73 | Jun 14 2023

Piperlongumine, an alkaloid derived from the long pepper plant, has demonstrated potent anti-necroptosis effects by inhibiting the phosphorylation of RIPK1 and showed potential therapeutic value for inflammatory and neurodegenerative diseases associated with necroptosis. [Read the Full Post]

CFTR modulates aquaporin-mediated glycerol permeability in mouse Sertoli cells

26 | May 24 2023

This study explores the potential molecular partnership between CFTR and AQPs in mouse Sertoli cells and suggests that the malfunction of CFTR and the consequent alteration in glycerol permeability is a potential link between male infertility and cystic fibrosis. [Read the Full Post]

Renal tubular epithelial cells treated with calcium oxalate up-regulate S100A8 and S100A9 expression in M1-polarized macrophages via interleukin 6

29 | May 23 2023

This study demonstrates that M1-polarized macrophages are the main source of S100A8 and S100A9 in the kidneys of nephrolithiasis patients, and that COM-induced IL6 secretion from renal tubular epithelial cells can up-regulate their expression in macrophages. [Read the Full Post]

Kv1.3 blockade by ShK186 modulates CD4+ effector memory T-cell activity of patients with Granulomatosis with polyangiitis

48 | May 19 2023

The study suggests that Kv1.3 blockade using ShK-186 may be a potential treatment strategy for GPA by modulating the activity of CD4+TEM cells and reducing the production of pro-inflammatory cytokines, with less harmful side effects than current immunosuppressive regimens. [Read the Full Post]

Eradication of Mycobacterium abscessus infection in cystic fibrosis with initiation of Elexacaftor/Tezacaftor/Ivacaftor

22 | May 19 2023

This case highlights the potential positive impact of ETI, a CFTR modulator combination, on the treatment of challenging infections such as M. abscessus in CF. [Read the Full Post]

Regulation of neuropathic pain by microglial Orai1 channels

59 | May 14 2023

The study found that Orai1 channels are key regulators of microglial reactivity in neuropathic pain, with sex-specific effects observed in female mice. [Read the Full Post]

Pharmacological activation of PIEZO1 in human red blood cells prevents Plasmodium falciparum invasion

18 | May 11 2023

Pharmacological activation of the PIEZO1 channel using Yoda1 and Jedi2 induces echinocytosis, altering the shape and surface area of red blood cells, which prevents efficient invasion by Plasmodium falciparum, providing a potential therapeutic target for malaria prevention. [Read the Full Post]

Non-Nucleoside Inhibitors Decrease Foot-and-Mouth Disease Virus Replication by Blocking the Viral 3Dpol

50 | May 10 2023

The study used virtual screening and cell-based assays to identify potential inhibitors targeting the RNA-dependent RNA polymerase of Foot-and-mouth disease virus, and identified four compounds with antiviral activity. [Read the Full Post]

Effects of Ertugliflozin on Kidney Outcomes in Patients With Heart Failure at Baseline in the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS CV) Trial

33 | May 04 2023

The post hoc analysis of the VERTIS CV trial found that the beneficial effects of ertugliflozin on kidney outcomes were not affected by baseline heart failure status in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. [Read the Full Post]

A Cardiologists' Survey on the Use of Anticoagulants and Antiplatelets in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Those Undergoing Percutaneous Coronary Intervention in India

89 | Apr 22 2023

The survey found that in India, the majority of cardiologists use triple therapy (NOAC + dual antiplatelet) or NOAC + single antiplatelet therapy to manage patients with AF and ACS or undergoing PCI, with NOACs being the preferred anticoagulant and ticagrelor and clopidogrel being the preferred P2Y12 inhibitors. [Read the Full Post]

Microglial VDAC1 signaling modulates sleep deprivation-induced transition to chronic postsurgical pain

42 | Apr 18 2023

This study demonstrates that sleep deprivation before and after surgery increases the risk of chronic pain by activating spinal microglia, and that VDAC1 signaling regulates microglial activation-related ATP release, inflammation, and pain chronicity in mice. [Read the Full Post]

Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19

21 | Apr 10 2023

The research on Casiopeina-analogs as TMPRSS2 inhibitors and their interaction with the catalytic triad provides valuable insights into potential drug candidates for treating COVID-19. [Read the Full Post]

Inhibition of KIR2.1 decreases pulmonary artery smooth muscle cell proliferation and migration

39 | Apr 08 2023

The study demonstrates that KIR2.1 regulates the TGF‑β1/SMAD2/3 signaling pathway and the expression of OPN and PCNA proteins, thereby regulating the proliferation and migration of PASMCs and participating in PVR, which could inform the development of effective therapeutic drugs for PH. [Read the Full Post]

The Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Improving Morbidity and Mortality of Heart Failure: A Systematic Review

64 | Apr 04 2023

SGLT2 inhibitors have shown a beneficial effect in reducing cardiovascular mortality and morbidity in patients with type 2 diabetes mellitus and may have a broader application beyond diabetes. [Read the Full Post]

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

46 | Mar 24 2023

Lut-7-O-rutin has been found to have a protective effect on high-glucose-induced toxicity to RIN-5F cells and improve insulin secretion and glucose uptake through various molecular mechanisms. [Read the Full Post]

Preparation and evaluation of injectable microsphere formulation for longer sustained release of donepezil

46 | Mar 23 2023

The study developed an injectable formulation of donepezil using microspheres made of PLA or PLGA and a hydrogel wrapping, which showed sustained release and reduced inflammatory response compared to the PLGA microspheres alone. [Read the Full Post]

Lorazepam in catatonia - Past, present and future of a clinical success story

52 | Mar 14 2023

This passage discusses the history, effectiveness, and potential future directions for the use of lorazepam in the treatment of catatonia, emphasizing the importance of empirical observation and clinical practice, while also calling for further scientific investigation. [Read the Full Post]

Loss of TRPV4 Cation Channel Inhibition of Macrophage Infiltration and Neovascularization in a Mouse Cornea

78 | Mar 12 2023

This study shows that TRPV4 plays a role in injury-induced neovascularization in the corneal stroma and may be a potential therapeutic target to prevent unfavorable neovascularization post-injury. [Read the Full Post]

Concentration dependence of active potassium transport in the human red blood cell in the presence of inhibitors

108 | Mar 09 2023

The passage describes the inhibition of active potassium influx in human red blood cells by several compounds, including strophanthidin, ethacrynic acid, and MK-870, and suggests a model for the behavior of the transport system in the presence of these compounds and potassium ions. [Read the Full Post]

Metabolic characterization and GAPDH dependent regulation of ENaC in hPheo1 wild-type and SDHB knockdown cells

50 | Mar 08 2023

The study investigates the expression and activity of ENaC and ASIC ion channels in hPheo1 WT and SDHB KD cells, which may provide important insights into understanding and treating SDHB-related disease. [Read the Full Post]

In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs

98 | Mar 07 2023

The study used mouse hypothermia as an in vivo screen for adenosinergic effects and identified several drugs that interact with adenosine receptors (ARs) in different ways, suggesting potential for repurposing and highlighting the importance of considering multiple mechanisms of action and potential off-target effects. [Read the Full Post]

Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway

38 | Mar 07 2023

The study found that the combination of atomoxetine and trazodone (Ato-Trazo) reduced obstructive sleep apnea severity without reducing the arousal threshold, but worsened subjective sleep quality. [Read the Full Post]

A case of ascetic fluid Mycobacterium aubagnense infection in a patient with severe peritoneal effusion

91 | Feb 27 2023

This is a case report of the first instance of Mycobacterium aubagnense being isolated from ascites in a patient with severe peritoneal effusion, highlighting the need for further research to determine the clinical significance of the infection and effective treatment strategies. [Read the Full Post]

Predictors of Poor Very Early Diuretic Response and Effectiveness of Early Tolvaptan in Symptomatic Acute Heart Failure

30 | Feb 27 2023

Early administration of tolvaptan (TLV) in patients with acute decompensated heart failure (ADHF) who have a predicted poor diuretic response (DR) can improve DR and reduce the risk of worsening renal function, according to a multicenter retrospective study. [Read the Full Post]

The Impact of N-nitrosamine Impurities on Clinical Drug Development

83 | Feb 26 2023

The presence of N-nitrosamine impurities in commercially available drugs has led to shortages of marketed drugs and complications in the clinical development of new investigational products, with alternative approaches being sought for commonly employed perpetrators in DDI studies. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

130 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

159 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation

47 | Feb 25 2023

Dapagliflozin, a SGLT2 inhibitor, improves cardiac function in doxorubicin-induced dilated cardiomyopathy by suppressing the activation of the NLRP3 inflammasome through decreased p38-dependent TLR4 expression. [Read the Full Post]

Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor

17 | Feb 25 2023

Our study found that high glucose conditions in kidney cells altered the metabolomic profile, and treatment with SGLT2 inhibitor dapagliflozin led to significant changes in the levels of metabolites such as asparagine, PC ae C34:1 and PC ae C36:2 in tubular epithelial cells, and PC aa C32:0 in podocytes, which affected multiple metabolic pathways. [Read the Full Post]

Combinational Inhibition of P-Glycoprotein-Mediated Etoposide Transport by Zosuquidar and Polysorbate 20

43 | Feb 22 2023

The study found that while combination of zosuquidar and polysorbate 20 showed additive P-gp inhibition in vitro, oral etoposide bioavailability decreased when co-administered with both agents in vivo due to high level of nonspecific zosuquidar adsorption. [Read the Full Post]

The study of Raddeanin A cerebrovascular endothelial cell trafficking through P-glycoprotein

49 | Feb 22 2023

Raddeanin A, a natural triterpenoid, is transported through the brain-blood barrier by P-glycoprotein and its transport is affected by its expression and function, providing important guidance on its pharmacodynamic effect in human brains. [Read the Full Post]

Roles of light transmission aggregometry and CYP2C19 genotype in predicting ischaemic complications during interventional therapy for intracranial aneurysms

83 | Feb 19 2023

The study concluded that maximum platelet aggregation induced by ADP (ADP-MPA) can predict ischaemic events during endovascular treatment of intracranial aneurysms and patients with flow diverters require stronger antiplatelet medication than patients with traditional stents. [Read the Full Post]

Long-term risk, clinical management, and healthcare resource utilization of stable patients with coronary artery disease and post-myocardial infarction in Greece-TIGREECE study

41 | Feb 19 2023

In Greece, one in ten patients experience a recurring cardiovascular event or death, mainly of ischemic origin, 1-3 years post myocardial infarction, according to results from the TIGREECE study. [Read the Full Post]

Crusted scabies in AIDS patient, a clinical challenge to be sorted out with a simple bedside test

71 | Feb 17 2023

A case of crusted scabies, a severe and highly contagious variant of scabies, was reported in an AIDS patient with hyperpigmented macules covered in thick crusts on the axilla, inguinal region, and gluteal region, and was treated with ivermectin, permethrin, and keratolytics after a KOH microscopy revealed a population of more than 1 million mites. [Read the Full Post]

A pilot study of chemotherapy combinations in rats: Focus on mammary cancer treatment in female dogs

95 | Feb 17 2023

This study found that the bioavailability of carboplatin increased when combined with ivermectin and cyclophosphamide in rats, but with a higher increase in the latter, suggesting a slight reduction in carboplatin's dose when combined with cyclophosphamide to avoid increased adverse effects. [Read the Full Post]

Effect of Gubenyiliu formula II and its disassembled prescriptions on cell autophagy in breast cancer through PI3K/AKT/mTOR pathway

145 | Feb 12 2023

This study confirmed that GYII can effectively treat breast cancer by inhibiting the PI3K/AKT/mTOR signaling pathway-mediated autophagy, while QX and FZ have different effects on tumor growth and metastasis. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

172 | Feb 12 2023

A novel method called "gene module pair-based target identification (GMPTI)" was developed to predict the targets of new compounds using consensus gene modules extracted from transcriptional profiles induced by perturbagens of known targets, resulting in the discovery of novel inhibitors for three PI3K pathway proteins. [Read the Full Post]

Mutual Effects of Single and Combined CFTR Modulators and Bacterial Infection in Cystic Fibrosis

23 | Jan 28 2023

Cristina Cigana et al. suggested optimizing host- and pathogen-directed therapies to improve efficacy for personalized treatment. [Read the Full Post]

The complement system in antineutrophil cytoplasmic antibody-associated vasculitis: pathogenic player and therapeutic target

46 | Dec 13 2022

Martina Mazzariol et al. found that avacopan, a C5aR inhibitor, showed beneficial effects in AAV and representd a promising therapy to achieve sustained remission and to spare glucocorticoids. [Read the Full Post]

Identification of potential drug targets for vascular dementia and carotid plaques by analyzing underlying molecular signatures shared by them

40 | Dec 13 2022

Jun Shu et al.found that inflammatory and immune-related processes be a crucial common pathophysiological mechanism shared by VaD and carotid plaques. [Read the Full Post]

OXPHOS deficiency induces mitochondrial DNA synthesis through non-canonical AMPK-dependent mRNA compartmentalization

20 | Nov 24 2022

Milon Banik et al. inferred that AMPK was locally activated by inhibition of the F1F0 ATP synthase to stimulate association of mtDNA replication factor mRNAs, leading to stimulation of mtDNA synthesis. [Read the Full Post]

Treatment effects of Elexacaftor/Tezacaftor/Ivacaftor in people with CF carrying non-F508del mutations

33 | Nov 18 2022

Galit Livnat et al. demonstrated the clinical efficacy of ETI in pwCF carrying CFTR processing non-F508del mutations which were predicted to respond by in vitro studies. [Read the Full Post]

Helicobacter pylori-infected human neutrophils exhibit impaired chemotaxis and a uropod retraction defect

24 | Nov 08 2022

Allan Prichard et al. suggested that H. pylori inhibited the dynamic changes in myosin IIA contractility and front-to-back polarity that were essential for chemotaxis. [Read the Full Post]

