Journal of Biochemical and Molecular Toxicology最新文献_第8页

Investigating the Role of Scd1 in OSAHS-Induced Vascular Changes 探讨Scd1在osahs诱导的血管改变中的作用

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-15 DOI: 10.1002/jbt.70221

Jing Yang, Hui Zhang, Lulu Yang, Shen Yi, Ting Zhang

{"title":"Investigating the Role of Scd1 in OSAHS-Induced Vascular Changes","authors":"Jing Yang, Hui Zhang, Lulu Yang, Shen Yi, Ting Zhang","doi":"10.1002/jbt.70221","DOIUrl":"https://doi.org/10.1002/jbt.70221","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>This study investigates the role of Stearoyl-CoA Desaturase-1 (Scd1) in vascular remodeling associated with Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) using multi-omics analysis. Transcriptomic and metabolomic datasets of OSAHS mouse models were analyzed to identify differentially expressed genes and metabolites, followed by functional enrichment analysis. Key genes were screened using weighted gene correlation network analysis (WGCNA) and machine learning, and a PPI network was constructed. An OSAHS mouse model was developed via intermittent hypoxia exposure. Human aortic smooth muscle cells (HASMCs) were subjected to hypoxia/reoxygenation cycles to simulate OSAHS in vitro. Blood pressure, plasma lipid profiles, histological changes in the thoracic aorta, and Scd1 protein expression were assessed. CCK-8 and Transwell assays evaluated HASMC proliferation and migration. Scd1 was identified as a critical factor in OSAHS-related vascular remodeling, with its expression significantly upregulated in vascular tissues of OSAHS mice. Metabolomic analysis revealed changes in fatty acid metabolism. Scd1 knockdown reduced blood pressure, lipid levels, aortic wall thickness, collagen deposition, elastic fiber accumulation, and mucin deposition in vivo. In vitro, hypoxia/reoxygenation cycles elevated Scd1 expression, while Scd1 knockdown inhibited HASMC proliferation and migration. Multi-omics analyses highlight Scd1 as a key regulator in OSAHS-associated vascular remodeling, driving pathological changes through its upregulation. These findings suggest Scd1 as a potential therapeutic target for managing OSAHS-related vascular pathologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836027","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

Modulation of AMPK/mTOR Autophagic Pathway Using Dapagliflozin Protects Against Cadmium-Induced Testicular and Renal Injury in Rats 达格列净调节AMPK/mTOR自噬通路对镉致大鼠睾丸和肾脏损伤的保护作用

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-15 DOI: 10.1002/jbt.70257

Doha M. Dagher, Marwa S. Zaghloul, Ghada M. Suddek

{"title":"Modulation of AMPK/mTOR Autophagic Pathway Using Dapagliflozin Protects Against Cadmium-Induced Testicular and Renal Injury in Rats","authors":"Doha M. Dagher, Marwa S. Zaghloul, Ghada M. Suddek","doi":"10.1002/jbt.70257","DOIUrl":"https://doi.org/10.1002/jbt.70257","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium is a widely distributed heavy metal found in the environment that poses serious hazards to human health. Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, exhibited antioxidant, antiapoptotic, and anti-inflammatory properties. Our data assessed the effect of DAPA against Cd-triggered renal and testicular impairment in rats, as well as the underlying mechanisms. Cd (30 mg/kg) and DAPA (5 and 10 mg/kg) were administrated by oral gavage to rats and continued for 21 days. DAPA attenuated Cd-triggered renal and testicular injury as shown by diminishing serum creatinine, BUN, and urinary total protein concentration in addition to increasing creatinine clearance, urinary creatinine, and serum testosterone. Moreover, it diminished renal and testicular histopathological alterations induced by Cd. DAPA stimulated the impaired autophagy flux as seen by significantly elevating the p-AMPK/total AMPK, decreasing p-mTOR/total mTOR ratios, and diminishing p62 & LC3 protein levels. Additionally, DAPA significantly lowered MDA content, increased GSH level and SOD activity. Moreover, it augmented the cytoprotective Nrf2/HO-1 signaling pathway. Furthermore, it attenuated renal and testicular apoptotic cell death via decreasing caspase-3 expression. Conclusion: Boosting autophagic events and combating oxidative stress and apoptosis by DAPA were engaged in alleviating Cd-induced renal and testicular impairment. This was accomplished by modulating the AMPK/mTOR and enhancing the Nrf2/HO-1 pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836028","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

