Glytabastan B, a coumestan isolated from Glycine tabacina, alleviated synovial inflammation, osteoclastogenesis and collagen-induced arthritis through inhibiting MAPK and PI3K/AKT pathways
In conclusion, these results strongly suggest GlyB is a promising multiple-target candidate for the development of agents for the prevention and treatment of RA.PMID:35032460 | DOI:10.1016/j.bcp.2022.114912 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - January 15, 2022 Category: Drugs & Pharmacology Authors: Yanbei Tu Lihua Tan Tao Lu Kai Wang Haiyong Wang Bing Han Yuxin Zhao Hanbin Chen Yanfang Li Haixia Chen Meiwan Chen Chengwei He Source Type: research

Nitazoxanide and related thiazolides induce cell death in cancer cells by targeting the 20S proteasome with novel binding modes
Biochem Pharmacol. 2022 Jan 12:114913. doi: 10.1016/j.bcp.2022.114913. Online ahead of print.ABSTRACTNitazoxanide and related thiazolides are a novel class of anti-infectious agents against protozoan parasites, bacteria and viruses. In recent years, it is demonstrated thatthiazolides also can induced cell cycle arrest and apoptotic cell death in cancer cells. Due to their fast proliferating nature, cancer cells highly depend on the proteasome system to remove aberrant proteins. Many of these aberrant proteins are regulators of cell cycle progression and apoptosis, such as the cyclins, BCL2 family members and nuclear factor...
Source: Biochemical Pharmacology - January 15, 2022 Category: Drugs & Pharmacology Authors: Zirui L ü Xiaona Li Kebin Li Paola Ripani Xiaomeng Shi Fengrong Xu Mopei Wang Liangren Zhang Thomas Brunner Ping Xu Yan Niu Source Type: research

Cannabidiol Promotes Adipogenesis of Human and Mouse Mesenchymal Stem Cells via PPAR γ by Inducing Lipogenesis but Not Lipolysis
Biochem Pharmacol. 2022 Jan 10:114910. doi: 10.1016/j.bcp.2022.114910. Online ahead of print.ABSTRACTCannabidiol (CBD) is a non-psychoactive phytocannabinoid found in the Cannabis sativa plant. Human exposure to CBD can be through recreational marijuana use, commercially available CBD-containing products, and medical treatments. Previous studies found that cannabidiol may activate the master regulator of adipogenesis, peroxisome proliferator activated receptor gamma (PPARγ). Here we investigated the effects of CBD on adipogenesis in human and mouse multipotent mesenchymal stromal stem cells (MSCs). We tested the effe...
Source: Biochemical Pharmacology - January 13, 2022 Category: Drugs & Pharmacology Authors: Richard C Chang Chloe S Thangavelu Erika M Joloya Angela Kuo Zhuorui Li Bruce Blumberg Source Type: research

Cannabidiol Promotes Adipogenesis of Human and Mouse Mesenchymal Stem Cells via PPAR γ by Inducing Lipogenesis but Not Lipolysis
Biochem Pharmacol. 2022 Jan 10:114910. doi: 10.1016/j.bcp.2022.114910. Online ahead of print.ABSTRACTCannabidiol (CBD) is a non-psychoactive phytocannabinoid found in the Cannabis sativa plant. Human exposure to CBD can be through recreational marijuana use, commercially available CBD-containing products, and medical treatments. Previous studies found that cannabidiol may activate the master regulator of adipogenesis, peroxisome proliferator activated receptor gamma (PPARγ). Here we investigated the effects of CBD on adipogenesis in human and mouse multipotent mesenchymal stromal stem cells (MSCs). We tested the effe...
Source: Biochemical Pharmacology - January 13, 2022 Category: Drugs & Pharmacology Authors: Richard C Chang Chloe S Thangavelu Erika M Joloya Angela Kuo Zhuorui Li Bruce Blumberg Source Type: research

Vascular endotheliitis associated with infections: its pathogenetic role and therapeutic implication
Biochem Pharmacol. 2022 Jan 9:114909. doi: 10.1016/j.bcp.2022.114909. Online ahead of print.ABSTRACTVascular endothelial cells are major participants in and regulators of immune responses and inflammation. Vascular endotheliitis is regarded as a host immune-inflammatory response of the endothelium forming the inner surface of blood vessels in association with a direct consequence of infectious pathogen invasion. Vascular endotheliitis and consequent endothelial dysfunction can be a principle determinant of microvascular failure, which would favor impaired perfusion, tissue hypoxia, and subsequent organ failure. Emerging ev...
Source: Biochemical Pharmacology - January 12, 2022 Category: Drugs & Pharmacology Authors: Yuichi Hattori Kohshi Hattori Takuji Machida Naoyuki Matsuda Source Type: research