Cardiac Sodium/Hydrogen Exchanger (NHE11) as a Novel Potential Target for SGLT2i in Heart Failure: A Preliminary Study

42 | Oct 28 2022

Lorena Pérez-Carrillo et al. showed alterations in several sodium transports and reinforced the importance of channels in HF progression. [Read the Full Post]

The XPO1 Inhibitor KPT-8602 Ameliorates Parkinson's Disease by Inhibiting the NF-κB/NLRP3 Pathway

35 | Oct 19 2022

Shuhan Liu et al. indicated that KPT-8602 could be used as a novel potential therapeutic agent for the treatment of inflammasome-related diseases such as Parkinson's disease, through the regulation of the NF-κB signaling pathway and the NLRP3 inflammasome. [Read the Full Post]

Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide

24 | Oct 18 2022

Katharina Otte et al. concluded that monotherapy with Eltanexor effectively induced apoptosis in GBM cells and could be combined with current adjuvant therapies to provide a more effective therapy of GBM. [Read the Full Post]

Pharmacologic inhibition of LAT1 predominantly suppresses transport of large neutral amino acids and downregulates global translation in cancer cells

19 | Sep 17 2022

Kou Nishikubo et al. demonstrated a predominant contribution of LAT1 to the transport of large neutral amino acids in cancer cells and the suppression of protein synthesis by JPH203 supposed to underly its broad anti-proliferative effects across various types of cancer cells. [Read the Full Post]

Impact of CFTR Modulators on Beta-Cell Function in Children and Young Adults with Cystic Fibrosis

26 | Aug 09 2022

Claudia Piona et al. showed that treatment of CF patients with CFTR modulators did not significantly ameliorate glucose homeostasis and/or any of its direct determinants. [Read the Full Post]

Selinexor in Patients from Argentina with Multiple Myeloma Treated with Multiple Prior Therapies: A Case Series

113 | Jul 15 2022

Guillermina Remaggi et al. thought that selinexor might help to address an important clinical need in the treatment of patients with relapsed/refractory MM. [Read the Full Post]

Enhancement of MDM2 inhibitory effects through blocking nuclear export mechanisms in ovarian cancer cells

84 | Jul 14 2022

Amal Alzahrani et al. confirmed that the combination of Selinexor with RG-7388 could induce a caspase-mediated apoptotic mechanism via up-regulation of p53 and p21. [Read the Full Post]

Chest computed tomography improvement in patients with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: Early report

47 | Jul 07 2022

Romain Bec et al. found that ETI decreased pulmonary and sinus morphological abnormalities after one year of treatment. [Read the Full Post]

Effect of Lactate Export Inhibition on Anaplastic Thyroid Cancer Growth and Metabolism

124 | Jun 17 2022

Bixiao Zhao et al. thought that targeting suppression of glycolytic and lactate processing pathways might represent an effective treatment strategy for ATC. [Read the Full Post]

Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis

103 | Jun 05 2022

Koya Ono et al. found that defective heme biosynthesis in XLSA clones could confer enhanced BACH1 expression, leading to increased susceptibility to ferroptosis. [Read the Full Post]

Dihydroquercetin Attenuates Silica-Induced Pulmonary Fibrosis by Inhibiting Ferroptosis Signaling Pathway

167 | Jun 02 2022

Leyong Yuan et al. found that inhibition of ferritinophagy-mediated HBE cells ferroptosis was responsible for DHQ to ameliorate SiO2-induced lung fibrosis, which provided a preliminary theoretical basis for the clinical application of DHQ in the treatment of silicosis. [Read the Full Post]

LAMP2-regulates-autophagy-in-the-thymic-epithelium-and-thymic-stroma-dependent-CD4-T-cell-development

181 | May 31 2022

Pedro M Rodrigues et al. suggested that LAMP2 interconnected the autophagy-lysosomal axis and the processing of selecting self-peptides:MHC II complexes in cTECs, underling its implications for the generation of a broad CD4 TCR repertoire. [Read the Full Post]

The role of autophagy in cadmium-induced acute toxicity in glomerular mesangial cells and tracking polyubiquitination of cytoplasmic p53 as a biomarker

183 | May 30 2022

Ki-Tae Jung et al. indicated that cytoplasmic polyUb-p53 was a potential biomarker for Cd-induced acute toxicity in mesangial cells. [Read the Full Post]

Primary Human Nasal Epithelial Cells: Biobanking in the Context of Precision Medicine

121 | May 13 2022

Mairead Kelly et al. showed that dual therapies combining a CFTR corrector with a CFTR potentiator had a comparable correction efficacy for CFTR activity in F508del-homozygous HNE cells. [Read the Full Post]

Discovery of novel 7,8-dihydropteridine-6(5H)-one-based DNA-PK inhibitors as potential anticancer agents via scaffold hopping strategy

86 | May 13 2022

Zongbao Ding et al. thought that DK1 was a novel DNA-PK inhibitor with great promise for further study. [Read the Full Post]

Interferon-γ increases sensitivity to chemotherapy and provides immunotherapy targets in models of metastatic castration-resistant prostate cancer

92 | Apr 25 2022

Dimitrios Korentzelos et al. suggested that IFNγ might be useful in combinatorial regimens to induce sensitivity to immunotherapy and chemotherapy in hepatic metastases of mCRPC. [Read the Full Post]

Erythrocyte-cancer Hybrid Membrane-camouflaged Mesoporous Silica Nanoparticles Loaded with Gboxin for Glioma-targeting Therapy

372 | Apr 15 2022

Xiuxiu Jiao et al. found that the (MSNs/Gboxin)@[RBC-U] exhibited significant anti-cancer effected in vitro and the specific self-recognition to GBM cells. [Read the Full Post]

An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer

244 | Apr 15 2022

Jing Xu et al. suggested that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients. [Read the Full Post]

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

157 | Apr 04 2022

Kuerbannisha Amahong et al. thought that EgGLUT1-ss was crucial for glucose uptake by the protoscoleces of E. granulosus s.s., and its inhibitor WZB117 had a therapeutic effect on CE. [Read the Full Post]

The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation

192 | Mar 13 2022

Feng Wang et al. found UPCDC-30245 exhibited antiviral effects against coronavirus by blocking viral entry. [Read the Full Post]

P-Glycoprotein (ABCB1/MDR1) and BCRP (ABCG2) Limit Brain Accumulation and Cytochrome P450-3A (CYP3A) Restricts Oral Exposure of the RET Inhibitor Selpercatinib (RETEVMO)

126 | Feb 28 2022

Yaogeng Wang et al. thought that CYP3A-mediated metabolism could limit selpercatinib oral exposure and hence its tissue concentrations. [Read the Full Post]

Acyclovir Brain Disposition: Interactions with P-gp, Bcrp, Mrp2, and Oat3 at the Blood-Brain Barrier

225 | Feb 27 2022

Yuheng Shan et al. demonstrated that P-gp, Bcrp, Mrp2, and Oat3 inhibition increased the penetration of acyclovir across the BBB, supporting the hypothesis that these efflux pumps restrict the distribution of acyclovir in the brain. [Read the Full Post]

