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

{"title":"Exploring the cognitive impacts of diabetic neuropathy: a comprehensive review","authors":"Maamoon Mian ,&nbsp;Farhood Salehi ,&nbsp;Rishi Patel ,&nbsp;Jihane Tahiri ,&nbsp;Adam Bel-Hadj-Kacem ,&nbsp;Ali Alhaque ,&nbsp;Ryan Eldin ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.bbadis.2025.167892","DOIUrl":"10.1016/j.bbadis.2025.167892","url":null,"abstract":"<div><div>Diabetic neuropathy (DPN) is known to affect various aspects of health, including cognitive function. This study explores how DPN influences cognitive performance and examines the interplay between DPN, gender differences, Alzheimer's Disease (AD), and the socioeconomic burden of neuropathic pain. The research involved a comprehensive review and analysis of 55 studies focusing on cognitive function in diabetic patients with and without DPN. Various cognitive assessments, including memory, processing speed, and olfactory function, were used to evaluate cognitive performance. Gender differences were analyzed in the context of cognitive impairment and neuropathic pain. Additionally, the relationship between peripheral neuropathy and AD was investigated through measures of nerve conduction velocities and amyloid protein deposits. The impact of physical and psychological factors on neuropathic pain and cognitive function was also examined. The findings indicate that diabetic patients with DPN exhibit more severe cognitive impairments compared to those without DPN and healthy controls. Cognitive deficits were particularly notable in memory and processing speed. Gender differences revealed that women with DPN experience more pronounced cognitive dysfunction and a higher incidence of painful neuropathy compared to men. Analysis of peripheral nerve conduction velocities and amyloid deposits suggested a link between neuropathy and AD. Furthermore, poor glycemic control emerged as a critical factor affecting both neuropathy and cognitive function. Psychological distress and socioeconomic factors were found to significantly influence the management and outcomes of neuropathic pain. The study underscores the complex interaction between DPN and cognitive impairment, highlighting the importance of integrated diagnostic and therapeutic approaches. The pronounced cognitive deficits in women and the link between DPN and AD emphasize the need for gender-specific and multifaceted treatment strategies. The socioeconomic impact of neuropathic pain and the role of psychological factors in exacerbating pain and cognitive decline suggest that comprehensive management plans should address both physical and mental health aspects to improve overall patient outcomes.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167892"},"PeriodicalIF":4.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906163","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}

{"title":"Generation and characterization of a chronic in vitro model to study the early stage of metabolic dysfunction-associated steatotic liver disease (MASLD)","authors":"Vandana Singh ,&nbsp;Partha Chattopadhyay ,&nbsp;Fabeha Fatima ,&nbsp;Praveen Singh ,&nbsp;Rajesh Pandey ,&nbsp;Anurag Agrawal ,&nbsp;Soumya Sinha Roy","doi":"10.1016/j.bbadis.2025.167886","DOIUrl":"10.1016/j.bbadis.2025.167886","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic and progressive liver disease with an increasing global burden that starts with an early stage of simple steatosis (MASL) which frequently progresses to liver cirrhosis and hepatocellular carcinoma (HCC). Despite its widespread occurrence, the MASL or steatotic stage, characterized by excessive fat accumulation in the liver and considered reversible and benign, has not been extensively studied. To study MASL effectively, it is imperative to have a clinically relevant model system that focuses solely on steatosis, in a progressive and time-dependent manner, recapitulating molecular changes associated with human disease. We established a chronic cellular model of MASL using a primary immortalized human hepatocyte cell line treated with a low dose mixture of fatty acids. This model mimics the pattern of chronic disease progression, shows minimal lipotoxicity, exhibits progressive lipid accumulation (from early to moderate steatosis), and demonstrates macrosteatosis, a hallmark of MASL. To determine whether this model recapitulates both morphological and molecular aspects of steatosis, we measured the expression of key genes and pathways found to be dysregulated in a recently available early MASL patient dataset as well as a non-human primate model of MASL. In support of the relevance of our model, we observed increased fatty acid uptake, lipogenesis, mitochondrial activity, metabolic rewiring, and autophagic alterations that significantly overlap with the pathological features of human and non-human primate MASL. In conclusion, we generate a relevant cellular model of steatosis that can serve as a robust platform for screening of existing chemical libraries to identify potent inhibitors of MASL as well as discovering novel therapeutic targets by mechanistically studying altered molecular signatures associating early stages of MASLD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167886"},"PeriodicalIF":4.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916522","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}

