FASEB bioAdvances最新文献

{"title":"Microbiome-Endocannabinoidome Crosstalk as an Immunometabolic Rheostat in Inflammatory Disease","authors":"Reuben S. Maghembe,&nbsp;Donath Damian,&nbsp;Samweli Bahati,&nbsp;Abdalah Makaranga","doi":"10.1096/fba.2026-00201","DOIUrl":"https://doi.org/10.1096/fba.2026-00201","url":null,"abstract":"<p>Chronic inflammatory diseases reflect disrupted coordination among microbial ecology, epithelial barriers, lipid signaling, and immunity. The microbiome-endocannabinoidome (eCBome) axis is already recognized as a regulator of metabolism, permeability, and inflammatory tone; the unresolved issue is how to distinguish direct crosstalk from parallel or associative changes. This review therefore operationalizes the axis as an immunometabolic rheostat defined by five measurable domains: microbial functions and metabolites, compartment-specific eCBome ligands and enzymes, barrier integrity and microbial translocation, immune-cell programming, and tissue or clinical outcomes. We distinguish classical endocannabinoids (anandamide and 2-arachidonoylglycerol) from the endocannabinoid-related N-acylethanolamines palmitoylethanolamide and oleoylethanolamide, which act prominently through PPARα, TRPV1, GPR119, and related pathways. Evidence is appraised as direct causal, mechanistically supportive, associative, or hypothesis-generating. The strongest causal foundation links microbiota manipulation to intestinal eCBome tone, permeability, and metabolic endotoxemia, while disease-specific evidence is most developed in obesity-associated inflammation and inflammatory bowel disease. Engineered <i>Lactobacillus paracasei</i> platforms that produce PEA or OEA in situ provide particularly informative proof-of-concept because they couple a defined microbial perturbation to lipid-mediator release, receptor-dependent barrier effects, and inflammatory or metabolic outcomes. By contrast, evidence in MASLD/MASH, neuroinflammation, and systemic autoimmunity remains more compartment-dependent and heterogeneous. Clinical translation must account for the psychiatric toxicity that ended centrally active CB1 antagonism with rimonabant, the target and off-target complexity of FAAH/MAGL inhibition, and limitations of surrogate barrier biomarkers. A causal roadmap should combine gnotobiotic and loss-of-function models, isotope tracing, organoids, and gut-on-chip systems with tissue-resolved lipidomics and longitudinal, biomarker-enriched human trials.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 10","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Proteome of Plasma Extracellular Vesicles in Latent and Active Tuberculosis Reveals Phase-Specific Composition and Immunometabolic Insights","authors":"Eliud S.-Peregrino,&nbsp;Jessica Castañeda-Casimiro,&nbsp;Luis Vallejo-Castillo,&nbsp;Mishelle Soria-Fragoso,&nbsp;Gloria M. Ortega-Díaz,&nbsp;Karen I. Mondragón-Lara,&nbsp;Alfonso Méndez-Tenorio,&nbsp;Rommel Chacón-Salinas,&nbsp;Blanca E. García-Pérez,&nbsp;Jeanet Serafín-López,&nbsp;Carlos Wong-Baeza,&nbsp;Víctor Hugo Rosales-García,&nbsp;Alejandro Hernández-Solis,&nbsp;Isabel Wong-Baeza","doi":"10.1096/fba.2026-00238","DOIUrl":"10.1096/fba.2026-00238","url":null,"abstract":"<p>Tuberculosis (TB) is an infectious disease that affects millions of people worldwide. Extracellular vesicles (EVs) are mediators of intercellular communication that participate in the immunopathogenesis of TB. Here, we characterized plasma EVs from healthy individuals and from individuals with latent (LTB) or active TB (ATB). We found increased total protein concentrations in EVs from LTB and ATB individuals compared to healthy controls, without significant differences in EV concentrations, but reduced exosome abundance in LTB. Proteomic and bioinformatic analysis showed that LTB EVs were enriched in proteins associated with the regulation of inflammation, tissue remodeling, and lipid metabolism, including TGFβ and apolipoproteins (APO) A1 and E. In contrast, ATB EVs were enriched in mycobacterial antigens and host proteins associated with acute inflammation, including serum amyloid A1 and A2 (SAA1/A2) and the calgranulin