Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Protective Effects of Galangin Against Cyclophosphamide-Induced Cardiotoxicity via Suppressing NF-κB and Improving Mitochondrial Biogenesis","authors":"Manar Ali Elsayed,&nbsp;Doaa A. Radwan,&nbsp;Hanem Mohamed Rabah,&nbsp;Hemat El-Sayed El-Horany,&nbsp;Nahla Anas Nasef,&nbsp;Rehab E. Abo El Gheit,&nbsp;Marwa N. Emam,&nbsp;Rasha Osama Elesawy,&nbsp;Walaa Elseady,&nbsp;Alia Mahmoud","doi":"10.1002/jbt.70193","DOIUrl":"https://doi.org/10.1002/jbt.70193","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclophosphamide (CYP) is an effective chemotherapeutic and immunosuppressive agent; however, its clinical application is limited by a variety of toxic side effects. Mitochondrial dysfunction has been associated with the pathogenesis of chemotherapy-induced cardiotoxicity. This work aimed to evaluate the possible protective effect of galangin (Gal) on CYP-induced cardiotoxicity, pointing to its ability to promote mitochondrial biogenesis. Thirty two male rats were allocated equally into four groups: control; Gal-treated; CYP-treated; and Gal + CYP-treated groups. Markers of cardiac injury, oxidative/antioxidant status, inflammation, apoptosis, and mitochondrial function were assessed in addition to histopathological and electrocardiographic (ECG) evaluation. The current results revealed that Gal treatment significantly attenuated the cardiac injury and retrieved the alterations in cardiac histopathology and ECG changes. Also, it restored redox balance, as evidenced by the alleviation of malondialdehyde (MDA) levels and increased glutathione peroxidase (GPx) activity. Gal activated the sirtuin (SIRT) 1/nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway, as indicated by upregulation of SIRT1, Nrf2, SIRT3, and mitochondrial transcription factor (TFAM), in addition to increased levels of superoxide dismutase 2 (SOD)2 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), together with increased activity of citrate synthase (CS), pointing to improved mitochondrial function. It ameliorated the inflammation and apoptosis-associated markers supported by biochemical and immunostaining data. Our study provided novel insights elucidating the mitigative potential of against CYP-induced cardiac oxidative damage, inflammation, apoptosis, and mitochondrial dysfunction by upregulating the SIRT1/Nrf2/SIRT3/PGC-1α/TFAM survival pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489914","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":"Unveiling Novel Targets in Lung Tumors for Enhanced Radiotherapy Efficacy: A Comprehensive Review","authors":"Faris Anad Muhammad,&nbsp;Ayat Hussein Adhab,&nbsp;Morug Salih Mahdi,&nbsp;Vicky Jain,&nbsp;Subbulakshmi Ganesan,&nbsp;Deepak Bhanot,&nbsp;K. Satyam Naidu,&nbsp;Sharnjeet Kaur,&nbsp;Aseel Salah Mansoor,&nbsp;Usama Kadem Radi,&nbsp;Nasr Saadoun Abd,&nbsp;Muthena Kariem","doi":"10.1002/jbt.70180","DOIUrl":"https://doi.org/10.1002/jbt.70180","url":null,"abstract":"<div>\u0000 \u0000 <p>Radiotherapy is a cornerstone of lung cancer management, though its efficacy is frequently undermined by intrinsic and acquired radioresistance. This review examines the complexity of lung tumors, highlighting their potential as a reservoir of novel targets for radiosensitization. Ionizing radiation (IR) primarily exerts its effects through oxidative damage and DNA double-strand breaks (DSBs). Lung cancer cells, however, develop mutations that enhance DNA damage response (DDR) and suppress cell death pathways. Additionally, interactions between tumor cells and tumor microenvironment (TME) components—including immune cells, stromal cells, and molecular mediators such as cytokines, chemokines, and growth factors—contribute to resistance against IR. Understanding these intricate relationships reveals potential targets to improve radiotherapy outcomes. Promising targets include DDR pathways, immunosuppressive cells and molecules, hypoxia, proangiogenic mediators, and other key signaling pathways. This review discusses emerging strategies, such as combining radiotherapy with immunomodulators, hypoxia and proangiogenic inhibitors, DDR-targeting agents, and other innovative approaches. By offering a comprehensive analysis of the lung TME, this review underscores opportunities to enhance radiotherapy effectiveness through targeted radiosensitization strategies.