Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Eupatorin Mitigates Airway Inflammation in Ovalbumin-Induced Allergic Asthma in Mice by Regulating Th2 Cytokines and Oxidative Stress","authors":"Juxiu Lu,&nbsp;Saud Alarifi,&nbsp;Anis Ahamed,&nbsp;Ruizhe Wang","doi":"10.1002/jbt.70219","DOIUrl":"https://doi.org/10.1002/jbt.70219","url":null,"abstract":"<div>\u0000 \u0000 <p>Asthma is a prevalent airway inflammatory condition caused by exposure to various allergens. It is defined by the presence of airway inflammation, airway hyperresponsiveness, and excessive production of mucus. This work was undertaken to study the curative potentials of eupatorin against ovalbumin (OVA)-exposed asthma in mice. The influence of eupatorin on the RAW 264.7 cell growth were assessed by MTT test. The inflammatory cytokines and nitric oxide (NO) concentration in the RAW 264.7 cells was examined using kits. The antibacterial effects of eupatorin against <i>H. influenza</i>, <i>S. pneumoniae</i>, and <i>C. pneumoniae</i> were evaluated using the well diffusion technique. The impact of eupatorin on the inflammatory cells in OVA-treated asthma mice was evaluated. The Th2 cytokines, TNF-α, IgE, and IFN-γ weres evaluated using assay kits. The oxidative stress parameter levels were examined using the kits. The histopathological examination was performed on the lungs of the experimental mice. The current work demonstrates that the eupatorin treatment did not affect the RAW 264.7 cell growth. It also reduced the NO, TNF-α, and IL-6 concentrations in the LPS-exposed RAW 264.7 cells. Furthermore, the eupatorin treatment to OVA-induced mice led to a diminution in Th2 cytokine levels and inflammatory cell counts. The eupatorin treatment was found to decrease OVA-specific IgE and pro-inflammatory markers, which results in the alleviation of airway inflammation. The eupatorin treatment also improved the antioxidant status. The findings of the histopathological analysis demonstrated the curative properties of eupatorin against on asthmatic mice. The anti-asthmatic effects of eupatorin are attributed to its capacity to decrease airway inflammation and enhance antioxidant processes. Therefore, it is evident that eupatorin possesses anti-asthmatic properties, making it a promising therapeutic candidate to treat allergic asthma.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689889","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}

{"title":"The First Chalcone Derivatives of Valine-Based Spiro-Cyclotriphosphazenes: In Vitro Cytotoxic Properties, Molecular Docking and DNA Damage Mechanism Studies","authors":"Yunus Yücel,&nbsp;Ferhan Sultan Şeker,&nbsp;Büşra Aksoy Erden,&nbsp;Mücahit Özdemir,&nbsp;Çiğdem Tekin,&nbsp;Eray Çalışkan,&nbsp;Suat Tekin,&nbsp;Kenan Koran,&nbsp;Fatih Biryan","doi":"10.1002/jbt.70233","DOIUrl":"https://doi.org/10.1002/jbt.70233","url":null,"abstract":"<p>Cancer treatment requires novel compounds with potent cytotoxic and genotoxic properties to effectively target cancer cells. In this study, new hybrid cyclotriphosphazene compounds were synthesized, characterized, and evaluated for their biological activity. Cytotoxicity against A2780 and Caco-2 cancer cell lines was assessed via the MTT assay, while genotoxic effects at 60–70% cell viability were examined using the Comet assay. Apoptotic cells were identified through TUNEL analyses, and reactive oxygen species levels were measured. Results showed that these compounds significantly reduced cell viability through DNA damage mechanisms. At high doses (50–100 µM), BV, BVK1, BVK2, and BVK4 decreased A2780 cell viability by 30–65%, whereas VPA had a milder effect (15–25%). In Caco-2 cells, viability was reduced by 10–35%. The compounds exhibited varying cytotoxicity across different cancer cell lines, reflecting cancer cell heterogeneity. Significant DNA damage, including changes in tail length, tail density, and tail moment, was observed in A2780 cells, confirming cell death via DNA damage. Molecular docking analyses further supported the potential of cyclotriphosphazene compounds (BV and BVK2) as targeted cancer inhibitors. Molecular docking revealed BVK2's high selectivity for Bcl-2, mutant p53, and VEGFR2. BVK2 and BV demonstrate strong binding affinities with key cancer-related targets, indicating their potential as multi-targeted inhibitors that regulate apoptosis, cell cycle control, and angiogenesis, making them promising candidates for targeted cancer therapy.