Biomolecules最新文献

{"title":"Brain Lymphatic Dysfunction in Subarachnoid Hemorrhage: Pathophysiology and Clinical Implications.","authors":"Shuangyi Guo, John H Zhang, Warren Boling, Lei Huang","doi":"10.3390/biom16040616","DOIUrl":"10.3390/biom16040616","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder with high morbidity and mortality, despite advances in aneurysm securing and neurocritical care. Clinical outcomes are determined by early brain injury (EBI), delayed cerebral ischemia (DCI), hydrocephalus, and long-term cognitive impairment, extending beyond the traditional focus on large-vessel vasospasm alone. Emerging evidence identifies the dysfunction of the glymphatic system and meningeal lymphatic pathway, the brain's primary clearance pathways, as a central and unifying mechanism linking acute hemorrhagic injury to delayed and chronic neurological sequelae. Following SAH, acute intracranial pressure elevation, subarachnoid blood clot burden, loss of arterial pulsatility, venous congestion, astrocytic aquaporin-4 perivascular depolarization, and neuroinflammation converge to suppress cerebrospinal fluid-interstitial fluid exchange and outflow in glymphatic system and subsequent meningeal lymphatic drainage. Persistent clearance failure promotes the retention of blood breakdown products, inflammatory mediators, and metabolic waste, amplifying microvascular dysfunction, cortical spreading depolarizations, blood-brain barrier disruption, and secondary ischemic injury. Importantly, accumulating data highlight venous pathology and meningeal lymphatic impairment as critical, yet underappreciated, contributors to delayed injury and post-SAH hydrocephalus. In this review, we synthesize the current knowledge of the physiological organization of glymphatic and meningeal lymphatic systems, delineate the mechanistic and molecular drivers of their dysfunction after SAH, and discuss clinical implications for EBI, DCI, hydrocephalus, and long-term cognitive outcomes. We further outline future directions, including translational imaging, biomarker development, and therapeutic strategies targeting clearance pathways, to advance disease-modifying approaches in SAH.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810517","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}

{"title":"Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.","authors":"Hengqian Dai, Ziyi Zhang","doi":"10.3390/biom16040613","DOIUrl":"10.3390/biom16040613","url":null,"abstract":"<p><p>Diabetes and related metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD), are increasingly recognized as diseases of inter-organ metabolic dysregulation rather than disorders of a single organ. The core of this process is the liver-pancreas axis, which integrates metabolic signals to maintain glucose and lipid homeostasis. Under physiological conditions, insulin and glucagon work together to regulate glucose production in the liver. The liver, in turn, regulates pancreatic β-cell function through hepatokines, metabolites and extracellular vesicles. Axis disorder driven by liver insulin resistance, lipid accumulation, inflammation or changes in hepatokine secretion exacerbates β-cell dysfunction, glucotoxicity and lipotoxic stress, thereby accelerating disease progression. This imbalance is involved in the pathogenesis of type 2 diabetes, type 1 diabetes, gestational diabetes, and monogenic diabetes, and makes MASLD a driving factor and early predictor of diabetes onset. This review summarizes the key molecular mechanisms behind liver-pancreas crosstalk and explores potential therapeutic strategies aimed at restoring coordinated metabolic regulation between the organs.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810913","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}

{"title":"Targeting Oxidative Stress to Treat Vitiligo: Clinical and Molecular Evidence.","authors":"Noemi Aprile, Simona Scano, Barbara Bellei, Alberto Marini, Angela Filoni","doi":"10.3390/biom16040612","DOIUrl":"10.3390/biom16040612","url":null,"abstract":"<p><p>Vitiligo is a chronic autoimmune disease characterized by the destruction of epidermal melanocyte, resulting in well-demarcated white patches on the skin. Despite the established use of corticosteroids and calcineurin inhibitors and the recent introduction of Janus kinase (JAK) inhibitors, a breakthrough targeted therapy that interrupts the IFN-γ signaling pathway, stable repigmentation remains a major clinical challenge, necessitating deeper investigation into its pathogenesis. Among the factors contributing to vitiligo, including genetic predisposition and autoimmunity, oxidative stress is a central driver of melanocyte damage and the subsequent autoimmune response. Chronic oxidative disequilibrium (high ROS level and impaired mitochondrial activity) and reduced antioxidant capacity (Nrf2/ARE pathway and catalase deficiency) function as triggering factors upstream of most other pathogenic pathways. Consequently, targeting oxidative stress, either as a monotherapy or in synergy with emerging targeted treatments, remains a pivotal area of therapeutic interest even in the current era of targeted therapies. Still, a significant gap remains the lack of standardized oxidative biomarkers to monitor disease activity and therapeutic response. Identifying these indicators is essential for personalized clinical management in vitiligo. This review examines how chronic oxidative disequilibrium and a reduced antioxidant capacity initiate and sustain the autoimmune cascade, leading to disease onset and progression.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810744","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}