{"title":"Targeting enhanced mitochondrial respiration chain activity as a potential therapeutic approach for endometriosis","authors":"Katarína Kalinová ,&nbsp;Benjamin Gottschalk ,&nbsp;Martin Hirtl ,&nbsp;Julian Ostaku ,&nbsp;Sonja Gabrijelčič ,&nbsp;Alwin Sokolowski ,&nbsp;Ernst Malle ,&nbsp;Wolfgang F. Graier ,&nbsp;Corina T. Madreiter-Sokolowski","doi":"10.1016/j.bbadis.2025.167885","DOIUrl":"10.1016/j.bbadis.2025.167885","url":null,"abstract":"<div><div>Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside the uterus. Since endometriotic cells share similarities with cancer cells, including uncontrolled cell growth and invasion, we investigated whether cancer cell-specific rewiring of mitochondrial signaling is also present in endometriotic cells.</div><div>We utilized the endometriotic cell line 12Z and investigated its mitochondrial function in comparison with the uterine cancer cell line SK-UT-1 and the mammary epithelial cell line hTERT-HME1. We could show that the endometriotic 12Z cells share structural similarities with cancerous SK-UT-1 cells with enhanced colocalization between the endoplasmic reticulum and mitochondria and increased cristae width and density associated with facilitated mitochondrial Ca²⁺ uptake. However, an increase in the reduction equivalent yield and oxygen consumption rate was exclusively found in 12Z cells, whereas the reduced ΔΨ_m and the reverse mode of F_OF₁-ATP synthase were also detected in SK-UT-1 cells. These features rendered both cell types susceptible to quercetin and oligomycin A treatment.</div><div>We assume that the complexes of the electron transport chain and the F_OF₁-ATP synthase in reverse mode have a crucial role in maintaining mitochondrial membrane potential and, thereby, mitochondrial integrity of endometriotic 12Z cells. Therefore, targeting the electron transport chain or the reverse mode of F_OF₁-ATP synthase may represent a promising new treatment strategy for endometriosis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167885"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912161","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}

{"title":"Galangin protects against acute pancreatitis by inhibiting ROS-induced acinar cell apoptosis and M1-type macrophage polarization","authors":"Xuyang Hou ,&nbsp;Cong Wang ,&nbsp;Chao Chen ,&nbsp;He Liu ,&nbsp;Lei Wang ,&nbsp;Yong Yi ,&nbsp;Shihe Jiang ,&nbsp;Xiaoyan Qi ,&nbsp;Zuxing Wei ,&nbsp;Yimiao Cheng ,&nbsp;Qunwang Pu","doi":"10.1016/j.bbadis.2025.167887","DOIUrl":"10.1016/j.bbadis.2025.167887","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is a common disease in the digestive tract and is characterized by elevated serum pancreatic proteases and abdominal pain. AP, especially severe AP, is still a deadly disease; thus, identifying potential therapies and exploring the underlying mechanism are essential for AP patients. Galangin, a flavonoid extracted from traditional medicinal herbs, shows robust anti-inflammatory and cell protection abilities in various diseases, but its role in AP has not been unveiled. We explored the function and mechanism of galangin in AP using caerulein-induced mouse, isolated acinar cell and bone marrow-derived macrophage models. The pancreas was analyzed using histology and immunofluorescent staining; cytokine levels, the activity of amylase and lipase, and reactive oxygen species (ROS) levels were determined; infiltrating macrophages were analyzed by flow cytometry; certain proteins and RNAs were analyzed; and the safety of galangin was also evaluated. We found that galangin significantly attenuated AP in mice and acinar cells by decreasing ROS and apoptosis via the promotion of Srxn1 expression through an NRF2-dependent pathway. Galangin significantly reduced the number of infiltrating macrophages and inhibited the activation of M1-type macrophages by negatively regulating NF-κB signaling. Compared to the control, no obvious side effects were observed in the galangin-treated group. Thus, our study demonstrated that galangin is a safe and efficient drug to treat AP by preventing injury to acinar cells and inhibiting M1-type macrophages, suggesting a potential therapy for AP in the future.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167887"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043476","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}