Vascular endotheliitis associated with infections: its pathogenetic role and therapeutic implication
Biochem Pharmacol. 2022 Jan 9:114909. doi: 10.1016/j.bcp.2022.114909. Online ahead of print.ABSTRACTVascular endothelial cells are major participants in and regulators of immune responses and inflammation. Vascular endotheliitis is regarded as a host immune-inflammatory response of the endothelium forming the inner surface of blood vessels in association with a direct consequence of infectious pathogen invasion. Vascular endotheliitis and consequent endothelial dysfunction can be a principle determinant of microvascular failure, which would favor impaired perfusion, tissue hypoxia, and subsequent organ failure. Emerging ev...
Source: Biochemical Pharmacology - January 12, 2022 Category: Drugs & Pharmacology Authors: Yuichi Hattori Kohshi Hattori Takuji Machida Naoyuki Matsuda Source Type: research

Long non-coding RNAs in gastrointestinal cancers: implications for protein phosphorylation
Biochem Pharmacol. 2022 Jan 7:114907. doi: 10.1016/j.bcp.2022.114907. Online ahead of print.ABSTRACTPhosphorylation of proteins is one of the most extensively investigated post-translational protein modifications. Threonine, serine and tyrosine in proteins are the most commonly phosphorylated amino acids. Dysregulated cancer-related signaling pathways due to aberrant phosphorylation status of the key protein(s) in these pathways exist in most malignancies. Intensive studies in the recent decade have implicated long non-coding RNAs (lncRNAs) in the precise regulation of protein phosphorylation in cancers. In this review, we...
Source: Biochemical Pharmacology - January 10, 2022 Category: Drugs & Pharmacology Authors: Tao Su Teng Wang Nasha Zhang Yue Shen Wenwen Li Huaixin Xing Ming Yang Source Type: research

Long non-coding RNAs in gastrointestinal cancers: implications for protein phosphorylation
Biochem Pharmacol. 2022 Jan 7:114907. doi: 10.1016/j.bcp.2022.114907. Online ahead of print.ABSTRACTPhosphorylation of proteins is one of the most extensively investigated post-translational protein modifications. Threonine, serine and tyrosine in proteins are the most commonly phosphorylated amino acids. Dysregulated cancer-related signaling pathways due to aberrant phosphorylation status of the key protein(s) in these pathways exist in most malignancies. Intensive studies in the recent decade have implicated long non-coding RNAs (lncRNAs) in the precise regulation of protein phosphorylation in cancers. In this review, we...
Source: Biochemical Pharmacology - January 10, 2022 Category: Drugs & Pharmacology Authors: Tao Su Teng Wang Nasha Zhang Yue Shen Wenwen Li Huaixin Xing Ming Yang Source Type: research

Identification of ritanserin analogs that display DGK isoform specificity
Biochem Pharmacol. 2022 Jan 6:114908. doi: 10.1016/j.bcp.2022.114908. Online ahead of print.ABSTRACTThe diacylglycerol kinase (DGK) family of lipid enzymes catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Both DAG and PA are lipid signaling molecules that are of notable importance in regulating cell processes such as proliferation, apoptosis, and migration. There are ten mammalian DGK enzymes that appear to have distinct biological functions. DGKα has emerged as a promising therapeutic target in numerous cancers including glioblastoma (GBM) and melanoma as treatment with small molecule DGK&...
Source: Biochemical Pharmacology - January 9, 2022 Category: Drugs & Pharmacology Authors: Mitchell E Granade Laryssa C Manigat Mike Lemke Benjamin W Purow Thurl E Harris Source Type: research

Identification of ritanserin analogs that display DGK isoform specificity
Biochem Pharmacol. 2022 Jan 6:114908. doi: 10.1016/j.bcp.2022.114908. Online ahead of print.ABSTRACTThe diacylglycerol kinase (DGK) family of lipid enzymes catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Both DAG and PA are lipid signaling molecules that are of notable importance in regulating cell processes such as proliferation, apoptosis, and migration. There are ten mammalian DGK enzymes that appear to have distinct biological functions. DGKα has emerged as a promising therapeutic target in numerous cancers including glioblastoma (GBM) and melanoma as treatment with small molecule DGK&...
Source: Biochemical Pharmacology - January 9, 2022 Category: Drugs & Pharmacology Authors: Mitchell E Granade Laryssa C Manigat Mike Lemke Benjamin W Purow Thurl E Harris Source Type: research

Caffeic acid phenethyl ester targets ubiquitin-specific protease 8 and synergizes with cisplatin in endometrioid ovarian carcinoma cells
This study reveals the therapeutic potential of CAPE in cisplatin-resistant ovarian tumors as well as in tumors expressing USP8.PMID:34995485 | DOI:10.1016/j.bcp.2021.114900 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - January 7, 2022 Category: Drugs & Pharmacology Authors: Diego Colombo Laura Gatti Linda Sj östrand Nives Carenini Matteo Costantino Elisabetta Corna Noemi Arrighetti Marco Zuccolo Michelandrea De Cesare Stig Linder P ádraig D'Arcy Paola Perego Source Type: research

Screening approaches and therapeutic targets: The two driving wheels of tuberculosis drug discovery
Biochem Pharmacol. 2022 Jan 4;197:114906. doi: 10.1016/j.bcp.2021.114906. Online ahead of print.ABSTRACTTuberculosis (TB) is an infectious disease, infecting a quarter of world's population. Drug resistant TB further exacerbates the grim scenario of the drying TB drug discovery pipeline. The limited arsenal to fight TB presses the need for thorough efforts for identifying promising hits to combat the disease. The review highlights the efforts in the field of tuberculosis drug discovery, with an emphasis on massive drug screening campaigns for identifying novel hits against Mtb in both industry and academia. As an intracell...
Source: Biochemical Pharmacology - January 6, 2022 Category: Drugs & Pharmacology Authors: Summaya Perveen Rashmi Sharma Source Type: research

