Cells最新文献

{"title":"Radiofrequency Radiation Alters Redox Homeostasis, ATP Status, and Apoptosis-Associated Responses in Human Ovarian Epithelial Cells.","authors":"Shaniya Ahmad, Garima Nagar, Neha Yadav, Sanjay Singh, Anju Shrivastava, Rajeev Singh","doi":"10.3390/cells15191826","DOIUrl":"10.3390/cells15191826","url":null,"abstract":"<p><p>With the expansion of wireless communication technologies, radiofrequency radiation (RFR) has become a persistent component of the environmental exposome. The 2450 MHz frequency is a widely used RF band in wireless and microwave technologies, providing an environmentally relevant model for evaluating non-ionising radiation effects. Although non-ionising, RFR may influence cellular homeostasis through non-thermal stress pathways, yet its cellular effects in ovarian-derived models remain insufficiently defined. This study examined whether 2450 MHz RFR was associated with redox, ATP-related, and apoptosis-associated responses in SKOV3 ovarian epithelial cells. Cells were exposed for 30, 60, and 120 min under controlled conditions at a measured electric field intensity of 13.44 V/m. MTT-based viability/metabolic activity at 24 h and 48 h post-exposure, ROS, nitrite, ATP, mitochondrial membrane potential, apoptosis-related gene expression, and Annexin V-FITC/PI staining were assessed. RFR exposure did not significantly reduce MTT-based viability/metabolic activity at 24 h post-exposure; at 48 h, a significant reduction was observed in the 120-min group compared with the control and 30-min groups. Exposed cells showed progressive ROS accumulation, increased nitrite levels, and changes in ATP levels, with an increase at 30 min followed by lower levels at 60 and 120 min relative to 30 min, while the JC-1 red/green ratio showed no significant change. Apoptosis-associated transcriptional changes were marked by increased Bak1, Nip-2, and Caspase-4 and reduced Bcl-xL and Bag3 expression and a non-significant increase in Bad expression. Annexin V-FITC/PI analysis demonstrated an exposure-duration-associated increase in Annexin V-positive populations, with a predominance of Annexin V⁺/PI⁺ cells following 120 min of exposure. Overall, these findings indicate an exposure-associated cellular stress phenotype involving redox, ATP status, and apoptosis-related alterations in SKOV3 cells under defined in vitro conditions.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191358","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":"Antiviral Activity of an Ethanolic Extract of <i>Cinnamomum cassia</i> and Cinnamaldehyde Against the Herpesviruses HSV-1 and VZV.","authors":"Baraa Alaasam, Yomna Alnabari, Mahmoud Huleihel","doi":"10.3390/cells15191829","DOIUrl":"10.3390/cells15191829","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) are clinically important alphaherpesviruses that establish lifelong latent infections and remain significant causes of morbidity despite the availability of antiviral drugs. The emergence of drug resistance and the inability of current therapies to eliminate latent virus reservoirs underscore the need for novel antiviral agents with alternative mechanisms of action. In the present study, we evaluated the antiviral activity of an ethanolic extract prepared from commercial cinnamon bark marketed as <i>Cinnamomum cassia</i> and cinnamaldehyde, a well-known constituent of cinnamon tested here as a purified compound, against HSV-1 and VZV in vitro. Antiviral activity was assessed using plaque reduction assays, time-of-addition experiments, and quantitative real-time PCR for viral DNA accumulation and specific viral immediate-early transcript levels. Both the <i>C. cassia</i> extract and cinnamaldehyde inhibited HSV-1 and VZV replication in a dose-dependent manner while exhibiting relatively low cytotoxicity. Nonlinear dose-response analysis yielded IC₅₀ values of 3.44 and 2.80 µg/mL for the <i>C. cassia</i> extract against HSV-1 and VZV, respectively, and 0.961 and 1.50 µg/mL for cinnamaldehyde. Time-of-addition experiments demonstrated that antiviral activity was greatest when treatment was maintained throughout infection or initiated after viral entry, whereas pretreatment of cells or direct incubation with virus particles produced minimal effects. Both agents markedly reduced intracellular production of infectious progeny viruses and decreased viral DNA accumulation and the abundance of the specific immediate-early transcripts examined. These findings support a predominantly post-entry antiviral effect of both materials, rather than a primary effect on viral attachment or direct virion inactivation. Collectively, these results support further investigation of these agents as promising natural inhibitors of HSV and VZV infections.