CFTR limits F-actin formation and promotes morphological alignment with flow in human lung microvascular endothelial cells

210 | Jan 25 2022

Adam J Causer showed that CFTR appeared to limit cytosolic actin polymerization, while maintaining a cortical rim actin distribution that was important for maintaining barrier integrity and promoting alignment with flow, without effects on endothelial nitrite or ET-1 production. [Read the Full Post]

PET imaging to assess the impact of P-glycoprotein on pulmonary drug delivery in rats

225 | Jan 24 2022

Irene Hernández-Lozano et al. found that P-gp could affect the pulmonary disposition of inhaled P-gp substrates. [Read the Full Post]

Prediction of Real-World Long-Term Outcomes of People with CF Homozygous for the F508del Mutation Treated with CFTR Modulators

169 | Dec 27 2021

Danya Muilwijk et al. thought that the PEx rate prior to CFTR modulator treatment initiation, sex and SwCl at baseline could be potential predictors of long-term PEx rate and of changes in SwCl after modulator initiation. [Read the Full Post]

Identification of Novel Kinase-Transcription Factor-mRNA-miRNA Regulatory Network in Nasopharyngeal Carcinoma by Bioinformatics Analysis

173 | Dec 15 2021

Li Gao et al. identified DEGs and an NPC regulatory network involving kinases, TFs, mRNAs, and miRNAs, which might provide promising insight into the pathogenesis, treatment, and prognosis of NPC. [Read the Full Post]

Healthcare resource utilization in patients treated with empagliflozin in East Asia

295 | Dec 04 2021

Wayne H-H Sheu et al. found that empagliflozin treatment was associated with lower inpatient care needs and other healthcare resource utilization than DPP-4 inhibitors in routine clinical practice in East Asia in this study. [Read the Full Post]

PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia

258 | Nov 25 2021

Inge Govaerts et al. thought that the antileukemic effect of PSEN1-selective gamma-secretase inhibition could be synergistically enhanced by the addition of other targeted inhibitors. [Read the Full Post]

Nuclear Export Inhibitor KPT-8602 Synergizes with PARP Inhibitors in Escalating Apoptosis in Castration Resistant Cancer Cells

0 | Nov 24 2021

Md Hafiz Uddin et al. found that KPT-8602 with or without olaparib reduced homologous recombination-regulated DNA damage response targets including BRCA1, BRCA2, CHEK1, EXO1, BLM, RAD51, LIG1, XRCC3 and RMI2. [Read the Full Post]

LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence

240 | Oct 26 2021

Tomoki Bo et al. showed that JPH203 might be a potent anti-cancer drug in combination with radiation therapy. [Read the Full Post]

Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR

284 | Sep 14 2021

David Drummond et al. suggested a potential beneficial effect of CFTR modulators on CF liver disease and warrant further investigation in larger, prospective studies. [Read the Full Post]

Neurocytological Advances in the Treatment of Glioblastoma Multiforme

275 | Aug 22 2021

Brian Fiani et al. discussed the recent neurocytological treatment strategies for GMB and the results of the studies. [Read the Full Post]

Optimal Supportive Care With Selinexor Improves Outcomes in Patients With Relapsed/Refractory Multiple Myeloma

331 | Aug 22 2021

Ajai Chari et al. suggested that in addition to more frequent dose reductions, prompter and more aggressive supportive care might have contributed to the low discontinuation rate, longer duration therapy, and greater efficacy rates observed in the MSSM cohort. [Read the Full Post]

A Precision Medicine Approach to Optimize Modulator Therapy for Rare CFTR Folding Mutants

276 | Aug 13 2021

Guido Veit et al. thought that HNE, as a precision medicine model, enabled the optimization of mutation-specific modulator combinations to maximize their efficacy and minimize life-long drug exposure of CF patients. [Read the Full Post]

Oncogenic Chromatin Modifier KAT2A Activates MCT1 to Drive the Glycolytic Process and Tumor Progression in Renal Cell Carcinoma

254 | Jul 27 2021

Yuanyuan Guo et al. proposed that MCT1 inhibitor (AZD3965) was useful for suppressing RCC. [Read the Full Post]

Mechanism of Ferroptosis and Its Role in Type 2 Diabetes Mellitus

486 | Jul 15 2021

Wenxin Sha et al. summarized the mechanism of ferroptosis and especially its association with type 2 diabetes mellitus (T2DM). [Read the Full Post]

Detection of autophagic flux in primary cerebral cortical neurons after oxygen glucose deprivation/reperfusion (OGD/R) using various methods

506 | Jul 12 2021

Lei Zhang et al. showed that different methods and indicators could be used to monitor different stages of autophagy. [Read the Full Post]

Inhibition of DNA-PK with AZD7648 Sensitizes Tumor Cells to Radiotherapy and Induces Type I IFN-Dependent Durable Tumor Control

264 | Jun 22 2021

Kyoko Nakamura et al. found that blocking the NHEJ DNA repair pathway with AZD7648 in combination with RT leaded to durable immune-mediated tumor control. [Read the Full Post]

Partial Rescue of F508del-CFTR Stability and Trafficking Defects by Double Corrector Treatment

293 | Jun 21 2021

Valeria Capurro et al. thought that it was still possible to further improve mutant CFTR rescue with the development of corrector combinations having maximal effects on mutant CFTR structural and functional properties. [Read the Full Post]

GDI2 is a target of paclitaxel that affects tumorigenesis of prostate cancer via the p75NTR signaling pathway

300 | May 31 2021

Chi Liu et al. found that knocking down of GDI2 inhibited cell proliferation and promoted cell apoptosis via the p75NTR signaling pathway in prostate cancer. [Read the Full Post]

Nonsense-mediated mRNA decay efficiency influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) knock-in mice

626 | May 10 2021

Zhanli Xie et al. found that NMD efficiency potentially influenced bleeding severity in ITGA2B c.2659C > T (p.Q887X) KI mice. [Read the Full Post]

High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer

572 | May 10 2021

Vikas Satyananda et al. thought that BRCA2 gene expression might become a candidate marker for aggressive biology and to tailor specific treatment strategies in the future. [Read the Full Post]

Involvement of GLUT1 and GLUT3 in the growth of canine melanoma cells

427 | Apr 25 2021

Yoko Suwabe et al. suggested that glucose uptake via GLUT1 and GLUT3 played a crucial role for the growth of canine melanoma cells. [Read the Full Post]

A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells

405 | Mar 26 2021

Gang Zhang et al. identified and characterized PPA as a selective covalent p97 inhibitor, which would allow future exploration to improve the potency of p97 inhibitors with different mechanisms of action. [Read the Full Post]

The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice

376 | Mar 10 2021

Belén Vicente et al. thought that even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model. [Read the Full Post]

Optimization of dose and route of administration of the P-glycoprotein inhibitor, valspodar (PSC-833) and the P-glycoprotein and breast cancer resistance protein dual-inhibitor, elacridar (GF120918) as dual infusion in rats

