Blog of Signaling Pathways

Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses

33 views | Feb 22 2023

The study determined the appropriate initial dose of intravenous calcitriol for reducing PTH levels in patients with uremic secondary hyperparathyroidism (2HPT) to be 1 microg per dialysis session, with a clear dose-dependent effect seen on PTH reduction. [Read the Full Post]

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

48 views | 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

52 views | 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]

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

80 views | Feb 22 2023

A young patient with relapsed/refractory Ph-like ALL was successfully treated with chimeric antigen receptor T (CAR-T) cells after bridging with compassionate-use ponatinib and low-dose prednisone, and maintained with low-dose ponatinib, resulting in measurable residual disease negativity and B-cell aplasia 20 months later, marking this as the first reported use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy. [Read the Full Post]

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

80 views | Feb 22 2023

In this study, results showed that TBI/Cy conditioning was associated with reduced risk of relapse and increased risk of grade 2-4 acute GVHD, while a matched-pair analysis revealed a reduced rate of relapse and no significant effect on other transplantation outcomes when compared to TBI/Flu, leading to the conclusion that TBI/Cy should be considered a preferable regimen for allo-HCT in adult patients with ALL in complete remission. [Read the Full Post]

Bowen's disease on two different unrelated anatomical sites (genitals and nail) in succession in an immunocompromised patient

57 views | Feb 21 2023

A 43-year-old immunocompromised male with a history of multiple unprotected sexual exposures was diagnosed with verruca vulgaris and pigmented Bowen's disease on biopsy of hyperpigmented lesions on his genitals, and later developed longitudinal melanonychia with a subungual hyperpigmented mass on his right middle finger nail which was treated successfully with 5-fluorouracil and podophyllin. [Read the Full Post]

HIV-Tat Exacerbates the Actions of Atazanavir, Efavirenz, and Ritonavir on Cardiac Ryanodine Receptor (RyR2)

79 views | Feb 21 2023

The study shows that HIV-Tat, ATV, EFV, and RTV can bind to and modulate the activity of the type 2 ryanodine receptor (RyR2) in the heart and that HIV-Tat can exacerbate the actions of ATV, EFV, and RTV on RyR2, potentially increasing the risk of cardiac arrhythmias and sudden cardiac death. [Read the Full Post]

Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration

25 views | Feb 21 2023

Neflamapimod, an oral small molecule p38α inhibitor, reduces Rab5 activity and restores the numbers and morphology of basal forebrain cholinergic neurons (BFCN) in a mouse model of BFCN degeneration and shows potential for treating diseases associated with BFCN loss, although a clinical trial in dementia with Lewy bodies did not show an effect on the primary endpoint. [Read the Full Post]

Pleckstrin Levels Are Increased in Patients with Chronic Periodontitis and Regulated via the MAP Kinase-p38α Signaling Pathway in Gingival Fibroblasts

43 views | Feb 21 2023

Pleckstrin levels were higher in saliva samples from patients with chronic periodontitis compared to controls and closely related to the severity of the disease, serving as a potential biomarker for periodontitis and regulated by the p38 MAP kinase pathway. [Read the Full Post]

Fibroblast Growth Factor 23 Exacerbates Cardiac Fibrosis in Deoxycorticosterone Acetate-Salt Mice With Hypertension

28 views | Feb 21 2023

Continuous intravenous administration of fibroblast growth factor 23 in a mouse model with mild chronic kidney disease and hypertension leads to heart failure with preserved ejection fraction, exacerbated myocardial fibrosis, and a decrease in Cyp27b1 expression, which is mitigated by calcitriol treatment that improves diastolic function via inhibiting transforming growth factor-β signaling, independently of the levels of FGF23. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

111 views | Feb 20 2023

Staurosporine and its analogues have strong inhibitory effects against a variety of kinases and have various biological properties such as antifungal, antibacterial, and immunosuppressive activities, but have limited clinical effectiveness due to cross-reactivity and poor selectivity. [Read the Full Post]

Therapeutic treatment with phosphodiesterase-4 inhibitors alleviates kidney injury and renal fibrosis by increasing MMP-9 in a doxorubicin-induced nephrotoxicity mouse model

35 views | Feb 20 2023

PDE-4 inhibitors rolipram and roflumilast showed beneficial effects in preserving glomerular filtration barrier function, reducing inflammation, and decreasing renal fibrosis in a doxorubicin-induced nephrotic syndrome model, with roflumilast having better effects in reducing glomerular and tubular lesions and MMP9 activity in renal tissue at later stages. [Read the Full Post]

Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium

32 views | Feb 20 2023

Levosimendan increased force of contraction in the mouse left atrial preparations in the presence of rolipram and had positive inotropic and chronotropic effects in both mouse and human atrial preparations, with the positive inotropic effect being explained by phosphodiesterase III inhibition leading to phospholamban phosphorylation in the human atrium. [Read the Full Post]

Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC

40 views | Feb 20 2023

Resistance to Eg5 inhibitors, a potential target for cancer chemotherapy, was explored using the HCT116 cell line and found to arise from a dominant point mutation in the P-loop of the ATP binding domain of Eg5, Eg5(T107N), causing strong non-exchangeable binding to microtubules and resistance to loop-L5 binding inhibitors, but potentially overcome by inhibitors that bind to sites other than the loop-L5 binding site. [Read the Full Post]

Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma

80 views | Feb 20 2023

The study investigates the important interactions between immune cells and their targeting drugs in liver carcinoma using single-cell and bulk transcriptomic data, revealing the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma and identifying five predictive drugs that may help improve the immunosuppressive microenvironment and prevent immune evasion. [Read the Full Post]

Critical Role of Position 10 Residue in the Polymyxin Antimicrobial Activity

75 views | Feb 19 2023

The study synthesized 30 novel analogues of polymyxin B1 modified at position 10 to examine their antimicrobial activity against Gram-negative bacteria and toxicity, revealing the role of the β-hydroxy side chain in promoting the correctly folded conformation of the polymyxin that drives outer membrane penetration and antibacterial activity, providing important information for developing new-generation polymyxin antibiotics. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

236 views | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Pregnancy and neonatal safety outcomes of timing of initiation of daily oral tenofovir disoproxil fumarate and emtricitabine pre-exposure prophylaxis for HIV prevention (CAP016): an open-label, randomised, non-inferiority trial

117 views | Feb 19 2023

In a study comparing the safety of tenofovir disoproxil fumarate and emtricitabine PrEP in pregnant women, PrEP was not associated with preterm birth or small for gestational age infants, supporting its use in pregnancy and allaying safety concerns. [Read the Full Post]

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

94 views | 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

47 views | 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]