International Journal of Biological Sciences最新文献_第7页

Updated review of research on the role of the gut microbiota and microbiota-derived metabolites in acute pancreatitis progression and inflammation-targeted therapy.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.108858

Qiang Liu, Kaiyi Ruan, Zihui An, Lingyun Li, Cong Ding, Dongchao Xu, Jianfeng Yang, Xiaofeng Zhang

{"title":"Updated review of research on the role of the gut microbiota and microbiota-derived metabolites in acute pancreatitis progression and inflammation-targeted therapy.","authors":"Qiang Liu, Kaiyi Ruan, Zihui An, Lingyun Li, Cong Ding, Dongchao Xu, Jianfeng Yang, Xiaofeng Zhang","doi":"10.7150/ijbs.108858","DOIUrl":"10.7150/ijbs.108858","url":null,"abstract":"Acute pancreatitis (AP) is characterized by autodigestion of the pancreas, and some patients may rapidly progress to systemic inflammation, pancreatic necrosis, and multi-organ failure. Numerous studies have detailed the bidirectional communication networks between the pancreas and the intestinal microbiota, as well as its metabolites. Such crosstalk affects the progression of AP and recovery through intestinal barrier disruption. Furthermore, advances in experimental research and clinical studies have indicated that gut microorganisms exhibit distinct alterations in response to different levels of severity and etiologies of AP. This information has greatly expanded our knowledge of the role of the gut microflora and microbial metabolites in the pathology of disease and has reinforced the basis of therapeutic approaches that target candidate intestinal microbiota. In this review, we aim to provide an overview of the composition and diversity of the gut microbial community, to highlight the candidate bacteria and microbiota-derived metabolites responsible for AP, and to elucidate their interactions with and regulation of immune-relevant receptors in intestinal epithelial cells (IECs) in the host. Future research should focus on identifying and characterizing AP-associated bacterial strains, elucidating their distinct pathogenic mechanisms across different etiologies and stages of AP, and leveraging these insights to develop preventive and therapeutic strategies.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1242-1258"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.107021

Yuzhu Xu, Xuanfei Xu, Renjie Chai, Xiaotao Wu

{"title":"Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.","authors":"Yuzhu Xu, Xuanfei Xu, Renjie Chai, Xiaotao Wu","doi":"10.7150/ijbs.107021","DOIUrl":"10.7150/ijbs.107021","url":null,"abstract":"Although mesenchymal stromal cell (MSC) implantation shows promise for repairing intervertebral disc (IVD) degeneration (IVDD), their limited retention within degenerative IVDs compromises therapeutic efficacy. The oxidative stress in the microenvironment of degenerated IVDs induces a surge in reactive oxygen species production within MSCs, disrupting the balance between oxidation and antioxidation, and ultimately inducing ferroptosis. Recent evidence has suggested that targeting ferroptosis in MSCs could enhance MSC retention, extend the survival of transplanted MSCs, and markedly delay the pathological progression of IVDD. By targeting ferroptosis, a novel approach emerges to boost the efficacy of MSC transplantation therapy for IVDD. In this review, current research on targeting ferroptosis in MSCs is discussed from various perspectives, including the targeting of specific genes and pathways, drug preconditioning, and hydrogel encapsulation. A detailed discussion on the effects of targeting ferroptosis in MSCs on the transplantation repair of degenerated IVDs is provided. Insights that could guide improvements in stem cell transplantation therapies are also offered. Significantly, this review presents specific ideas for our future foundational research. These insights outline promising avenues for future clinical translation and will contribute to developing and optimizing treatment strategies for MSC transplantation therapy, maximizing benefits for patients with lumbar IVDD.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1222-1241"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SERINC2-mediated serine metabolism promotes cervical cancer progression and drives T cell exhaustion.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105572

Yixuan Sun, Yang Zhou, Qihua Peng, Wanzhen Zhou, Xiao Li, Ruiwen Wang, Yifan Yin, Huixian Huang, Hongfei Yao, Qing Li, Xueli Zhang, Lipeng Hu, Shuheng Jiang, Zhigang Zhang, Dongxue Li, Xiaolu Zhu, Yincheng Teng