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70233","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medium-Chain Triglycerides Supplementation Protects Epilepsy-Associated Behavioral Impairments in a Mouse Model","authors":"Amit Kumar,&nbsp;Savita Kumari,&nbsp;Poonam Dhiman,&nbsp;Damanpreet Singh","doi":"10.1002/jbt.70213","DOIUrl":"10.1002/jbt.70213","url":null,"abstract":"<div>\u0000 \u0000 <p>Presently there has been a growing interest in the development of dietary-based interventions as alternative therapies to combat chronic neurological conditions like epilepsy. Medium-chain triglycerides (MCT) are composed of three fatty acids attached to a glycerol backbone and have shown several beneficial effects in various neurological diseases. The present study investigated MCT supplementation's impact on seizure severity and associated neurobehavioral comorbidities in a pentylenetetrazole (PTZ) mouse kindling model. Mice were administered 35 mg/kg (<i>i.p</i>.) of PTZ every other day for kindling induction. The kindled mice were then subjected to MCT supplementation for over 25 days with seizure scoring at every 5th day following PTZ exposure. Behavioral analysis was initiated at the end of 25 days of the MCT supplementation. After that, lipid peroxidation assay, and, gene and protein expression studies were performed in the isolated hippocampus. MCT significantly decreased seizure severity scores compared to control. The treatment reduced immobility duration in the forced swim and tail suspension tests, indicating a reversal of seizures-associated depression-like behavior. A significant reduction in the percentage of spontaneous alternation was observed in the kindled control group in the T-maze test, which remained unchanged following MCT supplementation in the treated group. Furthermore, no change was observed in the locomotion and anxiety index of the kindled mice supplemented with MCT compared to the control group. In addition, the supplementation attenuated the altered hippocampal lipid peroxidation, and mRNA and protein levels of mTOR and Gsk-3β. The study concluded that MCT supplementation suppresses epileptic seizures and associated depression-like behavior in kindled mice via interacting mTOR and Gsk-3β signaling.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669934","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}

{"title":"A Novel Circ_0004104/MiR-493-5p/SYPL1 Cascade Contributes to Colorectal Cancer Progression","authors":"Bin Zhang,&nbsp;Bin Shao,&nbsp;Zhixian Liu,&nbsp;Liangbin Wang,&nbsp;Bo Hong","doi":"10.1002/jbt.70226","DOIUrl":"10.1002/jbt.70226","url":null,"abstract":"<div>\u0000 \u0000 <p>Circular RNAs (circRNAs) play critical roles in human tumorigenesis. Circ_0004104 is abnormally expressed in the tumors of colorectal cancer (CRC). However, its specific function in CRC remains unknown. In this report, we explored the biological action and mechanism of circ_0004104 in CRC development. Quantitative real-time PCR was used to detect circ_0004104, microRNA (miR)-493-5p, and synaptophysin-like 1 (SYPL1) mRNA levels. Fluorescence in situ hybridization (FISH) assay was used to visualize circ_0004104. The impact of circ_0004104 on CRC cell phenotypes was assessed by measuring cell proliferation, migration, invasion, and apoptosis. Animal experiments were performed to analyze the effect of circ_0004104 on CRC xenograft growth in vivo. The potential interacting miRNAs were predicted using the Circular RNA Interactome database, and the binding sites