Journal of Biochemical and Molecular Toxicology最新文献

{"title":"METTL3-Mediated m6A Methylation Stabilizes IFI27 to Drive Esophageal Squamous Cell Carcinoma Progression Through an IGF2BP2-Dependent Mechanism","authors":"Xinhua Zhang,&nbsp;Yu Bai,&nbsp;Linlin Shang,&nbsp;Yinghao Wang,&nbsp;Wenjian Yao,&nbsp;Sen Wu","doi":"10.1002/jbt.70167","DOIUrl":"https://doi.org/10.1002/jbt.70167","url":null,"abstract":"<div>\u0000 \u0000 <p>Dysregulation of m6A modification has emerged as a vital factor in the development of esophageal squamous cell carcinoma (ESCC). Here, we sought to explore the critical role of m6A methylation mediated by the m6A methyltransferase METTL3 in ESCC. Protein expression analysis was performed by immunohistochemistry and immunoblot assays. The mRNA levels of METTL3 and IFI27 were detected by quantitative PCR. Cell sphere formation potential, migration, invasiveness, apoptosis, proliferation and viability were assessed by standard sphere formation, wound healing, transwell, flow cytometry, EdU and CCK-8 assays, respectively. The impact of METTL3 or IGF2BP2 on IFI27 mRNA was evaluated by methylated RNA immunoprecipitation (MeRIP), RIP or mRNA stability analysis. Xenograft assays were used to detect the in vivo function of METTL3. Elevated levels of METTL3 were observed in ESCC tumors and cells, and these increased levels were associated with the declined prognosis of ESCC. MELLT3 depletion impeded ESCC cell growth, invasiveness, migration, and sphere formation, and induced cell apoptosis in vitro. Elevated IFI27 expression was positively correlated with METTL3 levels in ESCC. Moreover, METTL3 mediated m6A methylation of IFI27 mRNA to stabilize the mRNA. The m6A reader IGF2BP2 also affected m6A methylation and expression of IFI27 mRNA. Additionally, IFI27 re-expression had a counteracting impact on the effects of METTL3 deficiency on in vitro ESCC cell behaviors and in vivo KYSE30 xenograft growth. Our findings demonstrate that METTL3-mediated IFI27 mRNA m6A methylation drives ESCC development through an IGF2BP2-dependent mechanism. Blocking the METTL3/IFI27 axis may be effective for preventing ESCC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475591","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":"Assessment of the Cytotoxicity Mechanism of Diazinon on HFFF2 Cells: A Bioinformatic and Experimental Study","authors":"Mehdi Sarailoo,&nbsp;Vahid Asghariazar,&nbsp;Sina Seifimansour,&nbsp;Mahtab Kadkhodayi,&nbsp;Erfan Zare,&nbsp;Parnia Vajdi,&nbsp;Mehdi Asghari Vostakolaei","doi":"10.1002/jbt.70146","DOIUrl":"https://doi.org/10.1002/jbt.70146","url":null,"abstract":"<div>\u0000 \u0000 <p>Pesticide exposure can cause many skin diseases such as hypopigmentation and contact dermatitis, but the underlying mechanisms remain unclear. Furthermore, Organophosphate pesticides (OPs) including Diazinon (DZN) can affect cellular pathways like ATPase, leading to mitochondrial energy deficit and even apoptosis in the cell's functions. Following cell exposure to the OP pesticide DZN through treatment, we evaluated alteration in gene expression and DNA damage. Bioinformatic analysis was performed based on the AutoDock, Protein Data Bank, STRING, Way2Drug, and Comparative Toxicogenomics databases and tools. The MTT assay, wound healing, DAPI staining, flow cytometry, and real-time PCR were applied in the current study. The results showed that the viability and migration capacity of HFFF2 cells decreased, and the apoptosis rate increased in the DZN-treated group. These findings revealed that DZN regulated the expression of the apoptotic genes in DZN cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475588","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 Impact of P-Glycoprotein on CNS Drug Efflux and Variability in Response","authors":"Priyanka R. Paul,&nbsp;Manish K. Mishra,&nbsp;Shivangi Bora,&nbsp;Samiksha Kukal,&nbsp;Anju Singh,&nbsp;Shrikant Kukreti,&nbsp;Ritushree Kukreti","doi":"10.1002/jbt.70190","DOIUrl":"https://doi.org/10.1002/jbt.70190","url":null,"abstract":"<div>\u0000 \u0000 <p>Resistance against CNS drugs may arise from various mechanisms, with limited drug penetration across the blood-brain barrier (BBB) being a significant contributing factor. The BBB