Frontiers in bioscience (Landmark edition)最新文献

{"title":"METTL3-Driven m6A Modification of <i>Cpt1a</i> Gene in High Fat Diet Related Liver Cancer Tumor Macrophages Facilitates Type II Macrophage Differentiation.","authors":"Limei Zhu, Xuelian Li, Wenting Wang","doi":"10.31083/FBL36971","DOIUrl":"https://doi.org/10.31083/FBL36971","url":null,"abstract":"<p><strong>Objective: </strong>Obesity induces chronic inflammation and hormonal imbalances that contribute to tumor growth. This study explores the less understood dynamics of tumor-related macrophages under a high-fat diet and its consequent impact on tumor growth, with a focus on elucidating the role of high-fat diets on macrophage behavior in liver cancer.</p><p><strong>Methods: </strong>We established a mouse obesity model using a high-fat diet, combined with a liver cancer implantation approach. Tumor-infiltrating macrophages were isolated for analysis. We investigated the specific effects of a high-fat diet on macrophages through transcriptomic and metabolomic studies and further explored the influence of N6-methyladenosine (m6A) RNA modification on macrophage differentiation using <i>in vitro</i> and <i>in vivo</i> models.</p><p><strong>Results: </strong>Our findings reveal that a high-fat diet significantly accelerates <i>in-situ</i> liver cancer growth and fosters type II differentiation of tumor-associated macrophages. RNA sequencing indicated upregulation of <i>Cpt1a</i> and <i>Mettl3</i> genes, which are crucial for m6A modification in macrophages. Using human and mouse macrophage cell lines with either elevated <i>Mettl3</i> expression or <i>Cpt1a</i> gene knockout, we demonstrated that methyltransferase-like 3 (METTL3) enhances fatty acid metabolism in macrophages, a process reversible by <i>Cpt1a</i> gene knockout. These effects were corroborated <i>in vivo</i>. Further, macrophages infused with high <i>Mettl3</i> expression, when combined with an <i>in-situ</i> implantation model and adoptive cell therapy, markedly promoted liver cancer growth and increased type II macrophage differentiation (<i>p</i> < 0.001). Knockout of the <i>Cpt1a</i> gene counteracted the METTL3 effect compared to the control group (<i>p</i> > 0.05). METTL3 and m6A RNA Immunoprecipitation (RIP) assays confirmed that METTL3 stabilizes <i>Cpt1a</i> mRNA. Additionally, multispectral staining of clinical specimens revealed a positive correlation between METTL3 protein levels in liver cancer tumor-associated macrophages and M2 macrophage prevalence, inversely correlating with M1 macrophages (<i>p</i> < 0.01). High <i>Mettl3</i> expression in macrophages was associated with poor prognosis in liver cancer patients, correlating significantly with tumor size and tumor node metastasis (TNM) classification stage.</p><p><strong>Conclusion: </strong>Our research identifies that a high-fat diet elevates METTL3-driven m6A modification of carnitine palmitoyltransferase 1A (CPT1A) in tumor macrophages, fostering type II macrophage differentiation, and exacerbating liver cancer growth and immune evasion.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"36971"},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Highly Selective and Sensitive Fluorescent Probe With a Large Stokes Shift for Near-Infrared Visualization of Endogenous and Exogenous Biothiols in Living Cells.","authors":"Xiaomin Li, Rongrong Yuan, Yangmin Ma, Guanglong Li, Siyue Ma","doi":"10.31083/FBL37240","DOIUrl":"https://doi.org/10.31083/FBL37240","url":null,"abstract":"<p><strong>Background: </strong>Fluorescent probes have become a powerful tool for monitoring biothiol concentrations, aiding in disease diagnosis and treatment while also facilitating the exploration of fundamental biological processes. However, the probes are limited by the short fluorescence emission wavelength and small Stokes shift, which makes them susceptible to background fluorescence interference and significant self-absorption. To overcome these limitations and achieve high-fidelity biothiols detection in complex biological systems, this study focuses on developing a near-infrared fluorescent probe with an extended Stokes shift.