Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure
Biochem Pharmacol. 2024 Feb 10:116056. doi: 10.1016/j.bcp.2024.116056. Online ahead of print.ABSTRACTLiver injury and acute liver failure caused by an acetaminophen (APAP) overdose is a significant clinical problem in western countries. With the introduction of the mouse model of APAP hepatotoxicity in the 1970 s, fundamental mechanisms of cell death were discovered. This included the recognition that part of the APAP dose is metabolized by cytochrome P450 generating a reactive metabolite that is detoxified by glutathione. After the partial depletion of glutathione, the reactive metabolite will covalently bind to sulfhydry...
Source: Biochemical Pharmacology - February 12, 2024 Category: Drugs & Pharmacology Authors: Anup Ramachandran Jephte Y Akakpo Steven C Curry Barry H Rumack Hartmut Jaeschke Source Type: research
Protein arginine methyltransferases (PRMTs): Orchestrators of cancer pathogenesis, immunotherapy dynamics, and drug resistance
In conclusion, PRMTs play critical roles in cancer pathogenesis, immunotherapy, and drug resistance. In this overview, we have endeavored to illuminate the mechanistic intricacies of PRMT-mediated processes. Shedding light on these aspects will offer valuable insights into the fundamental biology of cancer and establish PRMTs as promising therapeutic targets.PMID:38346542 | DOI:10.1016/j.bcp.2024.116048 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - February 12, 2024 Category: Drugs & Pharmacology Authors: Yihang Gao Chongchong Feng Jingru Ma Qingzhu Yan Source Type: research
The antiangiogenic effect of digitoxin is dependent on a ROS-elicited RhoA/ROCK pathway activation
Biochem Pharmacol. 2024 Feb 9:116049. doi: 10.1016/j.bcp.2024.116049. Online ahead of print.ABSTRACTWe previously showed that digitoxin inhibits angiogenesis and cancer cell proliferation and migration and these effects were associated to protein tyrosine kinase 2 (FAK) inhibition. Considering the interactions between FAK and Rho GTPases regulating cell cytoskeleton and movement, we investigated the involvement of RhoA and Rac1 in the antiangiogenic effect of digitoxin. Phalloidin staining of human umbilical vein endothelial cells (HUVECs) showed the formation of stress fibers in cells treated with 10 nM digitoxin. By Rhot...
Source: Biochemical Pharmacology - February 11, 2024 Category: Drugs & Pharmacology Authors: Carlotta Boscaro Gudula Schimdt Andrea Cignarella Lucia Dal Maso Chiara Bolego Lucia Trevisi Source Type: research
Is there a biochemical basis for purinergic P2X3 and P2X4 receptor antagonists to be considered as anti-seizure medications?
Biochem Pharmacol. 2024 Feb 8:116046. doi: 10.1016/j.bcp.2024.116046. Online ahead of print.ABSTRACTPatients with epilepsy require improved medications. Purinergic receptors were identified as late as 1976 and are slowly emerging as potential drug targets for the discovery of antiseizure medications. While compounds interacting with these receptors have been approved for use as medicines (e.g., gefapixant for cough) and continue to be explored for a number of diseases (e.g., pain, cancer), there have been no purinergic receptor antagonists that have been advanced for epilepsy. There are very few studies on the channel cond...
Source: Biochemical Pharmacology - February 10, 2024 Category: Drugs & Pharmacology Authors: Jeffrey M Witkin Hana Shafique Jodi L Smith Rok Cerne Source Type: research
A review of poly(ADP-ribose)polymerase-1 (PARP1) role and its inhibitors bearing pyrazole or indazole core for cancer therapy
Biochem Pharmacol. 2024 Feb 8;221:116045. doi: 10.1016/j.bcp.2024.116045. Online ahead of print.ABSTRACTCancer is a disease with a high mortality rate characterized by uncontrolled proliferation of abnormal cells. The hallmarks of cancer evidence the acquired cells characteristics that promote the growth of malignant tumours, including genomic instability and mutations, the ability to evade cellular death and the capacity of sustaining proliferative signalization. Poly(ADP-ribose) polymerase-1 (PARP1) is a protein that plays key roles in cellular regulation, namely in DNA damage repair and cell survival. The inhibition of ...