complex proteins S100A8 and S100A9. These host proteins were central and/or cohesive nodes in the protein–protein interaction networks of these EVs. Dot blot analysis confirmed the increased levels of these EV proteins in a second group of individuals with LTB or ATB. The EV levels of mycobacterial antigens correlated positively with the EV levels of SAA1/A2 and S100A8/A9, but negatively with their levels of TGFβ and APOA1. Principal component analysis and hierarchical clustering suggested that the simultaneous analysis of mycobacterial antigens and these EV proteins could discriminate between healthy, LTB, and ATB individuals. Our findings confirm that plasma EVs provide insights into the host immunometabolic response to TB and may be a source of clinically useful biomarkers.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 10","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin Attenuates NKCC2 Protein Expression and Alleviates Diabetic Kidney Disease in Salt Loaded-Hypertensive Diabetic Db/Db Mice","authors":"Zenab Shahzad,&nbsp;Niharika Bala,&nbsp;Arooba Illyas,&nbsp;Amir Kazory,&nbsp;Indra Chandrasekar,&nbsp;Abdel A. Alli","doi":"10.1096/fba.2026-00209","DOIUrl":"https://doi.org/10.1096/fba.2026-00209","url":null,"abstract":"<p>Dapagliflozin, a potent sodium-glucose cotransporter 2 (SGLT2) inhibitor, slows diabetic kidney disease (DKD) progression and reduces blood pressure in diabetic mice, potentially via modulation of tubular sodium transporters and inflammatory pathways. RING-type E3 ligases, including cullin-based complexes, regulate the stability of with-no-lysine kinases (WNK1/4), key upstream activators of the sodium-potassium-chloride cotransporter 2 (NKCC2). Twelve-week-old male db/db mice were placed on a high-salt diet to induce hypertension and accelerate DKD, then randomized to receive dapagliflozin or vehicle by oral gavage for 14 days. Metabolic cages were used for 24-h urine collection, and glomerular filtration rate was measured using FITC-sinistrin clearance. Blood pressure was assessed by tail-cuff plethysmography. Kidneys were processed for histology, immunohistochemistry, Western blotting, and label-free proteomics. Dapagliflozin markedly reduced systolic blood pressure and improved renal injury on Periodic acid–Schiff staining, accompanied by reduced lactic acid accumulation and a lower urinary albumin-to-creatinine ratio. Proteomic profiling demonstrated differential abundance of multiple signaling proteins between groups. Western blotting showed increased expression of cullin 1, 2, and 3 family members, with a significant reduction in NKCC2 and aquaporin-2 protein levels in dapagliflozin-treated mice. In cultured mouse thick ascending limb cells, dapagliflozin inhibited high glucose–induced activation of the NLRP3 inflammasome, indicating an additional anti-inflammatory effect. Dapagliflozin confers renoprotection in salt-loaded hypertensive db/db mice by lowering blood pressure, attenuating tubular and glomerular injury, reducing NKCC2 abundance possibly via enhanced cullin-mediated degradation, and attenuating high-glucose–induced NLRP3 protein expression.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 10","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatorenal and Full Blood Count Profiles of Stroke Survivors Compared With Controls: A Case–Control Study","authors":"Moses Banyeh,&nbsp;Lilian Ayimpoka Atindaana,&nbsp;Felicia Essuman,&nbsp;Alexander Asamoah,&nbsp;Benjamin Kwabena Nyadu,&nbsp;Sinclair Selorm Henyo,&nbsp;Emmanuel Louis Nyaaba,&nbsp;Alfred Dekomwine Bamile,&nbsp;Prosper Bafiil Baneor,&nbsp;Brain Abotsi,&nbsp;Yvonne Aduhene Kwarteng,&nbsp;Prospera Dobara,&nbsp;Tracey Amankwaah,&nbsp;Nketia-Anim Yeboah,&nbsp;Jennifer Ankamah,&nbsp;Mathias Mbabila Mbah,&nbsp;James Ayamsigiya Akanvae,&nbsp;Abdul-Wahab Draman,&nbsp;Emmanuel Osei Akoto","doi":"10.1096/fba.2026-00172","DOIUrl":"https://doi.org/10.1096/fba.2026-00172","url":null,"abstract":"<p>Stroke is not merely a cerebrovascular event but a systemic disorder with multi-organ implications, including the liver and kidneys. Despite this growing body of knowledge, significant gaps persist. Most