Single-cell RNA Sequencing Contributes to the Treatment of Acute Myeloid Leukaemia With Hematopoietic Stem Cell Transplantation, Chemotherapy, and Immunotherapy 单细胞RNA测序有助于用造血干细胞移植、化疗和免疫疗法治疗急性髓性白血病

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-15 DOI: 10.1002/jbt.70218

Raed Obaid Saleh, Ahmed Hjazi, Safia Obaidur Rab, Subasini Uthirapathy, Subbulakshmi Ganesan, Aman Shankhyan, M. Ravi Kumar, Girish Chandra Sharma, Muthena Kariem, Jawad Kadhim Ahmed

{"title":"Single-cell RNA Sequencing Contributes to the Treatment of Acute Myeloid Leukaemia With Hematopoietic Stem Cell Transplantation, Chemotherapy, and Immunotherapy","authors":"Raed Obaid Saleh, Ahmed Hjazi, Safia Obaidur Rab, Subasini Uthirapathy, Subbulakshmi Ganesan, Aman Shankhyan, M. Ravi Kumar, Girish Chandra Sharma, Muthena Kariem, Jawad Kadhim Ahmed","doi":"10.1002/jbt.70218","DOIUrl":"https://doi.org/10.1002/jbt.70218","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations and impaired apoptosis, all of which lead to excessive proliferation of malignant blood cells in the bone marrow. It is these mutations that cause tumor heterogeneity, which is linked to a higher risk of relapse and death and makes anti-AML treatments like HSCT, chemotherapy, and immunotherapy (ICI, CAR T-cell-based therapies, and cancer vaccines) less effective. Single-cell RNA sequencing (scRNA-seq) also makes it possible to find cellular subclones and profile tumors, which opens up new diagnostic and therapeutic targets for better AML management. The HSCT process works better when genetic and transcriptional information about the patient and donor stem cells is collected. This saves time and lowers the risk of harmful side effects happening in the body.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836267","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

Synthesis of Novel Isoindolinones: Carbonic Anhydrase Inhibition Profiles, Antioxidant Potential, Antimicrobial Effect, Cytotoxicity and Anticancer Activity 新型异吲哚酮的合成：碳酸酐酶抑制谱、抗氧化潜力、抗菌作用、细胞毒性和抗癌活性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70261

Yusuf Serdar Yazıcıoğlu, Şeydanur Elmas, Zeynep Kılıç, Murat Çelik, Buket Bakan, Ufuk Atmaca, Songül Bayrak

{"title":"Synthesis of Novel Isoindolinones: Carbonic Anhydrase Inhibition Profiles, Antioxidant Potential, Antimicrobial Effect, Cytotoxicity and Anticancer Activity","authors":"Yusuf Serdar Yazıcıoğlu, Şeydanur Elmas, Zeynep Kılıç, Murat Çelik, Buket Bakan, Ufuk Atmaca, Songül Bayrak","doi":"10.1002/jbt.70261","DOIUrl":"https://doi.org/10.1002/jbt.70261","url":null,"abstract":"<p>An efficient one-pot method has been developed for synthesizing novel isoindolinone derivatives from 2-benzoylbenzoic acid using chlorosulfonyl isocyanate and alcohols. This reaction occurs under mild, metal-free conditions, rendering it a sustainable and effective approach for isoindolinone synthesis. The inhibitory potential of the synthesized compounds against human carbonic anhydrase (hCA) I and II isozymes was evaluated and compared with the standard inhibitor, acetazolamide (AAZ). Additionally, their antimicrobial and antioxidant activities were assessed using various bioanalytical methods, with results benchmarked against standard reference compounds. Furthermore, cytotoxicity and anticancer activity were investigated in L929 and A549 cell lines via the WST-1 assay following a 24 h exposure. Among the synthesized derivatives, compounds <b>2c</b> and <b>2f</b> exhibited superior inhibitory effects on hCA I and II compared to AAZ, with Ki values ranging from 11.48 ± 4.18 to 16.09 ± 4.14 nM for hCA I and 9.32 ± 2.35 to 14.87 ± 3.25 nM for hCA II. These findings indicate that compounds <b>2c</b> and <b>2f</b> have a high affinity for the enzyme's active site, resulting in more effective inhibition of its catalytic activity. Compound 2e emerged as the most promising candidate, demonstrating potent carbonic anhydrase inhibition and significant antioxidant and antimicrobial properties. None of the synthesized compounds displayed cytotoxic effects on healthy cells at the tested concentrations. Additionally, compound <b>2a</b> exhibited dose-dependent anticancer activity against A549 cells. These results suggest that isoindolinone derivatives, particularly <b>2f</b>, hold substantial potential for further pharmaceutical development as multifunctional bioactive agents.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826753","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}