{"title":"SERINC2-mediated serine metabolism promotes cervical cancer progression and drives T cell exhaustion.","authors":"Yixuan Sun, Yang Zhou, Qihua Peng, Wanzhen Zhou, Xiao Li, Ruiwen Wang, Yifan Yin, Huixian Huang, Hongfei Yao, Qing Li, Xueli Zhang, Lipeng Hu, Shuheng Jiang, Zhigang Zhang, Dongxue Li, Xiaolu Zhu, Yincheng Teng","doi":"10.7150/ijbs.105572","DOIUrl":"10.7150/ijbs.105572","url":null,"abstract":"Cervical cancer remains the most prevalent gynecological malignant disease. Reprogramming tumor immune metabolism stands out as a novel promising therapeutic target. Here, we identified serine incorporator 2 (SERINC2) as a critical gene which highly expressed in cervical cancer and negatively correlated with clinical outcomes. Through functional assays, SERINC2 was determined to play a pro-tumoral role both in vivo and in vitro. Besides, the growth of cervical cancer cells was found to be largely dependent on serine in a manner influenced by SERINC2. As a serine transport associated protein, SERINC2 knockdown significantly reduced cervical cancer cells' intracellular serine level and altered the serine-associated-lipid metabolism. Immune infiltration analysis revealed that SERINC2 was negatively associated with CD8+ T cell infiltration and function. More importantly, we demonstrated a competitive relation between cancer cells and immune cells brought about by SERINC2. Mechanistically, cancer cells SERINC2 preferentially competed for micro-environmental serine over CD8+ T cells and rendered T cell exhaustion. Overall, SERINC2 remodels cancer development and serine metabolism in the tumor immune microenvironment (TIME), establishing an immunosuppressive and pro-tumoral milieu.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1361-1377"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105973

Wei Ouyang, Ziyao Xu, Shaoyu Guan, Yang Hu, Xiaoxue Gou, Zhe Liu, Wei Guo, Ye Huang, Lifen Zhang, Xingmei Zhang, Tian Li, Bin Yang

{"title":"Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer.","authors":"Wei Ouyang, Ziyao Xu, Shaoyu Guan, Yang Hu, Xiaoxue Gou, Zhe Liu, Wei Guo, Ye Huang, Lifen Zhang, Xingmei Zhang, Tian Li, Bin Yang","doi":"10.7150/ijbs.105973","DOIUrl":"10.7150/ijbs.105973","url":null,"abstract":"Small cell lung cancer (SCLC) is an intractable disease with rapid progression and high mortality, presenting a persistent obstacle impeding clinical management. Although recent advancements in immunotherapy have enhanced the response rates of platinum-based chemotherapy regimens, the emergence of acquired resistance invariably leads to recurrence and metastasis. Consequently, there is an urgent necessity to explore novel therapeutic targets and optimize existing treatment strategies. This article comprehensively reviews the currently available therapeutic modalities for SCLC. It delves into the immunologic prognostic implications by analyzing selected immune-related signatures. Moreover, it conducts an in-depth exploration of the molecular subtyping of SCLC and the associated molecular pathways to identify potential therapeutic targets. Specifically, the focus is on clinical interventions targeting delta-like ligand 3 (DLL3), elucidating its resistance mechanisms and demonstrating its notable antitumor efficacy. Furthermore, the study examines the mechanisms of chimeric antigen receptor (CAR) T and antibody-drug conjugate (ADC), covering resistance issues and strategies for optimizing resistance management, with particular emphasis being placed on analyzing the prospects and clinical value of CAR T therapy in the context of SCLC. Moreover, the effectiveness of poly ADP-ribose polymerase and ataxia telangiectasia and rad3/checkpoint kinase 1 inhibitors is discussed and underscores the advantages of combining these inhibitors with standard chemotherapy to combat chemoresistance and enhance the antitumor effects of immunotherapies. Overall, this study investigates emerging strategies for targeted therapies and optimized combination regimens to overcome resistance in SCLC and highlights future strategies for new therapeutic technologies for SCLC.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1322-1341"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-20 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.102251

Ying Li, Wen-Jing Li, Jia-Min Du, Hui-Hui Wu, Si-Yuan Zhou, Min Li, Yue-Yan Li, Shu-Ya Wang, Hui-Yun Wang, Yan Zheng, Qun-Ye Zhang, Li-Ming Li, Fan-Liang Meng, Guo-Hai Su

