Journal of Biochemical and Molecular Toxicology最新文献_第10页

A Novel circ_0075829/miR-326/GOT1 ceRNA Crosstalk Regulates the Malignant Phenotypes and Drug Sensitivity of Gemcitabine-Resistant Pancreatic Cancer Cells 一种新的circ_0075829/miR-326/GOT1 ceRNA串扰调控耐吉西他滨胰腺癌细胞的恶性表型和药物敏感性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-18 DOI: 10.1002/jbt.70089

Yongjia Xiang, Rubing Zhou, Yi Yang, Hao Bai, Fan Liang, Hongmei Wang, Xia Wang

{"title":"A Novel circ_0075829/miR-326/GOT1 ceRNA Crosstalk Regulates the Malignant Phenotypes and Drug Sensitivity of Gemcitabine-Resistant Pancreatic Cancer Cells","authors":"Yongjia Xiang, Rubing Zhou, Yi Yang, Hao Bai, Fan Liang, Hongmei Wang, Xia Wang","doi":"10.1002/jbt.70089","DOIUrl":"10.1002/jbt.70089","url":null,"abstract":"<div>\u0000 \u0000 <p>Although gemcitabine (GEM) is the cornerstone of the treatment of pancreatic cancer (PC), GEM resistance frequently arises. Circular RNA (circRNA) circ_0075829 is highly expressed in PC. However, whether circ_0075829 contributes to GEM resistance of PC is largely unknown. To generate GEM-resistant PC cells (BxPC-3/GR and SW1990/GR), we exposed GEM-sensitive PC cells to GEM. Circ_0075829, microRNA (miR)-326, and glutamic-oxaloacetic transaminase 1 (GOT1) were quantified by a qRT-PCR or western blot method. Cell survival and viability were gauged by MTS assay. Cell proliferation, apoptosis, invasion, and migration were assessed by EdU, flow cytometry, transwell, and wound-healing assays, respectively. Dual-luciferase reporter assays were used to verify the relationship between miR-326 and circ_0075829 or GOT1. Mouse xenografts were performed to evaluate the role of circ_0075829 in vivo. Our data showed that circ_0075829 was upregulated in GEM-resistant PC tissues and cells. Knockdown of circ_0075829 impeded the proliferation, invasion, migration, and glutamine metabolism, and promoted cell apoptosis and GEM sensitivity of GEM-resistant PC cells. Moreover, circ_0075829 silencing suppressed the tumorigenicity of SW1990/GR cells and sensitized them to the cytotoxic effect of GME in vivo. Mechanistically, circ_0075829 bound miR-326 and exerted regulatory effects by affecting miR-326 expression. GOT1 was a direct miR-326 target and a key downstream effector of miR-326. Furthermore, circ_0075829 modulated GOT1 expression via miR-326. Our findings establish a novel regulatory network, the circ_0075829/miR-326/GOT1 competing endogenous RNA (ceRNA) crosstalk, in the regulation of GEM resistance in PC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repeated Injection of Xylazine Causes Liver Injury Through the PPAR Signaling Pathway in Rats 反复注射噻嗪通过PPAR信号通路引起大鼠肝损伤。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-18 DOI: 10.1002/jbt.70101

Shanyong Yi, Tingting Mai, Ying Fang, Qishuo Tian, Shuquan Zhao

{"title":"Repeated Injection of Xylazine Causes Liver Injury Through the PPAR Signaling Pathway in Rats","authors":"Shanyong Yi, Tingting Mai, Ying Fang, Qishuo Tian, Shuquan Zhao","doi":"10.1002/jbt.70101","DOIUrl":"10.1002/jbt.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>With the gradual emergence of xylazine as a street drug, incidents of xylazine poisoning are now occurring worldwide. However, it remains unknown whether long-term exposure to xylazine causes nonalcoholic fatty liver disease (NAFLD). In the present study, the rats were injected with xylazine intraperitoneally for 28 consecutive days, and then serum and liver tissues were collected for analysis. Weight loss was observed in the 40 mg/kg group and elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. Histopathologic examination showed hepatic steatosis, necrosis, and fibrosis. By mRNA sequencing, 192 upregulated genes and 277 downregulated genes were found in the 40 mg/kg group, and the PPAR signaling pathway was ranked first in the KEGG pathway analysis. Four genes in the PPAR signaling pathway, <i>Fabp5</i>, <i>Acox2</i>, and <i>Cpt2</i>, were also verified in the 40 mg/kg group by RT-qPCR analysis and western blot. Our results demonstrated that long-term injection of xylazine causes NAFLD and the PPAR signaling pathway plays a core role in the process of xylazine-associated liver injury.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LMOD1 Exerts a Tumor-Suppressive Role in Breast Cancer by Restraining the JAK2/STAT3 Pathway LMOD1通过抑制JAK2/STAT3通路在乳腺癌中发挥肿瘤抑制作用