</p><p><strong>Methods: </strong>(E)-4-(5-(2-(4-(dicyanomethylene)-4H-chromen-2-yl)vinyl)thiophen-2-yl)phenyl 2,4-dinitrobenzenesulfonate (DCMOS-N), a near-infrared (NIR) fluorescent probe featuring a large Stokes shift, was designed and synthesized for biothiols detection. The optical properties of DCMOS-N were evaluated using ultraviolet-visible (UV-Vis) and fluorescence spectroscopy. Additionally, its imaging capabilities for detecting biothiols in living cells were assessed through confocal fluorescence microscopy.</p><p><strong>Results: </strong>Fluorescence spectral analysis confirmed that the DCMOS-N probe exhibits high selectivity and strong anti-interference properties in biothiol detection. Moreover, its fluorescence intensity increases upon the addition of biothiols. Notably, a strong linear correlation was observed across the concentration range of 0 to 100 μmol/L (R² = 0.9944 for glutathione (GSH), 0.9942 for cysteine (Cys), and 0.9946 for homocysteine (Hcy)), enabling the quantitative analysis of biothiol concentrations in biological systems. The detection limits for GSH, Cys, and Hcy were determined as 0.142 μmol/L, 0.129 μmol/L, and 0.143 μmol/L, respectively. Importantly, the practical application of DCMOS-N in living cells was validated, with confocal fluorescence imaging demonstrating its capability to detect both endogenous and exogenous biothiols in HeLa cells.</p><p><strong>Conclusion: </strong>An NIR fluorescent probe, DCMOS-N, was developed and effectively utilized to monitor biothiols in living HeLa cells. The successful design of DCMOS-N presents significant potential and serves as an innovative platform for developing fluorescence probes targeted at biothiols.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"37240"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 Mediates Microglia-Astrocyte/Neuron Crosstalk and Pyroptosis by the TLR4/NF-κB Pathway in Multiple Sclerosis.","authors":"Yang Feng, Liang Wang, Zhuofeng Mao, Weiping Wang","doi":"10.31083/FBL37838","DOIUrl":"https://doi.org/10.31083/FBL37838","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is characterized as a chronic inflammatory autoimmune disorder affecting the central nervous system (CNS). Prior research has explored the involvement of pyroptosis and high mobility group box 1 (HMGB1) in the pathophysiology of MS. Nevertheless, the underlying pathogenic mechanisms and their interactions have yet to be fully elucidated.</p><p><strong>Methods: </strong>Myelin oligodendrocyte glycoprotein (MOG)35-55-treated mice and BV-2 microglial cells were utilized as a model for MS. Subsequently, these subjects were transfected with lentiviral vectors that express short hairpin RNA targeting HMGB1. HT-22 cells and Ma-c cells were exposed to conditioned medium (CM) derived from BV-2 cells following treatment. The levels of HMGB1, tumor necrosis factor (TNF)-α, and interleukin-1β (IL-1β) were quantified using enzyme-linked immunosorbent assay (ELISA). Additionally, western blot (WB) analysis was performed to further elucidate the mechanisms involved.</p><p><strong>Results: </strong>Mice treated with MOG35-55 (experimental autoimmune encephalomyelitis, EAE) exhibited reduced body weights and significant nerve function impairment (<i>p</i> < 0.001), accompanied by increased activation of microglia within the CNS (<i>p</i> < 0.05). Additionally, the secretion of HMGB1 was found to be upregulated in the MS cell model (<i>p</i> < 0.05), and CM from these cells induced the release of pro-inflammatory cytokines in HT-22 and Ma-c cell lines (<i>p</i> < 0.001). Notably, the modulation of HMGB1 and NOD-like receptor family pyrin domain containing 3 (NLRP3) expression was shown to mitigate the release of pro-inflammatory cytokines (<i>p</i> < 0.01), TUNEL-positive cells (<i>p</i> < 0.01) in both HT-22 cells and Ma-c cells, which were induced by CM from BV-2 cells treated with MOG35-55. Furthermore, WB analysis indicated that the suppression of HMGB1 expression can inhibit the activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway, as well as pyroptosis in EAE mice and HT-22/ Ma-c cells exposed to CM from BV-2 cells (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>HMGB1 has the potential to act as a promoter of MS through the activation of TLR4/NF-κB signaling pathway and the induction of pyroptosis in microglial and other cells. Consequently, the modulation of HMGB1 may represent a novel therapeutic strategy for the management of MS.