{"title":"Downregulation of PGAM2 alleviates angiotensin II-induced cardiac hypertrophy by destabilizing HSP90 and inactivating the mTOR/IKKα signaling pathway.","authors":"Ying Li, Wen-Jing Li, Jia-Min Du, Hui-Hui Wu, Si-Yuan Zhou, Min Li, Yue-Yan Li, Shu-Ya Wang, Hui-Yun Wang, Yan Zheng, Qun-Ye Zhang, Li-Ming Li, Fan-Liang Meng, Guo-Hai Su","doi":"10.7150/ijbs.102251","DOIUrl":"10.7150/ijbs.102251","url":null,"abstract":"Pathological cardiac hypertrophy is a major contributor to heart failure. The present study aims to elucidate the role and mechanisms of phosphoglycerate mutase 2 (PGAM2) in the pathogenesis of cardiac hypertrophy. PGAM2 expression was increased in both primary neonatal rat ventricular myocytes (NRVMs) and rat models in response to angiotensin II (Ang II). Downregulation of PGAM2 alleviated cardiac hypertrophy. Mechanistically, we found PGAM2 directly interacts with HSP90 through residues 319-323 and 622-629 in the middle and carboxy-terminal domain of HSP90 respectively. This interaction was further enhanced under Ang II stimulation. Additionally, in the presence of PGAM2, it competed with E3 ubiquitin ligase SYVN1 to interact with HSP90, effectively inhibiting the ubiquitination and degradation of HSP90. Therefore, deficiency of PGAM2 results in the downregulation of the HSP90 and its downstream mTOR and client protein IKKα signaling pathway, both of which play crucial roles in the progression of cardiac hypertrophy. In vivo, we further confirmed that PGAM2 knockdown alleviated cardiac hypertrophy through downregulation of HSP90 and mTOR/IKKα signaling pathway. Taken together, we first demonstrated that downregulation of PGAM2 alleviates cardiac hypertrophy induced by Ang II, which provides a novel target for the treatment of myocardial hypertrophy and heart failure.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1308-1321"},"PeriodicalIF":8.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor-associated macrophages drive heterogenetic CD10^High cancer stem cells to implement tumor-associated neutrophils reprogramming in oral squamous cell carcinoma.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.100611

Yuanhe You, Zhong Du, Zhuowei Tian, Shunshun Li, Fan Yu, Meng Xiao, Yue He, Yanan Wang

{"title":"Tumor-associated macrophages drive heterogenetic CD10High cancer stem cells to implement tumor-associated neutrophils reprogramming in oral squamous cell carcinoma.","authors":"Yuanhe You, Zhong Du, Zhuowei Tian, Shunshun Li, Fan Yu, Meng Xiao, Yue He, Yanan Wang","doi":"10.7150/ijbs.100611","DOIUrl":"10.7150/ijbs.100611","url":null,"abstract":"Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) widely participate in the malignant progression in cancer. Previously, we have demonstrated that M1-like TAMs cascaded a stem-like phenotype of oral squamous cell carcinoma (OSCC). Yet, the underlying mechanisms still need to be demonstrated for the regulation of TAMs on cancer stem cells (CSCs) in OSCC. In this study, we investigated a group of CSCs with increased expression of cluster differentiation 10 (CD10), which acted as a mediator in the interaction network between TAMs and tumor-associated neutrophils (TANs) in OSCC. The results showed a significant association between TAMs infiltrations and increased expression of CD10 among all the CSCs-related molecules in OSCC. Then, we validated that OSCC cells with high CD10 expression possessed increased CSCs characteristics. TAMs could drive the heterogenetic CD10High CSCs by activating the IL6/STAT3/CD10 pathway. Furthermore, CD10High CSCs could recruit and reprogram tumor-associated neutrophils (TANs) in an immunosuppressive state by secreting S100A8/A9 in OSCC. These finding indicated that CD10High CSCs played great roles in signaling crosstalk between TAMs and TANs in OSCC, by which infiltrated TAMs drive CD 10High CSCs to recruit and reprogram TANs in an immunosuppressive state. Herein, we managed to demonstrate that TAMs could directly regulate a heterogenetic cluster of CSCs with high CD10 expression, and CD10High CSCs could recruit and reprogram TANs in OSCC. The novel crosstalk among OSCC-TAMs-CD10High CSCs-TANs might bring new prospects for improving the treatment strategies for OSCC patients.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1110-1126"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Revisiting of Cancer Immunotherapy: Insight from the Dialogue between Glycolysis and PD-1/PD-L1 Axis in the Tumor Microenvironment.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104079