for miR-493-5p in SYPL1 mRNA were predicted using the Starbase3.0 database. The circ_0004104/miR-493-5p and miR-493-5p/SYPL1 relationships were validated by dual-luciferase reporter assay. In CRC tissues and cell lines, circ_0004104 and SYPL1 levels were upregulated and miR-493-5p expression was decreased. Circ_0004104 was mainly located in the cytoplasm of CRC cells and exhibited resistance to RNase R digestion. High circ_0004104 expression predicted a poor prognosis of CRC patients. Functionally, circ_0004104 knockdown suppressed CRC cell proliferation, migration, and invasiveness and accelerated apoptosis in vitro, as well as diminished tumor growth in vivo. Circ_0004104 depletion also decreased N-cadherin and Vimentin levels and increased E-cadherin expression in CRC cells. Mechanistically, circ_0004104 could act as a miR-493-5p sponge, and SYPL1 was a direct target of miR-493-5p. Moreover, circ_0004104 targeted miR-493-5p to regulate SYPL1 expression. The effects of circ_0004104 knockdown on CRC cell behavior alterations were reversed by miR-493-5p inhibitor. Additionally, SYPL1 overexpression reversed the effects of miR-493-5p on CRC cell phenotypes. Our findings suggest that circ_0004104 enhances CRC malignant progression through the miR-493-5p/SYPL1 cascade, providing a potential target for CRC treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674038","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}

{"title":"FTO-mediated m6A Methylation of KCNAB2 Inhibits Tumor Property of Non-Small Cell Lung Cancer Cells and M2 Macrophage Polarization by Inactivating the PI3K/AKT Pathway","authors":"Yanguang Li,&nbsp;Jieting Niu,&nbsp;Zhiguang Sun,&nbsp;Junfeng Liu","doi":"10.1002/jbt.70232","DOIUrl":"10.1002/jbt.70232","url":null,"abstract":"<div>\u0000 \u0000 <p>Potassium voltage-gated channel subfamily A regulatory beta subunit 2 (KCNAB2) is a potassium voltage-gated channel subfamily A member that plays a role in non-small cell lung cancer (NSCLC). However, its functional impact and mechanism in NSCLC are not fully understood. Here, we analyzed its effects on NSCLC cell behaviors and the underlying mechanism.mRNA expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR),(qRT-PCR), while protein expression was quantified by western blotting blot analysis or immunohistochemistry assay. NSCLC cell proliferation, migration, invasion, macrophage polarization, and apoptosis were evaluated through cell-based assays including cell counting kit-8 (CCK-8)(CCK-8) assay, flow cytometry, Tunel assay, wound-healing assay, and transwell invasion assay. The role of FTO alpha-ketoglutarate dependent dioxygenase (FTO)-mediated(FTO)-mediated m6A methylation in the regulation of KCNAB2 expression and their impacts on NSCLC cell behavior and M2 macrophage polarization were assessed through m6A RNA immunoprecipitation assay and rescue experiments. Xenograft mouse model assay was used to determine the effect of KCNAB2 on tumor formation <i>in vivo</i>.in vivo.KCNAB2 expression was downregulated and FTO expression was upregulated in NSCLC tissues and cells when compared with controls. Moreover, the expression of KCNAB2 was found to be lower in stage III NSCLC patients compared to those at stages I and II, and it was also lower in patients with positive lymph node metastasis compared to those with negative lymph node metastasis. Overexpression of KCNAB2 inhibited NSCLC cell proliferation, migration, invasion, and M2 macrophage polarization, while inducing cell apoptosis. These effects were mediated, at least partially, by inactivating the phosphoinositide 3-kinase (PI3K)/AKT(PI3K)/AKT pathway. Moreover, ectopic expression of KCNAB2 delayed tumor formation <i>in vivo</i>. FTOin vivo. FTO was found to mediate m6A methylation of KCNAB2, and knockdown of FTO resulted in the upregulation of KCNAB2 expression, leading to inhibition of NSCLC cell behavior and M2 macrophage polarization.KCNAB2 overexpression inhibited NSCLC cell behavior and M2 macrophage polarization by inactivating the PI3KPI3K/AKT/AKT pathway. Furthermore, FTOFTO-mediated-mediated m6A methylation was involved in the regulation of KCNAB2 expression in NSCLC. These results enhance our understanding of the role of KCNAB2 in NSCLC and suggest its potential as a therapeutic target.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669929","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}

