Biochimica et biophysica acta. Molecular basis of disease最新文献

Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases 细胞外囊泡在神经炎症和神经退行性疾病相互作用中的多方面作用

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-27 DOI: 10.1016/j.bbadis.2025.167960

Zhujie Deng, Haiyan Chen, Jiazhi Chen, Zhiyun Du, Wei Zhou, Zhengqiang Yuan

{"title":"Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases","authors":"Zhujie Deng, Haiyan Chen, Jiazhi Chen, Zhiyun Du, Wei Zhou, Zhengqiang Yuan","doi":"10.1016/j.bbadis.2025.167960","DOIUrl":"10.1016/j.bbadis.2025.167960","url":null,"abstract":"<div><div>Despite advances in understanding neurodegenerative disease mechanisms, effective treatments remain elusive. Extracellular vesicles (EVs), key mediators of intercellular communication within the central nervous system (CNS), are increasingly recognized for their involvement in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's disease (HD). In vivo studies demonstrate EVs' crucial role in maintaining CNS homeostasis, modulating neuroinflammatory responses, and influencing tissue repair and regeneration following injury, thereby impacting disease progression and recovery. Their unique properties, including small size and ability to cross the blood-brain barrier (BBB), position them as promising candidates for both biomarkers and therapeutics in CNS diseases. This review delves into the significant impact of neuroinflammation on neurodegenerative conditions, specifically focusing on the multifaceted contributions of EVs and their intricate interplay with the inflammatory landscape. We explore EV biogenesis, cargo composition, diverse roles in neuroinflammation (including intercellular communication and neuroprotection), their potential as biomarkers and drug delivery vehicles across the BBB for diagnosis or treatment of neuroinflammation implemented neurodegenerative diseases.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167960"},"PeriodicalIF":4.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unraveling the protective role of m6A methylation in SLC22A3 expression for breast Cancer intervention 揭示m6A甲基化在SLC22A3表达中对乳腺癌干预的保护作用

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-24 DOI: 10.1016/j.bbadis.2025.167962

Yu Xiao , Congcong Cao , Yaqi Zhang , Chao Zhao , Yuchen Liu

{"title":"Unraveling the protective role of m6A methylation in SLC22A3 expression for breast Cancer intervention","authors":"Yu Xiao , Congcong Cao , Yaqi Zhang , Chao Zhao , Yuchen Liu","doi":"10.1016/j.bbadis.2025.167962","DOIUrl":"10.1016/j.bbadis.2025.167962","url":null,"abstract":"<div><h3>Background</h3><div>The interplay between SLC22A3 expression and m6A RNA methylation is emerging as a significant factor in breast cancer pathology, yet the specific correlations and underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>The prognostic significance of SLC22A3 expression in breast cancer was assessed using the Cancer Genome Atlas data. In vitro experiments were conducted using a custom-engineered dCas13b-METTL3 plasmid, designed to selectively enhance m6A methylation of SLC22A3 mRNA. Functional alterations in breast cancer cells post-transfection were evaluated. Additionally, overexpression of the m6A reader protein IGF2BP2 was achieved, and subsequent changes in SLC22A3 expression and overall breast cancer cell transcriptome were analyzed. MeRIP-seq and mRNA-seq were employed to analyze the expression and m6A methylation of Slc22a3 in a transgenic mouse model of breast cancer.</div></div><div><h3>Results</h3><div>Bioinformatics analysis demonstrated a significant reduction in SLC22A3 expression in cancer tissues compared to adjacent non-cancerous tissues. Enhancement of SLC22A3 mRNA m6A methylation via the dCas13b-M3 plasmid in breast cancer cells led to increased SLC22A3 expression, accompanied by reduced cell proliferation and migration and induced apoptosis. Overexpression of IGF2BP2 similarly increased SLC22A3 expression. Further, RNA-seq identified 25 genes downstream of SLC22A3. Analysis of breast cancer tissues from mice revealed a decrease in both SLC22A3 expression and its m6A methylation as the breast cancer progressed.</div></div><div><h3>Conclusion</h3><div>SLC22A3 acts as protective factor in breast cancer. Enhanced m6A methylation of SLC22A3 mRNA and overexpression of the m6A reader IGF2BP2 upregulate its expression. The induction of SLC22A3 mRNA methylation through the m6A CRISPR approach effectively mitigates the malignancy of breast cancer cells.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167962"},"PeriodicalIF":4.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

METTL1-mediated m7G modification of NEK1 mRNA promotes the proliferation of oral squamous cell carcinoma mettl1介导的m7G修饰NEK1 mRNA促进口腔鳞状细胞癌的增殖