引用次数: 0

KAT3B Promotes the Glycolysis and Malignant Progression of Lung Cancer by Mediating the Succinylation Modification of PKM2 KAT3B通过介导PKM2琥珀酰化修饰促进糖酵解和肺癌恶性进展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70259

Zhifeng Guo, Yan Hui, Siqi Sun, Fanlong Kong

{"title":"KAT3B Promotes the Glycolysis and Malignant Progression of Lung Cancer by Mediating the Succinylation Modification of PKM2","authors":"Zhifeng Guo, Yan Hui, Siqi Sun, Fanlong Kong","doi":"10.1002/jbt.70259","DOIUrl":"https://doi.org/10.1002/jbt.70259","url":null,"abstract":"<div>\u0000 \u0000 <p>Lysine succinyltransferase KAT3B plays a critical role in the progression of various cancers by modulating key metabolic pathways, including glycolysis. However, the function and underlying mechanism of KAT3B in glycolysis and lung cancer (LC) progression remain to be further studied. We determined mRNA expression levels of lysine succinyl-modifying enzymes through qRT-PCR. Protein expression and succinylation status of glycolysis-related proteins PKM2, LDHA, and ENO1 were analyzed via Western blot. Co-immunoprecipitation and immunofluorescence microscopy were employed to verify the interaction between KAT3B and PKM2. Bioinformatics analysis predicted succinylation sites on PKM2, which were subsequently validated through site-directed mutagenesis. The effects of KAT3B and PKM2 on LC cell malignancy and glycolysis were evaluated using CCK-8, transwell migration, glucose uptake, lactate production, ECAR, and OCR assays. A xenograft tumor model was utilized to assess the impact of KAT3B on LC tumor growth. We confirmed the augmentation of KAT3B in LC, which also was correlated with advanced TNM stages and elevated T stages of LC patients. Conversely, KAT3B knockdown suppressed the growth, metastasis, and glycolytic activity of LC cells in vitro, while also inhibiting tumor growth in vivo. KAT3B mediated succinylation at PKM2 K298, and the suppression of LC cell malignancy and glycolysis upon KAT3B downregulation was largely reversed by upregulation of PKM2. The KAT3B/PKM2 axis may be a novel target for LC therapy.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826751","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

Dose-Dependent Hepatotoxicity in Wistar Rat Neonates From Early-Life Arsenic Exposure 早期砷暴露对Wistar大鼠新生儿肝毒性的剂量依赖性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70254

Navneet Kumar, Astha Mathur, Suresh Kumar Bunker, Placheril J. John

{"title":"Dose-Dependent Hepatotoxicity in Wistar Rat Neonates From Early-Life Arsenic Exposure","authors":"Navneet Kumar, Astha Mathur, Suresh Kumar Bunker, Placheril J. John","doi":"10.1002/jbt.70254","DOIUrl":"https://doi.org/10.1002/jbt.70254","url":null,"abstract":"<div>\u0000 \u0000 <p>Arsenic, a highly toxic heavy metal widely found in the environment, is a known carcinogen and toxin. Our study examined the effects of sodium arsenite on Wistar rat neonates exposed during gestation and weaning periods. The pregnant and weaning rats were given the low dose (LDG), median dose (MDG), and high dose (HDG) daily as 8.2, 12.3, and 16.4 mg/kgbw of NaAsO<sub>2</sub>, respectively. The results revealed that despite not affecting litter size, gestation index, or immediate postnatal observations, prolonged exposure to high doses of sodium arsenite led to increased liver weights, indicating potential liver stress or damage. Arsenic accumulation in liver tissues was significant, and histological examinations revealed liver damage, vascular congestion, and inflammation. Elevated levels of ALT, AST, ALP, and GGT were observed in arsenic-exposed groups during liver function tests, indicating hepatocellular injury and impaired function. Exposure to arsenic led to a dose-dependent decline in the mRNA expression levels and activity of antioxidant enzymes, including GST, GR, GPx, SOD, and CAT, showing that oxidative stress is present. Furthermore, LPx levels were increased. Metallothionein gene expression was upregulated, indicating a protective response against arsenic toxicity. Our findings underscore the risks associated with gestational and weaning exposure to sodium arsenite, providing insight into potential mechanisms behind arsenic-induced health issues and highlighting the importance of understanding these risks during critical developmental stages.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827021","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

Circ_0038632 Acts as a Sponge of miR-4306 to Facilitate Breast Cancer Progression Through Regulating CXCR4 Expression Circ_0038632作为miR-4306的海绵，通过调节CXCR4的表达促进乳腺癌的进展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70249