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-18 DOI: 10.1002/jbt.70092

Xiansong Fang, Xiaoyun Wen, Ya Hou, Liang Zhou, Yingjie Jiang, Yu Chen

{"title":"LMOD1 Exerts a Tumor-Suppressive Role in Breast Cancer by Restraining the JAK2/STAT3 Pathway","authors":"Xiansong Fang, Xiaoyun Wen, Ya Hou, Liang Zhou, Yingjie Jiang, Yu Chen","doi":"10.1002/jbt.70092","DOIUrl":"10.1002/jbt.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer has seriously affected women's physical and mental health. This investigation aims at screening differentially expressed genes (DEGs) in breast cancer and illuminating the potential biological functions of Leiomodin 1 (LMOD1) and its behind mechanisms against breast cancer. The common DEGs (co-DEGs) between the GSE22820 and GSE29431 data sets and pivotal genes were screened out using bioinformatics methods. The biological roles of LMOD1 overexpression on malignant phenotypes were validated by functional assays and the impact on fatty acid synthesis was also elucidated in breast cancer cell lines. Additionally, colivelin, a STAT3 activator, was applied for further investigating the role of LMOD1 on the JAK2/STAT3 pathway in vitro. A total of 208 co-DEGs and 5 focal genes were screened through bioinformatics analysis, and 5 focal genes were downregulated in breast cancer cell lines. LMOD1 overexpression retarded proliferative, migratory, invasive capabilities of breast cancer cells. LMOD1 overexpression suppressed fatty acid synthesis. Furthermore, the inhibitory effects on malignant phenotypes of breast cancer cells with LMOD1 overexpression were partially abolished after colivelin treatment. Additionally, LMOD1 could impede fatty acid synthesis in breast cancer cells. Our study highlighted LMOD1 exerted as a tumor-suppressive role in breast cancer, which was correlated with restraining the JAK2/STAT3 pathway activation.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chimeric Antigen Receptor (CAR)-T Cells: A New Era for Hepatocellular Carcinoma Treatment 嵌合抗原受体(CAR)-T细胞：肝癌治疗的新时代。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-12 DOI: 10.1002/jbt.70091

Ming Xu, Yang Pan

{"title":"Chimeric Antigen Receptor (CAR)-T Cells: A New Era for Hepatocellular Carcinoma Treatment","authors":"Ming Xu, Yang Pan","doi":"10.1002/jbt.70091","DOIUrl":"10.1002/jbt.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is one of the most common cancers and a worldwide health concern that requires novel treatment approaches. Tyrosine kinase inhibitors (TKIs) and immune checkpoint blockades (ICBs) are the current standard of care; however, their clinical benefits are limited in some advanced and metastatic patients. With the help of gene engineering techniques, a novel adoptive cellular therapy (ACT) called chimeric antigen receptor (CAR)-T cells was recently introduced for treating HCC. A plethora of current clinical and preclinical studies are attempting to improve the efficacy of CAR-T cells by dominating the immunosuppressive environment of HCC and finding the best tumor-specific antigens (TSAs). The future of care for HCC patients might be drastically improved due to the convergence of novel therapeutic methods and the continuous progress in ACT research. However, the clinical application of CAR-T cells in solid tumors is still facing several challenges. In this study, we provide an overview of the advancement and prospects of CAR-T cell immunotherapy in HCC, as well as an investigation of how cutting-edge engineering could improve CAR-T cell efficacy and safety profile.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nephroprotective Potential of 1,3,4-Oxadiazole Derivative Against Methotrexate-Induced Nephrotoxicity in Rats by Upregulating Nrf2 and Downregulating NF-κB and TNF-α Signaling Pathways 1,3,4-恶二唑衍生物通过上调Nrf2和下调NF-κB和TNF-α信号通路抗甲氨蝶呤所致大鼠肾毒性的肾保护作用