{"title":"Resilience to Diabetic Retinopathy (RDR) Is Associated with a Pre-Retinopathy Transcriptional Program Induced by Diabetes.","authors":"Janani Rajasekar, Maria Paula Zappia, Maximilian A McCann, Maxim V Frolov, Andrius Kazlauskas","doi":"10.3390/biom16040614","DOIUrl":"10.3390/biom16040614","url":null,"abstract":"<p><p>The purpose of this project was to define gene expression changes associated with the acquisition and loss of resilience to diabetic retinopathy (RDR) in individual retinal cell types. A non-immune form of type 1 diabetes mellitus (DM) was induced by injecting male <i>C57Bl6J</i> mice with streptozotocin. Single-cell RNA sequencing was performed on retinas from mice that experienced DM for 5 or 15 days, along with retinas from age-matched, non-DM mice. The resulting data sets were analyzed to identify DM-associated differentially expressed genes and pathway enrichments after each duration of DM. We observed that acquisition of RDR, previously shown to arise after 5 days of DM was linked to altered expression of genes in a subset of retinal cells, mainly Müller cells. Pathway analysis indicated enhancement of numerous modes of protection, including reinforced neurovascular and structural homeostasis through phagocytosis, integrin signaling, and interferon-mediated defense. After 15 days of DM, when we previously showed that RDR is waning this pro-protection surge in gene expression subsided. We conclude that a duration of DM that is too short to cause diabetic retinopathy (DR) nonetheless evoked a profound change in the gene expression profile within a subset of retinal cell types. The nature and timing of this molecular shift indicated that it was not the preamble to DM-related damage that eventually develops. Rather, DM engaged numerous defense programs within Müller cells. The temporal alignment between RDR and activation of Müller cell-based defense provides a molecular foundation for the retina's transient ability to remain healthy in the face of DM.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810632","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}

{"title":"Cigarette Smoke Induces Canonical Stress Granule Formation in Human Bronchial Epithelial Cells in Reactive Oxygen Species- and PERK-Dependent Manners.","authors":"Mousumi Bhowmik, Chenkun Zheng, Bisrat Bekele, Jessica Failler, Carlie Klatt, Souren Farimani, Bryant Jones, Chung-Chun Tyan, Asmahan Abu-Arish","doi":"10.3390/biom16040615","DOIUrl":"10.3390/biom16040615","url":null,"abstract":"<p><p>Cigarette smoke (CS) is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). Investigating the impact of CS on human airway epithelium is important for understanding COPD development and combating its effects. While some studies show that long exposure to CS activates inflammasome formation in airway epithelium, leading to cytokines' maturation and release, its acute effect on inflammation regulation requires further elucidation. Due to the importance of acute cellular responses in modulating cell survival and controlling inflammatory outcomes, we examined the effect of acute cigarette smoke extract exposure on human bronchial epithelial cells. Due to the high reactive oxygen species content in CS, we hypothesize that acute CS exposure activates the integrated stress response (ISR) pathway leading to stress granules (SG) formation to facilitate oxidative stress resolution and promote cell survival. Immunostaining, fluorescence confocal imaging, quantitative analyses, and immunoblotting were performed to test our hypothesis. We report here that acute exposure to CS extract triggers canonical SG formation by activating the ISR pathway via the PERK/eIF2α arm in a reactive oxygen species-dependent manner. SG formation is abolished upon inhibiting PERK or eIF2α function, or by scavenging oxidants prior to smoke exposure. Characterizing SG formation in terms of measuring SG size and abundance and the sequestration of the SG marker G3BP1 reveals that SG formation is maximal at 15% CS extract exposure for 2 h and undergoes gradual disassembly at longer exposure times. This is closely dependent on cytoplasmic p-eIF2α levels. These results demonstrate that acute exposure to CS activates the protective ISR pathway to potentially reduce the detrimental effects of CS and promote stress resolution and cell survival.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810637","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}

