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

{"title":"Exploring the intersection of Alzheimer's disease and comorbidities: a review of the interplay between multiple chronic conditions","authors":"Sumaiya Khan ,&nbsp;Ali Imam ,&nbsp;Sunidhi Singh ,&nbsp;Anwar Ahmed ,&nbsp;Md. Imtaiyaz Hassan ,&nbsp;Mohammad Shahid ,&nbsp;Fareeda Athar ,&nbsp;Asimul Islam","doi":"10.1016/j.bbadis.2026.168190","DOIUrl":"10.1016/j.bbadis.2026.168190","url":null,"abstract":"<div><div>Alzheimer's disease (AD) represents degenerative brain disorder that impairs both cognitive functions and daily living activities gradually. It is frequently linked with other disorders such as psychosis, cardiovascular disorders, diabetes, and depression, all of which may influence the disease's onset, trajectory, and treatment approaches. These comorbidities can affect the onset, progression, and management of AD. This review focuses to explore the interplay of AD and comorbidities, and to examine the interplay between multiple chronic conditions. The review found that AD and comorbidities have a complex and bidirectional relationship. Comorbidities can affect the onset, progression, and management of AD, and AD can also affect the management and outcomes of comorbidities. The review also found that comorbidities may have an impact on caregiver burden, healthcare utilization and mortality. The findings suggest that the management of AD should take into account the presence and management of comorbidities to improve the overall outcomes for patients with AD. The literature also suggests that the management of comorbidities should be integrated in the management of AD patients. Furthermore, the review highlights the critical role of timely detection and treatment of comorbidities in AD patients to delay onset and mitigate disease progression. Additionally, it is crucial to consider the influence of comorbidities when selecting treatment options and the management of side effects and adverse events in AD patients. The literature reviewed in this article suggests that a multidisciplinary approach is needed in managing AD patients with comorbidities, which includes regular screening, early detection, and management of comorbidities in addition to managing AD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 4","pages":"Article 168190"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168448","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":"CCAT1 attenuates intermittent hypoxia associated endothelial cell pyroptosis through STAU1-mediated IRF1 mRNA degradation","authors":"Wen Liu ,&nbsp;Xinxin Li ,&nbsp;Qing Zhu ,&nbsp;Kaixin Wang ,&nbsp;Chen Zhao ,&nbsp;Xun Qi ,&nbsp;Cuiting Zhao ,&nbsp;Zhishuang Dong ,&nbsp;Chunyan Ma","doi":"10.1016/j.bbadis.2026.168155","DOIUrl":"10.1016/j.bbadis.2026.168155","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have established that vascular endothelial dysfunction is prevalent among obstructive sleep apnea (OSA) patients. Nonetheless, the mechanism by which intermittent hypoxia (IH) contributes to endothelial dysfunction remains unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis was conducted to identify the key molecules implicated in IH. The correlation between serum lncRNA CCAT1 and GSDMD levels with endothelial function in OSA patients was evaluated. IH-induced HUVECs were used as an in vitro OSA model. We assessed the expression and interaction of CCAT1 and IRF1, and their effects on endothelial cell pyroptosis and dysfunction to investigate the mechanism of CCAT1/IRF1/GSDMD in IH-induced HUVECs.</div></div><div><h3>Findings</h3><div>Bioinformatic analysis revealed the crucial role of pyroptotic pathway after IH. OSA patients exhibited elevated serum GSDMD levels, however, CCAT1 expression was decreased. There was a correlation between OSA severity, endothelial function, GSDMD and CCAT1 levels. CCAT1 was downregulated and IRF1 was upregulated in IH-induced HUVECs. Low CCAT1 and high IRF1 expression were associated with exacerbated GSDMD-mediated pyroptosis and impaired endothelial function. CCAT1 overexpression facilitated IRF1 mRNA degradation of via SMD pathway, mitigating GSDMD-mediated pyroptosis and endothelial dysfunction.</div></div><div><h3>Interpretation</h3><div>CCAT1 attenuates IH-induced endothelial cell pyroptosis through STAU1-mediated IRF1 mRNA degradation, suggesting its potential therapeutic value in OSA-related endothelial dysfunction.