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"37838"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-α2b Modulates AMPA and Kainate Receptors and Alters Cross Talk of AMPA and NMDA Receptors in the Frog Vestibular Epithelium.","authors":"Irina V Ryzhova, Elena A Vershinina, Alexander G Markov, Tatyana V Tobias","doi":"10.31083/FBL38852","DOIUrl":"https://doi.org/10.31083/FBL38852","url":null,"abstract":"<p><strong>Background: </strong>Interferons (IFNs) are ototoxic drugs leading to vestibular and auditory disorders. This study investigated the effect of pro-inflammatory cytokine IFN-α2b on the afferent glutamatergic synaptic transmission of the vestibular end organ, focusing on ionotropic glutamate receptors (iGluRs).</p><p><strong>Methods: </strong>In order to characterize the role of IFN-α2b in the glutamatergic synaptic transmission in vestibular epithelium, we investigated its influence on responses evoked by D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainic acid (kainate). This was carried out using external perfusion of the vestibular apparatus and multiunit recording of afferent firing activity of semicircular canal ampullary nerve fibers. The change in the ratio of the maximum frequency of pulse activity to the preceding background was chosen as a criterion for evaluating the evoked responses of glutamate receptor (GluR) agonists.</p><p><strong>Results: </strong>Acute perfusion of the vestibular apparatus with IFN-α2b and AMPA did not alter the AMPA-evoked response. However, a significant increase in the response was observed 15 min after cessation of drug application and washing with normal solution (paired-samples <i>t</i>-test <i>p</i> = 0.018; n = 20). IFN-α2b significantly increased the kainate-evoked response during cytokine application (Wilcoxon signed-rank test <i>p</i> = 0.016; n = 11), and further potentiates the response 15 min after rinsing with normal solution, compared to the test value (Wilcoxon signed-rank test <i>p</i> = 0.05; n = 11). IFN had no effect on NMDA-induced responses. AMPA receptors (AMPARs) potentiated by IFN-α2b increase NMDA-evoked responses (Repeated measures analysis of variance [ANOVA RM], <i>p</i> = 0.028; n = 10).</p><p><strong>Conclusions: </strong>IFN-α2b stimulates AMPARs and kainate receptors (KARs) through various mechanisms but has no direct effect on NMDA receptors (NMDARs). Interferon-activated AMPARs can stimulate NMDARs activity, thereby altering synaptic plasticity of the glutamatergic afferent synapse in vestibular epithelium.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"38852"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>HOTAIR</i> Knockdown Increases the Sensitivity of Hepatocellular Carcinoma Cells to Sorafenib by Disrupting miR-145-5p/HK2 Axis-Mediated Mitochondrial Function and Glycolysis.","authors":"Meiyu Cheng, Bingrong Wang, Lina Duan, Yu Jin, Wenda Zhang, Na Li","doi":"10.31083/FBL37368","DOIUrl":"https://doi.org/10.31083/FBL37368","url":null,"abstract":"<p><strong>Background: </strong>Frequent drug resistance seriously limits the therapeutic efficacy of sorafenib in advanced hepatocellular carcinoma (HCC). Strategies to increase the response to sorafenib are limited, and the underlying mechanism to facilitate such an increase is not entirely understood. Homeobox (HOX) transcript antisense intergenic RNA (<i>HOTAIR</i>) expression is high in HCC, promoting the occurrence and progression of HCC. In this study, we explored the mechanism through which <i>HOTAIR</i> knockdown affects the response of HCC cells to the chemotherapeutic sorafenib.</p><p><strong>Methods: </strong>Cell viability and apoptosis were assessed using MTT assay, flow cytometry, and nuclear staining. Mitochondrial function and isolation were determined using flow cytometry and a mitochondrial isolation kit. Glycolysis was measured by glucose and lactic acid assay kits. The underlying mechanisms were explored through western blotting, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and chromatin immunoprecipitation (ChIP).