Thrombopoietin treats erythropoietin resistance by correcting EPO-induced progenitorcell depletion
In conclusion, our study demonstrated the efficacy of combination therapy in addressing EPO-resistant anemia by correcting EPO-induced erythroid progenitor depletion.PMID:38154543 | DOI:10.1016/j.bcp.2023.116008 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 28, 2023 Category: Drugs & Pharmacology Authors: Huixi Zou Raymond S M Wong Xiaoyu Yan Source Type: research

Divergent effects of the antiretroviral drugs, dolutegravir, tenofovir alafenamide, and tenofovir disoproxil fumarate, on human adipocyte function
Biochem Pharmacol. 2023 Dec 26:116010. doi: 10.1016/j.bcp.2023.116010. Online ahead of print.ABSTRACTCombined antiretroviral therapy (cART) has been associated with increased body weight accompanied by metabolic alterations in people living with human immunodeficiency virus (PLWH). To gain insight into the combined effects of cART components on adipocyte dysfunction, we assessed whether and how treatment of human adipocytes with dolutegravir (DTG) and the nucleotide-analog reverse-transcriptase inhibitors (NRTIs), tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), alone and in combination, altered biologi...
Source: Biochemical Pharmacology - December 28, 2023 Category: Drugs & Pharmacology Authors: T Quesada-L ópez R Cereijo A Blasco-Roset A Mestres-Arenas P Prieto J C Domingo F Villarroya P Domingo M Giralt Source Type: research

Pharmacological modulation of cholesterol 7 α-hydroxylase (CYP7A1) as a therapeutic strategy for hypercholesterolemia
Biochem Pharmacol. 2023 Dec 26:115985. doi: 10.1016/j.bcp.2023.115985. Online ahead of print.ABSTRACTDespite the availability of many therapeutic options, the prevalence of hypercholesterolemia remains high. There exists a significant unmet medical need for novel drugs and/or treatment combinations to effectively combat hypercholesterolemia while minimizing adverse reactions. The modulation of cholesterol 7α-hydroxylase (CYP7A1) expression via perturbation of the farnesoid X receptor (FXR) - dependent pathways, primarily FXR/small heterodimer partner (SHP) and FXR/ fibroblast growth factor (FGF)-19/ fibroblast growth fact...
Source: Biochemical Pharmacology - December 28, 2023 Category: Drugs & Pharmacology Authors: Megan Yu Cai Lim Han Kiat Ho Source Type: research

PCSK9 regulates myofibroblast transformation through the JAK2/STAT3 pathway to regulate fibrosis after myocardial infarction
This study suggests that PCSK9 may function as a novel regulator of myocardial fibrosis, primarily via the JAK2/STAT3 pathway.PMID:38154546 | DOI:10.1016/j.bcp.2023.115996 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 28, 2023 Category: Drugs & Pharmacology Authors: Hailong Bao Xu Wang Haiyan Zhou Wei Zhou Fujun Liao Fang Wei Shiyu Yang Zhenhua Luo Wei Li Source Type: research

Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice
This study aims to investigate the role and mechanism of TRIM16 in DOX cardiotoxicity. Following TRIM16 overexpression in hearts with AAV9-TRIM16, mice were intravenously administered DOX at a dose of 4 mg/kg/week for 4 weeks to assess the impact of TRIM16 on doxorubicin-induced cardiotoxicity. Transfection of OE-TRIM16 plasmids and siRNA-TRIM16 was performed in neonatal rat cardiomyocytes (NRCMs). Our results revealed that DOX challenge elicited a significant upregulation of TRIM16 proteins in cardiomyocytes. TRIM16 overexpression efficiently ameliorated cardiac function while suppressing inflammation, ROS generation, apo...
Source: Biochemical Pharmacology - December 28, 2023 Category: Drugs & Pharmacology Authors: Xinyu Guo Mengqing Liu Bing Han Yeqing Zheng Kaina Zhang Gaowa Bao Chenying Gao Hongwen Shi Qiang Sun Zhenghang Zhao Source Type: research

Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis
In this study, we demonstrated that Sinularin inhibited the viability of human prostate cancer cells in a dose-dependent manner and displayed significant cytotoxicity only at high concentration against normal prostate epithelial cell RWPE-1. Flow cytometry assay demonstrated that Sinularin induced tumor cell apoptosis. Further investigations revealed that Sinularin exerted anti-tumor activity through intrinsic apoptotic pathway along with up-regulation of pro-apoptotic protein Bax and PUMA, inhibition of anti-apoptotic protein Bcl-2, mitochondrial membrane potential collapses, and release of mitochondrial proteins. Further...
Source: Biochemical Pharmacology - December 28, 2023 Category: Drugs & Pharmacology Authors: Xiang-Yu Meng Ke-Jie Wang Sha-Zhou Ye Jun-Feng Chen Zhao-Yu Chen Zuo-Yan Zhang Wei-Qi Yin Xiao-Long Jia Yi Li Rui Yu Qi Ma Source Type: research

Research progress on phosphatidylinositol 4-kinase inhibitors
We describe the biological characteristics of PI4Ks; summarize the physiological functions and effector proteins of PI4P; and analyze the structural basis of selective PI4K inhibitors for the treatment of human diseases in this review. Herein, this review mainly summarizes the developments in the structure and enzyme activity of PI4K inhibitors.PMID:38151075 | DOI:10.1016/j.bcp.2023.115993 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 27, 2023 Category: Drugs & Pharmacology Authors: Gang Li Yanting Wu Yali Zhang Huamin Wang Mengjie Li Dengqin He Wen Guan Hongliang Yao Source Type: research

Larixol is not an inhibitor of G α < sub > i < /sub > containing G proteins and lacks effect on signaling mediated by human neutrophil expressed formyl peptide receptors
In this study, we applied Larixol, obtained from two different commercial sources, to determine the receptor- and G protein- selectivity of this compound in human neutrophils. However, our data show that Larixol not only lacks inhibitory effect on neutrophil responses mediated through FPR1, but also on responses mediated through FPR2, a Gαi coupled GPCR closely related to FPR1. Furthermore, Larixol did not display any features as a selective inhibitor of neutrophil responses mediated through the Gαq coupled GPCRs for platelet activating factor and ATP. Hence, our results imply that the inhibitory effects described for th...
Source: Biochemical Pharmacology - December 27, 2023 Category: Drugs & Pharmacology Authors: Lena Bj örkman Huamei Forsman Linda Bergqvist Claes Dahlgren Martina Sundqvist Source Type: research

Basal interaction of the orphan receptor GPR101 with arrestins leads to constitutive internalization
In conclusion, we uncovered a constitutive intracellular trafficking of GPR101 that potentially represents an important layer of regulation of its signaling and function.PMID:38151077 | DOI:10.1016/j.bcp.2023.116013 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 27, 2023 Category: Drugs & Pharmacology Authors: Dayana Abboud Clauda Abboud Asuka Inoue Jean-Claude Twizere Julien Hanson Source Type: research

Research progress on phosphatidylinositol 4-kinase inhibitors
We describe the biological characteristics of PI4Ks; summarize the physiological functions and effector proteins of PI4P; and analyze the structural basis of selective PI4K inhibitors for the treatment of human diseases in this review. Herein, this review mainly summarizes the developments in the structure and enzyme activity of PI4K inhibitors.PMID:38151075 | DOI:10.1016/j.bcp.2023.115993 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 27, 2023 Category: Drugs & Pharmacology Authors: Gang Li Yanting Wu Yali Zhang Huamin Wang Mengjie Li Dengqin He Wen Guan Hongliang Yao Source Type: research