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 4","pages":"Article 168155"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954241","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":"Circ_0075691 regulates lipid metabolism in granulosa cells by interacting with EIF4A3 to promote PTGS2 mRNA stability","authors":"Pengyu Huang ,&nbsp;Jianshu Cai ,&nbsp;Gangxin Chen ,&nbsp;Huiling Xu ,&nbsp;Suzhu Chen ,&nbsp;Haiyan Li ,&nbsp;Yun Fu ,&nbsp;Beihong Zheng ,&nbsp;Zhengmian Zhang","doi":"10.1016/j.bbadis.2026.168173","DOIUrl":"10.1016/j.bbadis.2026.168173","url":null,"abstract":"<div><h3>Background</h3><div>Circular RNAs (circRNAs) are implicated in polycystic ovary syndrome (PCOS), yet their roles in granulosa cell dysfunction remain unclear. This study explores the mechanistic role of circ_0075691 in PCOS-associated metabolic dysregulation.</div></div><div><h3>Methods</h3><div>The circular structure of circ_0075691 was confirmed through gel electrophoresis and RNase R resistance assays. Its expression levels and subcellular localization were assessed using RT-PCR and fluorescence in situ hybridization (FISH). Subsequent to the overexpression of circ_0075691, the cell function assays were conducted, including CCK-8, colony formation, flow cytometry, and analyses of oxidative stress and lipid metabolism-related indicators. Bioinformatics analyses were employed to predict RNA-binding proteins (RBPs) that potentially interact with circ_0075691, and these interactions were validated using RNA immunoprecipitation (RIP) and RNA pulldown assays.</div></div><div><h3>Results</h3><div>Circ_0075691 was verified to possess a circular structure and was predominantly localized in the nucleus. Its expression was significantly elevated in both follicular fluid (FF) and granulosa cells from PCOS patients compared to normal controls. In vitro experiments demonstrated that overexpression of circ_0075691 led to reduced cell viability and proliferation, decreased oxygen consumption rate (OCR), and increased apoptosis, oxidative stress, and lipid accumulation. Mechanistically, circ_0075691 was found to interact with and stabilize the EIF4A3 protein, thereby enhancing the stability of PTGS2 mRNA. Silencing PTGS2 mitigated the metabolic and apoptotic abnormalities induced by circ_0075691.</div></div><div><h3>Conclusion</h3><div>This study revealed that circ_0075691 played a crucial role in PCOS-related granulosa cell functions and lipid metabolism. The circ_0075691/EIF4A3/PTGS2 axis provided new insights into the molecular mechanism of PCOS and potential therapeutic targets.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 4","pages":"Article 168173"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074774","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":"NADPH oxidase 5 promotes adhesion and infiltration of immune cells in the brain. Implications in ischemic stroke","authors":"Javier Marqués ,&nbsp;Leyre Basurco ,&nbsp;Elena Ainzúa ,&nbsp;Victor Marqués ,&nbsp;Maite Solas ,&nbsp;Enrique Santamaría ,&nbsp;Joaquín Fernández-Irigoyen ,&nbsp;Davide Maselli ,&nbsp;María Martínez-Azcona ,&nbsp;Carmen Roncal ,&nbsp;Maria S. Aymerich ,&nbsp;Aleksandar Ivetic ,&nbsp;Josune Orbe ,&nbsp;Guillermo Zalba","doi":"10.1016/j.bbadis.2026.168188","DOIUrl":"10.1016/j.bbadis.2026.168188","url":null,"abstract":"<div><div>Blood-brain barrier (BBB) disruption and immune cell infiltration increase the pathological outcomes present in aging, neurodegenerative diseases, and stroke. NADPH oxidase 5 (NOX5) is a ROS-producing enzyme that promotes BBB-permeability <em>in vivo</em> by altering the endothelial junctions (EJs). The aim of this project was to elucidate the mechanisms by which NOX5 dysregulates EJs in endothelial cells and whether it increases immune infiltrates in a systemic inflammatory condition, using a murine model of ischemic stroke. A brain microvascular endothelial cell line (hCMEC/D3) and HUVECs infected with a NOX5 overexpressing adenovirus were used to study the effects of this protein on EJs, endothelial phenotype, and immune cell adhesion and infiltration <em>in vitro</em>. An endothelial NOX5 <em>knock-in</em> mouse was used to study EJs expression in the brain. Finally, in an experimental model of ischemic stroke induced by FeCl₃ we analyzed the potential effects of NOX5 on the infiltration of immune cells to the brain. NOX5 overexpression dysregulated EJs and increased permeability in hCMEC/D3 cells. In HUVECs, overexpression of NOX5 promoted the remodeling of the cytoskeleton and increased inflammatory cell adhesion and infiltration. Under inflammatory conditions, such as those present in ischemic stroke, mice expressing endothelial NOX5 exhibited an increase in the infiltration of immune cells in the brain across the vasculature of the non-infarcted (contralateral) hemisphere and increased inflammatory markers in the infarcted (ipsilateral) hemisphere. NOX5 promotes the dysregulation of EJs and cytoskeletal changes in endothelial cells, which leads to an increased immune cell infiltration in the brain at proinflammatory situations.