studies characterizing poststroke renal, hepatic, and hematological profiles originate from high-income settings, with limited data from sub-Saharan African populations who face distinct genetic, environmental, and healthcare access challenges. A case–control study was conducted at the Tamale Teaching Hospital between March and September 2025. The study involved 69 participants, aged 31–78 years, of whom 20 (29.0%) were stroke survivors (cases). Of the 69 participants, 39 (56.5%) were female. A single venous blood sample was collected and analyzed for full blood count, liver and renal function variables. Bivariate analysis revealed no significant differences in liver and renal function; however, the mean cell volume (MCV [fL]), the red cell distribution width (RDW-CV [%]), eosinophils (%), and plateletcrit (PCT [%]) were lower, whereas the mean cell hemoglobin concentration (MCHC [g/dL]) was higher in the stroke group. After adjusting for confounders, including body mass index (BMI) and occupation, the indirect bilirubin level was 0.143 mmol/L higher in the stroke group. In addition, the MCHC was 0.398 g/dL higher, while the hematocrit (HCT), MCV, and RDW-CV were lower in the stroke group by 0.206 (%), 0.121 (fL), and 0.514 (%), respectively. This study suggests that stroke survivors exhibit distinct hematological profiles, characterized by alterations in RBC morphology and possibly low-grade hemolysis or altered bilirubin metabolism independent of major liver or renal dysfunction. These changes may reflect the persistent systemic inflammation, oxidative stress, and erythropoietic adaptation following a stroke.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 10","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Algorithmic Phase Transitions: Integrating Evolutionary Contingency, Biophysical Constraints, and System-Level Organization in Eukaryogenesis","authors":"Antonio Salas","doi":"10.1096/fba.2026-00213","DOIUrl":"https://doi.org/10.1096/fba.2026-00213","url":null,"abstract":"<p>Understanding the origins and determinants of biological complexity requires integrating theoretical and empirical perspectives across the tree of life. The present work discusses a recent theoretical proposal suggesting that the emergence of eukaryotes can be understood as an algorithmic phase transition governed by universal scaling laws in gene structure. The model identifies broad regularities including protein length stabilization and increased regulatory complexity. The predicted stabilization of protein length around 500 amino acids (~1500 bp), coinciding with the prokaryote-to-eukaryote transition, represents a distinctive strength of the proposed framework. Drawing on evolutionary theory, this analysis highlights the importance of historical contingency, natural selection, and stochastic processes in shaping biological complexity. At the same time, biophysical, biochemical, and evolutionary mechanisms may contribute to constraining protein length, although these mechanisms do not currently explain the specific ~500-amino-acid threshold predicted by the phase-transition model. More broadly, complexity emerges from the interplay between evolutionary dynamics, physical constraints, and system-level organization. Factors such as epistasis, epigenetic regulation, population dynamics, gene–environment interactions, and ecological dynamics contribute to shaping evolutionary trajectories and constraining possible outcomes. This perspective therefore proposes an integrative framework in which phenomenological scaling relationships, mechanistic constraints, evolutionary dynamics, and historical contingency are viewed as complementary levels of explanation.