Immuno-modulatory biomaterials as anti-inflammatory therapeutics
Biochem Pharmacol. 2022 Jan 3;197:114890. doi: 10.1016/j.bcp.2021.114890. Online ahead of print.ABSTRACTBiocompatible and biodegradable biomaterials are used extensively in regenerative medicine and serve as a tool for tissue replacement, as a platform for regeneration of injured tissue, and as a vehicle for delivery of drugs. One of the key factors that must be addressed in developing successful biomaterial-based therapeutics is inflammation. Whilst inflammation is initially essential for wound healing; bringing about clearance of debris and infection, prolonged inflammation can result in delayed wound healing, rejection ...
Source: Biochemical Pharmacology - January 6, 2022 Category: Drugs & Pharmacology Authors: Roisin I Lynch Ed C Lavelle Source Type: research

Bisphenol-A analogs induce lower urinary tract dysfunction in male mice
The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p
Source: Biochemical Pharmacology - January 3, 2022 Category: Drugs & Pharmacology Authors: Nguyen Jl Ricke Ea Liu Tt R Gerona L MacGillivray Z Wang Timms Bg Bjorling DE Vom Saal Fs Ricke Wa Source Type: research

Pyrroloquinoline quinone attenuated benzyl butyl phthalate induced metabolic aberration and a hepatic metabolomic analysis
Biochem Pharmacol. 2021 Dec 29;197:114883. doi: 10.1016/j.bcp.2021.114883. Online ahead of print.ABSTRACTBenzyl butyl phthalate (BBP) has recently been implicated as an obesogen. Our recent study demonstrated that BBP can exacerbate high fat diet (HFD) induced diabesity in male mice. Here, we explored if pyrroloquinoline quinone (PQQ), a natural antioxidant andphytochemical, can attenuate metabolic aberrations induced by HFD or HFD-BBPcombination. C57Bl/6 male and female mice were fed either a chow diet (CD) or HFD with or without BBP (3 mg/kg body weight/day)and/or PQQ (20 mg/kg/day)for 16 weeks. The mice's body and tissu...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Jian Zhang Catherine Powell Sunitha Meruvu Ravi Sonkar Mahua Choudhury Source Type: research

A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb
This study provides a unique insight into resveratrol modified derivatives as promising leads for preclinical LRAs, which in turn may help toward inhibitor design and chemical optimization for improving HIV-1 shock-and kill-based efforts.PMID:34971588 | DOI:10.1016/j.bcp.2021.114901 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Taizhen Liang Ziyao Wu Yibin Li Chao Li Kangni Zhao Xinman Qiao Heng Duan Xuanxuan Zhang Shuwen Liu Baomin Xi Lin Li Source Type: research

Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy
In this study, we aimed to investigate whether the novel autophagy activator trehalose could prevent cisplatin-induced damage in the auditory cell line HEI-OC1 and mouse cochlear explants and to further explore its mechanisms. Our data demonstrated that trehalose alleviated cisplatin-induced hair cell (HC) damage by inhibiting apoptosis, attenuating oxidative stress and rescuing mitochondrial dysfunction. Additionally, trehalose significantly enhanced autophagy levels in HCs, and inhibiting autophagy with 3-methyladenine (3-MA) abolished these protective effects. Mechanistically, we showed that the effect of trehalose was ...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Zhuangzhuang Li Qingxiu Yao Yuxin Tian Yumeng Jiang Maoxiang Xu Hui Wang Yuanping Xiong Jia Fang Wen Lu Dongzhen Yu Haibo Shi Source Type: research

Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice
In this study, we compared the metabolic effects of TCPOBOP using lipidomic, transcriptomic, and proteomic analyses in wild-type and humanized CAR-PXR-CYP3A4/3A7 mice. In the model, human CAR retains its constitutive activity in metabolism regulation; however, it is not activated by TCPOBOB. Notably, we observed that TCPOBOP affected lipid homeostasis by elevating serum and liver triglyceride levels and promoted hepatocyte hypertrophy in humanized CAR mice. Hepatic lipidomic analysis revealed a significant accumulation of triglycerides and decrease of its metabolites in humanized CAR mice. RNA-seq analysis has shown diverg...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Josef Skoda Klara Dohnalova Karel Chalupsky Aaron Stahl Markus Templin Jana Maixnerova Stanislav Micuda Lars Gr øntved Albert Braeuning Petr Pavek Source Type: research