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191504","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":"Lacrimal Secretory Niche Remodeling in Dry Eye Disease: Single-Cell and Spatial Insights into Acinar Dysfunction.","authors":"Yuan Zhong, Xiyuan Liu, Qinghua Peng, Jun Peng","doi":"10.3390/cells15191828","DOIUrl":"10.3390/cells15191828","url":null,"abstract":"<p><p>Reduced tear output can arise from altered neural regulation, impaired epithelial secretion, or loss of secretory tissue, with different implications for recovery. This focused narrative review integrates physiological, single-cell, spatial, organoid, and mechanistic studies identified through a structured PubMed search and targeted reference checking. We examine how remodeling of the lacrimal secretory niche affects acinar secretory competence, the capacity of viable acinar cells to convert stimulation into coordinated fluid, electrolyte, and protein secretion. Omics studies identify disease-associated expression patterns and candidate interactions, while selected perturbation studies link neural, inflammatory, and metabolic mechanisms to secretory dysfunction. We use residual functional reserve as a working concept for secretion that surviving tissue and its supporting niche can recruit through stimulation or relief of suppression. Potentially reversible functional suppression, persistent niche dysfunction, and structural failure describe overlapping constraints on secretion, not validated disease stages. These descriptions are distinct from the cellular, glandular, and lacrimal functional-unit levels at which outcomes are measured. The framework organizes questions about mechanism and recovery but does not establish a clinical treatment algorithm. Progress requires functional testing of candidate mechanisms and assessment of recovery at the level relevant to each claim.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191552","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 Gut Microbiota, Inflammation, and Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: Therapeutic Strategies and the Emerging Role of Time-Restricted Feeding.","authors":"Sthembiso Msane, Andile Khathi","doi":"10.3390/cells15191831","DOIUrl":"10.3390/cells15191831","url":null,"abstract":"<p><p>Time-restricted feeding has emerged as a promising non-pharmacological intervention for the management of metabolic disorders, particularly type 2 diabetes mellitus and its associated complications. Time-restricted feeding involves restricting food intake to a specific daily eating window while fasting for the remaining hours within 24 h. Furthermore, time-restricted feeding can be combined with specific dietary modifications to enhance its therapeutic benefits. Type 2 diabetes mellitus has been strongly linked to gut dysbiosis, adipose tissue dysfunction, chronic low-grade inflammation, metabolic dysfunction-associated steatotic liver disease, and an increased risk of acute pancreatitis. Given the rising global prevalence of type 2 diabetes mellitus, early intervention strategies are becoming increasingly important. Prediabetes, as an intermediate stage preceding type 2 diabetes mellitus, provides a critical opportunity to understand the mechanisms underlying disease progression and to develop effective preventive strategies. However, the effects of time-restricted feeding on gut dysbiosis, adipose tissue dysfunction, dysregulated inflammatory responses, metabolic dysfunction-associated steatotic liver disease and the risk of acute pancreatitis at prediabetic state remain incompletely understood. Therefore, this review summarizes the current evidence regarding the therapeutic potential of time-restricted feeding in the management of type 2 diabetes mellitus and its related complications, while highlighting areas that require further investigation.