employs efflux transporters like P-glycoprotein (P-gp) to safeguard the brain by removing toxins and xenobiotics, however, P-gp also pumps out therapeutic drugs, and its upregulation in disease states can contribute to variability in drug response. While inhibiting P-gp to prevent drug efflux seems appealing, it could lead to toxicity since P-gp is also important for expulsion of toxins from the brain. This necessitates the incorporation of P-gp substrate liability assessment into early drug discovery stages using appropriate experimental approaches. Therefore, this review aims to draw interest in this crucial area by analyzing the existing research on P-gp's impact on brain distribution of major CNS drugs and exploring the detection methods for identifying P-gp substrates. By identifying confirmed P-gp substrates and evaluating effective detection methods, this work emphasizes the continued importance of monitoring P-gp-mediated CNS drug efflux out of the brain tissue. This knowledge can empower clinicians to anticipate potential treatment inefficacy and guide therapeutic decision-making, ultimately leading to improved patient treatment outcomes.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475581","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":"Mechanism of the microRNA-373-3p/LATS2 Axis in the Prognosis and Metastasis of Thyroid Cancer Patients","authors":"Yingchao Gu,&nbsp;Hongbing Liu,&nbsp;Ming Shi,&nbsp;Fei Pu","doi":"10.1002/jbt.70181","DOIUrl":"https://doi.org/10.1002/jbt.70181","url":null,"abstract":"<div>\u0000 \u0000 <p>This study focused on the role of the microRNA (miR)-373-3p/LATS2 axis in the prognosis and metastasis of thyroid cancer patients. miR-373-3p and LATS2 expression were assessed in thyroid cancer tissues and cells. The relationship between miR-373-3p and clinicopathological characteristics of patients with thyroid cancer and the impact of miR-373-3p and LATS2 expression levels on the survival and prognosis of thyroid cancer patients were analyzed. The targeting relationship between miR-373-3p and LATS2 was predicted and verified, and their impact on the malignant cell phenotype was assessed. Compared with adjacent normal tissues and normal human thyroid cells, miR-373-3p was highly expressed, while LATS2 was expressed at low levels in thyroid cancer tissues and cells (both <i>p</i> &lt; 0.001). miR-373-3p expression was independent of age (<i>p</i> = 0.201) and gender (<i>p</i> = 0.516), and it was correlated with lymph node metastasis and TNM stage of thyroid cancer (both <i>p</i> &lt; 0.001). Moreover, high miR-373-3p expression was associated with poor patient prognosis (<i>p</i> = 0.034). Interference with miR-373-3p or overexpression of LATS2 repressed KMH-2 cell malignant phenotypes (all <i>p</i> &lt; 0.05). miR-373-3p targeted and suppressed LATS2 expression. Interference with miR-373-3p blocked its inhibition on LATS2, thereby repressing thyroid cancer progression and metastasis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475582","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":"Efficacy of In Vitro Addition of Low-Dose Arachidonic Acid in Improving the Sperm Motility of Obese Infertile Men With Asthenozoospermia","authors":"Yongjie Liu,&nbsp;Liang Dai,&nbsp;Fan Zhang,&nbsp;Yang Liu,&nbsp;Xu Li,&nbsp;Wenzhi Ma","doi":"10.1002/jbt.70165","DOIUrl":"https://doi.org/10.1002/jbt.70165","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;This study aimed to investigate the impact of in vitro low-dose arachidonic acid (AA) addition on enhancing sperm motility in obese infertile men with asthenozoospermia. Semen samples were collected from 115 infertile men, categorized into two BMI groups: 18.5–23.9 kg/m&lt;sup&gt;2&lt;/sup&gt; and ≥ 28 kg/m&lt;sup&gt;2&lt;/sup&gt;, with all subjects demonstrating a sperm concentration of ≥ 15 × 10&lt;sup&gt;6&lt;/sup&gt;/mL. These were further divided into four cohorts based on the percentage of sperm progressive motility (PR): control-normal, control-asthenozoospermia, obese-normal, and obese-asthenozoospermia. Normal PR was classified as ≥ 32%, while asthenozoospermia was characterized by PR &lt; 32%. Metabolomic analysis was employed to quantify seminal plasma metabolites, with differential