388 | Mar 09 2021

Christopher Rowbottom rt al. demonstrated that doses greater than 0.9 mg/hr/kg valspodar and 8.9 mg/hr/kg elacridar were sufficient to inhibit P-gp- and BCRP-mediated efflux at the blood-brain barrier in rats without any tolerability issues. [Read the Full Post]

Transcriptomic analysis of CFTR-impaired endothelial cells reveals a pro-inflammatory phenotype

276 | Feb 01 2021

Mathias Declercq et al. thought that normalisation of vascular inflammation might be a novel therapeutic strategy to ameliorate the disease severity of CF. [Read the Full Post]

Relation of Metal-Binding Property and Selective Toxicity of 8-Hydroxyquinoline Derived Mannich Bases Targeting Multidrug Resistant Cancer Cells

404 | Jan 31 2021

Veronika F S Pape et al. showed that the MDR-selective anticancer activity of the studied 8-hydroxyquinoline derived Mannich bases was associated with the iron deprivation of MDR cells and the preferential formation of redox-active copper(II) complexes, which underwent intracellular redox-cycling to induce oxidative stress. [Read the Full Post]

Repurposing FDA approved drugs inhibiting mitochondrial function for targeting glioma-stem like cells

398 | Jan 11 2021

Sandipan Datta et al. demonstrated that FDA-approved mitochondrial inhibitors induced GSC-selective cytotoxicity, and targeting mitochondrial function could present a potential therapeutic option for GBM treatment. [Read the Full Post]

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

290 | Jan 05 2021

Renée V E Dagenais et al. thought that pharmacists played a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies. [Read the Full Post]

Switching between blebbing and lamellipodia depends on the degree of Nonmuscle Myosin II activity

334 | Dec 26 2020

Indranil Ghosh et al. revealed that relative activity of ROCK and MLCK, which controled both NMII's ATPase activity and filamentous property was a determining factor for a cell to exhibit blebbing or lamellipodia. [Read the Full Post]

Empagliflozin and the Diabetic Kidney: Pathophysiological Concepts and Future Challenges

457 | Dec 16 2020

Georgios S Papaetis discussed the safety of empagliflozin therapy and its future role in order to ameliorate the global burden of CKD both in patients with and without diabetes. [Read the Full Post]

The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia

393 | Dec 07 2020

Delphine Verbeke et al. demonstrated that KPT-8602 enhanced the effects of dexamethasone to inhibit B-ALL and T-ALL cells via NR3C1- and E2F-mediated transcriptional complexes, allowing to achieve increased dexamethasone effects for patients. [Read the Full Post]

Melphalan and Exportin 1 Inhibitors Exert Synergistic Antitumor Effects in Preclinical Models of Human Multiple Myeloma

364 | Dec 06 2020

Joel G Turner et al. found that inhibition of exportin 1 with selinexor synergistically sensitizeed human multiple myeloma to melphalan by inhibiting Fanconi anemia pathway-mediated DNA repair. [Read the Full Post]

Small molecule inhibitors provide insights into the relevance of LAT1 and LAT2 in materno-foetal amino acid transport

296 | Nov 04 2020

Jonas Zaugg et al. thought that differential specificity of the applied inhibitors allowed for estimation of the contribution of LAT1 and LAT2 in materno-foetal AA transfer and their potential impact in pregnancy diseases associated with impaired foetal growth. [Read the Full Post]

An integrated drug repurposing strategy for the rapid identification of potential SARS-CoV-2 viral inhibitors

302 | Sep 01 2020

Alfonso Trezza et al. showed that Simeprevir and Lumacaftor bound the receptor-binding domain of the Spike protein with high affinity and prevented ACE2 interaction. [Read the Full Post]

In Vitro and In Vivo Efficacy of AZD3965 and Alpha-Cyano-4-Hydroxycinnamic Acid in the Murine 4T1 Breast Tumor Model

0 | Aug 07 2020

Xiaowen Guan et al. indicated AZD3965 is a potent MCT1 inhibitor that accumulates to high concentrations in 4T1 xenograft tumors, where it increases tumor lactate concentrations and produces beneficial effects on markers of TNBC [Read the Full Post]

Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition

296 | Jul 30 2020

Isabel Jiménez et al. highlighted the pathogenic role of the innate immune microenvironment in PCNSL and provided pre-clinical evidence for the development of selinexor and ibrutinib as a new promising therapeutic option with cytotoxic and immunomodulatory potential. [Read the Full Post]

Clinical Utility of Selinexor/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma: A Review of Current Evidence and Patient Selection

285 | Jul 30 2020

Panagiotis Malandrakis et al. showed that selinexor was a new anti-myeloma drug that seemed to be effective in patients who had no other therapeutic options, including patients who had received novel cellular therapies such as CAR-T cells. [Read the Full Post]

The impact of ivacaftor on sinonasal pathology in S1251N-mediated cystic fibrosis patients

408 | Jul 21 2020

Romee Gostelie et al. found that Ivacaftor appeared to improve sinonasal outcome parameters and thereby sinonasal health in patients with cystic fibrosis with an S1251N mutation. [Read the Full Post]

In Vitro and In Vivo Efficacy of AZD3965 and Alpha-Cyano-4-Hydroxycinnamic Acid in the Murine 4T1 Breast Tumor Model

380 | Jun 25 2020

Xiaowen Guan et al. indicated AZD3965 was a potent MCT1 inhibitor that accumulated to high concentrations in 4T1 xenograft tumors, where it increased tumor lactate concentrations and produced beneficial effects on markers of TNBC [Read the Full Post]

HMGB1-induced Aberrant Autophagy Contributes to Insulin Resistance in Granulosa Cells in PCOS

518 | Jun 04 2020

Chuyue Zhang et al. indicated that increased HMGB1 contributes to IR development in granulosa cells of PCOS patients, which was associated with exacerbation of autophagy by HMGB1. Control of HMGB1 production might be benefical for the improvement of insulin sensitivity in granulosa cells in PCOS. [Read the Full Post]

Berberine Represses Human Gastric Cancer Cell Growth in Vitro and in Vivo by Inducing Cytostatic Autophagy via Inhibition of MAPK/mTOR/p70S6K and Akt Signaling Pathways

491 | Jun 04 2020

Qiang Zhang et al. indicated that berberine repressed human gastric cancer cell growth in vitro and in vivo by inducing cytostatic autophagy via inhibition of MAPK/mTOR/p70S6K and Akt, and provided a molecular basis for the treatment of gastric cancer. [Read the Full Post]

Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential

376 | Apr 14 2020

Rauscher AÁ et al. discussed the pharmacological perspectives of these efforts, as myosins are becoming promising drug target candidates for a variety of conditions ranging from neurodegeneration to muscle disease, wound healing, and cancer metastasis. [Read the Full Post]

How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial

569 | Mar 12 2020

Inzucchi SE et al. indicated in this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo. [Read the Full Post]

The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity Against Acute Lymphoblastic Leukemia

367 | Mar 01 2020

Thomas Vercruysse et al. showed that KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. [Read the Full Post]