{"title":"The role of FLVCR1 and FLVCR2 in choline transport in the Caco-2 intestinal epithelial cell model and rat small intestine","authors":"Tomoya Yasujima ,&nbsp;Chitaka Namba ,&nbsp;Yosuke Azuma ,&nbsp;Yutaro Shinoda ,&nbsp;Isamu Matake ,&nbsp;Mione Yamasaki ,&nbsp;Haruka Morimoto ,&nbsp;Mana Namai ,&nbsp;Hiroyuki Kusuhara ,&nbsp;Katsuhisa Inoue ,&nbsp;Takahiro Yamashiro ,&nbsp;Hiroaki Yuasa","doi":"10.1016/j.bbadis.2025.167883","DOIUrl":"10.1016/j.bbadis.2025.167883","url":null,"abstract":"<div><div>Choline is a vital cationic nutrient for maintaining organismal homeostasis, partially synthesized in the liver but primarily obtained from dietary sources. While previous studies have explored mechanisms of choline absorption in intestinal cells, the precise roles of specific transporters remain to be fully elucidated. This study aimed to investigate the roles of the choline transporters feline leukemia virus subgroup C receptor 1 (FLVCR1) and FLVCR2. Using MDCKII cells expressing human FLVCR1 or FLVCR2, the study revealed that FLVCR1 facilitates choline efflux from the basolateral membrane, while FLVCR2 enables choline uptake through the apical membrane. Functional analyses of FLVCR1 and FLVCR2 variants identified mutations that significantly reduce choline uptake activity. Knockdown experiments in Caco-2 cells resulted in significantly reduced cellular uptake of choline. Functional analysis of choline transport in the everted tissue sacs of the rat small intestine suggested that Flvcr2 aids intestinal choline uptake. Conclusively, the findings of this study indicate that FLVCR1 and FLVCR2 work cumulatively to regulate intestinal choline absorption. These findings provide novel insights into the roles of FLVCR1 and FLVCR2 and offer bases for further research into choline transport mechanisms in the small intestine.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167883"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929400","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}

{"title":"Oncogenic HNF4α inhibits ferroptotic cell death through activating SLC7A11 by recruiting p300/CBP in breast cancer","authors":"Zhuang Wang ,&nbsp;Sen Xu ,&nbsp;Jinxia Hu ,&nbsp;Hongfang Sun ,&nbsp;Yuan Yu ,&nbsp;Shuling Song ,&nbsp;Shuyang Xie ,&nbsp;Guangbin Sun","doi":"10.1016/j.bbadis.2025.167884","DOIUrl":"10.1016/j.bbadis.2025.167884","url":null,"abstract":"<div><div>As an iron-dependent novel form of cell death caused by the accumulation of lipid peroxides, ferroptosis has been gradually recognized as a new cancer therapeutic target in recent years. Although the precise mechanisms underlying iron-induced cell death remain incompletely elucidated, this study identifies its distinctive role. A decrease in hepatocyte nuclear factor 4-alpha (HNF4α) activity could increase ferroptosis in breast cancer (BC) cells both in vitro and in vivo. Mechanistically, it was found that HNF4α binds directly to the promoter of SLC7A11, where it recruits the histone acetyltransferase p300/CBP to promote transcription of SLC7A11. Our study shows that HNF4α is crucial for ferroptosis in breast cancer, which may open up the possibility of developing a new therapeutic approach for advanced cancers resistant to chemotherapy.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167884"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901989","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}

{"title":"Integrated transcriptomics profile reveals the role of Gal-1 and miR-21 in intrahepatic cholangiocarcinoma progression","authors":"Huasong Yu ,&nbsp;Huahong Duan ,&nbsp;Ruiqi He ,&nbsp;Yu Tian ,&nbsp;Jiayang Jiang ,&nbsp;Fen Xiao ,&nbsp;Qiao Liu ,&nbsp;Jie Liu ,&nbsp;Hao Li ,&nbsp;Xing Yu","doi":"10.1016/j.bbadis.2025.167882","DOIUrl":"10.1016/j.bbadis.2025.167882","url":null,"abstract":"<div><div>Intrahepatic cholangiocarcinoma (ICC) is a highly invasive liver tumor with a poor prognosis, arises from the intrahepatic bile ducts. It is the second most common type of liver cancer. Understanding the mechanisms driving ICC progression is crucial for identification of biomarkers and therapeutic targets. Galectin-1 (Gal-1), encoded by the LGALS1 gene, is known to be upregulated in various malignancies and plays a significant role in cancer progression. However, its underlying mechanisms in ICC have yet to be fully elucidated. The study employed RNA-seq analysis, western blot, cell migration, colony forming, EdU assay, qRT-PCR, luciferase assay and mIHC to investigate the expression pattern of Gal-1 in ICC and its role in the progression of the disease. Our findings revealed a significant upregulation of Gal-1 in ICC tissues. Notably, downregulation of Gal-1inhibited ICC cell proliferation and migration. Further, Gal-1 appears to promote ICC progression through miR-21/STAT3-related pathways, playing a critical role to the tumor microenvironment. These results suggest that Gal-1 may serve as a promising molecular diagnostic marker and therapeutic target for ICC.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167882"},"PeriodicalIF":4.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899155","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}