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 4","pages":"Article 168188"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168363","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":"Leveraging macrophage plasticity for precision-targeted tumor immunotherapy","authors":"Shu-Jin Li ,&nbsp;Xiao-He Wang ,&nbsp;Ling-Rui Li ,&nbsp;Lei Chen ,&nbsp;Zhi-Jun Sun","doi":"10.1016/j.bbadis.2026.168176","DOIUrl":"10.1016/j.bbadis.2026.168176","url":null,"abstract":"<div><div>While immunotherapy has demonstrated remarkable therapeutic potential in certain malignancies, its overall clinical efficacy remains suboptimal. Emerging evidence indicates that the tumor microenvironment (TME) plays a pivotal role in determining immunotherapy response, with tumor-associated macrophages (TAMs) – the predominant immune cell population within TME – being closely associated with poor prognosis, metastatic progression, and therapeutic resistance. Traditionally, macrophages are classified into two primary activation states: the pro-inflammatory M1 (classically activated) phenotype and the anti-inflammatory M2 (alternatively activated) phenotype. However, this binary classification system fails to fully capture the functional complexity and phenotypic plasticity of TAMs. This comprehensive review critically examines TAM heterogeneity and explores emerging subtyping paradigms beyond conventional M1/M2 dichotomization. Furthermore, we systematically examine three principal therapeutic strategies: recruitment inhibition, TAM depletion, and phenotypic reprogramming, emphasizing their synergistic potential with existing immunotherapies. These multifaceted approaches provide novel insights for developing combination therapies to overcome current limitations in cancer treatment.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 4","pages":"Article 168176"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097718","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":"Adipose-derived mesenchymal stem cell exosomes enhance diabetic wound healing via the amelioration of fibroblast senescence through the SMARCAL1-Drp1 signaling pathway","authors":"Hang Wu ,&nbsp;Xuan Jiang ,&nbsp;Jieyun Cai ,&nbsp;Changhong Li ,&nbsp;Xihang Yuan ,&nbsp;Yifeng Huang ,&nbsp;Yang Xiong ,&nbsp;Xiangdong Qi ,&nbsp;Chiyang Li","doi":"10.1016/j.bbadis.2026.168187","DOIUrl":"10.1016/j.bbadis.2026.168187","url":null,"abstract":"<div><div>Delayed healing of diabetic wounds (DW) represents a significant complication among diabetic patients, for which current therapeutic approaches remain suboptimal. Accumulating evidence indicates that fibroblast senescence plays a critical role in the impaired healing of diabetic wounds. Abnormal mitochondrial morphology has long been associated with cellular senescence and age-related pathologies, suggesting that mitochondrial dynamics are compromised during senescence. In this study, we explored the potential mechanisms through which adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos) facilitate diabetic wound repair. We initially confirmed the presence of a substantial number of senescent fibroblasts in diabetic wound tissues. Subsequent investigations demonstrated that exosomes derived from adipose-derived stem cells can effectively alleviate fibroblast senescence. In-depth mechanistic analyses revealed that these exosomes suppress the expression of SMARCAL1, a chromatin remodeling protein, thereby enhancing the transcription of mitochondrial dynamin-related protein 1 (Drp1), and ultimately restoring mitochondrial dynamics and alleviating senescence in human dermal fibroblasts (HDFs). In vivo experiments further demonstrated that exosome administration significantly reduced HDFs senescence and accelerated wound healing in a diabetic mouse model. Collectively, our findings suggest that ADSC-Exos promote diabetic wound healing by mitigating HDFs senescence via the SMARCAL1-Drp1-mitochondrial dynamics pathway. This study elucidated the molecular mechanisms underlying exosome-mediated fibroblast senescence rescue and proposed a novel therapeutic strategy for diabetes-related wound management through targeted clearance of senescent cells.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 4","pages":"Article 168187"},"PeriodicalIF":4.