Pyrroloquinoline quinone attenuated benzyl butyl phthalate induced metabolic aberration and a hepatic metabolomic analysis
Biochem Pharmacol. 2021 Dec 28:114883. doi: 10.1016/j.bcp.2021.114883. Online ahead of print.ABSTRACTBenzyl butyl phthalate (BBP) has recently been implicated as an obesogen. Our recent study demonstrated that BBP can exacerbate high fat diet (HFD) induced diabesity in male mice. Here, we explored if pyrroloquinoline quinone (PQQ), a natural antioxidant andphytochemical, can attenuate metabolic aberrations induced by HFD or HFD-BBPcombination. C57Bl/6 male and female mice were fed either a chow diet (CD) or HFD with or without BBP (3 mg/kg body weight/day)and/or PQQ (20 mg/kg/day)for 16 weeks. The mice's body and tissue we...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Jian Zhang Catherine Powell Sunitha Meruvu Ravi Sonkar Mahua Choudhury Source Type: research

A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb
This study provides a unique insight into resveratrol modified derivatives as promising leads for preclinical LRAs, which in turn may help toward inhibitor design and chemical optimization for improving HIV-1 shock-and kill-based efforts.PMID:34971588 | DOI:10.1016/j.bcp.2021.114901 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Taizhen Liang Ziyao Wu Yibin Li Chao Li Kangni Zhao Xinman Qiao Heng Duan Xuanxuan Zhang Shuwen Liu Baomin Xi Lin Li Source Type: research

Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy
In this study, we aimed to investigate whether the novel autophagy activator trehalose could prevent cisplatin-induced damage in the auditory cell line HEI-OC1 and mouse cochlear explants and to further explore its mechanisms. Our data demonstrated that trehalose alleviated cisplatin-induced hair cell (HC) damage by inhibiting apoptosis, attenuating oxidative stress and rescuing mitochondrial dysfunction. Additionally, trehalose significantly enhanced autophagy levels in HCs, and inhibiting autophagy with 3-methyladenine (3-MA) abolished these protective effects. Mechanistically, we showed that the effect of trehalose was ...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Zhuangzhuang Li Qingxiu Yao Yuxin Tian Yumeng Jiang Maoxiang Xu Hui Wang Yuanping Xiong Jia Fang Wen Lu Dongzhen Yu Haibo Shi Source Type: research

Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice
In this study, we compared the metabolic effects of TCPOBOP using lipidomic, transcriptomic, and proteomic analyses in wild-type and humanized CAR-PXR-CYP3A4/3A7 mice. In the model, human CAR retains its constitutive activity in metabolism regulation; however, it is not activated by TCPOBOB. Notably, we observed that TCPOBOP affected lipid homeostasis by elevating serum and liver triglyceride levels and promoted hepatocyte hypertrophy in humanized CAR mice. Hepatic lipidomic analysis revealed a significant accumulation of triglycerides and decrease of its metabolites in humanized CAR mice. RNA-seq analysis has shown diverg...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Josef Skoda Klara Dohnalova Karel Chalupsky Aaron Stahl Markus Templin Jana Maixnerova Stanislav Micuda Lars Gr øntved Albert Braeuning Petr Pavek Source Type: research

Pyrroloquinoline quinone attenuated benzyl butyl phthalate induced metabolic aberration and a hepatic metabolomic analysis
Biochem Pharmacol. 2021 Dec 28:114883. doi: 10.1016/j.bcp.2021.114883. Online ahead of print.ABSTRACTBenzyl butyl phthalate (BBP) has recently been implicated as an obesogen. Our recent study demonstrated that BBP can exacerbate high fat diet (HFD) induced diabesity in male mice. Here, we explored if pyrroloquinoline quinone (PQQ), a natural antioxidant andphytochemical, can attenuate metabolic aberrations induced by HFD or HFD-BBPcombination. C57Bl/6 male and female mice were fed either a chow diet (CD) or HFD with or without BBP (3 mg/kg body weight/day)and/or PQQ (20 mg/kg/day)for 16 weeks. The mice's body and tissue we...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Jian Zhang Catherine Powell Sunitha Meruvu Ravi Sonkar Mahua Choudhury Source Type: research

A synthetic resveratrol analog termed Q205 reactivates latent HIV-1 through activation of P-TEFb
This study provides a unique insight into resveratrol modified derivatives as promising leads for preclinical LRAs, which in turn may help toward inhibitor design and chemical optimization for improving HIV-1 shock-and kill-based efforts.PMID:34971588 | DOI:10.1016/j.bcp.2021.114901 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Taizhen Liang Ziyao Wu Yibin Li Chao Li Kangni Zhao Xinman Qiao Heng Duan Xuanxuan Zhang Shuwen Liu Baomin Xi Lin Li Source Type: research

Trehalose protects against cisplatin-induced cochlear hair cell damage by activating TFEB-mediated autophagy
In this study, we aimed to investigate whether the novel autophagy activator trehalose could prevent cisplatin-induced damage in the auditory cell line HEI-OC1 and mouse cochlear explants and to further explore its mechanisms. Our data demonstrated that trehalose alleviated cisplatin-induced hair cell (HC) damage by inhibiting apoptosis, attenuating oxidative stress and rescuing mitochondrial dysfunction. Additionally, trehalose significantly enhanced autophagy levels in HCs, and inhibiting autophagy with 3-methyladenine (3-MA) abolished these protective effects. Mechanistically, we showed that the effect of trehalose was ...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Zhuangzhuang Li Qingxiu Yao Yuxin Tian Yumeng Jiang Maoxiang Xu Hui Wang Yuanping Xiong Jia Fang Wen Lu Dongzhen Yu Haibo Shi Source Type: research

Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice
In this study, we compared the metabolic effects of TCPOBOP using lipidomic, transcriptomic, and proteomic analyses in wild-type and humanized CAR-PXR-CYP3A4/3A7 mice. In the model, human CAR retains its constitutive activity in metabolism regulation; however, it is not activated by TCPOBOB. Notably, we observed that TCPOBOP affected lipid homeostasis by elevating serum and liver triglyceride levels and promoted hepatocyte hypertrophy in humanized CAR mice. Hepatic lipidomic analysis revealed a significant accumulation of triglycerides and decrease of its metabolites in humanized CAR mice. RNA-seq analysis has shown diverg...
Source: Biochemical Pharmacology - December 31, 2021 Category: Drugs & Pharmacology Authors: Josef Skoda Klara Dohnalova Karel Chalupsky Aaron Stahl Markus Templin Jana Maixnerova Stanislav Micuda Lars Gr øntved Albert Braeuning Petr Pavek Source Type: research

The role of FUNDC1 in mitophagy, mitochondrial dynamics and human diseases
Biochem Pharmacol. 2021 Dec 27:114891. doi: 10.1016/j.bcp.2021.114891. Online ahead of print.ABSTRACTMitochondria are the principal sites of energy metabolism and provide most of the energy needed for normal cellular function. They are dynamic organelles that constantly undergo fission, fusion and mitophagy to maintain their homeostasis and function. However, dysregulated mitochondrial dynamics and mitophagy leads to reduced ATP generation and mutation of their DNA, which ultimately leads to cell death. Increasing evidence has shown that the FUN14 domain-containing protein 1 (FUNDC1), a novel mitophagy receptor, participat...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Hui Liu Caixia Zang Fangyu Yuan Cheng Ju Meiyu Shang Jingwen Ning Yang Yang Jingwei Ma Gen Li Xiuqi Bao Dan Zhang Source Type: research

Drug-oxidizing and conjugating non-cytochrome P450 (non-P450) enzymes in cynomolgus monkeys and common marmosets as preclinical models for humans
Biochem Pharmacol. 2021 Dec 27:114887. doi: 10.1016/j.bcp.2021.114887. Online ahead of print.ABSTRACTMany drug oxidations and conjugations are mediated by a variety of cytochromes P450 (P450) and non-P450 enzymes in humans and non-human primates. These non-P450 enzymes include aldehyde oxidases (AOX), carboxylesterases (CES), flavin-containing monooxygenases (FMO), glutathione S-transferases (GST), arylamine N-acetyltransferases (NAT),sulfotransferases (SULT), and uridine 5'-diphospho-glucuronosyltransferases (UGT) and their substrates include both endobiotics and xenobiotics. Cynomolgus macaques (Macaca fascicularis, an O...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Yasuhiro Uno Shotaro Uehara Hiroshi Yamazaki Source Type: research

Suicide Gene Therapy in Cancer and HIV-1 infection: an alternative to conventional treatments
Biochem Pharmacol. 2021 Dec 27:114893. doi: 10.1016/j.bcp.2021.114893. Online ahead of print.ABSTRACTSuicide Gene Therapy (SGT) aims to introduce a gene encoding either a toxin or an enzyme making the targeted cell more sensitive to chemotherapy. SGT represents an alternative approach to combat pathologies where conventional treatments fail such as pancreatic cancer or the high-grade glioblastoma which are still desperately lethal. We review the possibility to use SGT to treat these cancers which have shown promising results in vitro and in preclinical trials. However, SGT has so far failed in phase III clinical trials thu...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Sepideh Saeb Jeanne Van Assche Thomas Loustau Olivier Rohr Cl émentine Wallet Christian Schwartz Source Type: research

DIAPH1 facilitates paclitaxel-mediated cytotoxicity of ovarian cancer cells
Biochem Pharmacol. 2021 Dec 27:114898. doi: 10.1016/j.bcp.2021.114898. Online ahead of print.ABSTRACTThe chemotherapeutic agent paclitaxel (PTX) selectively binds to and stabilizes microtubule (MTs). Also, the activated formin Diaphanous Related Formin 1 (DIAPH1) binds to MTs and increases its stability. In a recent study, we found that high DIAPH1 levels correlated with increased survival of ovarian cancer (Ovca) patients. A possible explanation for this finding is that Ovca cells with high DIAPH1 levels are more sensitive to PTX. To examine this assumption, in this study the effect of DIAPH1 depletion on PTX-mediated cyt...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Wilhelm Flat Sarah Borowski Themistoklis Paraschiakos Christine Blechner Sabine Windhorst Source Type: research