</p><p><strong>Results: </strong><i>HOTAIR</i> knockdown increased sorafenib-induced apoptosis in the HCC cells. <i>HOTAIR</i> and hexokinase 2 (<i>HK2</i>) expression levels were upregulated in human HCC tissues, demonstrating a significant correlation. The knockdown of <i>HOTAIR</i> or <i>HK2</i> aggravated mitochondrial dysfunction and inhibited glycolysis. Further, <i>HOTAIR</i> knockdown promoted sorafenib-mediated <i>HK2</i> mRNA downregulation, resulting in decreased HK2 protein levels in cells and mitochondria. This ultimately facilitated the mitochondrial apoptotic pathway. Moreover, it was demonstrated that <i>HOTAIR</i> regulated HK2 via polycomb repressive complex 2 (PRC2)-mediated epigenetic modification of miR-145-5p in HCC.</p><p><strong>Conclusions: </strong><i>HOTAIR</i> knockdown increased the sensitivity of HCC cells to sorafenib by disrupting the miR-145-5p/HK2 axis-mediated mitochondrial function and glycolysis, suggesting new strategies for HCC treatment.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"37368"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesity-Derived Biomolecules Promote the Differentiation of THP1 Monocytes to Macrophages <i>In Vitro</i>.","authors":"Luis I Terrazas, Valeria Gutiérrez-Almaraz, Valentina García-Garay, Victoria Hernández-Gómez, Nohemí Salinas-Jazmín, Mónica Graciela Mendoza-Rodríguez, Jonadab Efraín Olguín","doi":"10.31083/FBL36637","DOIUrl":"https://doi.org/10.31083/FBL36637","url":null,"abstract":"<p><strong>Background: </strong>It is well known that the microenvironment in which an immune response develops, generally pro-inflammatory or immunosuppressive, along with other overproduced biomolecules recognized by pattern recognition receptors, may promote the stimulation and differentiation of monocytes into macrophages with effector functions. Low-density lipoprotein (LDL) plays a fundamental role in cholesterol transport. By contrast, its oxidized form (ox-LDL), which is overexpressed in conditions of obesity and chronic low-grade inflammation, has been associated with cardiovascular diseases. Depending on the microenvironmental context, prostaglandin E2 (PGE2) participates in various scenarios such as inflammation, anti-inflammation, and homeostasis. Therefore, obesity-derived biomolecules such as LDL, ox-LDL, and PGE2 could induce the differentiation of immune cells into effector populations with either pro-inflammatory or immunosuppressive profiles.</p><p><strong>Methods: </strong>In the present work, we studied the effects of LDL, ox-LDL, and PGE2 on the differentiation of the human THP1 monocytic cell line into macrophages under two different protocols, analyzing several activation markers associated with either pro-inflammatory M1 or anti-inflammatory M2 profiles by flow cytometry and quantitative PCR (qPCR).</p><p><strong>Results: </strong>Our data suggest that native LDL induces the differentiation of human THP1 monocytes into M1 macrophages even more efficiently than classic phorbol 12-myristate 13-acetate (PMA) stimulation, whereas ox-LDL and PGE2 induce the expression of activation markers similarly to interferon gamma or interleukin 4 during PMA preactivation of macrophages.</p><p><strong>Conclusions: </strong>The results of this study add evidence to the role of obesity-derived biomolecules as non-canonical differentiation stimuli in macrophages, which could be relevant in contexts where these biomolecules are chronically overproduced, such as obesity, low-grade inflammation, type 2 diabetes, and cancer.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"36637"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Phosphoglycerate Kinase 1 Enhances Radiosensitivity of Esophageal Squamous Cell Carcinoma to X-rays and Carbon Ion Irradiation.","authors":"Junru Chen, Hongtao Luo, Xun Wu, Meng Dong, Dandan Wang, Yuhong Ou, Yuhang Wang, Shilong Sun, Zhiqiang Liu, Zhen Yang, Quanlin Guan, Qiuning Zhang","doi":"10.31083/FBL36430","DOIUrl":"https://doi.org/10.31083/FBL36430","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy is crucial for managing esophageal squamous cell carcinoma (ESCC). This research explored the potential and mechanism of enhancing ESCC radiosensitivity through targeting phosphoglycerate kinase 1 (PGK1).