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191651","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":"Small Wonders: How Nanotechnology Is Redefining Shoulder and Elbow Surgery.","authors":"Alexander Shao-Rong Pang, Joel Louis Lim, Dinesh Kumar Srinivasan, Zi Qiang Glen Liau","doi":"10.3390/cells15191830","DOIUrl":"10.3390/cells15191830","url":null,"abstract":"<p><strong>Objective: </strong>Nanotechnology has been increasingly incorporated into shoulder and elbow surgery, from bioinductive collagen scaffolds for rotator cuff repair to nanostructured implant surfaces for arthroplasty and nanoparticle-functionalized sutures for elbow tendon repair. This review evaluates the current evidence base for these applications and clarifies which technologies are supported by clinical data versus preclinical/mechanistic evidence alone.</p><p><strong>Methods: </strong>A narrative review was conducted using PubMed/MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus (January 2005-September 2026), supplemented by manual screening of society guidelines. Of 1842 records identified, 77 articles and 6 guideline documents were considered in the initial evidence synthesis, with 54 references ultimately retained in the published review. Because of heterogeneity in study design (randomized trials, cohorts, and preclinical models), findings were synthesized narratively.</p><p><strong>Results: </strong>In rotator cuff repair, bioinductive collagen (REGENETEN) and acellular dermal matrix augmentation have the most mature clinical evidence, with randomized and cohort data showing reduced retear rates, whereas the collagen-PLLA biocomposite (BioBrace) remains largely preclinical. In shoulder and elbow arthroplasty, nanostructured and nanotextured titanium surfaces have preclinical and early clinical support for enhanced osseointegration, while antimicrobial silver and titanium dioxide nanocoatings and metal-phenolic network coatings remain supported chiefly by in vitro and animal data, with cytotoxicity and photocatalytic limitations still unresolved. In elbow surgery specifically, nanoparticle- and gene-functionalized sutures have shown benefit in flexor tendon models with anatomically agnostic translational potential, but direct elbow-specific clinical data are lacking, and applications to the ulnar collateral ligament, cartilage, and total elbow arthroplasty bearings remain at the preclinical or expert-opinion stage.</p><p><strong>Conclusions: </strong>Nanotechnology is clinically established only for a small number of shoulder and elbow applications, principally bioinductive collagen augmentation of rotator cuff repair; most other applications, including antimicrobial nanocoatings and elbow-specific nanoparticle delivery systems, remain mechanistically promising but clinically unproven. Progress toward clinical translation will depend on adequately powered trials that separate device-specific effects from the heterogeneous preclinical literature currently supporting the field.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191550","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":"TRPA1 as the Intersection of Sensory Perception, Innate Immunity, and Adaptive Immune Regulation in Cutaneous Immunity.","authors":"Alessandra Torsello, Caterina Cattani, Christian Napoli, Andrea Cavani, Fernanda Scopelliti","doi":"10.3390/cells15191827","DOIUrl":"10.3390/cells15191827","url":null,"abstract":"<p><p>Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel best known for its role in nociception and environmental sensing. However, TRPA1 is now recognized to be expressed in several non-neuronal cell types, including keratinocytes and immune cells, suggesting a broader role in the regulation of cutaneous immune responses. This comprehensive review examines the current evidence linking TRPA1 to cutaneous immunity under both physiological and pathological conditions with particular focus on inflammatory skin disorders such as atopic dermatitis, allergic contact dermatitis and psoriasis. The available literature reveals a complex picture in which TRPA1 can either amplify or restrain immune responses depending on the cellular context, disease setting, and nature of the triggering stimulus. Moreover, TRPA1 is dynamically regulated by cytokines, oxidative stress, and tissue-derived signals. Discrepancies among experimental studies further highlight the impact of species-specific differences, disease models, and methodological approaches on the interpretation of TRPA1 function. Through a critical appraisal of the existing literature, this review seeks to disentangle the complex and sometimes contradictory evidence surrounding TRPA1 in cutaneous immunity, identifying emerging concepts, highlighting unresolved issues, and providing a clearer framework for understanding TRPA1 biology and guiding future research.