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-23 DOI: 10.1016/j.bbadis.2025.167961

Yuan Chen , Xinyu Zhang , Min Li , Bo Fu , Huimin Li , Fengjiao Yuan , Guangyao Li , Qingcui Song

{"title":"METTL1-mediated m7G modification of NEK1 mRNA promotes the proliferation of oral squamous cell carcinoma","authors":"Yuan Chen , Xinyu Zhang , Min Li , Bo Fu , Huimin Li , Fengjiao Yuan , Guangyao Li , Qingcui Song","doi":"10.1016/j.bbadis.2025.167961","DOIUrl":"10.1016/j.bbadis.2025.167961","url":null,"abstract":"<div><div>Oral squamous cell carcinoma (OSCC) is the most common malignant tumor found in the head and neck region, representing a significant public health concern. The 7-methylguanylate (m7G) RNA modification is a newly recognized regulatory mechanism influencing gene expression, and methyltransferase-like 1 (METTL1) has been linked to tumor progression in various cancers; however, its specific role in OSCC remains largely unexplored. This study reveals that METTL1 expression is notably increased in OSCC and correlates with a poor prognosis for patients. Functional assays indicate that reducing METTL1 levels inhibits OSCC cell proliferation both in laboratory settings and in animal models, resulting in a G1 phase cell cycle arrest. To delve deeper into the mechanisms at play, we utilized m7G Methylated RNA Immunoprecipitation Sequencing (m7G MeRIP-seq) alongside RNA sequencing (RNA-seq) to pinpoint the downstream targets of METTL1 in OSCC cells. Our results confirm that METTL1-catalyzed m7G modification on the 5′ untranslated region (5’UTR) of NEK1 mRNA enhances its stability and positively regulates NEK1 expression. Additionally, silencing NEK1 also inhibits OSCC cell proliferation, diminishes clonogenic formation, and induces G1 phase cell cycle arrest. These findings indicate that METTL1-mediated m7G modification is vital for OSCC proliferation, with NEK1 identified as a significant downstream target. In conclusion, METTL1 stands out as a potential prognostic marker and therapeutic target in OSCC, highlighting the need for further exploration of its molecular mechanisms and clinical implications.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167961"},"PeriodicalIF":4.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LILRB4 exacerbates myocardial ischemia-reperfusion injury by promoting inflammation and pyroptosis LILRB4通过促进炎症和焦亡加重心肌缺血再灌注损伤。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-21 DOI: 10.1016/j.bbadis.2025.167959

Jian Yang , Mengting Zhang , Li Liu , Peiyue Zhang , Haiyin Liu , Zishu Yang , Chu Chen , Ruonan Li , Yuhong Zhai , Wenqiang Li , Wei Wang , Jun Yang , Cuiyuan Huang , Jing Zhang

{"title":"LILRB4 exacerbates myocardial ischemia-reperfusion injury by promoting inflammation and pyroptosis","authors":"Jian Yang , Mengting Zhang , Li Liu , Peiyue Zhang , Haiyin Liu , Zishu Yang , Chu Chen , Ruonan Li , Yuhong Zhai , Wenqiang Li , Wei Wang , Jun Yang , Cuiyuan Huang , Jing Zhang","doi":"10.1016/j.bbadis.2025.167959","DOIUrl":"10.1016/j.bbadis.2025.167959","url":null,"abstract":"<div><div>Inflammation and pyroptosis are pivotal in myocardial ischemia-reperfusion injury. Although leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) modulates inflammation in conditions such as myocardial hypertrophy, its involvement in myocardial ischemia-reperfusion injury (MIRI) remains ambiguous. Recombinant adenoviral vectors were designed to induce the overexpression or knockdown of LILRB4 in H9C2 cardiomyocytes or rat myocardial tissue. H9C2 cells were subjected to hypoxia for 2 h and reoxygenation for 4 h (H/R), while myocardial tissue experienced 30 min of ischemia followed by 2 h of reperfusion (I/R). Biochemical assay, histopathology, ELISA, and other tests were performed on myocardial cells and tissues. Meanwhile, LILRB4 knockout mice were used for further validation. LILRB4 promotes the release of inflammatory factors induced by I/R and H/R, thereby increasing the size of myocardial infarction and leading to functional impairment. Downregulation of LILRB4 suppressed SHP-2 phosphorylation and activation, consequently reducing the expression of the thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), Caspase-1, and Gasdermin D (GSDMD). The SHP2 inhibitor PHPS1 mitigated the inflammatory and pyroptotic effects of LILRB4 in cardiomyocytes induced by H/R. Compared to wild-type mice, LILRB4<sup>−/−</sup> mice exhibited markedly diminished myocardial tissue swelling, decreased release of inflammatory cytokines, and a notable reduction in the expression of p-SHP2, TXNIP, NLRP3, Caspase-1, and GSDMD proteins after I/R induction.LILRB4 promotes inflammation and pyroptosis, which in turn worsens MIRI, likely through activating the TXNIP/NLRP3 signaling pathway, providing mechanistic insights into the MIRI.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167959"},"PeriodicalIF":4.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EGFR inhibitor suppresses tumor growth by blocking lipid uptake and cholesterol synthesis in non-small cell lung cancer EGFR抑制剂通过阻断非小细胞肺癌的脂质摄取和胆固醇合成来抑制肿瘤生长。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-20 DOI: 10.1016/j.bbadis.2025.167957