Yuesheng Zhao, Haiou Liu, Qi Wang, Zubin Li, Kun Zhao, Huibo Sun, Yanyong Zhang, Na Li, Wenhui Li

{"title":"Circ_0038632 Acts as a Sponge of miR-4306 to Facilitate Breast Cancer Progression Through Regulating CXCR4 Expression","authors":"Yuesheng Zhao, Haiou Liu, Qi Wang, Zubin Li, Kun Zhao, Huibo Sun, Yanyong Zhang, Na Li, Wenhui Li","doi":"10.1002/jbt.70249","DOIUrl":"https://doi.org/10.1002/jbt.70249","url":null,"abstract":"<div>\u0000 \u0000 <p>CircRNA plays an important role in the progression of breast cancer. This study focused on the molecular mechanism of circ_0038632 in regulating breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0038632, microRNA-4306 (miR-4306) and C-X-C chemokine receptor type 4 (CXCR4) mRNA in BC tissues and cells. Western blot was applied to detect the expression of CXCR4 protein and metastasis-related proteins (MMP2 and MMP9). Cell proliferation and apoptosis were observed by colony formation assay and flow cytometry. Scratch and Transwell assays were performed to detect the cell transfer ability. The angiogenesis ability of human vascular endothelial cells (HUVECs) was measured by the tube forming assay. Dual luciferase reporting assay was used to verify the relationship between miR-4306 and circ_0038632 or CXCR4. In vivo assay was used to detect the influence of circ_0038632 on the formation of BC tumors. Circ_0038632 and CXCR4 were highly expressed in BC tissue and cells, while miR-4306 was lowly expressed. Inhibition of circ_0038632 would restrain BC cell colony formation, migration, invasion, enhance cells apoptosis, and decrease HUVECs tube formation. Circ_0038632 acted as a sponge of miR-4306, and miR-4306 inhibitor would reverse the suppression effect of si-circ_0038632 in BC cells. CXCR4 was a target of miR-4306, and the overexpression of CXCR4 turned the growth inhibition of BC cells caused by exogenetic miR-4306. Importantly, circ_0038632 increased CXCR4 expression via sponging miR-4306. Finally, circ_0038632 knockdown inhibited the BC tumor formation. In conclusion, circ_0038632 contributed to the malignant progression of BC via regulating miR-4306/CXCR4 axis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826754","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

miR-126-3p Serves as a Biomarker for Hepatitis B Virus-Associated Chronic Acute Liver Failure and Regulates Inflammation by Regulating ERRFI1 miR-126-3p作为乙型肝炎病毒相关慢性急性肝衰竭的生物标志物，通过调节ERRFI1调节炎症

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70252

Yiping Luo, Qiuping Ren, Jun He, Menghang Wu

{"title":"miR-126-3p Serves as a Biomarker for Hepatitis B Virus-Associated Chronic Acute Liver Failure and Regulates Inflammation by Regulating ERRFI1","authors":"Yiping Luo, Qiuping Ren, Jun He, Menghang Wu","doi":"10.1002/jbt.70252","DOIUrl":"https://doi.org/10.1002/jbt.70252","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis B virus-associated chronic acute liver failure (HBV-ACLF) is the leading cause of ACLF, affecting approximately 90% of patients with ACLF. The objective of this study was to investigate the clinical relevance of miR-126-3p on HBV-ACLF as well as the regulatory impact of ERRFI1 and miR-126-3p on the inflammatory response caused by ACLF via in vitro experimental methodologies. RT-qPCR was utilized to quantify the expression levels of miR-126-3p, ERRFI1, NLRP3, caspase 1, and IL-1β. The clinical function of miR-126-3p was assessed using ROC analysis or Kaplan-Meier curve. Cell proliferation was quantified via the CCK-8 assay, while the dual-luciferase reporter assay was employed to confirm the specific binding interaction between miR-126-3p and ERRFI1. In patients with HBV-ACLF, a significant downregulation of miR-126-3p expression was observed; The level of miR-126-3p served as a prognostic indicator for the progression of HBV-ACLF, with reduced expression being associated with an unfavorable clinical outcome. In addition, miR-126-3p was found to modulate LPS-induced cell proliferation, and inflammation in THLE-2 cells through the regulation of ERRFI1 expression. Therefore, miR-126-3p might serve as a biomarker for HBV-ACLF.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827020","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

USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40 USP30通过抑制TOMM40泛素化加速乳腺癌恶性进展及其对他莫昔芬的耐药性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70258