Larixol is not an inhibitor of G α < sub > i < /sub > containing G proteins and lacks effect on signaling mediated by human neutrophil expressed formyl peptide receptors
In this study, we applied Larixol, obtained from two different commercial sources, to determine the receptor- and G protein- selectivity of this compound in human neutrophils. However, our data show that Larixol not only lacks inhibitory effect on neutrophil responses mediated through FPR1, but also on responses mediated through FPR2, a Gαi coupled GPCR closely related to FPR1. Furthermore, Larixol did not display any features as a selective inhibitor of neutrophil responses mediated through the Gαq coupled GPCRs for platelet activating factor and ATP. Hence, our results imply that the inhibitory effects described for th...
Source: Biochemical Pharmacology - December 27, 2023 Category: Drugs & Pharmacology Authors: Lena Bj örkman Huamei Forsman Linda Bergqvist Claes Dahlgren Martina Sundqvist Source Type: research

Basal interaction of the orphan receptor GPR101 with arrestins leads to constitutive internalization
In conclusion, we uncovered a constitutive intracellular trafficking of GPR101 that potentially represents an important layer of regulation of its signaling and function.PMID:38151077 | DOI:10.1016/j.bcp.2023.116013 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 27, 2023 Category: Drugs & Pharmacology Authors: Dayana Abboud Clauda Abboud Asuka Inoue Jean-Claude Twizere Julien Hanson Source Type: research

Role of endothelin ET < sub > A < /sub > receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats
Biochem Pharmacol. 2023 Dec 23:116007. doi: 10.1016/j.bcp.2023.116007. Online ahead of print.ABSTRACTReceptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatinib, are associated with hypertensive side effects. Doppler flowmetry was used to evaluate regional haemodynamic profiles of axitinib and lenvatinib. Male Sprague Dawley rats (350-500 g) were instrumented with Doppler flow probes (renal and mesenteric arteries and descending abdom...
Source: Biochemical Pharmacology - December 25, 2023 Category: Drugs & Pharmacology Authors: Patrizia Pannucci Marieke Van Daele Samantha L Cooper Edward S Wragg Julie March Marleen Groenen Stephen J Hill Jeanette Woolard Source Type: research

Role of endothelin ET < sub > A < /sub > receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats
Biochem Pharmacol. 2023 Dec 23:116007. doi: 10.1016/j.bcp.2023.116007. Online ahead of print.ABSTRACTReceptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatinib, are associated with hypertensive side effects. Doppler flowmetry was used to evaluate regional haemodynamic profiles of axitinib and lenvatinib. Male Sprague Dawley rats (350-500 g) were instrumented with Doppler flow probes (renal and mesenteric arteries and descending abdom...
Source: Biochemical Pharmacology - December 25, 2023 Category: Drugs & Pharmacology Authors: Patrizia Pannucci Marieke Van Daele Samantha L Cooper Edward S Wragg Julie March Marleen Groenen Stephen J Hill Jeanette Woolard Source Type: research

Role of endothelin ET < sub > A < /sub > receptors in the hypertension induced by the VEGFR-2 kinase inhibitors axitinib and lenvatinib in conscious freely-moving rats
Biochem Pharmacol. 2023 Dec 23:116007. doi: 10.1016/j.bcp.2023.116007. Online ahead of print.ABSTRACTReceptor tyrosine kinase inhibitors (RTKIs) suppress tumour growth by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) which is an important mediator of angiogenesis. Here, we demonstrate that two potent RTKIs, axitinib and lenvatinib, are associated with hypertensive side effects. Doppler flowmetry was used to evaluate regional haemodynamic profiles of axitinib and lenvatinib. Male Sprague Dawley rats (350-500 g) were instrumented with Doppler flow probes (renal and mesenteric arteries and descending abdom...
Source: Biochemical Pharmacology - December 25, 2023 Category: Drugs & Pharmacology Authors: Patrizia Pannucci Marieke Van Daele Samantha L Cooper Edward S Wragg Julie March Marleen Groenen Stephen J Hill Jeanette Woolard Source Type: research