</p><p><strong>Methods: </strong>After ESCC cells were exposed to X-rays and C-ions, hub genes were identified through proteomic analysis and bioinformatics. To elucidate PGK1's function, small interfering RNAs and plasmids were used to silence and overexpress PGK1 in two human ESCC cell lines. Plate colony formation, cell counting kit 8, and 5-ethynyl-2'-deoxyuridine assays were conducted to detect cell proliferation after irradiation with different linear energy transfer rays (X-rays and carbon ions). Flow cytometry was used to assess radiation-induced perturbations in the cell cycle, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential. Western blotting was performed to detect the protein expressions of protein kinase B (Akt), phosphorylated protein Kinase B (pAkt), mammalian target of rapamycin (mTOR), and phosphorylated mammalian target of rapamycin (pmTOR).</p><p><strong>Results: </strong>Proteomics and bioinformatics analyses revealed that PGK1 plays a key role in modulating ESCC radiosensitivity. Knockdown of PGK1 resulted in the suppression of cancer cell proliferation and viability, promoted apoptotic processes, and demonstrated a synergistic anti-tumor effect in conjunction with radiation. Conversely, overexpression of PGK1 promoted cancer cell growth and increased radiation resistance. This may be attributed to the accumulation of ROS and the inhibition of Akt/mTOR pathway following PGK1 inhibition.</p><p><strong>Conclusion: </strong>Targeting PGK1 may be an effective strategy to increase ESCC radiation sensitivity, offering a promising strategy for improving treatment outcomes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"36430"},"PeriodicalIF":3.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Swimming Training in a T2DM Zebrafish Model Restores Mitochondrial Function to Alleviate Anxiety-Like Behaviors and Metabolic Dysregulation.","authors":"Yimeng Fang, Junying Qu, Jing Zhao, Linkai Qu, Lei Wang, Cheng Luo, Qinsi Yang, Wei Wu, Da Sun, Dongjuan He","doi":"10.31083/FBL37100","DOIUrl":"https://doi.org/10.31083/FBL37100","url":null,"abstract":"<p><strong>Introduction: </strong>Anxiety and depression-like behaviors are common in patients with type 2 diabetes mellitus (T2DM). This study explored the potential of swimming training (ST) to alleviate these symptoms by restoring mitochondrial function. While aerobic exercise is known to influence mitochondrial dysfunction and behavioral abnormalities, the mechanism by which ST achieves this remains unclear.</p><p><strong>Objective: </strong>To investigate how ST improves T2DM and associated anxiety-like behaviors by regulating mitochondrial structure and function.</p><p><strong>Methods: </strong>T2DM was induced in zebrafish with a high-sugar diet, followed by 20 days of ST. Behavioral analysis assessed anxiety-like behaviors, while ELISA and microscopic imaging techniques were used to evaluate changes in mitochondrial structure and function in liver tissue.</p><p><strong>Results: </strong>ST significantly alleviated anxiety-like behavior and mitigated mitochondrial damage. Furthermore, ST counteracted mitochondrial dysfunction induced by oxidative stress through regulation of reactive oxygen species levels (<i>p</i> < 0.01), stabilization of mitochondrial membrane potential (<i>p</i> < 0.0001), and increasing the production of adenosine triphosphate (<i>p</i> < 0.01). ST also improved T2DM markers, including blood glucose regulation (<i>p</i> < 0.001), insulin level (<i>p</i> < 0.05), and lipid metabolism (<i>p</i> < 0.01 for low-density lipoprotein cholesterol (LDL-C), <i>p</i> < 0.01 for high-density lipoprotein cholesterol (HDL-C), <i>p</i> < 0.01 for total cholesterol (T-CHO)).</p><p><strong>Conclusions: </strong>This research provides insights into the intricate interplay between mitochondrial dysfunction in T2DM and behavioral outcomes while highlighting the potential of ST as a holistic therapeutic strategy for T2DM patients.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"37100"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNIK Regulates Cytoskeletal Organization to Promote Focal Adhesion Turnover and Mitosis in Lung Adenocarcinoma.","authors":"Yao Li, Meng-Yao Song, Xing Hu, Xue-Hua Sun, Tao Zhang, Lu Zhang, Ying-Xiong Wang, Qian Zhang, Chun-Dong Zhang, Lian Zhang","doi":"10.31083/FBL38875","DOIUrl":"https://doi.org/10.31083/FBL38875","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the primary cause of cancer-related mortality, but the molecular mechanisms behind this malignancy remain unclear.