Butyrate promotes kidney resilience through a coordinated kidney protective response in tubular cells
In conclusion, butyrate promotes kidney resilience to AKI and decreases inflammation by preventing the downregulation of kidney protective genes such as Klotho. This information may be relevant to optimize antibiotic management during hospitalization.PMID:38615919 | DOI:10.1016/j.bcp.2024.116203 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - April 14, 2024 Category: Drugs & Pharmacology Authors: Chiara Favero Aranzazu Pintor-Chocano Ana Sanz Alberto Ortiz Maria D Sanchez-Ni ño Source Type: research
CaMK4: Structure, physiological functions, and therapeutic potential
Biochem Pharmacol. 2024 Apr 12:116204. doi: 10.1016/j.bcp.2024.116204. Online ahead of print.ABSTRACTCalcium/calmodulin-dependent protein kinase IV (CaMK4) is a versatile serine/threonine kinase involved in various cellular functions. It regulates T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, β cell mass, and insulin sensitivity. However, the underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the regulatory mechanisms of CaMK4 underlying T-cell imbalance and parenchymal cell mass in multiple diseas...
Source: Biochemical Pharmacology - April 14, 2024 Category: Drugs & Pharmacology Authors: Hao Xu Liang Yong Xianxian Gao Yandong Chen Yixuan Wang Fuyan Wang Xin Hou Source Type: research
ACSL4 promotes malignant progression of Hepatocellular carcinoma by targeting PAK2 transcription
Biochem Pharmacol. 2024 Apr 12:116206. doi: 10.1016/j.bcp.2024.116206. Online ahead of print.ABSTRACTLong-chain fatty acyl-Coa ligase 4 (ACSL4) is an important enzyme that converts fatty acids to fatty acyl-Coa esters, there is increasing evidence for its role in carcinogenesis. However, the precise role of ACLS4 in hepatocellular carcinoma (HCC) is not clearly understood. In the present study, we provide evidence that ACSL4 expression was specifically elevated in HCC and is associated with poor clinical outcomes. ACSL4 significantly promotes the growth and metastasis of HCC both in vitro and in vivo. RNA sequencing and fu...
Source: Biochemical Pharmacology - April 14, 2024 Category: Drugs & Pharmacology Authors: Dandan Wu Zongchao Zuo Xinning Sun Xin Li Fangzhou Yin Wu Yin Source Type: research
Brain histamine improves colonic hyperpermeability through the basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats
This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorphen...
Source: Biochemical Pharmacology - April 12, 2024 Category: Drugs & Pharmacology Authors: Masatomo Ishioh Tsukasa Nozu Saori Miyagishi Sho Igarashi Takuya Funayama Nobuhiro Ueno Toshikatsu Okumura Source Type: research
Brain histamine improves colonic hyperpermeability through the basal forebrain cholinergic neurons, adenosine A2B receptors and vagus nerve in rats
This study explores the involvement and function of brain histamine, linked to BFCNs, in the regulation of intestinal barrier function. Colonic permeability, assessed by quantifying absorbed Evans blue in rat colonic tissue, showed that histamine did not affect increased colonic permeability induced by LPS when administered subcutaneously. However, intracisternal histamine administration improved colonic hyperpermeability. Elevating endogenous histamine levels in the brain with SKF91488, a histamine N-methyltransferase inhibitor, also improved colonic hyperpermeability. This effect was abolished by intracisternal chlorphen...
Source: Biochemical Pharmacology - April 12, 2024 Category: Drugs & Pharmacology Authors: Masatomo Ishioh Tsukasa Nozu Saori Miyagishi Sho Igarashi Takuya Funayama Nobuhiro Ueno Toshikatsu Okumura Source Type: research
Potential small effector molecules restoring cellular defects due to sialic acid biosynthetic enzyme deficiency: Pathological relevance to GNE myopathy
Biochem Pharmacol. 2024 Apr 9;223:116199. doi: 10.1016/j.bcp.2024.116199. Online ahead of print.ABSTRACTGNEM (GNE Myopathy) is a rare neuromuscular disease caused due to biallelic mutations in sialic acid biosynthetic GNE enzyme (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine Kinase). Recently direct or indirect role of GNE in other cellular functions have been elucidated. Hyposialylation of IGF-1R leads to apoptosis due to mitochondrial dysfunction while hyposialylation of β1 integrin receptor leads to altered F-actin assembly, disrupted cytoskeletal organization and slow cell migration. Other cellular defects i...