Byung-Ho Rhie , Sang Hyeon Woo , Hyun-Yi Kim , Janardhan Keshav Karapurkar , Won-Jun Jo , Jusong Kim , Dong Ha Kim , Jaesang Kim , Myeong Jun Choi , Young Jun Park , Yoonki Hong , Seok-Ho Hong , Suresh Ramakrishna , Kye-Seong Kim

{"title":"EGFR inhibitor suppresses tumor growth by blocking lipid uptake and cholesterol synthesis in non-small cell lung cancer","authors":"Byung-Ho Rhie , Sang Hyeon Woo , Hyun-Yi Kim , Janardhan Keshav Karapurkar , Won-Jun Jo , Jusong Kim , Dong Ha Kim , Jaesang Kim , Myeong Jun Choi , Young Jun Park , Yoonki Hong , Seok-Ho Hong , Suresh Ramakrishna , Kye-Seong Kim","doi":"10.1016/j.bbadis.2025.167957","DOIUrl":"10.1016/j.bbadis.2025.167957","url":null,"abstract":"<div><div>Accelerated cholesterol and lipid metabolism are hallmarks of non-small cell lung cancer (NSCLC). Recently, epidermal growth factor receptor (EGFR) signaling has been shown to regulate de novo cholesterol synthesis and low-density lipoprotein receptor (LDLR) expression through SREBP-1-dependent pathways. This suggests that targeting EGFR signaling in cholesterol metabolism might provide a new therapeutic strategy for NSCLC. In this study, we demonstrated that AX-0085, a small-molecule drug, significantly inhibits EGFR kinase activity and subsequently suppresses cholesterol and lipid metabolism in NSCLC. Transcriptomic analysis showed that cholesterol and lipid metabolism-related transcripts were significantly downregulated in AX-0085-treated NSCLC cells compared to the mock control. In addition, AX-0085 downregulates EGF signaling-dependent SREBP1-mediated cholesterol biosynthesis-related enzymes and LDLR in NSCLC. Moreover, AX-0085 dramatically reduced proliferation, colony-forming ability, and migration in NSCLC cells by blocking EGFR signaling. Furthermore, treatment with AX-0085 decreased both tumor size and volume in the LLC-xenograft model. These results demonstrate that AX-0085 effectively suppresses cholesterol metabolism in NSCLC cells by inhibiting EGF-mediated SREBP1 signaling, suggesting a potential therapeutic strategy targeting cholesterol metabolism in NSCLC.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167957"},"PeriodicalIF":4.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIM34 inhibits triple-negative breast cancer progression by attenuating fatty acid synthesis via facilitating FASN ubiquitination TRIM34通过促进FASN泛素化来抑制脂肪酸合成，从而抑制三阴性乳腺癌的进展

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-19 DOI: 10.1016/j.bbadis.2025.167958

Yong Li , Jijun Shan , Shanqing Liu , Yan Shen , Lianjie Niu , Qixin Mao , Xiaobing Chen

引用次数: 0

A review on targeting tunable nanocarrier interaction, physiochemical properties, and futuristic nanocarrier 靶向可调纳米载体的相互作用、理化性质及未来发展趋势

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-18 DOI: 10.1016/j.bbadis.2025.167956

Sonia Pandey , Shrikant Joshi , Purnima Tripathi , Arti Gupta , Jitendra Singh Yadav