</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":"143475583","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":"Low-Power Blue LED Modulates NF-κB and Proinflammatory Cytokines in Doxorubicin-Treated MDA-MB-231 Cells","authors":"Adilson Fonseca Teixeira,&nbsp;Bruno Ricardo Barreto Pires,&nbsp;Carolina Panis,&nbsp;Andréa Monte-Alto-Costa,&nbsp;Adenilson de Souza da Fonseca,&nbsp;Andre Luiz Mencalha","doi":"10.1002/jbt.70192","DOIUrl":"https://doi.org/10.1002/jbt.70192","url":null,"abstract":"<div>\u0000 \u0000 <p>Doxorubicin is a crucial chemotherapy used in the treatment of triple-negative breast cancer (TNBC) patients, but elevated doxorubicin doses may induce therapeutic resistance. To overcome this limitation, we have previously established a photodynamic therapeutic (PDT)-like strategy that irradiates doxorubicin-treated cells with a low-power nonionizing blue LED device. This combined treatment increases the production of reactive oxygen species to promote cell death, consequently enabling reduced doxorubicin dosages. Yet, precisely determining the molecular mechanisms that drive this outcome is still required for advancing such PDT-like approach. Here, we aimed to correlate the expression of the inflammatory markers NF-κB, IL-8, IL-6, and IL-1β with the survival of TNBC cells submitted to our PDT-like protocol. Our results show that NF-κB/p65 nuclear levels were enhanced in MDA-MB-231 cells treated with doxorubicin and blue LED. Moreover, this PDT-like strategy increased IL-6 mRNA levels in MDA-MB-231 cells. IL-1β and IL-8 mRNA were upregulated in samples incubated with doxorubicin regardless of concomitant irradiation with blue LED. These results show that our PDT-like protocol is effective in elevating inflammatory signals, shedding light on the molecular mechanisms that underlie the efficacy of this innovative anticancer therapeutic approach.</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":"143475587","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":"Methyl Donor Ameliorates CCl4-Induced Nephrotoxicity by Inhibiting Oxidative Stress, Inflammation, and Fibrosis Through the Attenuation of Kidney Injury Molecule 1 and Neutrophil Gelatinase-Associated Lipocalin Expression","authors":"Nirmal Manhar,&nbsp;Sumeet Kumar Singh,&nbsp;Poonam Yadav,&nbsp;Manish Bishnolia,&nbsp;Amit Khurana,&nbsp;Jasvinder Singh Bhatti,&nbsp;Umashanker Navik","doi":"10.1002/jbt.70188","DOIUrl":"https://doi.org/10.1002/jbt.70188","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbon tetrachloride (CCl₄), a volatile organic compound, is harmful to multi-organs, including the liver, lungs, muscles, and kidneys. Methyl donors, such as methionine, choline, betaine, and folic acid, are vital to one-carbon metabolism and have great potential to alleviate oxidative stress and inflammation, thus mitigating disease onset. Hence, the current study aims to examine the therapeutic effect of methyl donors against CCl₄-induced nephrotoxicity. Nephrotoxicity was developed in male Sprague Dawley rats using CCl₄ at a dose of 1 mL/kg (4-week model induction) twice a week via the intraperitoneal route. Thereafter, methyl donor treatments through oral gavage were given for the next 6 weeks with a continuation of CCl₄ administration. Biochemical, oxidative stress parameters, histopathological, and qRT-PCR analyses were done at the completion of the 10-week. Biochemical analyses revealed that CCl₄ induces nephrotoxicity, as evidenced by increased urea and creatinine levels and decreased albumin levels. These detrimental effects were significantly ameliorated by methyl donor treatment. Moreover, CCl₄ decreased the antioxidant enzyme activity (superoxide dismutase; SOD and catalase; CAT) while increasing oxidative stress markers (malondialdehyde; MDA and nitrite). Methyl donor treatment effectively mitigated these oxidative changes. Histopathological analysis demonstrated the nephroprotective effect of methyl donors against CCl₄-induced nephrotoxicity, showing reduced tissue damage and protection of renal architecture. At the molecular level, methyl donor treatment alleviated the CCl₄-induced increase in kidney injury biomarkers (Kidney injury molecule 1; KIM-1 and Neutrophil gelatinase-associated lipocalin; NGAL), as well as inflammatory (IL-6 and TNF-α) and fibrosis-related genes (Acta-2 and TGF-β). In conclusion, our findings suggest that methyl donors possess anti-inflammatory and anti-fibrotic properties. They protect against CCl₄-induced oxidative damage to renal cells, likely due to their reactive oxygen species scavenging capabilities and their ability to restore key early renal injury biomarkers (KIM-1 and NGAL). Methyl donors hold great promise as a cutting-edge therapy approach for preventing CCl₄-induced nephrotoxicity.</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":"143475590","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":"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}