metabolites identified through statistical evaluation. Additionally, semen samples from 10 infertile men—5 with a body mass index (BMI) of 18.5–23.9 kg/m&lt;sup&gt;2&lt;/sup&gt; and 5 with a BMI of ≥ 28 kg/m&lt;sup&gt;2&lt;/sup&gt;—underwent further scrutiny. Post-initial semen analysis, 1 mL of semen stock was extracted, treated with 100 pg of AA, incubated at 37°C for 1 h, and reanalyzed to determine the impact on sperm motility. Additionally, 16 Sprague Dawley (SD) rats were split into two groups: control and obese. The control group received a standard diet, while the obese group was subjected to a 45% high-fat diet. After 3 months, the rats were euthanized via cervical dislocation, and their prostate and seminal vesicles were collected for metabolite analysis. A comprehensive analysis of 4635 metabolites in seminal plasma revealed that bile acid secretion emerged as the most significant pathway within the organic systems category, accounting for 0.6% of the total metabolites. Meanwhile, metabolic pathways overwhelmingly dominated the metabolism category, with AA metabolism contributing 4.62%. Notably, 29 metabolites were associated with bile acid secretion, yet no significant differences were observed between the PR ≥ 32% and &lt; 32% groups. In contrast, 214 metabolites were linked to AA metabolism, exhibiting a predominantly downregulated trend, with no upregulated metabolites identified. Within the seminal plasma AA metabolic network, indicators showed a positive association with the induced acrosome reaction, seminal plasma Ca&lt;sup&gt;2+&lt;/sup&gt; levels, PR, and the proportion of grade A sperm (rapid forward motion, speed ≥ 25 μm/s). Additionally, secretory phospholipase A2 (sPLA2), AA, and cyclooxygenase-1 (COX1) levels demonstrated a negative correlation with anthropometric measurement parameters in the Control-SP group, though this correlation did not reach statistical significance, while a positive correlation was evident in the Obesity-SP group. The concentrations of sPLA2, AA, and COX1 within the AA metabolic network exhibited the following trend: Control-SP-N &gt; Obesity-SP-N &gt; Control-SP-A &gt; Obesity-SP-A. In vitro addition of 100 pg AA significantly enhanced the proportio","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475580","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":"HOXA10-AS Enhances Gastric Cancer Cell Proliferation, Migration, and Invasion via the p38 MAPK/STAT3 Signaling Pathway","authors":"Yu Hu,&nbsp;Ying Zhang,&nbsp;Meng Ding,&nbsp;Ruisi Xu","doi":"10.1002/jbt.70187","DOIUrl":"https://doi.org/10.1002/jbt.70187","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric cancer (GC) represents a major global health concern, with over 1 million new cases diagnosed annually worldwide. Emerging studies have highlighted the significant correlation between long noncoding RNAs (lncRNAs) and the progression of GC. The objective of the current study is to investigate the roles and mechanism of lncRNA homeobox A10 antisense RNA (HOXA10-AS) in modulating malignant properties of GC cells. RT-qPCR was employed to detect HOXA10-AS expression in GC cells or human normal gastric epithelium cells. The cellular localization of HOXA10-AS and mRNA HOXA10 were detected using RNA fractionation assays. Colony forming assays and Transwell assays were performed to assess the proliferative, invasive, and migratory capabilities of GC cells. Western blot analysis was used to determine protein levels of epithelial mesenchymal transition (EMT) markers in GC cells. RNA immunoprecipitation, RNA pulldown assays and luciferase assays were conducted to explore gene interaction. As shown by experimental results, HOXA10-AS showed high expression in GC cells. The silencing of HOXA10-AS led to weakened proliferative, invasive, and migratory abilities of GC cells, as well as inhibition of the EMT process. Moreover, HOXA10-AS positively regulated HOXA10 expression by interacting with miR-29a/b/c-3p. Additionally, overexpression of HOXA10 counteracted the repressive impacts on malignant cellular process caused by the knockdown of HOXA10-AS. Furthermore, HOXA10-AS activated the p38 MAPK/STAT3 signaling pathway via upregulation of HOXA10. In conclusion, HOXA10-AS upregulates HOXA10 expression through interaction with miR-29a/b/c-3p. The resultant increase in HOXA10 expression activates the p38 MAPK/STAT3 signaling, thereby promoting GC cell growth, migration, invasion, and EMT process.