{"title":"Evaluation of the Protective Effects of Alpha Lipoic Acid on Bleomycin-Induced Ovarian Toxicity","authors":"Nese Colcimen,&nbsp;Seda Keskin","doi":"10.1002/jbt.70230","DOIUrl":"10.1002/jbt.70230","url":null,"abstract":"<div>\u0000 \u0000 <p>Chemotherapeutic drugs administered during cancer therapy, may lead to the depletion of ovarian follicles, and subsequent infertility in fertile patients. We aimed to determine toxic effects of bleomycin (BLM) on rat ovary, and to evaluate protective effects of alpha lipoic acid (ALA) on BLM toxicity. The total of 30 adult female rats were split into 4 groups. First, an intramuscular injection (i.m) of BLM (30 mg/m²) was administered to BLM and BLM + ALA groups except the control and ALA groups on the 1st, 8th and 15th days. The control group received 0.1 mL (i.m) saline on those days. BLM + ALA group received ALA (50 mg/kg) subcutaneously (s.c) for 2 weeks at the same time with BLM injections, and ALA group received ALA s.c for the same period. Ovarian tissues were evaluated by histopathological, stereological, immunohistochemical (StAR, VDAC2, Caspase-3, Bcl-2, and expression levels) and ELISA (AMH serum levels) methods. The vascular areas and collagen density increased in the medulla, and the volumes of medulla, cortex, and total ovary increased in BLM group, whereas these changes decreased in BLM + ALA group. On the other hand, VDAC2 and Caspase-3 expressions decreased, StAR and Bcl-2 expressions increased in BLM group, whereas VDAC2 and Caspase-3 expressions increased, and StAR and Bcl-2 expression levels significantly decreased in BLM + ALA group. Besides, follicle number and AMH levels decreased in the BLM group, but remarkably increased in the BLM + ALA group. We established that ALA may have ameliorative effects on the harmful effects of BLM on ovary.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674040","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}

{"title":"LINC00942 Accelerates Esophageal Cancer Progression by Raising PRKDC Through Interaction With PTBP1","authors":"Zhongqiu Wang,&nbsp;Kang Li,&nbsp;Xing Zhang,&nbsp;Feng Jiang,&nbsp;Lin Xu","doi":"10.1002/jbt.70220","DOIUrl":"https://doi.org/10.1002/jbt.70220","url":null,"abstract":"<div>\u0000 \u0000 <p>Aberrantly expressed LINC00942 is participated in the progression of several cancers. However, the function of LINC00942 in esophageal cancer (ESCA) is unclear. The objective of this study was to explore the effect of LINC00942 on ESCA and its possible molecular mechanisms. First, differentially expressed lncRNAs in ESCA were analyzed using GSE192662 microarray. catRAPID omics v2.1 was applied to predict the proteins that might interact with LINC00942. SDS-PAGE silver staining assay, RNA pull down, and RIP assay were utilized to validate proteins interacting with LINC00942. Then, RNA seq was applied to detect the downstream targets of PTBP1, and KEGG enrichment analysis was used to analyze the genes involved in proliferation and migration-related signaling pathways. In addition, CCK-8, EdU and transwell were used to detect the impact of LINC00942 on ESCA cell function. Bioinformatics revealed that LINC00942 was significantly overexpressed in ESCA. Patients in low-expression of LINC00942 had an obviously better prognosis. After LINC00942 knockdown, the proliferation and migration of TE-1 and OE19 were dramatically reduced. Subsequently, PTBP1 was found to interact with LINC00942, and PRKDC was a downstream target of PTBP1. Functional analysis showed that TE-1 and OE19 cell proliferation and migration were markedly elevated after LINC00942 overexpression, and knockdown of PRKDC significantly reversed this effect. Mechanistically, LINC00942 promoted PRKDC expression by interacting with PTBP1. In summary, LINC00942 facilitated the proliferation and migration of ESCA cells via binding to PTBP1 to promote PRKDC expression.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645795","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}