Mithramycin suppresses tumor growth by regulating CD47 and PD-L1 expression
In this study, we found CD47 expression was higher in melanoma of pan-tissue array. MIT inhibited CD47 expression both in mRNA and protein level in melanoma cells (SK-MEL-28 and B16). MIT inhibited c-Myc, Sp-1 and CD47 expression in a concentration-dependent way. MIT inhibited the surface CD47 expression and promoted the phagocytosis of SK-MEL-28 cells by THP-1 cells. We found MIT inhibited tumor growth in melanoma allograft mice and CD47 expression in tumor mass. We also found MIT upregulated PD-L1 expression in cancer cells possibly via inhibiting PD-L1 ubiquitination, increasing ROS and IFN-γ. Combination of MIT a...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Jianhua Gong Yuying Ji Xiujun Liu Yanbo Zheng Yongsu Zhen Source Type: research

PIWI-interacting RNA-23210 protects against acetaminophen-induced liver injury by targeting HNF1A and HNF4A
In conclusion, our findings provided new mechanistic clues revealing potential protective role of a piRNA against the hepatoxicity of APAP.PMID:34968487 | DOI:10.1016/j.bcp.2021.114897 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Lin Xu Wendi Chen Jing Chen Yuan Jin Wanli Ma Guangshuai Qi Xueying Sun Jiao Luo Chuanhai Li Kunming Zhao Yuxin Zheng Dianke Yu Source Type: research

Virus-mediated decrease of LKB1 activity in the mPFC diminishes stress-induced depressive-like behaviors in mice
This study also provides support for the potential use of LKB1 inhibition strategies against the chronic stress-related neuropsychiatric disorders.PMID:34968488 | DOI:10.1016/j.bcp.2021.114885 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Wen-Qian Tang Yue Liu Chun-Hui Ji Jiang-Hong Gu Yan-Mei Chen Jie Huang Wei Guan Da-Wei Xu Bo Jiang Source Type: research

Relaxin as an anti-fibrotic treatment: perspectives, challenges and future directions
Biochem Pharmacol. 2021 Dec 27:114884. doi: 10.1016/j.bcp.2021.114884. Online ahead of print.ABSTRACTFibrosis refers to the scarring and hardening of tissues, which results from a failed immune system-coordinated wound healing response to chronic organ injury and which manifests from the aberrant accumulation of various extracellular matrix components (ECM), primarily collagen. Despite being a hallmark of prolonged tissue damage and related dysfunction, and commonly associated with high morbidity and mortality, there are currently no effective cures for its regression. An emerging therapy that meets several criteria of an ...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Chrishan S Samuel Robert G Bennett Source Type: research

Association between urinary bisphenol A concentrations and semen quality: a meta-analytic study
In conclusion, the overall estimates of data produced by clinical studies point to a clinically negligible, if any, association between urinary BPA concentrations and semen quality. Further studies in workers at high risk of occupational exposure are warranted to corroborate the herein revealed weak correlation with a worse sperm motility.PMID:34968490 | DOI:10.1016/j.bcp.2021.114896 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Chiara Castellini Mario Muselli Antonio Parisi Maria Totaro Daniele Tienforti Giuliana Cordeschi Marco Giorgio Baroni Mauro Maccarrone Stefano Necozione Sandro Francavilla Arcangelo Barbonetti Source Type: research

The potential value of amlexanox in the treatment of cancer: molecular targets and therapeutic perspectives
Biochem Pharmacol. 2021 Dec 27:114895. doi: 10.1016/j.bcp.2021.114895. Online ahead of print.ABSTRACTAmlexanox (AMX) is an azoxanthone drug used for decades for the treatment of mouth aphthous ulcers and now considered for the treatment of diabetes and obesity. The drug is usually viewed as a dual inhibitor of the non-canonical IκB kinases IKK-ɛ (inhibitor-kappaB kinase epsilon) and TBK1 (TANK-binding kinase 1). But a detailed target profile analysis indicated that AMX binds directly to twelve protein targets, including different enzymes (IKK-ɛ, TBK1, GRK1, GRK5, PDE4B, 5- and 12-lipoxygenases) and non-enzyme prote...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Christian Bailly Source Type: research

Mechanisms of Ketamine and its Metabolites as Antidepressants
Biochem Pharmacol. 2021 Dec 27:114892. doi: 10.1016/j.bcp.2021.114892. Online ahead of print.ABSTRACTTreating major depression is a medical need that remains unmet by monoaminergic therapeutic strategies that commonly fail to achieve symptom remission. A breakthrough in the treatment of depression was the discovery that the anesthetic (R,S)-ketamine (ketamine), when administered at sub-anesthetic doses, elicits rapid (sometimes within hours) antidepressant effects in humans that are otherwise resistant to monoaminergic-acting therapies. While this finding was revolutionary and led to the FDA approval of (S)-ketamine (esket...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Evan M Hess Lace M Riggs Michael Michaelides Todd D Gould Source Type: research

Per- and Polyfluoroalkyl Substances Target and Alter Human Prostate Stem-Progenitor Cells
Biochem Pharmacol. 2021 Dec 27:114902. doi: 10.1016/j.bcp.2021.114902. Online ahead of print.ABSTRACTPer- and polyfluorinated alkyl substances (PFAS) are a large family of widely used synthetic chemicals that are environmentally and biologically persistent and present in most individuals. Chronic PFAS exposure have been linked to increased prostate cancer risk in occupational settings, however, underlying mechanisms have not been interrogated. Herein we examined exposure of normal human prostate stem-progenitor cells (SPCs) to 10 nM PFOA or PFOS using serial passage of prostasphere cultures. Exposure to either PFAS for 3-4...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Wen-Yang Hu Ranli Lu Dan Ping Hu Ozan Berk Imir Qianying Zuo Dan Moline Parivash Afradiasbagharani Lifeng Liu Scott Lowe Lynn Birch Donald J Vander Griend Zeynep Madak-Erdogan Gail S Prins Source Type: research