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144992","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":"Urolithin A protects against calcium oxalate-induced crystal formation and kidney injury by regulating PCK1 to restore mitophagy function in kidney stone disease","authors":"Xiaoyi Sun ,&nbsp;Chunlin Gao ,&nbsp;Pei Zhang ,&nbsp;Yingchao Peng ,&nbsp;Meiqiu Wang ,&nbsp;Jiuyu Liu ,&nbsp;Chenxi Ma ,&nbsp;Shan Li ,&nbsp;Zhengkun Xia","doi":"10.1016/j.bbadis.2025.168106","DOIUrl":"10.1016/j.bbadis.2025.168106","url":null,"abstract":"<div><div>Kidney stone disease (KSD) is one of the most common urological disorders, and oxalate-induced tubular epithelial cell injury plays a crucial role in stone-related renal damage. However, the mechanisms linking oxalate exposure to mitochondrial dysfunction remain unclear.</div><div>Urolithin A (UA), a gut microbiota–derived metabolite of ellagitannins, is recognized for its antioxidant and mitophagy-promoting properties. This study investigated the renoprotective effects and mechanisms of UA in calcium oxalate (CaOx) crystal–induced renal injury. In mice, UA markedly reduced renal CaOx deposition, improved renal function, and alleviated kidney injury. Consistently, both in vivo and in vitro experiments demonstrated that UA restored oxalate-suppressed mitophagy while also alleviating oxidative stress, apoptosis, and mitochondrial dysfunction.</div><div>Transcriptomic and molecular docking analyses identified phosphoenolpyruvate carboxykinase 1 (PCK1) as a downstream target of UA. UA restored PCK1 expression under oxalate stress both in vivo and in vitro, whereas pharmacological inhibition of PCK1 weakened the renal protective and mitophagy-promoting effects. Conversely, PCK1 overexpression enhanced mitophagy under high-oxalate conditions.</div><div>These findings indicate that UA alleviates CaOx-induced renal injury by activating PCK1-dependent mitophagy and restoring mitochondrial homeostasis. Given its natural origin and favorable safety profile, UA represents a promising candidate for preventing or treating calcium oxalate–associated renal injury.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 3","pages":"Article 168106"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566690","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":"USP38 deficiency mitigates arrhythmogenic remodeling in obese mice by inhibiting TLR4/CaMKII signaling","authors":"Tao Chen ,&nbsp;Hongjie Yang ,&nbsp;Yang Gong ,&nbsp;Jingjing Zhang ,&nbsp;He Huang ,&nbsp;Wei Shuai","doi":"10.1016/j.bbadis.2025.168122","DOIUrl":"10.1016/j.bbadis.2025.168122","url":null,"abstract":"<div><div>Obesity-associated metabolic disturbances and cardiac remodeling significantly contribute to ventricular arrhythmias (VAs), a leading cause of sudden cardiac death. Although our previous studies have implicated the deubiquitinase USP38 in cardiovascular pathology, its precise role in obesity-related VAs remains unclear. Here, we aimed to elucidate the functional role and underlying mechanisms of USP38 in obesity-induced VAs.Cardiac-specific Usp38 knockout (CKO) mice were commercially generated. Obesity was induced by feeding mice a high-fat diet (HFD), while control mice received a normal diet (ND). We found the USP38 expression was significantly elevated in cardiac tissues of obese mice. Cardiac-specific deletion of USP38 markedly improved metabolic profiles and attenuated pathological remodeling, evidenced by reduced fibrosis markers (α-SMA, collagen I, collagen III), hypertrophy markers (ANP, BNP, β-MHC), and aberrant ion channel expression (Cav1.2, Kv1.5, Kv2.1, Kv4.2, Kv4.3). Correspondingly, the incidence of inducible VAs was significantly reduced. Co-immunoprecipitation confirmed a direct interaction between USP38 and the Toll-like receptor-4 (TLR4) signaling pathway. Further analyses demonstrated that USP38 knockout effectively blunted TLR4-mediated CaMKII activation both in vivo and in vitro. Cardiac-specific USP38 knockout effectively mitigates obesity-induced cardiac hypertrophy, fibrosis, and electrical remodeling, significantly reducing susceptibility to ventricular arrhythmias via inhibition of the TLR4/CaMKII signaling pathway. Mechanically, USP38 interacts with TLR4 and prevents the proteasomal degradation of TLR4, stabilizing TLR4 and promoting the activation of its downstream mediators. Therefore, targeted inhibition of USP38 may represent a promising therapeutic strategy for preventing obesity-associated ventricular arrhythmias.