{"title":"Circ_0022587 Regulates Tumor Properties of Human Breast Cancer Cells by Targeting miR-335-5p/Phosphoglycerate Kinase 1 Pathway","authors":"Dian Yin,&nbsp;Li Yang,&nbsp;Ying Chen","doi":"10.1002/jbt.70205","DOIUrl":"https://doi.org/10.1002/jbt.70205","url":null,"abstract":"<div>\u0000 \u0000 <p>Increasing research indicates that circular RNAs (circRNAs) affect the development of breast cancer (BC) through specific molecular mechanisms. However, there is no data regarding the role of circ_0022587 in BC progression. This investigation aims to reveal the mechanism of circ_0022587 in regulating the malignant progression of BC. The study recruited 27 BC patients undergoing a surgical operation in Nantong First People's Hospital, Affiliated Hospital 2 of Nantong University. Quantitative real-time polymerase chain reaction and RNase R degradation assay were used to verify the circular structure of circ_0022587. 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-Ethynyl-2’-deoxyuridine, flow cytometry analysis, transwell and tube formation assays were used to detect the viability, proliferation, apoptosis, invasion and tumor angiogenesis of BC cells, respectively. Glycolysis was evaluated by glycolysis metabolism assays. The associations among miR-335-5p, circ_0022587 and phosphoglycerate kinase 1 (PGK1) were identified by dual-luciferase reporter assays and RNA immunoprecipitation. The effects of circ_0022587 knockdown on tumor growth were evaluated by xenograft nude mouse model assays. The positive expression rates of PGK1, nuclear proliferation marker and matrix metalloprotein 9 were analyzed by immunohistochemistry assays. The results showed that circ_0022587 expression was upregulated in BC tumor tissues and BC cells. Downregulation of circ_0022587 inhibited cell viability, proliferation, invasion ability, tube angiogenesis and glycolysis, and promoted cell apoptosis. Overexpression of circ_0022587 relieved the effect of glycolysis inhibitor (2-Deoxy-D-glucose, 2-DG) on glucose consumption, lactate production, and ATP/ADP ratios. In addition, circ_0022587 interacted with miR-335-5p, and miR-335-5p inhibitors attenuated circ_0022587 silencing-induced effects in BC cells. miR-335-5p bound to PGK1, and PGK1 overexpression relieved miR-335-5p mimics-induced effects in BC cells. Further, circ_0022587 knockdown inhibited tumor formation in vivo. The above results demonstrate that circ_0022587 regulates PGK1 expression by absorbing miR-335-5p, thereby affecting BC development, which may provide a new therapeutic strategy for BC. The study's novelty and innovative potential lie in its discovery of a new regulatory mechanism involving circ_0022587 in the miR-335-5p/PGK1 pathway and its potential clinical relevance. These aspects contribute to the expanding knowledge base of breast cancer research and could potentially lead to improved therapeutic strategies in the future.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638820","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}