Qiong Liu, Zihan Liu, Xi Zhang, Anqi Zeng, Linjiang Song

{"title":"Revisiting of Cancer Immunotherapy: Insight from the Dialogue between Glycolysis and PD-1/PD-L1 Axis in the Tumor Microenvironment.","authors":"Qiong Liu, Zihan Liu, Xi Zhang, Anqi Zeng, Linjiang Song","doi":"10.7150/ijbs.104079","DOIUrl":"10.7150/ijbs.104079","url":null,"abstract":"The interplay between metabolic pathways and immune escape has emerged as a captivating research area in oncobiology. Among these, the Warburg effect stands out as a hallmark metabolic reprogramming in cancer, characterized by elevated glucose utilization and excessive lactic acid production through anaerobic glycolysis. Key glycolytic enzymes not only fulfill the bioenergetic demands of cancer cells but also exhibit moonlighting roles, including regulation of epigenetic modifications, protein kinase activity, and immune escape mechanisms, thereby reshaping the tumor microenvironment. Tumor-specific vascular architecture facilitates lactate accumulation, which drives tumor progression by impairing immune cell function and acting as a signaling molecule to recruit immunosuppressive cells and modulate immune checkpoint pathways. The PD-1/PD-L1 co-stimulatory pathway plays a crucial role in negatively modulating the activation, proliferation, and cytokine secretion by T-lymphocytes. This review primarily focuses on elucidating the regulation and mechanisms underlying PD-1/PD-L1 signaling axis during glycolysis in tumor cells as well as surrounding cells. In the era of precision medicine, there is a particular interest in leveraging 18F-FDG PET/CT imaging as a valuable tool to assess PD-L1 expression status for more targeted therapeutic interventions. Additionally, the development of natural compounds capable of modulating metabolism opens new avenues for metabolism-based immunotherapy, though further studies are required to validate their in vivo efficacy.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1202-1221"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ugonin inhibits chondrosarcoma metastasis through suppressing cathepsin V via promoting miR-4799-5p expression.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.106827

Nguyen Bao Tran, Ting-Kuo Chang, Nguyen Duong Phuong Chi, Kuan-Ying Lai, Hsien-Te Chen, Yi-Chin Fong, Chih-Chuang Liaw, Chih-Hsin Tang

{"title":"Ugonin inhibits chondrosarcoma metastasis through suppressing cathepsin V via promoting miR-4799-5p expression.","authors":"Nguyen Bao Tran, Ting-Kuo Chang, Nguyen Duong Phuong Chi, Kuan-Ying Lai, Hsien-Te Chen, Yi-Chin Fong, Chih-Chuang Liaw, Chih-Hsin Tang","doi":"10.7150/ijbs.106827","DOIUrl":"10.7150/ijbs.106827","url":null,"abstract":"Chondrosarcoma is a rare type of bone cancer that develops in cartilage cells. In recent years, the incidence of chondrosarcomas has steadily increased worldwide. During the advanced stages, chondrosarcoma carries a significant risk of metastasis and exhibits resistance to both chemotherapy and radiation therapy. Hence, the development of potent treatments for chondrosarcoma is an urgent requirement. Ugonin V is a flavonoid compound that has been extracted from the plant Helminthostachys zeylanica (L.) Hook. This study examined the molecular therapeutic effects of ugonin V on chondrosarcoma metastasis. Analysis of the GSE30835 dataset, which consists of chondrosarcoma tissues and normal cartilage, revealed significant upregulation of three cathepsin proteases in chondrosarcoma, namely cathepsin (CTS) A, L, and V. Notably, ugonin V specifically suppressed cathepsin V mRNA expression. We also found that ugonin V strongly inhibits chondrosarcoma cell motility by regulating CTSV expression. In addition, through miRNA sequencing, we observed that ugonin V targets CTSV via miR-4799-5p to effectively suppress chondrosarcoma cell migration and invasion. Our in vitro and in vivo studies provide an initial investigation of the involvement of cathepsin V and miR-4799-5p in chondrosarcoma metastasis after ugonin V treatmen.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1144-1157"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tetramethylpyrazine attenuates sodium arsenite-induced acute kidney injury by improving the autophagic flux blockade via a YAP1-Nrf2-p62-dependent mechanism.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.104107