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475589","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 Purinergic Ligand-Gated Ion Channel 7 Receptor Promotes the Proliferation, Invasion, and Migration of Breast Cancer Cells","authors":"Xin Wang,&nbsp;Xiaoxiang Peng,&nbsp;Yahui Cao,&nbsp;Xiaodi Zhu,&nbsp;Yanan Du,&nbsp;Qingqing Yu,&nbsp;Ronglan Zhao","doi":"10.1002/jbt.70184","DOIUrl":"https://doi.org/10.1002/jbt.70184","url":null,"abstract":"<div>\u0000 \u0000 <p>Purinergic ligand-gated ion channel 7 receptor (P2X7R) has essential functions in tumor proliferation, apoptosis, metastasis, and invasion, and the purpose of this study was to explore the effects of P2X7R on the biological behaviors of MCF-7 and MDA-MB-231 cells. A bioinformatics analysis of P2X7R expression in breast cancer was performed and its relationships with overall survival and immune cell infiltration were determined. P2X7R ion channel function was detected via a Fluo-4-AM assay. Proliferation, migration and invasion were investigated using CCK-8, scratch wound healing, and Transwell assays, respectively. The levels of P2X7R, JNK, p-JNK, Akt, p-Akt, E-cadherin, N-cadherin, vimentin and GAPDH were detected by western blotting. The role of P2X7R on the biological behaviors of MCF-7 cells was detected in vivo. Bioinformatics analysis revealed an obvious increase in the expression of P2X7R in breast cancer and differences were observed among the different subtypes. High expression of P2X7R was negatively correlated with overall survival and affected immune cell infiltration. The experimental results revealed that both types of cells express functional P2X7R. ATP and BzATP can promote proliferation, invasion, and metastasis after P2X7R activation; upregulate p-Akt, p-JNK, N-cadherin and vimentin; and downregulate E-cadherin compared with the control group, and the addition of the antagonist A438079 or oxATP or the knockdown of P2X7R could weaken these effects. The activation of P2X7R in breast cancer cells can promote their biological behaviors, indicating that P2X7R is a latent therapeutic target in breast cancer.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439113","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_0070934 Regulates the Proliferation, Metastasis, and Epithelial–Mesenchymal Transition of Colorectal Cancer Cells by Targeting miR-203a-3p/HOXA13 Axis","authors":"Xin Zhang,&nbsp;Changjiang Lei,&nbsp;Hongxia Lu,&nbsp;Biao Kang,&nbsp;Maoxi Liu,&nbsp;Huiyuan Jiang,&nbsp;Likun Zan","doi":"10.1002/jbt.70173","DOIUrl":"https://doi.org/10.1002/jbt.70173","url":null,"abstract":"<div>\u0000 \u0000 <p>The present work explored the functions of circ_0070934 in regulating malignant phenotype of colorectal cancer (CRC) cells and its underlying mechanisms. Gene expression data set was acquired based on Gene Expression Omnibus (GEO) database for examining circ_0070934 levels within CRC cells and tissues through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan–Meier curve and log-rank test were adopted for assessing CRC patient prognosis based on circ_0070934 level. Functional assays including Cell Counting Kit (CCK)-8, EdU incorporation, Transwell invasion, and scratch assays were conducted to determine CRC cell malignancy. Molecular interactions were predicted using circInteractome and StarBase databases, and validated through luciferase reporter assay. Circ_0070934 was upregulated within CRC cells and tissues, which was related to a dismal prognostic outcome in CRC patients. Knocking down circ_0070934 inhibited CRC cell proliferation, epithelial–mesenchymal transition (EMT), and migration. Further, we identified miR-203a-3p as a target miRNA of circ_0070934, and miR-203a-3p negatively regulated Homeobox A13 (HOXA13) expression. miR-203a-3p/HOXA13 axis mediates the function of circ_0070934 in modulating CRC cell malignancy. These data revealed that circ_0070934 was important for maintaining the malignant phenotype of CRC cells, and circ_0070934 knockdown undermined CRC cell