{"title":"Unraveling the Protective Effect of Hesperetin In Experimentally Induced Colitis: Inhibition of NF-κB and NLRP3 Inflammasome Activation","authors":"Marwa Mohanad,&nbsp;Sally A. El-Awdan,&nbsp;Basma E. Aboulhoda,&nbsp;Ahmed Ibrahim Nossier,&nbsp;Wessam H. Elesawy,&nbsp;Maha A. E. Ahmed","doi":"10.1002/jbt.70229","DOIUrl":"https://doi.org/10.1002/jbt.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the protective effects of hesperetin (HES) against acetic acid (AA)-induced colitis (AAC) in rats through suppression of nuclear factor kappa B (NF-κB) and modulation of the NOD-like receptor pyrin-containing protein 3 (NLRP3) inflammasome. Forty-eight rats were allocated into four groups: control, AAC, HES-treated, and HES pre-treatment followed by AAC. Disease activity index (DAI), macroscopic and histological colonic changes were assessed. Moreover, inflammatory markers, and signaling pathways were evaluated through qRT-PCR, Western blot analysis, ELISA, and immunohistochemistry.</p>\u0000 <p>HES pre-treatment significantly decreased the DAI by 61.31%, macroscopic colonic damage by 61.25% and the histological score by 41.86% compared to the AAC group. HES also reduced the expression of miR-155 by 73.79%, NLRP3 by 66.07%, Apoptosis-associated speck-like protein containing CARD (ASC) by 66.09%, cleaved caspase-1 by 63.86%, and the pyroptosis marker gasdermin-N (GSDMD-N) by 61.29%. Concurrently, HES attenuated the NF-κB pathway, reducing NF-κB-positive cells by 74.47% and p-inhibitory κB kinaseα (IκBα)/IκBα and p-Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα/β)/IKKα/β levels by 43.77% and 38.68%, respectively. Inflammatory cytokines IL-1β and IL-18 were diminished by 73.41% and 71.88%, respectively. HES pre-treatment increased peroxisome proliferator-activated receptors-γ (<i>PPAR-γ</i>) expression by 259.97%, while reducing CD68+ macrophage infiltration by 72.72%.</p>\u0000 <p>In conclusion, HES alleviated AAC in rats by targeting the NF-κB and NLRP3 inflammasome signaling pathways. This protective effect was mediated through the downregulation of miR-155 expression and the concurrent enhancement of <i>PPAR-γ</i> expression, resulting in reduced inflammation and pyroptosis. These findings highlight HES as a potential therapeutic protective agent for colitis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638750","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}

{"title":"USP18 Confers Paclitaxel Resistance in Non-Small Cell Lung Cancer by Stabilizing SHANK1 Expression Via Deubiquitination","authors":"Lixun Chai,&nbsp;Yanlong Sun,&nbsp;Yunfei Wang,&nbsp;Chenhui Zhao","doi":"10.1002/jbt.70197","DOIUrl":"https://doi.org/10.1002/jbt.70197","url":null,"abstract":"<div>\u0000 \u0000 <p>Ubiquitin-specific protease 18 (USP18) has been identified to promote lung cancer growth and metastasis by deubiquitinating protein substrates. Herein, the action and mechanism of USP18 on paclitaxel resistance in non-small cell lung cancer (NSCLC) were investigated in this study. The mRNA and protein levels of USP18 and SH3 and multiple ankyrin repeat domains protein 1 (SHANK1) were detected by qRT-PCR and western blot analysis analyses. PTX resistance in NSCLC cells was determined by analyzing cell proliferation, apoptosis, and IC50 values using colony formation assay, flow cytometry, and CCK-8 assay, respectively. The glycolysis was determined by detecting glucose consumption, lactate production and ATP levels. Protein interaction was validated using Co-IP assay. Cellular ubiquitination analyzed the deubiquitination effect of USP18 on SHANK1. Animal experiments was performed for in vivo analysis. USP18 was highly expressed in PTX-resistant NSCLC tissues and cells. Silencing of USP18 promoted PTX sensitivity by suppressing the proliferation and glycolysis and inducing apoptosis in PTX-resistant NSCLC cells. Mechanically, USP18 deubiquitinated SHANK1 and stabilized its expression. SHANK1 was highly expressed in PTX-resistant NSCLC tissues and cells, and the deficiency of SHANK1 promoted the sensitivity of PTX-resistant NSCLC cells to PTX. Moreover, the enhanced sensitivity of PTX-resistant NSCLC cells to PTX that was caused by USP18 silencing could be reversed by SHANK1 overexpression. In addition, USP18 silencing reinforced PTX-induced growth inhibition in NSCLC by regulating SHANK1. In conclusion, USP18 conferred paclitaxel resistance in NSCLC by stabilizing SHANK1 expression via deubiquitination.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638819","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}