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191666","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":"A Small-Molecule TrkB Agonist Promotes Synaptic Resilience Against Aβ and Tau Oligomers and Mitigates Alterations in TrkB-Akt and Fyn Signaling.","authors":"Tao Yang, Kevin C Tran, Albert Leng, Vanessa F Langness, Stephen M Massa, Frank M Longo","doi":"10.3390/cells15191822","DOIUrl":"10.3390/cells15191822","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic amyloid-beta and tau oligomers (oAβ, oTau) drive synaptic degeneration and cognitive decline in Alzheimer's disease (AD). Tropomyosin receptor kinase B (TrkB), expressed in neurons and glia, supports synaptic integrity in AD-affected regions. We tested whether PTX-BD4-3, a small-molecule TrkB partial agonist, promotes neuroprotective signaling, reduces degenerative signaling, and prevents synaptic loss in an AD mouse model and hippocampal neurons exposed to oAβ or oTau.</p><p><strong>Methods: </strong>Cultured hippocampal neurons were treated with oAβ or oTau ± PTX-BD4-3. Effects on synaptic proteins (±TrkB-blocking antibody), spine density, and Fyn, NR2B, and tau phosphorylation as well as tau oligomerization were assessed. Two cohorts of APP^L/S mice, 5 and 12 months of age, received intraperitoneal PTX-BD4-3 or vehicle for 3 months, followed by assessment of synaptic proteins, dendritic spines, TrkB signaling, and Y-maze analysis.</p><p><strong>Results: </strong>In vitro, PTX-BD4-3 prevented oAβ-induced synaptic marker loss in a TrkB-dependent manner, reduced phosphorylation of Fyn, NR2B, and tau, suppressed oligomeric tau formation, and attenuated oTau-induced spine loss. In APP^L/S mice, PTX-BD4-3 mitigated deficient TrkB/Akt signaling, reduced phosphorylation of Fyn and tau, preserved synaptic markers and dendritic spines, and improved Y-maze performance.</p><p><strong>Conclusions: </strong>Small-molecule TrkB partial agonists may normalize TrkB signaling and promote synaptic resilience, supporting their potential as AD therapeutics.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191508","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":"Pharmacological Perturbation of the Golgi Checkpoint Synergizes with Apoptotic Priming to Selectively Induce Tumor Cell Death.","authors":"Roberta Iannitti, Antonino Colanzi, Fabiola Mascanzoni","doi":"10.3390/cells15191825","DOIUrl":"10.3390/cells15191825","url":null,"abstract":"<p><p>Proper mitotic progression requires not only completion of DNA replication but also structural remodelling of the Golgi complex, including unlinking of the Golgi ribbon into isolated stacks during G2. This process activates a Golgi-dependent checkpoint that ensures accurate spindle assembly and cytokinesis. We previously showed that preventing GRASP65 phosphorylation through JNK inhibition blocks Golgi unlinking, impairs Aurora-A recruitment to centrosomes and, upon forced mitotic entry, induces multipolar spindles and binucleation. These studies established the mechanistic framework linking Golgi unlinking to mitotic entry and spindle formation. Here, building on this established framework, we asked whether the resulting mitotic vulnerability could be pharmacologically exploited. We therefore used SP600125 (SP) together with MK1775 (MK) as a previously characterized pharmacological platform and screened for compounds capable of further sensitizing these cells to death. This screen identified Navitoclax, a BCL-2/BCL-XL inhibitor, as the strongest enhancer of the SP+MK response. The triple combination selectively inhibited proliferation and induced apoptosis in tumor cells, while non-transformed RPE-1 cells remained largely resistant. Importantly, its activity depended on Golgi integrity: disrupting Golgi architecture with Brefeldin A partially restored cell viability, and efficacy correlated with Golgi compaction. Annexin V analysis confirmed apoptosis rather than mitotic slippage. Together, these findings identify a tumor-selective vulnerability linked to Golgi checkpoint disruption and support a therapeutic strategy combining Golgi checkpoint inhibition, forced mitotic entry and apoptotic priming to selectively eliminate cancer cells.