Nuclear-Cytoplasmic Transport Is a Therapeutic Target in Myelofibrosis

430 | Feb 28 2020

Dongqing Yan et al. implicated NCT as a potential therapeutic target in myelofibrosis and provide a rationale for clinical evaluation in ruxolitinib-exposed patients with myelofibrosis. [Read the Full Post]

JPH203, a selective L-type amino acid transporter 1 inhibitor, induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells

441 | Jan 08 2020

Choi DW et al. suggested that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells. [Read the Full Post]

Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR

414 | Nov 12 2019

Loo TW et al. suggested that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. [Read the Full Post]

KPT-330 inhibition of chromosome region maintenance 1 is cytotoxic and sensitizes chronic myeloid leukemia to Imatinib

381 | Oct 13 2019

Nie D et al. indicated that KPT-330 showed anti-leukemic activity and sensitized CML to IM in CRM1-dependent manner in vitro and in vivo. KPT-330 represents an alternative therapy for IM-refractory CML, warranting further investigation of CRM1 as therapeutic target. [Read the Full Post]

Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis

539 | Oct 10 2019

Machlus KR et al. revealed (1) the mechanism of selinexor-induced thrombocytopenia, (2) an effective way to reverse the dose-limiting thrombocytopenia, and (3) a novel role for XPO1 in megakaryopoiesis. The improved selinexor dosing regimen described herein is crucial to help reduce thrombocytopenia in selinexor patients, allowing them to continue their course of chemotherapy and have the best chance of survival. [Read the Full Post]

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

823 | Sep 29 2019

Veit G et al. indicated that VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. [Read the Full Post]

Bafilomycin A1 disrupts autophagic flux by inhibiting both V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion

463 | Sep 07 2019

Mauvezin C et al. identified the ER-calcium ATPase Ca-P60A/dSERCA as a novel target of bafilomycin A1. Autophagosome-lysosome fusion was defective in Ca-P60A/dSERCA-depleted cells, and bafilomycin A1 induced a significant increase in cytosolic calcium concentration and disrupted Ca-P60A/SERCA-mediated fusion. Thus, bafilomycin A1 disrupts autophagic flux by independently inhibiting V-ATPase-dependent acidification and Ca-P60A/SERCA-dependent autophagosome-lysosome fusion. [Read the Full Post]

Treatment of γ-Hydroxybutyric Acid and γ-Butyrolactone Overdose with Two Potent Monocarboxylate Transporter 1 Inhibitors, AZD3965 and AR-C155858

863 | Aug 26 2019

Follman KE et al. indicated that inhibition of MCT1 is an effective treatment of GHB/GBL overdose. [Read the Full Post]

Inhibition of the amino-acid transporter LAT1 demonstrates anti-neoplastic activity in medulloblastoma

482 | Aug 10 2019

Cormerais Y et al. demonstrated that a long-term treatment with JPH203 does not lead to resistance in MB cells. Therefore, this study suggests that targeting LAT1 with JPH203 is a promising therapeutic approach for MB treatment. [Read the Full Post]

Bafilomycin A1 triggers proliferative potential of senescent cancer cells in vitro and in NOD/SCID mice

523 | Aug 01 2019

Was H et al. suggested that senescent cancer cells that appear during therapy, can be considered as dormant cells that contribute to cancer re-growth, when chemotherapeutic treatment is stopped. These data unveil new mechanisms of TIS-related cancer maintenance and re-population, triggered by a single pulse of BAF A1 treatment. [Read the Full Post]

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia

554 | Mar 14 2019

Chen C et al. concluded that selinexor in combination with dexamethasone is active in heavily pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone given twice weekly. This trial was registered at clinicaltrials.gov as #NCT01607892. [Read the Full Post]

Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer

536 | Mar 14 2019

Arango NP et al. showed that Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC50 > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively). [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

0 | Feb 16 2019

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9

694 | Feb 12 2019

Guo D et al. found that pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

0 | Jan 20 2019

Sun F et al. indicated the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]

Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation

537 | Jan 18 2019

Accurso FJ et al. evaluated the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. [Read the Full Post]

Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis

585 | Jan 17 2019

Rowe SM et al. showed that CFTR modulator therapy with tezacaftor-ivacaftor or ivacaftor alone was efficacious in patients with cystic fibrosis who were heterozygous for the Phe508del deletion and a CFTR residual-function mutation. [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

756 | Jan 16 2019

Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]

CFTR protects against vascular inflammation and atherogenesis in apolipoprotein E-deficient mice

530 | Jan 08 2019

Li Z et al. suggested that CFTR may present a potential therapeutic target for the treatment of vascular inflammation and development of atherosclerotic disease. [Read the Full Post]

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

0 | Dec 28 2018

Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]

Spinal Glutamate Transporters Are Involved in the Development of Electroacupuncture Tolerance

1130 | Dec 16 2018

Cui L et al. indicated the participation of the spinal GTs in EAT. [Read the Full Post]

Transcriptomic profiling of a chicken lung epithelial cell line (CLEC213) reveals a mitochondrial respiratory chain activity boost during influenza virus infection

600 | Dec 10 2018

Meyer L et al. suggested that AIV is able to boost the metabolic capacities of its avian host in order to provide the important energy needs required to produce progeny virus. [Read the Full Post]

Cellular uptake pathways of sepiolite nanofibers and DNA transfection improvement

626 | Nov 27 2018

Castro-Smirnov FA et al. showed that sepiolite can be spontaneously internalized into mammalian cells through both non-endocytic and endocytic pathways, macropinocytosis being one of the main pathways. Interestingly, exposure of the cells to endocytosis inhibitors, such as chloroquine, two-fold increase the efficiency of sepiolite-mediated gene transfer, in addition to the 100-fold increased resulting from sepiolite sonomechanical treatment. As sepiolite is able to bind various biological molecules, this nanoparticulate silicate could be a good candidate as a nanocarrier for simultaneous vectorization of diverse biological molecules. [Read the Full Post]

Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor

644 | Nov 23 2018

Shao BZ et al. demonstrated for the first time that activating α7nAChR enhances monocyte/microglia autophagy, which suppresses neuroinflammation and thus plays an alleviative role in EAE. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

0 | Nov 20 2018

Chufan EE et al. revealed that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

Myosin-IIA regulates leukemia engraftment and brain infiltration in a mouse model of acute lymphoblastic leukemia

525 | Nov 14 2018

Wigton EJ et al. implicated myosin-IIA as a key mediator of leukemia cell migration, making it a promising target to inhibit leukemia dissemination in vivo and potentially reduce leukemia relapses. [Read the Full Post]

High-expressing cystic fibrosis transmembrane conductance regulator interacts with histone deacetylase 2 to promote the development of Ph+ leukemia through the HDAC2-mediated PTEN pathway

0 | Oct 04 2018

Yan T et al. provides strong evidence that high-expression CFTR plays an important role in the development of Ph+ leukemia through the HDAC2-mediated PTEN pathway. [Read the Full Post]

SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery

851 | Sep 23 2018

Han Y et al. suggested that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

0 | Sep 17 2018

Tao YF et al. may provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

1066 | Sep 14 2018

Sun F et al. found that the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]

Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma

1621 | Sep 13 2018

Fan TF et al. found that inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma. [Read the Full Post]

Disruption of clathrin-dependent trafficking results in the failure of grass carp reovirus cellular entry

1449 | Sep 08 2018

Wang H et al. suggested that GCRV might enter CIK cells via clathrin-mediated endocytosis in a pH-dependent manner. Additionally, dynamin is critical for efficient viral entry. [Read the Full Post]

PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models of hypertension

1011 | Sep 06 2018

Berger JM et al. found that PCSK9-deficiency did not alter both basal blood pressure and its increase in salt-insensitive (l-NAME) and salt-sensitive (Ang-II and DOCA-salt) hypertension models. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

0 | Sep 06 2018

Cui R et al. provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

The Nonmetabolized β-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3

2877 | Sep 05 2018

Misaka S et al. indicated that these data will aid future in vivo studies on potential transporter-mediated drug-drug or drug-food interactions with involvement of nadolol. [Read the Full Post]

The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

851 | Aug 26 2018

Villani LA et al. indicated that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations. [Read the Full Post]

Structure-dependent complexation of Fe3+ by anthracyclines. 2. The roles of methoxy and daunosamine functionalities

929 | Aug 18 2018

Nawara K et al. illustrated the important role of methoxy and daunosamine moieties in anthracycline-iron(III) complex formation and stability. [Read the Full Post]

VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal

654 | Aug 12 2018

Bastola P et al. provided a proof-of-concept that VCP inhibitors can be used as a single agent and can be synergized with compounds that enhance CHOP expression to induce cell death in ovarian cancer cells. [Read the Full Post]

Acute hyperglycemia suppresses left ventricular diastolic function and inhibits autophagic flux in mice under prohypertrophic stimulation

814 | Jul 28 2018

Xie J et al. found that acute hyperglycemia suppresses diastolic function, damages mitochondrial energy signaling, and inhibits autophagic flux in prohypertrophic factor-stimulated cardiomyocytes. [Read the Full Post]

Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models

1388 | Jul 12 2018

Bullova P et al. reported for the first time that PL mediates PHEO cell death by activating both apoptosis and necroptosis in vitro and in vivo. This effect is magnified in hypoxic conditions, making PL a promising potential candidate for use as a therapeutic option for patients with PHEO/PGL, including those with SDHB mutations. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

1215 | Jul 06 2018

Chufan EE et al. reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

1550 | Jun 20 2018

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

Gp130-mediated STAT3 activation by S-propargyl-cysteine, an endogenous hydrogen sulfide initiator, prevents doxorubicin-induced cardiotoxicity

1274 | May 11 2018

Wu J et al. offered a novel molecular basis and therapeutic strategy of H2S donor for the treatment of heart failure. [Read the Full Post]

A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen

1136 | Apr 30 2018

Chen Y et al. suggested their retention time was closely related to the antiplatelet aggregation activities. This study provides a rapid, effective and novel method for screening the potential antiplatelet activity components from Chinese herb medicines. [Read the Full Post]

Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats.

1031 | Feb 10 2018

Zhou X, et al. revealed that the activity for CYP3A and UGT was decreased in ZDF rats using the probe substrates, and decreased unbound intrinsic clearance in vitro for glibenclamide, canagliflozin, and troglitazone was consistent with lower plasma clearance in vivo. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

3200 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Oxidized Low-Density Lipoprotein-Induced Cyclophilin A Secretion Requires ROCK-Dependent Diphosphorylation of Myosin Light Chain

913 | Feb 01 2018

Su Z et al. indicated that ox-LDL-induced CyPA secretion requires vesicle transportation, actin remodeling and ROCK-dependent diphosphorylation of MLC. VSMC-derived CyPA induced by ox-LDL may be associated with increased CyPA expression in atherosclerotic lesions. [Read the Full Post]

Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells

1458 | Jan 20 2018

Rouhi A et al. identified potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies. [Read the Full Post]

High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

1032 | Dec 28 2017

Choi HY et al. demonstrated that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission [Read the Full Post]

Weak binding to E3 ubiquitin ligase c-Cbl increases EGFRvA protein stability

1090 | Dec 04 2017

Song F et al. found that EGFRvA is more stable than EGFR because of its decreased binding to c-Cbl. [Read the Full Post]

Tissue-specific variation in nonsense mutant transcript level and drug-induced read-through efficiency in the Cln1(R151X) mouse model of INC

1009 | Nov 22 2017

Thada V et al. identified a new challenge/hurdle for read-through drug therapy: variable efficiency of read-through therapy in the different tissues/organs because of tissue-specific variations in nonsense mutant transcript levels. [Read the Full Post]

Impairment of Cargo Transportation Caused by gbf1 Mutation Disrupts Vascular Integrity and Causes Hemorrhage in Zebrafish Embryos

1497 | Oct 25 2017

Chen J et al. showed that endothelial endoplasmic reticulum stress and subsequent apoptosis induced by gbf1 deficiency may account for the vascular collapse and hemorrhage. [Read the Full Post]

Nuclear Export of Ubiquitinated Proteins Determines the Sensitivity of Colorectal Cancer to Proteasome Inhibitor

875 | Oct 20 2017

Wu T et al. indicated that nuclear p53 is a major mediator in the synergistic antitumor effect of bortezomib and KPT330, and provides a rationale for the use of proteasome inhibitor together with nuclear export blocker in the treatment of colorectal cancer. It is conceivable that targeting nuclear exportation may serve as a novel strategy to overcome resistance and raise chemotherapeutic efficacy, especially for the drugs that activate the p53 system. [Read the Full Post]

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds

0 | Oct 15 2017

Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]

Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis

963 | Oct 14 2017

Bali V et al. emphasized that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi. [Read the Full Post]

Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

1183 | Oct 07 2017

Jang BC et al. show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. [Read the Full Post]

Improved fluorescence assays to measure the defects associated with F508del-CFTR allow identification of new active compounds

1232 | Oct 04 2017

Langron E et al. showed that most known potentiators have a negative influence on F508del-CFTR biogenesis/stability, which means membrane exposure needs to be monitored early during the development of drugs targeting CFTR. The combined use of the two fluorescence assays described here provides a useful tool for the identification of improved potentiators and correctors. The assays could also prove useful for basic scientific investigations on F508del-CFTR, and other CF-causing mutations. [Read the Full Post]

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

2422 | Sep 21 2017

Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

1099 | Sep 20 2017

Kim HJ et al. observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. [Read the Full Post]

miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

1321 | Sep 12 2017

Zheng L et al. provideD evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management. [Read the Full Post]

Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory

1938 | Sep 11 2017

Brothers HM et al. showed that highlight the therapeutic potential of reducing glutamatergic function upon memory impairment in neurodegenerative diseases associated with aging. [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