Zhiyong Song, Tom K Hei, Xuezhong Gong

{"title":"Tetramethylpyrazine attenuates sodium arsenite-induced acute kidney injury by improving the autophagic flux blockade via a YAP1-Nrf2-p62-dependent mechanism.","authors":"Zhiyong Song, Tom K Hei, Xuezhong Gong","doi":"10.7150/ijbs.104107","DOIUrl":"10.7150/ijbs.104107","url":null,"abstract":"With increased application, sodium arsenite (AS III)-induced acute kidney injury (AI-AKI) is becoming a new clinical challenge, but its potential pathogenesis remains poorly studied. Our previous data demonstrated that inducing autophagy and mitochondrial dysfunction in renal tubular cells are important links of AI-AKI and could be inhibited by tetramethylpyrazine (TMP). Recently, co-transcription factor YAP1 is reported to control autophagy and is mandatory to stimulate autophagic flux. This study constructed in vitro and in vivo models using clinically related dosages of AS III. Mitophagy, upregulated YAP1 expression, and Nrf2 activation were observed, with upregulation of p62 representing the occurrence of autophagic flux blockade. In HK-2 cells, oxidative stress induced by AS III promoted sustained Nrf2 activation, which enhanced p62 transcription at an early phase. Subsequently, p62 accumulation induced Nrf2 nuclear translocation, which in turn promoted p62 expression, forming a feedback loop to induce autophagic flux blockade, which was aggravated by the autophagic flux blocker chloroquine (CQ). TMP reversed such processes and protected tubular cells, while silencing YAP1 and Nrf2 attenuated TMP renoprotections. YAP1 agonist PY-60 increased Nrf2 expression, while YAP1 knockdown counteracted it and diminished TMP effect on autophagic flux. Furthermore, blocking Nrf2 caused YAP1 accumulation. CO-IP and immunofluorescence co-localization results confirmed co-nuclear translocations of YAP1 bound to dissociated Nrf2 that induced autophagic flux blockade. In conclusion, the present study identified novel mechanisms that TMP alleviated AI-AKI by improving the autophagic flux blockade via a YAP1-Nrf2-p62-dependent mechanism.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1158-1173"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer's Disease.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.103028

Yeji Kim, Tae-Young Ha, Myung-Shik Lee, Keun-A Chang

{"title":"Regulatory Mechanisms and Therapeutic Implications of Lysosomal Dysfunction in Alzheimer's Disease.","authors":"Yeji Kim, Tae-Young Ha, Myung-Shik Lee, Keun-A Chang","doi":"10.7150/ijbs.103028","DOIUrl":"10.7150/ijbs.103028","url":null,"abstract":"Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs) formed from hyperphosphorylated Tau, and widespread neuronal loss. The autophagy-lysosomal pathway plays a crucial role in maintaining cellular homeostasis by degrading and recycling of damaged organelles and aggregate amyloid proteins implicated in AD. Lysosomes are key effectors of autophagic process, responsible for the breakdown of a variety of damaged organelles and aggregate or dysfunctional proteins. This review examines the role of lysosomal dysfunction in AD pathophysiology, focusing on genetic factors, acidification abnormalities, and other contributing factors. We also explore the involvement of lysosomal dysfunction of microglia in AD pathology, and cover the role of lysosomal stress response (LSR) in cellular response to neuronal injury associated with AD. Furthermore, we discuss potential therapeutic strategies targeting lysosomal proteolysis pathway and addressing lysosomal dysfunction for AD treatment, including the pharmacologically activating lysosomal activity, regulating TFEB, and considering other emerging approaches.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 3","pages":"1014-1031"},"PeriodicalIF":8.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0