malignancy. Targeting circ_0070934/miR-203a-3p/HOXA13 axis is the promising intervention approach for managing CRC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438842","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":"NK1R Antagonist, CP-99,994 Ameliorates Dry Eye Disease via Inhibiting the Plk1-Cdc25c-Cdk1 Axis","authors":"Ruifan Zhang,&nbsp;Yuhao Zou,&nbsp;Huan Li,&nbsp;Dongfeng Li,&nbsp;Yi Liu,&nbsp;Bo Gong,&nbsp;Man Yu","doi":"10.1002/jbt.70177","DOIUrl":"https://doi.org/10.1002/jbt.70177","url":null,"abstract":"<div>\u0000 \u0000 <p>Substance P/high-affinity neurokinin-1 receptor (SP/NK1R) system plays a crucial role in the pathogenesis of dry eye disease (DED). NK1R antagonist can improve DED, but the mechanism of NK1R antagonist treating DED remains unclear. We examined the role of NK1R antagonist, CP-99,994 in DED model by possessing the phenol red cotton thread test, corneal fluorescein staining, and hematoxylin and eosin staining. Enzyme linked immunosorbent assay was performed to determine the concentration of inflammatory factors. Additionally, RNA sequencing, enrichment analysis and protein-protein interaction network were employed to identify the key targets. Real-time quantitative PCR and western blot analysis were utilized to determine the expression of hub genes. Plk1 inhibitor, GSK461364 was applied to explore the treatment mechanism of CP-99,994. The NK1R antagonist CP-99,994 alleviated dry eye symptoms and the concentrations of IL-6, IL-1β, and TNF-α were significantly decreased after CP-99,994 treatment. We obtained 68 differentially expressed genes after CP-99,994 treatment by RNA sequencing and pyroptosis-related genes (Plk1, Cdc25c, Cdk1) were identified from protein-protein interaction network as key targets of CP-99,994 treating DED. The expression levels of the Plk1, Cdc25c, and Cdk1 were significantly upregulated in the DED group, and CP-99,994 downregulated the expression of Plk1, Cdc25c, and Cdk1. Moreover, Plk1 inhibitor considerably promoted the therapeutic effect of CP-99,994 on DED model by reducing the release of IL-6, IL-1β, and TNF-α. The NK1R antagonist, CP-99,994 mitigated DED symptoms via inhibiting Plk1-Cdc25c-Cdk1 axis, which served as a novel therapeutic target for DED treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439042","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":"Borneol Ameliorates Non-Alcoholic Fatty Liver Disease via Promoting AMPK-Mediated Lipophagy","authors":"Shalemraju Sriramdasu,&nbsp;Shivam Sharma,&nbsp;Abid Reza Ansari,&nbsp;Nikhil Vinayak Phatak,&nbsp;Kulbhushan Tikoo","doi":"10.1002/jbt.70182","DOIUrl":"https://doi.org/10.1002/jbt.70182","url":null,"abstract":"<div>\u0000 \u0000 <p>Despite the worldwide surge in the prevalence of non-alcoholic fatty liver disease (NAFLD), however, no efficacious treatment has been clinically approved to date for combating this condition, necessitating elucidation of new therapeutic compounds. Our research presented evidence pertaining to the successful induction of NAFLD in C57BL/6 mice using a multiple liver insults paradigm. This was achieved by concurrently administering thioacetamide (100 mg/kg i.p.) along with high-fat and high-fructose diet (HFFrD) for 10 weeks. Following this, the beneficial effect of borneol, a bicyclic monoterpenoid, was observed in NAFLD mice in a dose-dependent manner. Borneol administration for 4 weeks led to significant improvement in morphometric, metabolic profiles, liver functions, and oxidative stress parameters. Accumulation of lipids in hepatic tissues, which is characteristic feature of NAFLD, was confirmed by H&amp;E, as well as oil-red O staining was alleviated by borneol. Our investigation elucidated the pro-autophagic effect of borneol via AMPK activation, thereby leading to the downstream activation of autophagy effector proteins, that is, Beclin1, ATG5, ATG7, and LC3 I-II, which helps to diminish the hepatic lipid loads through augmentation of lipophagy. This study demonstrates that borneol combats NAFLD through augmentation of AMPK-mediated lipophagy offering a promising therapeutic strategy against NAFLD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439043","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}