{"title":"Endosialin-directed CAR-T cell therapy: A promising approach for targeting triple-negative breast cancer","authors":"Adil Farooq Wali ,&nbsp;Sirajunisa Talath ,&nbsp;Sathvik B. Sridhar ,&nbsp;Mohamed El-Tanani ,&nbsp;Imran Rashid Rangraze","doi":"10.1016/j.bbadis.2025.167852","DOIUrl":"10.1016/j.bbadis.2025.167852","url":null,"abstract":"<div><div>In triple-negative breast cancer, this review article explores into the utilization of Chimeric antigen receptor T-cell (CAR-T) cell therapy to target cells expressing endosialin. Even with all the new treatments available, breast cancer still kills more women than any other disease. Drug resistance and ineffective cancer cell targeting are two major problems with targeted medications, chemotherapy, and surgery. Among cancer treatments, CAR-T cell therapy stands out. To identify endosialin as a therapeutic target, it is essential to understand its molecular structure and its involvement in tumor angiogenesis and progression. An effective target for CAR-T cells is breast cancer, which overexpresses endosialin. The development of CARs that are specific to endosialin and the results of early trials are covered in relation to CAR-T cell therapy that targets endosialin. Perhaps the most effective cancer treatment is endosialin targeting, since it is expressed only in tumors and plays a crucial role in the course of cancer. This article reviews endosialin-directed CAR-T cell breast cancer treatments' safety and efficacy from current and completed clinical trials. Despite promising results, these trials reveal that clinical translation must overcome significant challenges. The report suggests further research and combination tactics to improve endosialin-targeted CAR-T cell treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167852"},"PeriodicalIF":4.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929491","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}

{"title":"Quercetin induces keratinocytes apoptosis via triple inhibition of Notch, PI3K/AKT signaling and Glut1 in the treatment of psoriasis","authors":"Bai-lin Chen ,&nbsp;Wei-ming Zhang ,&nbsp;Xiao-wan Dong ,&nbsp;Jia-yi Liu ,&nbsp;Yan-ping Bai","doi":"10.1016/j.bbadis.2025.167879","DOIUrl":"10.1016/j.bbadis.2025.167879","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is an immune-mediated inflammatory skin disorder marked by excessive keratinocyte proliferation and inflammatory cell infiltration. Quercetin has shown a range of biological activities, highlighting its potential as a therapeutic agent for psoriasis.</div></div><div><h3>Purpose</h3><div>This study aims to explore the mechanisms by which quercetin treats psoriasis.</div></div><div><h3>Methods</h3><div>An Imiquimod-induced psoriasis mouse model and a TNF-α-induced keratinocyte proliferation model were utilized, supplemented with quercetin and DAPT. The expression of K10, K14, Notch1, NICD, AKT and Glut1 in psoriatic lesions and normal skin was assessed. Techniques employed included hematoxylin-eosin staining, immunohistochemical staining, western blotting, quantitative polymerase chain reaction, cell counting kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Notch1, AKT, and Glut1 were highly expressed in psoriasis. Quercetin induced keratinocyte apoptosis and inhibited the Notch signaling pathway, as well as the expression of AKT and Glut1. Inhibition of Notch signaling led to keratinocyte apoptosis and downregulation of the AKT and Glut1 expression. The results of network pharmacology and molecular docking are consistent with this.</div></div><div><h3>Conclusion</h3><div>This study provides the first evidence that quercetin induces keratinocyte apoptosis and promotes keratinocyte differentiation to treat psoriasis through the triple inhibition of the Notch and PI3K/AKT signaling pathways, as well as Glut1. The downregulation of the PI3K/AKT pathway and Glut1 is achieved partially via Notch inhibition. These findings suggest that quercetin could be a novel agent for improving psoriasis treatment, especially in patients exhibiting high expression of Notch1, AKT, and Glut1 in their skin lesions.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167879"},"PeriodicalIF":4.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912162","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}

{"title":"Angiogenesis and immune microenvironment in triple-negative breast cancer: Targeted therapy","authors":"Ying Zhang,&nbsp;Hao Yang,&nbsp;Yanhong Jiang,&nbsp;Yijing Jiang,&nbsp;Renfang Mao","doi":"10.1016/j.bbadis.2025.167880","DOIUrl":"10.1016/j.bbadis.2025.167880","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that typically lacks effective targeted therapies, leading to limited treatment options. Chemotherapy remains the primary treatment modality; however, in recent years, new immunotherapy approaches, such as immune checkpoint inhibitors, have shown positive results in some patients. Although the development of TNBC is closely associated with BRCA gene mutations, the tumor immune microenvironment (TIME) plays a crucial role in tumor progression and immune escape. Tumor angiogenesis, the accumulation of immunosuppressive cells, and alterations in immune molecules collectively shape an environment unfavorable for anti-tumor immune responses. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) promote immune escape by secreting immunosuppressive factors. Therefore, combination strategies of anti-angiogenic and immune checkpoint inhibitory therapies have shown synergistic effects in clinical trials, while new targeted therapies such as TGF-β inhibitors and IL-1β inhibitors offer new options for TNBC treatment. With the development of personalized medicine, combining immunotherapy and targeted therapies brings new hope for TNBC patients.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167880"},"PeriodicalIF":4.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906269","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}