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 3","pages":"Article 168122"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145590297","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":"Vimentin-targeting adaptogen withaferin A: Potential to selectively suppress cervical cancer – Single-cell microspectroscopic and molecular analysis","authors":"Ewa Pięta ,&nbsp;Agnieszka Panek ,&nbsp;Monika Szczepanek-Dulska ,&nbsp;Katarzyna Pogoda","doi":"10.1016/j.bbadis.2025.168125","DOIUrl":"10.1016/j.bbadis.2025.168125","url":null,"abstract":"<div><div>This study investigates the preferential anticancer effects of withaferin A, an adaptogenic compound, on primary and metastatic cervical cancer cells (C-33 A and CaSki, respectively) and non-cancerous skin fibroblast cells (Detroit-551). Employing a multi-modal approach, we combined biological assays with advanced vibrational spectroscopic imaging techniques, including Fourier-transform infrared (FT-IR), Raman (RS), and atomic force microscopy (AFM). The results revealed a dose-dependent reduction in cell viability, with a more pronounced effect observed in C-33 A cells compared to CaSki and fibroblasts, indicating a heightened sensitivity of C-33 A cells to withaferin A. The comet assay revealed significantly higher levels of DNA damage in primary tumor C-33A cells, whereas minimal DNA breaks were observed in fibroblasts and metastatic cells, further confirming the higher sensitivity of cancer cells compared to fibroblasts. Fluorescence staining and AFM topography imaging showed morphological alterations in cancer cells at higher withaferin A doses and longer incubation times. Flow cytometry analysis revealed significant apoptotic changes in primary C-33A cells due to withaferin A treatment, highlighting a large amount of cells undergoing late apoptosis, compared to a weaker apoptotic effect on metastatic CaSki cells and negligible effect for fibroblasts. Spectroscopic analyses revealed molecular alterations in lipid, protein, and nucleic acid composition, indicative of withaferin A's impact on cellular membranes and genetic material. These findings highlight withaferin A as a promising therapeutic agent with the potential to preferentially target primary cervical cancer cells, while minimizing toxicity to healthy cells.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 3","pages":"Article 168125"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615755","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":"Multifaceted role of primary cilia and ciliary proteins: A potential nexus for hedgehog signaling and prostate cancer","authors":"Jyoti B. Kaushal ,&nbsp;Parthasarathy Seshacharyulu ,&nbsp;Surinder K. Batra ,&nbsp;Sakthivel Muniyan","doi":"10.1016/j.bbadis.2025.168120","DOIUrl":"10.1016/j.bbadis.2025.168120","url":null,"abstract":"<div><div>The primary cilium is a solitary, non-motile, microtubule-based organelle that extends from the cell membrane and functions as a critical coordinator of multiple signaling pathways. Despite its association with hundreds of proteins, only a subset is essential for its biogenesis and signal transmission. Malfunctions in primary cilia are associated with developmental disorders and various malignancies, including prostate cancer (PCa). Recent studies highlight the regulation of ciliogenesis, cilia length, and interaction among cilia-resident proteins, particularly within the ciliary hedgehog (Hh) signaling axis in oncogenesis, thereby positioning primary cilia as potential therapeutic targets. Nevertheless, the precise contribution of ciliary components to Hh pathway modulation in PCa remains poorly defined. This review integrates emerging evidence to elucidate the current state of knowledge on the structural and functional attributes of primary cilia, cilia-mediated molecular dynamics with Hh signaling, and their intersection in the context of PCa progression, including prostate development, carcinogenesis, and tumor microenvironment dynamics. Particular emphasis is placed on cilia-associated proteins, such as SCL/TAL1 interrupting locus (STIL), intraflagellar transport (IFT) family proteins, ADP-ribosylation factor (Arf) family proteins, transforming acidic coiled-coil protein-3 (TACC3), mitotic kinase Aurora A, and dual-specificity tyrosine-regulated kinase (DYRK), which have been mechanistically linked to PCa and modulate Hh signaling. However, their detailed contributions remain insufficiently characterized and warrant further investigation. This review underscores the role of primary cilia in PCa progression, highlights unresolved mechanistic gaps in their regulation, and proposes future directions for targeted molecular and therapeutic research.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1872 3","pages":"Article 168120"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535121","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}