{"title":"A review on targeting tunable nanocarrier interaction, physiochemical properties, and futuristic nanocarrier","authors":"Sonia Pandey , Shrikant Joshi , Purnima Tripathi , Arti Gupta , Jitendra Singh Yadav","doi":"10.1016/j.bbadis.2025.167956","DOIUrl":"10.1016/j.bbadis.2025.167956","url":null,"abstract":"<div><div>Targeting nanotechnology has emerged as a promising approach in drug delivery systems, offering enhanced therapeutic efficacy and reduced side effects. The physicochemical properties of nanocarriers largely influence the interaction of the nanocarrier within the body and its intended targets. Factors such as size, shape, surface charge, and elasticity play crucial roles in determining the nanocarrier's ability to navigate biological barriers, evade the immune system, and selectively accumulate at the target site. Recent advancements in nanotechnology have led to the development of newer nanocarriers with improved targeting capabilities. These innovative designs incorporate smart materials that respond to specific stimuli, such as pH changes or enzyme activity, allowing precise control over drug release. The understanding and optimization of these physicochemical properties are essential for designing more effective and efficient targeted drug delivery systems, potentially revolutionizing the treatment of various diseases, particularly in cancer therapy. Additionally, surface modifications with ligands further enhance the specificity of nanocarrier-target interactions. The intersection of protein corona, tumor microenvironment, biological barriers, and nanoparticles' physicochemical properties offers several challenges in cancer-targeted treatment. Moreover, we discussed the current situation and remaining challenges of various targeting methods with receptors, nanocarrier systems targeting carcinoma, which could facilitate the advancement of targeted nanodrug delivery systems in the future. This review synthesizes advances in nanocarriers design from 2015 to 2025, focusing on cancer-specific targeting, offering a thorough analysis of all critical parameters that need to be meticulously studied to select the most suitable nanocarrier approaches for successful clinical translation.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167956"},"PeriodicalIF":4.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144331415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nuclear receptor coactivator 4 linked to follicular dysplasia in polycystic ovary syndrome: A key regulator that aggravates ovarian granulosa cells ferritinophagy and ferroptosis 核受体共激活因子4与多囊卵巢综合征卵泡发育不良相关：一个加重卵巢颗粒细胞铁蛋白吞噬和铁凋亡的关键调节因子

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-17 DOI: 10.1016/j.bbadis.2025.167955

Dejian Chen , Yu Wang , Xiaomin Wang , Xiaosa Si , Yajing Weng , Shengbing Liu , Weiwei Pan , Ying Xu , Yong Wang , Yaling Zhang

{"title":"Nuclear receptor coactivator 4 linked to follicular dysplasia in polycystic ovary syndrome: A key regulator that aggravates ovarian granulosa cells ferritinophagy and ferroptosis","authors":"Dejian Chen , Yu Wang , Xiaomin Wang , Xiaosa Si , Yajing Weng , Shengbing Liu , Weiwei Pan , Ying Xu , Yong Wang , Yaling Zhang","doi":"10.1016/j.bbadis.2025.167955","DOIUrl":"10.1016/j.bbadis.2025.167955","url":null,"abstract":"<div><div>Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and excessive production of reactive oxygen species (ROS). Hyperandrogen exposure can induce ovarian ferroptosis in polycystic ovary syndrome (PCOS). However, there is not enough direct evidence regarding ovarian ferroptosis in PCOS to prove the role of ferroptosis in PCOS and the underlying mechanism. Nuclear receptor coactivator 4 (NCOA4) expression in ovarian granulosa cells and its mechanism of mediating ferroptosis have not been studied. In this study, we aimed to investigate how iron overload in ovarian granulosa cells and hyperandrogen exposure-induced ferroptosis affect ovarian development in a PCOS model. Increased ferroptosis was observed in hyperandrogenic mice with PCOS and in 5α-dihydrotestosterone (DHT)-induced primary granulosa cells. Iron deposition increased significantly, followed by increased cellular Fe<sup>2+</sup> concentration, whereas ROS accumulation, malondialdehyde (MDA), glutathione (GSH), and the glutathione/oxidized glutathione (GSH/GSSG) ratio decreased. NCOA4 and transferrin receptor expression increased; however, ferritin heavy chain 1 expression decreased in ovarian tissues. Androgen receptor and NCOA4 showed increased colocalization in the ovarian granulosa cell layer. Notably, DHT induced ferroptosis by activating NOCA4-dependent ferritin autophagy. However, deferoxamine mesylate inhibited ferroptosis in the ovarian granulosa mice cells, ameliorating the PCOS phenotype. Steroid hormone biosynthesis, arachidonic acid metabolism, and unsaturated fatty acid pathways were most significantly affected, providing a reference for PCOS diagnosis and treatment and corresponding drug development.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167955"},"PeriodicalIF":4.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Indole-3 propionate inhibits NF-κB/NLRP3-mediated osteoclastogenesis and improves bone quality in high-fat-diet induced obese mice 吲哚-3丙酸抑制NF-κB/ nlrp3介导的破骨细胞生成，改善高脂饮食诱导的肥胖小鼠骨质量。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-16 DOI: 10.1016/j.bbadis.2025.167952