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-11 DOI: 10.1002/jbt.70084

Zubaria Rafique, Muhammad Aabid, Humaira Nadeem, Ayema Rehman, Jehan zeb Khan, Muhammad Waqas, Nadeem Irshad

{"title":"Nephroprotective Potential of 1,3,4-Oxadiazole Derivative Against Methotrexate-Induced Nephrotoxicity in Rats by Upregulating Nrf2 and Downregulating NF-κB and TNF-α Signaling Pathways","authors":"Zubaria Rafique, Muhammad Aabid, Humaira Nadeem, Ayema Rehman, Jehan zeb Khan, Muhammad Waqas, Nadeem Irshad","doi":"10.1002/jbt.70084","DOIUrl":"10.1002/jbt.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Nephrotoxicity is a prominent complication of methotrexate (MTX) therapy that limits clinicians in its extensive use. MTX triggers oxidative burden and inflammation, so the nephroprotective potential of the synthetic derivative of 1,3,4-oxadiazole (5b) was explored in this research. Male Wistar rats were divided into four groups i.e., control group, MTX group, 5b (5 mg/kg) + MTX group and 5b (10 mg/kg) + MTX group, respectively. All treatments were given, intraperitoneally (<i>i.p</i>.) during 12 days of the animal model. The MTX-induced nephrotoxicity was evaluated by renal function markers i.e., serum creatinine (Cret), blood urea nitrogen (BUN), and albumin (Alb). Furthermore, antioxidant markers, catalase (CAT), glutathione-S-transferase (GST), and reduced glutathione (GSH), and oxidative stress, markers lipid peroxidase (LPO) and nitric oxide (NO), were analyzed. Pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were also calculated. DNA damage was assessed by the comet assay. Histopathological staining (Hematoxylin and eosin, Masson's trichrome) was done and immunohistochemistry was performed against Caspase-3, Nrf2, HO-1, TLR-4, TNF-α, and NF-κB. A significant improvement in the serum Cret, BUN, and Alb was observed in (5b) treated groups. Antioxidant markers were elevated, oxidative stress markers and pro-inflammatory cytokines were reduced, moreover, histopathological analysis revealed less tissue damage in (5b) administered groups. Immunohistochemistry showed increased immune expression of Nrf2 and HO-1 and decreased expression of TLR-4, TNF-α, Caspase-3, and NF-κB in 5b (5 mg/kg) + MTX group and 5b (10 mg/kg) + MTX group as compared to the MTX group. Hence, the results of this study favor the use of (5b) against MTX-induced nephrotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum to “Inhibition of Autophagy Reduces the Rate of Fluoride-Induced LS8 Apoptosis via Regulating ATG5 and ATG7” “抑制自噬通过调节ATG5和ATG7降低氟化物诱导的LS8细胞凋亡率”的勘误。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-10 DOI: 10.1002/jbt.70093

引用次数: 0

An Experimental Insight Into the Role of Agomelatine in Renal Ischemia/Reperfusion Injury 阿戈美拉汀对肾缺血再灌注损伤作用的实验研究。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-10 DOI: 10.1002/jbt.70090

Damla Aykora, Mehmet Refik Bahar, Kevser Tanbek, Dilara Altay Öztürk, Elif Karaca, Süleyman Sandal, Suat Tekin