Role of nitric oxide in type 1 diabetes-induced osteoporosis
Biochem Pharmacol. 2021 Dec 27:114888. doi: 10.1016/j.bcp.2021.114888. Online ahead of print.ABSTRACTType 1 diabetes (T1D)-induced osteoporosis is characterized by decreased bone mineral density, bone quality, rate of bone healing, bone formation, and increased bone resorption. Patients with T1D have a 2-7-fold higher risk of osteoporotic fracture. The mechanisms leading to increased risk of osteoporotic fracture in T1D include insulin deficiency, hyperglycemia, insulin resistance, lower insulin-like growth factor-1, hyperglycemia-induced oxidative stress, and inflammation. In addition, a higher probability of falling, kid...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Sajad Jeddi Nasibeh Yousefzadeh Khosrow Kashfi Asghar Ghasemi Source Type: research

Underappreciated roles for Rho GDP Dissociation Inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell
Biochem Pharmacol. 2021 Dec 27:114886. doi: 10.1016/j.bcp.2021.114886. Online ahead of print.ABSTRACTRho subfamily of G proteins (e.g., Rac1) have been implicated in glucose-stimulated insulin secretion from the pancreatic β-cell. Interestingly, metabolic stress (e.g., chronic exposure to high glucose) results in sustained activation of Rac1 leading to increased oxidative stress, impaired insulin secretion and β-cell dysfunction. Activation-deactivation of Rho G proteins is mediated by three classes of regulatory proteins, namely the guanine nucleotide exchange factors (GEFs), which facilitate the conversion of i...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: Anjaneyulu Kowluru Noah F Gleason Source Type: research

Prolyl oligopeptidase acts as a link between chaperone-mediated autophagy and macroautophagy
Biochem Pharmacol. 2021 Dec 27:114899. doi: 10.1016/j.bcp.2021.114899. Online ahead of print.ABSTRACTThe accumulation of aggregated α-synuclein (α-syn) has been identified as the primary component of Lewy bodies that are the pathological hallmarks of Parkinson's disease (PD). Several preclinical studies have shown α-syn aggregation, and particularly the intermediates formed during the aggregation process to be toxic to cells. Current PD treatments only provide symptomatic relief, and α-syn serves as a promising target to develop a disease-modifying therapy for PD. Our previous studies have revealed ...
Source: Biochemical Pharmacology - December 30, 2021 Category: Drugs & Pharmacology Authors: H Cui S Norrbacka T T My öhänen Source Type: research

Anti-inflammatory, but not osteoprotective, effect of the TRAF6/CD40 inhibitor 6877002 in rodent models of local and systemic osteolysis
In conclusion, TRAF6 inhibitors may be of value in the management of the inflammatory component of bone disorders, but may not offer protection against local or systemic bone loss, unless combined with anti-resorptive therapy such as bisphosphonates.PMID:34896056 | DOI:10.1016/j.bcp.2021.114869 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Silvia Marino Nicole Hannemann Ryan T Bishop Feier Zeng Giovana Carrasco Sandrine Meurisse Boya Li Antonia Sophocleous Anna Sparatore Tobias Baeuerle Slobodan Vukicevic Marielle Auberval Patrick Mollat Aline Bozec Aymen I Idris Source Type: research

MICAL1 inhibits colorectal cancer cell migration and proliferation by regulating the EGR1/ β-catenin signaling pathway
This study aims to investigate the cellular functions and molecular mechanisms of MICAL1 in CRC cells. Here, we found that both mRNA and protein levels of MICAL1 were down-regulated in colorectal cancer tissues compared with matched adjacent non-tumor tissues, and the expression level of MICAL1 was correlated with the metastatic status of colorectal cancer. Importantly, overexpression of MICAL1 significantly inhibited colorectal cancer cell migration and growth, and increased the level of E-cadherin and Occludin, and suppressed the expression level of Vimentin and N-cadherin; while silencing of MICAL1 promoted CRC cell mig...
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Huanyu Gu Yi Li Xiuping Cui Huiru Cao Zhijuan Hou Yunhe Ti Dahua Liu Jing Gao Yu Wang Pushuai Wen Source Type: research

Molecular basis for stereoselective transport of fenoterol by the organic cation transporters 1 and 2
Biochem Pharmacol. 2021 Dec 10;197:114871. doi: 10.1016/j.bcp.2021.114871. Online ahead of print.ABSTRACTStereoselectivity is important in many pharmacological processes but its impact on drug membrane transport is scarcely understood. Recent studies showed strong stereoselective effects in the cellular uptake of fenoterol by the organic cation transporters OCT1 and OCT2. To provide possible molecular explanations, homology models were developed and the putative interactions between fenoterol enantiomers and key residues explored in silico through computational docking, molecular dynamics simulations, and binding free ener...
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Lukas Gebauer N Arul Murugan Ole Jensen J ürgen Brockmöller Muhammad Rafehi Source Type: research

