Blog of Signaling Pathways

Inclusion complex of ketoconazole and p-sulfonic acid calix[6]arene improves antileishmanial activity and selectivity against Leishmania amazonensis and Leishmania infantum

42 views | Feb 18 2023

An inclusion complex (IC6HKTZ) of ketoconazole and p-sulfonic acid calix[6]arene (CX6SO3H) was prepared to improve solubility and efficacy of ketoconazole against Leishmania amazonensis and Leishmania infantum, and results showed a 95-fold solubility enhancement and improved antileishmanial activities. [Read the Full Post]

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

105 views | Feb 18 2023

Rigosertib, a dual PLK1 and PI3K inhibitor, showed dose- and time-dependent efficacy against 5 human tumor cell lines in vitro, with A549 cells being the most sensitive and U87-MG cells the most resistant, with p53 levels affecting the efficacy, making Rigosertib a potential antineoplastic agent against lung cancer in humans. [Read the Full Post]

PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation

84 views | Feb 18 2023

Rigosertib, an anticancer agent under clinical trials, targets PLK1 and modulates ELAVL1/HuR-miR-122 signaling to effectively inhibit the proliferation of wild-type and sofosbuvir resistance-associated HCVs, suggesting it could be useful for treating HCV and HCV-associated diseases. [Read the Full Post]

Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis

122 views | Feb 18 2023

Tfr2 deletion results in increased joint swelling and bone erosion in a K/BxN serum-transfer arthritis model, which may be due to Tfr2's role in suppressing pro-inflammatory M1-like polarization in macrophages. [Read the Full Post]

Predicting the systemic exposure and lung concentration of nafamostat using physiologically-based pharmacokinetic modeling

52 views | Feb 18 2023

This study used a physiologically based pharmacokinetic (PBPK) approach and global sensitivity analysis to predict and evaluate the pharmacokinetic profiles of nafamostat in a virtual healthy population under various dosing regimens and found that the approach is valuable in predicting the PK profile and designing an appropriate dosage regimen for the treatment of COVID-19. [Read the Full Post]

Can pharmaceutical pollution alter the spread of infectious disease? A case study using fluoxetine

94 views | Feb 17 2023

Fluoxetine exposure affects the severity of a bacterial infection in water fleas in a non-monotonic manner, but the effect varies with both the infection outcome measured and the genotype of the pathogen, leading to complex genotype-by-environment interactions in its influence on disease dynamics. [Read the Full Post]

Sample stability and heparin interference in ionized calcium and ionized magnesium measurements in horses using the Stat Profile Prime Plus co-oximetry electrolyte analyzer

107 views | Feb 17 2023

Stored samples at 4°C can be used to determine iCa and iMg concentrations up to 7 days after collection in horses, but heparin interference should be considered when using homemade heparin syringes and other metabolites are stable for only 8 hours. [Read the Full Post]

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

73 views | 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

101 views | 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]

Phytochemical Analysis, Antifungal, and Antioxidant Properties of Two Herbs ( Tristemma mauritianum and Crassocephalum bougheyanum) and One Tree ( Lavigeria macrocarpa) Species

76 views | Feb 17 2023

Tristemma mauritianum, Crassocephalum bougheyanum, and Lavigeria macrocarpa showed promising antifungal and antioxidant properties due to high phenolic, tannin, and flavonoid content, with T. mauritianum displaying the highest antifungal and antioxidant activities and a synergistic effect with ketoconazole against clinical resistant Candida isolates. [Read the Full Post]

Allolobophora caliginosa coelomic fluid and extract alleviate glucocorticoid-induced osteoporosis in mice by suppressing oxidative stress and regulating osteoblastic/osteoclastic-related markers

90 views | Feb 16 2023

This study investigated the chemo-preventive activity of A.calignosa coelomic fluid and extract on glucocorticoid-induced osteoporosis in mice, revealing that both showed chemo-preventive activity by inhibiting oxidative stress and regulating expression and activity of osteoblast/osteoclast-related markers, resulting in increased bone mineral density and decreased activity of alkaline phosphatase and parathyroid hormone. [Read the Full Post]

16a-Methyl corticosteroids; a new series of anti-inflammatory compounds; clinical appraisal of their antirheumatic potencies

72 views | Feb 16 2023

Four new derivatives of hydrocortisone with a methyl grouping at the 16a-carbon position were synthesized and studied in human subjects for anti-inflammatory activity, with 16a-methyl 9a-fluoroprednisolone showing the highest potency per milligram and potential for long-term therapeutic use. [Read the Full Post]

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

38 views | Feb 16 2023

Benzimidazole-1,2,4-triazole derivatives were synthesized and screened for their antifungal activity against C. albicans, C. glabrata, C. krusei, and C. parapsilopsis, with three compounds (6b, 6i, and 6j) showing higher antifungal activity than voriconazole and fluconazole, and potential for use as a new fungicidal lead targeting 14α-demethylase with effects on the L929 cell line and C. glabrata cells evaluated. [Read the Full Post]

Pulmonary cryptococcosis after immunomodulator treatment in patients with Crohn's disease: Three case reports

25 views | Feb 16 2023

Three patients with Crohn's disease developed pulmonary cryptococcosis after receiving immunomodulatory treatment and were successfully treated with fluconazole; increased incidence of this opportunistic infection highlights the need for clinical vigilance and early identification for standardized treatment. [Read the Full Post]

Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study

64 views | Feb 16 2023

A case-control study in Taiwan found a higher risk of epilepsy among patients exposed to antidepressants, particularly with longer-term use, and showed a higher risk for escitalopram, venlafaxine, mirtazapine, paroxetine, and fluoxetine, but not for sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion. [Read the Full Post]

Change in Cutibacterium acnes phylotype abundance and improvement of clinical parameters using a new dermocosmetic product containing Myrtus communis and Celastrol enriched plant cell culture extracts in patients with acne vulgaris

119 views | Feb 15 2023

The new dermocosmetic product containing Myrtus communis and Celastrol-enriched plant cell culture extracts improved acne severity by decreasing pro-pathogen phylotype IC and increasing non-pathogen phylotype IB of Cutibacterium acnes and decreasing acne lesion count and improving the Global Evaluation Acne score. [Read the Full Post]

Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway

48 views | Feb 15 2023

The study shows that ALPK1 activation in diabetic nephropathy causes renal injury and fibrosis through the activation of the canonical caspase-1-GSDMD pyroptosis pathway, which is regulated by the ALPK1/NF-κB pathway. [Read the Full Post]

Synthesis and mechanical properties of highly structure-controlled Zr-based metallic glasses by thermal rejuvenation technique

85 views | Feb 15 2023

A new thermal rejuvenation process was developed for Zr-based bulk metallic glass to improve ductility by re-introducing free volume through rapid heating and indirect liquid nitrogen quenching, which was confirmed to reduce STZ volume and enhance homogeneous deformation by molecular dynamics simulations. [Read the Full Post]

Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy

58 views | Feb 15 2023

A young girl with early-onset deafness, progressive external tooth root resorption, and increased bone turnover due to a 12-bp duplication within exon 1 of TNFRSF11A was successfully treated with bisphosphonates, preventing further skeletal disease. [Read the Full Post]

The effects of neoadjuvant zoledronic acid in breast cancer patients: A meta-analysis of randomized controlled trials

76 views | Feb 15 2023

Our study showed that adding Zoledronic acid (ZA) to neoadjuvant therapy for breast cancer did not improve the pathological complete response rate and resulted in worse mortality compared to the control group, but subgroup analysis revealed a potential benefit for postmenopausal women and patients with triple-negative BC, warranting further investigation. [Read the Full Post]