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191773","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":"Olfactory Swab-Derived Human Neuroepithelium Cell Culture as a Novel Model to Study Neurodegeneration-Related Proteins.","authors":"Francesco Silvestri, Erika Bronzato, Ilaria Scambi, Valerio Arietti, Luca Sacchetto, Raffaella Mariotti, Gianluigi Zanusso, Matilde Bongianni, Ermanna Turano","doi":"10.3390/cells15191824","DOIUrl":"10.3390/cells15191824","url":null,"abstract":"<p><p>The olfactory neuroepithelium (ON) collected with nasal swabs (NS) is a valuable source for studying brain processes in physiological and pathological conditions, due to its anatomical proximity to the brain and heterogeneous neural cell population. In this proof-of-concept study, we developed a protocol for co-culturing distinct cellular populations from ON, establishing a human olfactory neuroepithelium cell culture (hON) model from healthy individuals (HIs) without differentiation factors. We characterized the cellular composition of ON samples at harvesting, identifying sustentacular cells (Pan-CK⁺), neuronal cells (PGP9.5⁺), and ciliated respiratory cells (βIV-tubulin⁺) by immunofluorescence and flow cytometry. We assessed the expression and distribution of TDP-43, Tau, and α-synuclein, together with their phosphorylated isoforms, to establish a physiological reference profile. Furthermore, Seeding Amplification Assay (SAA) analysis, including disease-positive and healthy control cohorts, confirmed the absence of aggregated protein species in HIs. While p-Tau and p-α-syn localization was preserved between collection and culture, p-TDP-43 displayed neuron-specific nuclear redistribution upon culture, suggesting distinct regulatory dynamics. Longitudinal monitoring revealed that hON cultures maintain a stable neuronal population for up to 21 days, after which cells transition toward a fibroblast-like phenotype. This study establishes NS-derived hON as a feasible model for investigating neurodegenerative mechanisms, providing a baseline for disease comparisons.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191637","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":"The Adipovascular Unit in Lipedema: A Framework for Regional Adipose Tissue Dysregulation.","authors":"Jörg Faulhaber, C William Hanke, Martin Barsch, Matthias Sandhofer","doi":"10.3390/cells15191820","DOIUrl":"10.3390/cells15191820","url":null,"abstract":"<p><p>Lipedema is a chronic, predominantly female disorder characterized by disproportionate regional expansion of subcutaneous adipose tissue, pain, tenderness, and easy bruising. Reported abnormalities involve adipocytes, stromal/progenitor cells, microvascular and immune compartments, extracellular matrix (ECM), and, variably, lymphatic function, but their causal and temporal relationships remain unresolved. Here, we propose the adipovascular unit (AVU) as a systems-level framework that links these compartments within a spatially organized regenerative niche. The conceptual advance is not the identification of a new anatomical structure, but the prediction that regional disease expression depends on reciprocal interactions among adipose stem and progenitor cells (ASPCs), endothelial and mural cells, immune populations, ECM, and mature adipocytes, rather than on a universal defect in any single cell type. We hypothesize that physiological female reproductive signals may expose a regionally susceptible AVU in which regenerative responses are inadequately constrained in space, magnitude, or duration. This framework also distinguishes lipedema from obesity-associated adipose dysfunction: lipedema is regionally patterned and may coexist with relatively preserved systemic metabolic function, whereas obesity-related adipose dysfunction is more closely linked to whole-body energy excess, ectopic fat, insulin resistance and cardiometabolic risk. Evidence demonstrated directly in lipedema is separated throughout from general adipose-tissue biology used to establish plausibility and from mechanisms that remain hypothetical. We derive falsifiable predictions involving depot-specific molecular states, endocrine context, multicellular cross-talk, extracellular-vesicle cargo and transfer, spatial biological boundaries, and persistence after stimulus withdrawal. Testing these predictions in paired-depot, spatially resolved and multicellular systems will determine whether AVU dysregulation is a causal organizing principle of lipedema or a descriptive consequence of established disease.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 19","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191594","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}