Source: Biochemical Pharmacology - February 9, 2024 Category: Drugs & Pharmacology Authors: In ês M Bastos Sandra Rebelo Vera L M Silva Source Type: research
LncRNA SNHG11 reprograms glutaminolysis in hepatic stellate cells via Wnt/ β-catenin/GLS axis
Biochem Pharmacol. 2024 Feb 7:116044. doi: 10.1016/j.bcp.2024.116044. Online ahead of print.ABSTRACTLong non-coding RNAs (lncRNAs) have been identified as decisive regulators of liver fibrosis. Hepatic stellate cells (HSCs), major hepatic cells contributing to liver fibrosis, undergo metabolic reprogramming for transdifferentiation and activation maintenance. As a crucial part of metabolic reprogramming, glutaminolysis fuels the tricyclic acid (TCA) cycle that renders HSCs addicted to glutamine. However, how lncRNAs reprogram glutamine metabolism in HSCs is unknown. For this research, we characterized the pro-fibrogenic fu...
Source: Biochemical Pharmacology - February 9, 2024 Category: Drugs & Pharmacology Authors: Kanglei Ying Yuan Zeng Jun Xu Xiao Wu Huiya Ying Weimin Cai Ruoru Zhou Qian Xu Xiangting Zhang Fujun Yu Source Type: research
TP53 < sup > R175H < /sup > mutation promotes breast cancer cell proliferation through CORO1A-P38 MAPK pathway regulation
In this study, our aim was to examine the impact of TP53 mutations on the prognosis of patients with breast cancer bioinformatics techniques. To detect cell proliferation, a CCK8 assay was performed, and western blotting was used to identify the expression of p53, p38, and p-p38 proteins. Cellular mRNA sequencing was used to screen target genes of TP53 mutations, and molecular docking was performed to identify the drugs that could hinder the proliferation of breast cancer cells.The results showed that the TP53 mutation rate is higher in patients with triple-negative breast cancer than non-triple-negative breast cancer, and...
Source: Biochemical Pharmacology - February 8, 2024 Category: Drugs & Pharmacology Authors: Yali Su Jiaxuan Zhao Haoran Fu Zeliang Liu Panyan Du Jianxia Zheng Jinghua Wu Jinghua Zhang Source Type: research
Prolonged FGF21 treatment increases energy expenditure and induces weight loss in obese mice independently of UCP1 and adrenergic signaling
Biochem Pharmacol. 2024 Feb 6;221:116042. doi: 10.1016/j.bcp.2024.116042. Online ahead of print.ABSTRACTFibroblast growth factor 21 (FGF21) reduces body weight, which was attributed to induced energy expenditure (EE). Conflicting data have been published on the role of uncoupling protein 1 (UCP1) in this effect. Therefore, we aimed to revisit the thermoregulatory effects of FGF21 and their implications for body weight regulation. We found that an 8-day treatment with FGF21 lowers body weight to similar extent in both wildtype (WT) and UCP1-deficient (KO) mice fed high-fat diet. In WT mice, this effect is solely due to incr...
Source: Biochemical Pharmacology - February 7, 2024 Category: Drugs & Pharmacology Authors: Sara Stanic Kristina Bardova Petra Janovska Martin Rossmeisl Jan Kopecky Petr Zouhar Source Type: research
Adipose organ dysfunction and type 2 diabetes: Role of nitric oxide
Biochem Pharmacol. 2024 Feb 5;221:116043. doi: 10.1016/j.bcp.2024.116043. Online ahead of print.ABSTRACTAdipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide...
Source: Biochemical Pharmacology - February 7, 2024 Category: Drugs & Pharmacology Authors: Zahra Bahadoran Parvin Mirmiran Asghar Ghasemi Source Type: research
Significance of TRAIL/Apo-2 ligand and its death receptors in apoptosis and necroptosis signalling: Implications for cancer-targeted therapeutics
Biochem Pharmacol. 2024 Feb 3;221:116041. doi: 10.1016/j.bcp.2024.116041. Online ahead of print.ABSTRACTThe human immune defensesystem routinely expresses the tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), which is the most prevalent element for antitumor immunity. TRAIL associates with its death receptors (DRs), DR4 (TRAIL-R1), and DR5 (TRAIL-R2), in cancer cells to initiate the intracellular apoptosis cascade. Accordingly, numerous academic institutions and pharmaceutical companies havetried to exploreTRAIL's capacity to kill tumourcells by producing recombinant versions of it (rhTRAIL) or TRAIL ...