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Fluencephila Mashangva Jyoti Oswalia Shagun Singh Ranjana Arya Source Type: research
GPCR kinase subtype requirements for arrestin-2 and -3 translocation to the cannabinoid CB < sub > 1 < /sub > receptor and the consequences on G protein signalling
This study supports the hypothesis that arrestin-biased ligands for CB1 must engage GRK5/6 rather than GRK2/3, and G protein-biased ligands must have inherently low efficacy.PMID:38604257 | DOI:10.1016/j.bcp.2024.116190 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Jamie J Manning David B Finlay Michelle Glass Source Type: research
Notch3 as a novel therapeutic target for the treatment of ADPKD by regulating cell proliferation and renal cyst development
Biochem Pharmacol. 2024 Apr 9:116200. doi: 10.1016/j.bcp.2024.116200. Online ahead of print.ABSTRACTAutosomal dominant polycystic kidney disease (ADPKD) is a common monogenic kidney disease. Emerging research indicates that the Notch signaling pathway plays an indispensable role in the pathogenesis of numerous kidney diseases, including ADPKD. Herein, we identified that Notch3 but not other Notch receptors was overexpressed in renal tissues from mice with ADPKD and ADPKD patients. Inhibiting Notch3 with γ-secretase inhibitors, which blocks a proteolytic cleavage required for Notch3 activation, or shRNA knockdown of Notch3...
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Limin Su Ting Chen Hongtao Hu Zifan Xu Xiande Luan Kequan Fu Ying Ren Dong Sun Ying Sun Dong Guo Source Type: research
Potential small effector molecules restoring cellular defects due to sialic acid biosynthetic enzyme deficiency: Pathological relevance to GNE myopathy
Biochem Pharmacol. 2024 Apr 9:116199. doi: 10.1016/j.bcp.2024.116199. Online ahead of print.ABSTRACTGNEM (GNE Myopathy) is a rare neuromuscular disease caused due to biallelic mutations in sialic acid biosynthetic GNE enzyme (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine Kinase). Recently direct or indirect role of GNE in other cellular functions have been elucidated. Hyposialylation of IGF-1R leads to apoptosis due to mitochondrial dysfunction while hyposialylation of β1 integrin receptor leads to altered F-actin assembly, disrupted cytoskeletal organization and slow cell migration. Other cellular defects in pr...
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Fluencephila Mashangva Jyoti Oswalia Shagun Singh Ranjana Arya Source Type: research
GPCR kinase subtype requirements for arrestin-2 and -3 translocation to the type-1 cannabinoid receptor and the consequences on G protein signalling
This study supports the hypothesis that arrestin-biased ligands for CB1 must engage GRK5/6 rather than GRK2/3, and G protein-biased ligands must have inherently low efficacy.PMID:38604257 | DOI:10.1016/j.bcp.2024.116190 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Jamie J Manning David B Finlay Michelle Glass Source Type: research
Notch3 as a novel therapeutic target for the treatment of ADPKD by regulating cell proliferation and renal cyst development
Biochem Pharmacol. 2024 Apr 9:116200. doi: 10.1016/j.bcp.2024.116200. Online ahead of print.ABSTRACTAutosomal dominant polycystic kidney disease (ADPKD) is a common monogenic kidney disease. Emerging research indicates that the Notch signaling pathway plays an indispensable role in the pathogenesis of numerous kidney diseases, including ADPKD. Herein, we identified that Notch3 but not other Notch receptors was overexpressed in renal tissues from mice with ADPKD and ADPKD patients. Inhibiting Notch3 with γ-secretase inhibitors, which blocks a proteolytic cleavage required for Notch3 activation, or shRNA knockdown of Notch3...