{"title":"APOC3 Promotes DGAT2-Dependent Triglyceride Accumulation in Hepatocytes During Early Metabolic Dysfunction.","authors":"Thi Nhi Nguyen, Hye-Jeong Kim, Hye Min Shim, Junho Kang, Eun Young Ha, Hochan Cho, Jae-Hyung Park","doi":"10.3390/biom16040607","DOIUrl":"10.3390/biom16040607","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic triglyceride accumulation in the setting of obesity and insulin resistance. Although apolipoprotein C-III (APOC3) is a well-established regulator of plasma triglyceride metabolism, its hepatocyte-intrinsic role in intracellular lipid accumulation remains unclear. In this study, we investigated whether APOC3 contributes to hepatocellular triglyceride synthesis during early metabolic dysfunction. In 6-week-old db/db mice, early hepatic lipid accumulation was observed without detectable fibrosis. Transcriptomic profiling identified <i>APOC3</i> as an upregulated gene associated with lipid metabolic pathways, and its hepatic upregulation was confirmed at both mRNA and protein levels. Gain- and loss-of-function experiments in HepG2 cells demonstrated that APOC3 overexpression significantly increased intracellular triglyceride content, whereas APOC3 knockdown reduced triglyceride accumulation. Mechanistically, APOC3 selectively regulated diacylglycerol acyltransferase 2 (DGAT2), which catalyzes the final step of triglyceride synthesis, without significantly affecting major lipogenic transcription factors. Furthermore, under de novo lipogenesis-inducing conditions triggered by the liver X receptor agonist T0901317 and insulin, APOC3 markedly amplified DGAT2 expression and triglyceride accumulation. Collectively, these findings suggest a hepatocyte-intrinsic role for APOC3 in promoting triglyceride accumulation through DGAT2-dependent mechanisms. The APOC3-DGAT2 axis may represent a relevant pathway contributing to hepatic lipid accumulation in metabolic liver disease.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810381","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}

{"title":"Lysine Acetyltransferase 6A Drives M1 Macrophage Polarization Through Metabolic Reprogramming in Sepsis-Induced Acute Lung Injury.","authors":"Xin Wang, Junlin Chen, Yimei Lai, Yumeng Wang, Kaixia Hu, Mengshi Wu, Niansheng Yang, Yuefang Huang","doi":"10.3390/biom16040609","DOIUrl":"10.3390/biom16040609","url":null,"abstract":"<p><p>Macrophage-mediated inflammation is a key driver of sepsis-induced acute lung injury (ALI). M1 macrophage polarization relies on metabolic reprogramming, yet the upstream regulatory factors remain unclear. Lysine acetyltransferase 6A (KAT6A), a MYST-family acetyltransferase, regulates transcriptional programs in immune cells, but its role in macrophage function and ALI progression remains unknown. Public single-cell and bulk transcriptomic datasets were used to assess KAT6A expression changes and its association with inflammatory and metabolic pathways in macrophages. KAT6A inhibition with WM1119 was used to evaluate effects on M1 polarization, cytokine production, metabolic reprogramming, and PI3K-AKT-mTOR signaling. The therapeutic potential of KAT6A inhibition was validated in a cecal ligation and puncture (CLP)-induced sepsis model by assessing lung injury, bacterial clearance, and survival. KAT6A expression was upregulated in sepsis and particularly enriched in M1 macrophages. Inhibition of KAT6A reduced inflammatory and glycolytic transcriptional programs, suppressed glycolysis and enhanced oxidative phosphorylation, leading to decreased cytokine production and limited M1 polarization accompanied by suppression of PI3K-AKT-mTOR pathway. In CLP-induced septic mice, treatment with the KAT6A inhibitor WM1119 alleviated lung injury, improved bacterial clearance, and prolonged survival. KAT6A expression is associated with macrophage glucose metabolism, pro-inflammatory responses, and M1 macrophage polarization in sepsis-induced acute lung injury. Pharmacologic inhibition of KAT6A may provide a promising therapeutic strategy for reducing macrophage-driven lung injury.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810815","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}