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) online database and tissue chips were used to analyze the expression levels of tumor necrosis factor receptor-associated factor 2 (TRAF2)- and non-catalytic region of tyrosine kinase adaptor protein (NCK)- interacting kinase (TNIK) protein in lung cancer. A549 and PC-9 lung adenocarcinoma (LUAD) cells with stable TNIK knockdown were generated by lentivirus infection. The tumor phenotypes were subsequently examined both <i>in vitro</i> and <i>in vivo</i>. The TCGA online database and RNA-sequencing of TNIK-knockdown cells were used to study the molecular mechanism underlying the TNIK-mediated phenotype of LUAD cells. The effects of TNIK knockdown on focal adhesion dynamics and mitosis were examined by indirect immunofluorescence and Western blot, on the sensitivity to chemotherapy drugs by cell counting kit-8 (CCK-8) assay, on apoptosis by flow cytometry, and on cell proliferation by 5-ethynyl-2'-deoxyuridine (EDU).</p><p><strong>Results: </strong>TNIK was highly expressed in LUAD (<i>p</i> < 0.0001), predominantly in the cytosol. Phenotype assays revealed that TNIK knockdown in LUAD cells led to a significant increase in cell spreading (<i>p</i> < 0.0001), but also inhibition of cell growth and movement (<i>p</i> < 0.01). Mechanistically, TNIK was found to regulate F-actin and microtubule organization, as well as the Ras homolog gene family (RHO)/RHO-associated kinase 2 (ROCK2)/LIM motif-containing protein kinase 1 (LIMK1) signaling pathway, thereby playing a crucial role in the control of focal adhesion turnover and mitosis. Additionally, the silencing of TNIK enhanced the sensitivity of LUAD cells to chemotherapeutic drugs.</p><p><strong>Conclusions: </strong>Our findings suggest that TNIK regulates focal adhesion turnover and mitosis to promote tumor malignancy via the RHO/ROCK2/LIMK1 pathway. The combination of TNIK targeting with chemotherapeutic drugs could be an effective strategy to overcome resistance in LUAD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"38875"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimethylamine N-oxide Supplementation Enhances the Quality of Oocytes in Mice of Polycystic Ovary Syndrome.","authors":"Jiayu Huang, Yin Tian, Xuemei Liu, Zixin Xu, Chong Li, Ling Zhu, Xiru Liu, Jiying Hou, Jingyu Li","doi":"10.31083/FBL38078","DOIUrl":"https://doi.org/10.31083/FBL38078","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) has increasingly emerged as a significant cause of impaired reproductive outcomes, primarily characterized by a combination of ovulatory dysfunction and decreased oocyte quality. However, the molecular mechanisms underlying the decreased oocyte quality caused by PCOS and preventative strategies still require further investigation.</p><p><strong>Method: </strong>All procedures were approved by the Animal Ethics Committee of Chongqing Medical University. We established a mice model of PCOS using dehydroepiandrosterone (DHEA) treatment. The estrous cycle was recorded, and plasma sex hormone and trimethylamine N-oxide (TMAO) levels were measured. Ovarian indices and follicular formation were compared. Time-lapse imaging was used to observe <i>in vitro</i> maturation and blastocyst formation. Reactive oxygen species (ROS), MitoSOX level, and mitochondrial membrane potential were measured to analyze the mitochondrial function of oocytes. Confocal laser scanning microscopy was used to detect spindle function and chromosomes.</p><p><strong>Results: </strong>Our study found that DHEA-induced PCOS mice exhibited significantly lower plasma TMAO levels compared to normal mice. Consequently, we supplemented TMAO in PCOS mice and found that the abnormal estrous cycle and reduced ovarian function induced by PCOS could be restored. Additionally, TMAO rescued PCOS-induced defects in oocyte maturation, spindle and chromosome morphology, and embryonic developmental potential. Mechanically, we found that TMAO effectively reduced ROS levels by improving mitochondrial function in PCOS oocytes.</p><p><strong>Conclusion: </strong>Our findings indicate that the reduction in TMAO levels induced by PCOS may be a key factor influencing reproductive outcomes. TMAO supplementation <i>in vivo</i> can effectively enhance mitochondrial function and oocyte quality in PCOS, holding significant clinical importance for improving assisted reproductive outcomes in patients with PCOS.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"38078"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}