1410 | Jun 30 2017

Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

0 | Jun 24 2017

Zhu J et al. showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway

4417 | May 15 2017

Song ZH et al. found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines. [Read the Full Post]

Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

0 | Apr 10 2017

Li Z et al found that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]

Beneficial metabolic actions of a stable GIP agonist following pretreatment with a SGLT2 inhibitor in high fat fed diabetic mice

1483 | Mar 26 2017

Millar PJ et al demonstratd that (DAla(2))GIP can exert beneficial metabolic control in high fat fed diabetic mice pre-treated with DAPA. The results highlight possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions

3 | Mar 26 2017

Pattanawongsa A et al found that since the sodium-glucose cotransporter 2 inhibitors share common structural features, notably a glycoside moiety, investigation of drugs in this class for effects on UGT to identify (or exclude) potential drug-drug interactions is warranted. [Read the Full Post]

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

0 | Mar 17 2017

Doherty KR et al. showed that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. [Read the Full Post]

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

1770 | Mar 16 2017

Doherty KR et al. found that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions

1789 | Jan 29 2017

Pattanawongsa A et al. reported the inhibition of human recombinant UGTs by CNF and DPF, along with the Ki values for selected recombinant and human liver microsomal UGTs. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

2527 | Dec 28 2016

Zhu J, et al found that compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. [Read the Full Post]

Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

1688 | Nov 22 2016

Jang BC et al. showed that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. [Read the Full Post]

Mechanistic Approaches to Improve Correction of the Most Common Disease-Causing Mutation in Cystic Fibrosis

1427 | Nov 14 2016

Bali V et al. found that stabilization of ΔF508 CFTR band B in the ER might improve its functional rescue by Orkambi. [Read the Full Post]

Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons

2491 | Oct 27 2016

Manchon JF et al. found that levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

5719 | Oct 27 2016

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Seminal plasma induces inflammation in the uterus through the γδ T/IL-17 pathway

2023 | Oct 13 2016

Song ZH et al. found a new mechanism by which seminal plasma could influence the inflammation in the uterus through the γδ T/IL-17 pathway to regulate the expression of various chemokines and cytokines. [Read the Full Post]

Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

2128 | Sep 13 2016

Li Z, et al. showed that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]

Beneficial metabolic actions of a stable GIP agonist following pre-treatment with a SGLT2 inhibitor in high fat fed diabetic mice

1734 | Sep 05 2016

Millar PJ, et al. demonstrated possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]

Two strategies to overcome eribulin resistance: pharmacokinetic imaging and nanoparticle delivery system

5463 | Nov 17 2014

Laughney et al. developed strategies of pharmacokinetic for to reveal drug-resistant mechanisms, and nanoparticle system to overcome the resistance. [Read the Full Post]

A new neurogenic receptor activator of P2Y1——Up4A

4701 | Nov 13 2014

Recently, researchers from Nevada School of Medicine found a novel factor, Up4A, may contribute in mediating enteric inhibitory neurotransmission of the intestines, acts through P2Y1 receptors and apamin-sensitive small-conductance SK channels. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research

4472 | Jan 27 2014

Tariquidar (XR9576) is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research

4479 | Dec 30 2013

Tariquidar displays high-affinity binding to P-gp with Bmax of 275 pmol/mg. [Read the Full Post]

Zosuquidar is a compound of antineoplastic drug

4128 | Dec 30 2013

Zosuquidar (LY335979) is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. [Read the Full Post]

Brefeldin A used to enhance intracellular cytokine staining signals

3203 | Dec 23 2013

Brefeldin A is a lactone antibiotic and ATPase inhibitor for protein transport with IC50 of 0.2 μM in HCT 116 cells, induces cancer cell differentiation and apoptosis. [Read the Full Post]

Dapagliflozin is a drug used to treat type 2 diabetes

0 | Dec 20 2013

Dapagliflozin is 32-fold more potent than phlorizin against hSGLT2 but 4-fold less than phlorizin against hSGLT1. [Read the Full Post]

LY335979 is a potent inhibitor that contains a cyclopropyldibenzosuberane moiety

4336 | Dec 16 2013

LY335979 competitively inhibits equilibrium binding of vinblastine to Pgp by blocking azidopine photoaffinity labeling of the Pgp in CEM/VLB100 plasma membranes. [Read the Full Post]

VX 770 is a drug approved for patients with a certain mutation of cystic fibrosis

2765 | Dec 09 2013

Ivacaftor (VX-770, Kalydeco) is a potentiator of CFTR targeting G551D-CFTR and F508del-CFTR with EC50 of 100 nM and 25 nM, respectively. [Read the Full Post]

Dapagliflozin is a drug used to treat type 2 diabetes

2778 | Nov 27 2013

Dapagliflozin is not sensitive to hSGLT1 with a 1200-fold IC50. [Read the Full Post]

VX809 is an experimental drug for the treatment of cystic fibrosis

2905 | Oct 28 2013

VX-809 acts at the level of the ER to allow a fraction of the F508del-CFTR to adopt a properly folded form, to exit the ER and mobilize to the cell surface for normal functioning. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research as an adjuvant

4035 | Oct 23 2013

Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]

MRS2578 is a selective antagonist of P2Y6 nucleotide receptors

3131 | Jul 29 2013

MRS 2578 (10 μM) significant reduces TNF-α–induced proinflammatory gene expression in HMEC-1 cells. [Read the Full Post]

Ouabain isolated from plants is widely used by scientists in in vitro studies

3445 | May 30 2013

In many non rodent species, low concentrations of this substance (i.e., in the subnanomolar range) may stimulate the Na-K-ATPase. The mechanism of the stimulatory effect is not understood and remains controversial. Further, the issue in rodents is more complicated because there are different isoforms of the Na-K-ATPase - some of which are very sensitive to ouabain while others are not. [Read the Full Post]

Ouabain is found in the ripe seeds of African plants

3415 | May 14 2013

It is well understood that the classical mechanism of action of ouabain involves its binding to and inhibition of the plasma membrane Na+/K+-ATPase (sodium pump) especially at the higher concentrations attainable in vitro or with intravenous dosage. [Read the Full Post]

Tolbutamide is a type of medicine called a sulphonylurea

3101 | Feb 17 2013

Surgery was performed using aseptic procedures. Anaesthesia was induced using ketamine, which was followed by 2 C5% isofluorane Tolbutamide mixed with oxygen administered by inhalation for the length of the surgical procedure. The skin and fascia were removed from the dorsal surface of the skull. [Read the Full Post]

Tolbutamide is a first generation potassium channel blocker

3104 | Feb 01 2013

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive and chronic activation of inflammatory pathways via immune Tolbutamide complex deposition, complement activation, and Fc receptor (FcR) ligation, often leading to significant clinical pathologies including glomerulonephritis [Read the Full Post]

Oligomycin A CGMP or cAMP in the lysates were by radioimmunoassay

4127 | Oct 23 2012

CGMP or cAMP in the lysates were by radioimmunoassay of cGMP from Amersham or with protein kinase type I muscle beef, each determined. Activity t and PIP3 [Read the Full Post]