Anti-inflammatory, but not osteoprotective, effect of the TRAF6/CD40 inhibitor 6877002 in rodent models of local and systemic osteolysis
In conclusion, TRAF6 inhibitors may be of value in the management of the inflammatory component of bone disorders, but may not offer protection against local or systemic bone loss, unless combined with anti-resorptive therapy such as bisphosphonates.PMID:34896056 | DOI:10.1016/j.bcp.2021.114869 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Silvia Marino Nicole Hannemann Ryan T Bishop Feier Zeng Giovana Carrasco Sandrine Meurisse Boya Li Antonia Sophocleous Anna Sparatore Tobias Baeuerle Slobodan Vukicevic Marielle Auberval Patrick Mollat Aline Bozec Aymen I Idris Source Type: research

MICAL1 inhibits colorectal cancer cell migration and proliferation by regulating the EGR1/ β-catenin signaling pathway
This study aims to investigate the cellular functions and molecular mechanisms of MICAL1 in CRC cells. Here, we found that both mRNA and protein levels of MICAL1 were down-regulated in colorectal cancer tissues compared with matched adjacent non-tumor tissues, and the expression level of MICAL1 was correlated with the metastatic status of colorectal cancer. Importantly, overexpression of MICAL1 significantly inhibited colorectal cancer cell migration and growth, and increased the level of E-cadherin and Occludin, and suppressed the expression level of Vimentin and N-cadherin; while silencing of MICAL1 promoted CRC cell mig...
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Huanyu Gu Yi Li Xiuping Cui Huiru Cao Zhijuan Hou Yunhe Ti Dahua Liu Jing Gao Yu Wang Pushuai Wen Source Type: research

Molecular basis for stereoselective transport of fenoterol by the organic cation transporters 1 and 2
Biochem Pharmacol. 2021 Dec 10;197:114871. doi: 10.1016/j.bcp.2021.114871. Online ahead of print.ABSTRACTStereoselectivity is important in many pharmacological processes but its impact on drug membrane transport is scarcely understood. Recent studies showed strong stereoselective effects in the cellular uptake of fenoterol by the organic cation transporters OCT1 and OCT2. To provide possible molecular explanations, homology models were developed and the putative interactions between fenoterol enantiomers and key residues explored in silico through computational docking, molecular dynamics simulations, and binding free ener...
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Lukas Gebauer N Arul Murugan Ole Jensen J ürgen Brockmöller Muhammad Rafehi Source Type: research

Anti-inflammatory, but not osteoprotective, effect of the TRAF6/CD40 inhibitor 6877002 in rodent models of local and systemic osteolysis
In conclusion, TRAF6 inhibitors may be of value in the management of the inflammatory component of bone disorders, but may not offer protection against local or systemic bone loss, unless combined with anti-resorptive therapy such as bisphosphonates.PMID:34896056 | DOI:10.1016/j.bcp.2021.114869 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Silvia Marino Nicole Hannemann Ryan T Bishop Feier Zeng Giovana Carrasco Sandrine Meurisse Boya Li Antonia Sophocleous Anna Sparatore Tobias Baeuerle Slobodan Vukicevic Marielle Auberval Patrick Mollat Aline Bozec Aymen I Idris Source Type: research

MICAL1 inhibits colorectal cancer cell migration and proliferation by regulating the EGR1/ β-catenin signaling pathway
This study aims to investigate the cellular functions and molecular mechanisms of MICAL1 in CRC cells. Here, we found that both mRNA and protein levels of MICAL1 were down-regulated in colorectal cancer tissues compared with matched adjacent non-tumor tissues, and the expression level of MICAL1 was correlated with the metastatic status of colorectal cancer. Importantly, overexpression of MICAL1 significantly inhibited colorectal cancer cell migration and growth, and increased the level of E-cadherin and Occludin, and suppressed the expression level of Vimentin and N-cadherin; while silencing of MICAL1 promoted CRC cell mig...
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Huanyu Gu Yi Li Xiuping Cui Huiru Cao Zhijuan Hou Yunhe Ti Dahua Liu Jing Gao Yu Wang Pushuai Wen Source Type: research

Molecular basis for stereoselective transport of fenoterol by the organic cation transporters 1 and 2
Biochem Pharmacol. 2021 Dec 10;197:114871. doi: 10.1016/j.bcp.2021.114871. Online ahead of print.ABSTRACTStereoselectivity is important in many pharmacological processes but its impact on drug membrane transport is scarcely understood. Recent studies showed strong stereoselective effects in the cellular uptake of fenoterol by the organic cation transporters OCT1 and OCT2. To provide possible molecular explanations, homology models were developed and the putative interactions between fenoterol enantiomers and key residues explored in silico through computational docking, molecular dynamics simulations, and binding free ener...
Source: Biochemical Pharmacology - December 13, 2021 Category: Drugs & Pharmacology Authors: Lukas Gebauer N Arul Murugan Ole Jensen J ürgen Brockmöller Muhammad Rafehi Source Type: research