Xinran Gao, Junbiao Liu, Baoqing Jia, Jiaxin Guo

{"title":"USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40","authors":"Xinran Gao, Junbiao Liu, Baoqing Jia, Jiaxin Guo","doi":"10.1002/jbt.70258","DOIUrl":"https://doi.org/10.1002/jbt.70258","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Breast cancer (BC) is the most common malignancy among women, with high incidence and mortality rates globally. Translocase of outer mitochondrial membrane 40 (TOMM40) has also been identified as an important prognostic biomarker for BC. Meanwhile, the ubiquitin-specific protease 30 (USP30) has also been shown to promote BC progression. However, the specific mechanisms underlying the role of USP30/TOMM40 in BC development remain unclear. Therefore, this study aims to delve into the potential mechanisms of USP30/TOMM40 in the progression of BC. The expression of TOMM40 and USP30 in BC tumors and cells was verified by bioinformatics analysis and western blot (WB). The effects of USP30/TOMM40 on BC cell proliferation, angiogenesis, glycolysis, and ferroptosis were determined by colony formation, tube formation assays and commercial kits. The co-immunoprecipitation (Co-IP) experiment was applied to verify the interaction between USP30 and TOMM40. The ubiquitination level of TOMM40 was detected by ubiquitinated antibodies. The effect of tamoxifen (TAM) on BC cell viability was measured by MTT assay. TOMM40 and USP30 were highly expressed in BC tumors and cells. Silencing TOMM40 blocked the proliferation, angiogenesis, glycolytic, and induced ferroptosis of BC cells. USP30 bound to TOMM40 and reduced its ubiquitination level. TOMM40 overexpressed abolished the tumor suppressive effect of USP30 knockdown and enhanced the resistance of BC to TAM. In conclusion, USP30 deubiquitinating TOMM40 promoted BC development and TAM resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826752","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

MYCN/MNX1 Axis Drives NSCLC Progression by Inducing Macrophage M2 Polarization and CD8+ T Cell Apoptosis via the Wnt/β-Catenin Pathway MYCN/MNX1轴通过Wnt/β-Catenin通路诱导巨噬细胞M2极化和CD8+ T细胞凋亡驱动NSCLC进展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70251

Chengzhang Cao, Haiyin Lai, Yuzhen Shi

{"title":"MYCN/MNX1 Axis Drives NSCLC Progression by Inducing Macrophage M2 Polarization and CD8+ T Cell Apoptosis via the Wnt/β-Catenin Pathway","authors":"Chengzhang Cao, Haiyin Lai, Yuzhen Shi","doi":"10.1002/jbt.70251","DOIUrl":"https://doi.org/10.1002/jbt.70251","url":null,"abstract":"<div>\u0000 \u0000 <p>Enhanced macrophage M2 polarization and CD8<sup>+</sup> T cell dysfunction contribute to the pathophysiology of non-small cell lung cancer (NSCLC). Motor neuron and pancreatic homeobox 1 (MNX1) has emerged as a potential tumor-promoting player. Here, we clarified the activity of MNX1 in NSCLC. PMA-induced THP-1 M0-like macrophages or CD8<sup>+</sup> T cells were co-cultured with NSCLC cells. Cell colony formation, migration, proliferation, apoptosis, and invasiveness were assessed by colony formation, wound healing, CCK-8, flow cytometry, and transwell assays, respectively. The ratio of CD206<sup>+</sup> macrophages was analyzed by flow cytometry. Ki-67 expression was tested by immunofluorescence. ChIP and luciferase assays were used to evaluate the relationship between MYCN and MNX1. MNX1 was highly expressed in NSCLC, and its loss-of-function suppressed cell growth, motility, and invasiveness in NSCLC cells. MNX1 depletion also diminished macrophage M2 polarization and CD8<sup>+</sup> T cell apoptosis. Mechanistically, MYCN increased MNX1 expression at the transcriptional level. MNX1 increase reversed the impact of MYCN depletion on NSCLC cell malignant behaviors, macrophage M2 polarization, and CD8<sup>+</sup> T cell viability. MYCN depletion diminished the in vivo growth of A549 subcutaneous xenografts. Additionally, MNX1 increase counteracted the impact of MYCN depletion on the Wnt/β-catenin pathway. Our findings elucidate the oncogenic role of the MYCN/MNX1/Wnt/β-catenin pathway in NSCLC by driving macrophage M2 polarization and diminishing CD8<sup>+</sup> T cell viability. Our study thus uncovers a novel mechanism underlying NSCLC development and highlights potential targets for combating NSCLC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826750","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