{"title":"An Experimental Insight Into the Role of Agomelatine in Renal Ischemia/Reperfusion Injury","authors":"Damla Aykora, Mehmet Refik Bahar, Kevser Tanbek, Dilara Altay Öztürk, Elif Karaca, Süleyman Sandal, Suat Tekin","doi":"10.1002/jbt.70090","DOIUrl":"10.1002/jbt.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute kidney injury (AKI) is one of the leading causes of chronic kidney disease and accounts for 50%–75% of mortality following renal pathologies or organ transplantation. Ischemia‒reperfusion injury (IRI) involves an interrupted blood supply to organs and the kidney; IRI exacerbates AKI development. Owing to several pharmacological treatment methods, AKI still has a poor prognosis, and novel therapeutic options are needed. Agomelatine (AGM) is a melatonin receptor agonist (MT1 and MT2) with increased bioavailability and lipophilicity. In this study, we aimed to investigate the antioxidant and anti-inflammatory effects of AGM in experimental renal IRI via long-term and short-term applications. Sixty male Sprague–Dawley rats were randomly divided into six groups (<i>n</i> = 10): the control, I/R, AGM20S, AGM40S, AGM20L, and AGM40L groups. Following the establishment of the renal IRI model, the rats received agomelatine at 20 and 40 mg/kg orally, and agomelatine solvent (hydroxyethylcellulose) was used as a vehicle. At the end of the experiment, blood samples and renal tissues were harvested for histopathological and biochemical analysis. Urea, creatinine, tumor necrosis factor (TNF-α), and interleukin-1 beta (IL-1β) levels were measured in blood serum samples. Malondialdehyde (MDA) levels and increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and total glutathione (GSH) levels were measured in renal tissue supernatants. Our biochemical results indicated that AGM reduced creatinine, TNF-α, IL-1β, and malondialdehyde levels and increased SOD, CAT, GSHPx, and total GSH levels. Agolematine reduced infiltration, intratubular hemorrhage, and intratubular cast formation histopathologically. Our results suggest that AGM could be a potential therapeutic adjuvant agent for ischemia‒reperfusion injury in the kidney and several other organs.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Study on the Role of microRNA-138-5p Through Sorbin and SH3 Domain-Containing Protein 2 in Breast Cancer microRNA-138-5p通过Sorbin和SH3结构域蛋白2在乳腺癌中的作用研究

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-10 DOI: 10.1002/jbt.70081

LiGong Zhang, Chao Zhu, Chenxu Guo, FaXiang Yin, Qiang Xie, Min Tao

引用次数: 0

Innovation in CRC Research: Targeting SPACA6P-AS for Progression CRC研究的创新：靶向spacac6p - as的进展。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-10 DOI: 10.1002/jbt.70039

Tianyi Ma, Yinghu Jin, Song Wang, Hanqing Hu, Meng Wang, Guoqing Yan, Qingchao Tang, Rui Huang, Guiyu Wang

引用次数: 0

MiR-200a-3p Attenuates Neuropathic Pain by Suppressing the Bromodomain-Containing Protein 3-Nuclear Factor-κB Pathway MiR-200a-3p通过抑制含溴结构域蛋白3-核因子-κB通路减轻神经性疼痛。

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-09 DOI: 10.1002/jbt.70041

Chao Deng, Xuequan Yuan, Xuezheng Lin, Sitong Liu

{"title":"MiR-200a-3p Attenuates Neuropathic Pain by Suppressing the Bromodomain-Containing Protein 3-Nuclear Factor-κB Pathway","authors":"Chao Deng, Xuequan Yuan, Xuezheng Lin, Sitong Liu","doi":"10.1002/jbt.70041","DOIUrl":"10.1002/jbt.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>MicroRNAs (miRNAs) have key roles in the pathological processes of neuropathic pain. Here, our aim was to elucidate the function of miR-200a-3p as well as its related regulatory mechanism in neuropathic pain. An animal model of neuropathic pain was established by chronic constriction injury (CCI) induction. The knockdown experiments are performed by injecting a lentiviral construct intrathecally. MiR-200a-3p and bromodomain-containing protein 3 (BRD3) expression in rat spinal cord was determined using RT-qPCR. The mechanical, thermal, and cold responses in animals were assessed at the indicated time after surgery. The levels of inflammatory cytokines in rat spinal cord were measured by ELISA. The changes in NF-κB signaling-related molecules in rat spinal cord were determined using western blot and immunofluorescence. MiR-200a-3p was underexpressed in CCI rats in a time-dependent manner. Overexpression of miR-200a-3p decreased mechanical hyperalgesia and thermal sensitivity to attenuate neuropathic pain in rats. BRD3 was targeted by miR-200a-3p. Additionally, downregulation of BRD3 inhibited neuropathic pain progression. Moreover, overexpression of BRD3 rescued the effect of miR-200a-3p on NF-κB signaling and neuropathic pain in CCI rats. MiR-200a-3p attenuates neuropathic pain via downregulating BRD3 to block NF-κB signaling.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0