{"title":"Hepatocyte-Specific Deletion of Betaine-Homocysteine Methyltransferase Disrupts Methionine Metabolism and Promotes the Spontaneous Development of Hepatic Steatosis.","authors":"Ramachandran Rajamanickam, Sathish Kumar Perumal, Ramesh Bellamkonda, Sundararajan Mahalingam, Kurt W Fisher, Rolen Quadros, Channabasavaiah B Gurumurthy, Madan Kumar Arumugam, Karuna Rasineni, Kusum K Kharbanda","doi":"10.3390/biom16040606","DOIUrl":"10.3390/biom16040606","url":null,"abstract":"<p><p>Betaine-homocysteine methyltransferase (BHMT) is an enzyme involved in one-carbon metabolism and plays a crucial role in maintaining liver health. In this study, we investigated the impact of liver-specific deletion of BHMT on liver dysfunction using a mouse model. We generated BHMT floxed mice and bred them with albumin Cre to generate liver-specific BHMT knockout (BHMT LKO) mice. Liver tissues harvested from six-month-old chow-fed BHMT floxed and LKO mice were characterized through histological, biochemical, and molecular analyses. BHMT LKO mice displayed a complete loss of hepatic expression of BHMT mRNA, protein and enzyme activity. Histopathological analysis revealed the development of hepatic steatosis in BHMT LKO mice compared to the floxed mice. These morphological changes were supported by biochemical analysis showing elevated levels of hepatic triglycerides in conjunction with a profound decrease in the methylation potential (i.e., reduced S-adenosylmethionine (SAM): S-adenosylhomocysteine (SAH) ratio), which was mainly driven by a six- to sevenfold increase in SAH levels. BHMT LKO mice also exhibited increased lipid peroxidation and lysosomal dysfunction compared to floxed mice. Early signs of inflammation were seen in the livers of BHMT LKO mice of both sexes, as evident from significant increase in CD68-positive cells and interleukin 1β levels. Additionally, there was a moderate increase in fibrosis, as evidenced by the upregulated expression of α-smooth muscle actin and collagen II levels and the histological assessment of picrosirius red-stained liver sections of BHMT LKO mice of both sexes compared to their respective counterparts. These findings demonstrate that hepatic BHMT deficiency promotes lipid accumulation, lysosomal/proteasomal dysfunction, and early inflammatory and fibrotic changes in the liver by reducing the methylation potential. Collectively, our results underscore BHMT as a critical regulator of liver homeostasis and a potential therapeutic target in liver-related disorders.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810570","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}

{"title":"Extracellular Vesicles as Biomarkers for Vascular Disease.","authors":"Davide Costa, Michele Andreucci, Nicola Ielapi, Teresa Faga, Antonio Mazza, Giulio Accarino, Umberto Marcello Bracale, Raffaele Serra","doi":"10.3390/biom16040608","DOIUrl":"10.3390/biom16040608","url":null,"abstract":"<p><p>Vascular diseases (VD) remain a leading global cause of morbidity and mortality, often developing silently before manifesting as severe complications like stroke or ischemia. Traditional diagnostic imaging provides essential anatomical data but frequently fails to capture the dynamic molecular processes underlying vascular pathology. This narrative review summarizes current evidence regarding Extracellular Vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, as emerging biomarkers and mediators in vascular conditions. The review evaluates the biological mechanisms of EVs across several disorders, including arterial aneurysms, peripheral artery disease, carotid stenosis, and venous thromboembolism. Findings indicate that EVs concentration and molecular cargo, particularly microRNAs and proteins, reflect the physiological state of parent cells, offering a \"liquid biopsy\" for vascular inflammation, endothelial dysfunction, and plaque vulnerability. Furthermore, the review explores the therapeutic potential of stem cell-derived EVs in promoting angiogenesis and tissue repair in chronic vascular ulcers. Despite these advances, the review concludes that the clinical implementation of EV-based diagnostics faces significant hurdles, primarily due to the lack of standardized isolation and characterization methods. Addressing these methodological challenges is crucial for translating EV research into routine clinical practice.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810222","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}

{"title":"Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.","authors":"Yifan Qiao, Jin Zhao, Minna Liu, Jie Liu, Qiao Zheng, Ruotong Xu, Xiaoxuan Ning, Shiren Sun, Xiangmei Chen","doi":"10.3390/biom16040611","DOIUrl":"10.3390/biom16040611","url":null,"abstract":"<p><p>Acute kidney injury (AKI), a life-threatening disorder marked by abrupt renal dysfunction, is increasingly recognized as a global healthcare challenge. It not only triggers immediate organ dysfunction but also heightens long-term risks of chronic kidney disease (CKD). The senescence of proximal tubular epithelial cells (PTECs) has a major impact on the occurrence and development of AKI. This review systematically analyzes existing evidence, which suggests that the senescence of PTECs may have a dual effect. Acute cellular senescence typically mitigates uncontrolled replication of damaged cells by inducing cell cycle arrest, thereby limiting the further expansion of tissue damage. In contrast, the pathological retention of chronic senescent cells and the excessive production of the senescence-associated secretory phenotype (SASP) exacerbate the local inflammatory response and the process of fibrosis, accelerating the transformation of AKI into CKD. Despite incomplete elucidation of the spatiotemporal mechanisms governing the transition from acute to chronic cellular senescence, therapeutic interventions can be precisely targeted to specific disease stages based on their characteristic progression dynamics. This review summarizes the intervention strategies applicable at different stages of AKI, including prevention, early induction of senescence, senoreverse, senolysis, and senomorphics. Additionally, we highlight potential therapeutic targets to provide a theoretical basis for optimizing clinical management.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810989","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}