Source: Biochemical Pharmacology - February 5, 2024 Category: Drugs & Pharmacology Authors: Avik Maji Abhik Paul Arnab Sarkar Sourin Nahar Rudranil Bhowmik Ajeya Samanta Pankaj Nahata Balaram Ghosh Sanmoy Karmakar Tapan Kumar Maity Source Type: research
WP1066, a small molecule inhibitor of STAT3, chemosensitizes paclitaxel-resistant ovarian cancer cells to paclitaxel by simultaneously inhibiting the activity of STAT3 and the interaction of STAT3 with Stathmin
Biochem Pharmacol. 2024 Feb 3;221:116040. doi: 10.1016/j.bcp.2024.116040. Online ahead of print.ABSTRACTPaclitaxel is widely used to treat cancer, however, drug resistance limits its clinical utility. STAT3 is constitutively activated in some cancers, and contributes to chemotherapy resistance. Currently, several STAT3 inhibitors including WP1066 are used in cancer clinical trials. However, whether WP1066 reverses paclitaxel resistance and the mechanismremains unknown. Here, we report that in contrast to paclitaxel-sensitive parental cells, the expressions of several pro-survival BCL2 family members such as BCL-2, BCL-XL a...
Source: Biochemical Pharmacology - February 4, 2024 Category: Drugs & Pharmacology Authors: Jun Yang Nanjing Li Xinyu Zhao Wenhao Guo Yang Wu Chunlai Nie Zhu Yuan Source Type: research
Mitochondrial targets in hyperammonemia: Addressing urea cycle function to improve drug therapies
Biochem Pharmacol. 2024 Jan 31:116034. doi: 10.1016/j.bcp.2024.116034. Online ahead of print.ABSTRACTThe urea cycle (UC) is a critically important metabolic process for the disposal of nitrogen (ammonia) produced by amino acids catabolism. The impairment of this liver-specific pathway induced either by primary genetic defects or by secondary causes, namely those associated with hepatic disease or drug administration, may result in serious clinical consequences. Urea cycle disorders (UCD) and certain organic acidurias are the major groups of inherited rare diseases manifested with hyperammonemia (HA) with UC dysregulation. ...
Source: Biochemical Pharmacology - February 2, 2024 Category: Drugs & Pharmacology Authors: M F Moedas R J M Sim ões M F B Silva Source Type: research
Deficiency of purinergic P2X4 receptor alleviates experimental autoimmune hepatitis in mice
This study is the first to reveal that the absence of the P2X4 receptor may mitigate immune-mediated liver damage, potentially by restraining inflammation, oxidation, and programmed cell death mechanisms. And highlight P2X4 receptor is essential for ConA-induced acute hepatitis.PMID:38301964 | DOI:10.1016/j.bcp.2024.116033 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - February 1, 2024 Category: Drugs & Pharmacology Authors: Zejin Liu Mengyang Sun Wenhua Liu Fangyu Feng Xinyu Li Chaolei Jin Yijie Zhang Junpeng Wang Source Type: research
CXCL13 promotes TNF- α synthesis in rheumatoid arthritis through activating ERK/p38 pathway and inhibiting miR-330-3p generation
Biochem Pharmacol. 2024 Feb 1;221:116037. doi: 10.1016/j.bcp.2024.116037. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a well-known autoimmune disorder associated with joint pain, joint swelling, cartilage and bone degradation as well as deformity. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays a crucial role in multiple cellular pathogenesis processes, including RA. TNF-α is a vital proinflammatory factor in the progression of RA. However, the role of CXCL13 in TNF-α production in RA has not been fully explored. Our analysis of both database and clinical samples revealed higher levels of CXCL13 and T...
Source: Biochemical Pharmacology - February 1, 2024 Category: Drugs & Pharmacology Authors: David Achudhan Yu-Liang Lai Yen-You Lin Yuan-Li Huang Chun-Hao Tsai Trung-Loc Ho Chih-Yuan Ko Yi-Chin Fong Chien-Chung Huang Chih-Hsin Tang Source Type: research
FGF1 < sup > ΔHBS < /sup > ameliorates retinal inflammation via suppressing TSPO signal in a type 2 diabetes mouse model
In this study, intravitreal injection of FGF1ΔHBS was administrated every week for one month in db/db mice, which are genetically predisposed to develop type 2 diabetes mellitus and early retinopathy. Changes in retinal function and structure in the animal models were detected by electrophysiology (ERG) and optical tomography coherence (OCT). TSPO expression and retinal inflammation were analyzed by immunofluorescence, Western blot and real-time qPCR. In the retina of T2D (db/db) mice, FGF1 was significantly down-regulated while FGFR1 was up-regulated (both p < 0.05). TSPO and retinal inflammatory factors were all up-r...
Source: Biochemical Pharmacology - February 1, 2024 Category: Drugs & Pharmacology Authors: Qunwu Tang Zhewei Cheng Sixiu Liu Jianlou Niu Jingzhou Xu Jin Huang Jiandong Pan Fan Lu Ding Chen Source Type: research