Runze Wu , Yinghong Kong , Jianfeng Li , Hao Chen , Yujie Jiao , Cheng Sun , Yuejun Ju

{"title":"Indole-3 propionate inhibits NF-κB/NLRP3-mediated osteoclastogenesis and improves bone quality in high-fat-diet induced obese mice","authors":"Runze Wu , Yinghong Kong , Jianfeng Li , Hao Chen , Yujie Jiao , Cheng Sun , Yuejun Ju","doi":"10.1016/j.bbadis.2025.167952","DOIUrl":"10.1016/j.bbadis.2025.167952","url":null,"abstract":"<div><h3>Objective</h3><div>Obesity is a global health issue that causes altered gut microbiota and a wide variety of diseases, such as osteoporosis. The association between altered gut microbiota metabolites and high-fat diet (HFD)-induced osteoporosis has not been thoroughly investigated. 3-Indolepropionic acid (IPA) is a gut microbiota metabolite that is deficient in obese mice. The purpose of this study is to examine wheter IPA affects osteoporosis in HFD-induced obese mice.</div></div><div><h3>Materials and methods</h3><div>Mice were fed with HFD for 12 weeks, during which IPA or vancomycin was administered. Micro-computed tomography, hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining were used to evaluate osteoporosis and osteoclast activation in vivo. Cultured bone marrow macrophages were used to examine osteoclast activation in vitro. Western blot, immunohistochemical staining, and immunofluorescence staining were used to investigate the nuclear factor kappa B (NF-κB) and NLRP3 signaling pathways.</div></div><div><h3>Results</h3><div>Reduced bone mass and noticeable osteoclast activation were observed in mice fed with HFD and vancomycin. IPA supplementation alleviated systemic inflammatory response, inhibited osteoclast activation, and improved bone mass in mice. Mechanistically, IPA inhibited the phosphorylation of NF-κB, thus, reducing the expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and inhibiting osteoclast activation.</div></div><div><h3>Conclusion</h3><div>These findings suggest that IPA-induced inhibition of osteoclast activation in the HFD environment was mediated via the NF-κB/NLRP3 pathway. Our study suggests that IPA consumption may help manage obesity-induced osteoporosis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167952"},"PeriodicalIF":4.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The interplay between lipid droplets and Parkinson's disease 脂滴与帕金森病之间的相互作用。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-06-12 DOI: 10.1016/j.bbadis.2025.167953

Xin-ru Zhao , Ying-ying Gu , Jia-yi Wang , Ying Yi , Yan-qiu Zhang , Qian-hang Shao , Ming-xuan Liu , Xiao-ling Zhang

{"title":"The interplay between lipid droplets and Parkinson's disease","authors":"Xin-ru Zhao , Ying-ying Gu , Jia-yi Wang , Ying Yi , Yan-qiu Zhang , Qian-hang Shao , Ming-xuan Liu , Xiao-ling Zhang","doi":"10.1016/j.bbadis.2025.167953","DOIUrl":"10.1016/j.bbadis.2025.167953","url":null,"abstract":"<div><div>Lipid droplets (LDs), also known as lipid bodies, are dynamic intracellular organelles that are rich in lipids. They serve critical functions in metabolic regulation, membrane dynamics, and cellular signaling pathways. LD homeostasis plays a key role in neurotransmission, receptor activation, and neural development. Intracellular LD accumulation contributes to lipotoxicity and precedes neurodegeneration such as Parkinson's disease (PD). While recent studies have advanced our knowledge regarding how LD accumulation influences PD progression, several fundamental aspects of LD biology remain unclear. This review explores key mechanisms of LD buildup in PD pathogenesis. First, we discuss the formation and physiological roles of LD, followed by an analysis of how impaired LD generation contributes to PD development. Second, we analyze the causal relationship between LD formation and degradation. Lastly, we evaluate the therapeutic potential of LDs as diagnostic biomarkers and molecular targets for innovative neuroprotective and anti-inflammatory strategies. Thus, advancing the mechanistic understanding of LD biology can provide key insights into PD pathogenesis, facilitating the design of targeted therapies.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 7","pages":"Article 167953"},"PeriodicalIF":4.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0