Source: Biochemical Pharmacology - April 11, 2024 Category: Drugs & Pharmacology Authors: Limin Su Ting Chen Hongtao Hu Zifan Xu Xiande Luan Kequan Fu Ying Ren Dong Sun Ying Sun Dong Guo Source Type: research
Co-inhibition of BET and NAE enhances BIM-dependent apoptosis with augmented cancer therapeutic efficacy
In this study, we focus on the combination of BET inhibitors (BETis) and NAE inhibitors (NAEis) as a cancer therapeutic strategy and investigate its underlying mechanisms to explore and expand the application scope of both types of drugs. The results showed that this combination synergistically inhibited the proliferative activity of tumor cells from different tissues. Compared to a single drug, combination therapy had a weak effect on cycle arrest but significantly enhanced cell apoptosis. Furthermore, the growth of NCI-H1975 xenografts in nude mice was significantly inhibited by the combination without obvious body weigh...
Source: Biochemical Pharmacology - April 8, 2024 Category: Drugs & Pharmacology Authors: Qian Zhang Qian Wu Xia-Juan Huan Shan-Shan Song Xu-Bin Bao Ze-Hong Miao Ying-Qing Wang Source Type: research
Diabetes and the fabkin complex: A dual-edged sword
Biochem Pharmacol. 2024 Apr 6;223:116196. doi: 10.1016/j.bcp.2024.116196. Online ahead of print.ABSTRACTThe Fabkin complex, composed of FABP4, ADK, and NDPKs, emerges as a novel regulator of insulin-producing beta cells, offering promising prospects for diabetes treatment. Our approach, which combines literature review and database analysis, sets the stage for future research. These findings hold significant implications for both diabetes treatment and research, as they present potential therapeutic targets for personalized treatment, leading to enhanced patient outcomes and a deeper comprehension of the disease. The multi...
Source: Biochemical Pharmacology - April 8, 2024 Category: Drugs & Pharmacology Authors: Safir Ullah Khan Karla Daniela Hern ández-González Amir Ali Syed Shakeel Raza Rizvi Source Type: research
Co-inhibition of BET and NAE enhances BIM-dependent apoptosis with augmented cancer therapeutic efficacy
In this study, we focus on the combination of BET inhibitors (BETis) and NAE inhibitors (NAEis) as a cancer therapeutic strategy and investigate its underlying mechanisms to explore and expand the application scope of both types of drugs. The results showed that this combination synergistically inhibited the proliferative activity of tumor cells from different tissues. Compared to a single drug, combination therapy had a weak effect on cycle arrest but significantly enhanced cell apoptosis. Furthermore, the growth of NCI-H1975 xenografts in nude mice was significantly inhibited by the combination without obvious body weigh...
Source: Biochemical Pharmacology - April 8, 2024 Category: Drugs & Pharmacology Authors: Qian Zhang Qian Wu Xia-Juan Huan Shan-Shan Song Xu-Bin Bao Ze-Hong Miao Ying-Qing Wang Source Type: research
Diabetes and the fabkin complex: A dual-edged sword
Biochem Pharmacol. 2024 Apr 6;223:116196. doi: 10.1016/j.bcp.2024.116196. Online ahead of print.ABSTRACTThe Fabkin complex, composed of FABP4, ADK, and NDPKs, emerges as a novel regulator of insulin-producing beta cells, offering promising prospects for diabetes treatment. Our approach, which combines literature review and database analysis, sets the stage for future research. These findings hold significant implications for both diabetes treatment and research, as they present potential therapeutic targets for personalized treatment, leading to enhanced patient outcomes and a deeper comprehension of the disease. The multi...
Source: Biochemical Pharmacology - April 8, 2024 Category: Drugs & Pharmacology Authors: Safir Ullah Khan Karla Daniela Hern ández-González Amir Ali Syed Shakeel Raza Rizvi Source Type: research