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 10","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Simple Temperature-Controlled Method for Preserving Viability in Human Pluripotent Stem Cell-Derived Retinal Organoids During Shipment","authors":"Karen Cusato,&nbsp;Matthew J. Tarchick,&nbsp;Michael Ha,&nbsp;Jessica R. Onyak,&nbsp;Aimee C. Saunders,&nbsp;Joseph A. Brzezinski IV,&nbsp;Jordan M. Renna,&nbsp;M. Natalia Vergara","doi":"10.1096/fba.2026-00043","DOIUrl":"https://doi.org/10.1096/fba.2026-00043","url":null,"abstract":"<p>Retinal organoids derived from human induced pluripotent stem cells (hiPSCs) hold significant promise as a tool for advancing our understanding of human retinal development and disease, as well as for the development of therapeutic strategies. However, research utilizing hiPSC-derived retinal organoid models has been constrained by logistical challenges. A notable issue is the increasing need for scientific collaboration, as experiments requiring coordination across multiple institutions often rely on the shipping of live tissues. Transporting retinal organoids over long distances without adequate climate control can lead to tissue degradation, which may interfere with histopathological analyses and impact the results of drug screening assays. Retinal organoids are most often shipped either without temperature regulation or with lithium-ion battery-powered ambient environment systems, which are heavily regulated by standard shipping companies, thus raising costs and introducing further logistical complications. In this study, we developed and evaluated a straightforward, cost-effective, and dependable temperature-controlled technology for shipping retinal organoids that can maintain adequate shipping temperature in colder months and decrease temperature fluctuations during shipment year-round, preserving organoid tissue structure and viability.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 10","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2026-00043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyromonas gingivalis-Derived Phosphoglycerol-isoC17:0-Dihydroceramide Reprograms Sphingolipid Metabolism in Human OECM-1 Oral Squamous Cell Carcinoma Cells","authors":"Chiaki Yamada,&nbsp;Anny Ho,&nbsp;Natasha Sanz,&nbsp;Gang Peng,&nbsp;Ruijuan Xu,&nbsp;Cungui Mao,&nbsp;Xue Yuan,&nbsp;Fatemeh Momen-Heravi,&nbsp;Paul C. Edwards,&nbsp;Frank Nichols,&nbsp;Alexandru Movila","doi":"10.1096/fba.2026-00032","DOIUrl":"10.1096/fba.2026-00032","url":null,"abstract":"<p>Intracellular sphingolipids play a complex role in the survival and migration of oral squamous cell carcinoma (OSCC). For instance, dihydroceramide and ceramide sphingolipids suppress proliferation, whereas sphingosine-1-phosphate (S-1-P) promotes it. The balance between ceramide/S-1-P is critically regulated by the ceramide-hydrolyzing enzyme, acid ceramidase (aCDase), in OSCC. Indeed, aCDase mRNA expression is significantly upregulated compared with that in healthy epithelial cells. Our group identified that <i>Porphyromonas gingivalis</i> synthesizes a structurally unique phosphoglycerol-isoC17:0-dihydroceramide (PGDHC) sphingolipid. Our understanding of whether PGDHC modulates the critical ceramide/S-1-P balance and aCDase levels in OSCC remains limited. The effects of PGDHC on human OSCC cell lines and healthy oral epithelial cells were evaluated in vitro using conventional assays combined with untargeted and ceramide-targeted lipidomic screenings. Human tongue oral malignancy and the adjacent normal tissue from the same patient were also evaluated for the prevalence of anti-<i>P. gingivalis</i> IgG. Additionally, aCDase levels were evaluated in OSCC cell lines, clinical oral malignancy samples, and mouse models of 4-nitroquinoline-1-oxide (4-NQO)-induced OSCC. We identified the accelerated prevalence of aCDase in clinical and experimental malignant lesions. In contrast, we observed a lower prevalence of PGDHC-producing <i>P. gingivalis</i> in malignant lesions than in adjacent normal tissue. Indeed, our in vitro observations further demonstrated that PGDHC accelerates the accumulation of C16:0 dihydroceramide in OSCC by inhibiting acid ceramidase/ASAH1 mRNA expression. Altogether, PGDHC alters sphingolipid metabolism in human OSCC cells through the acid ceramidase/dihydroceramide axis. This finding lays the foundation for developing novel therapeutic strategies for oral cancer using PGDHC as a novel class of OSCC-suppressing compounds.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13599971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Hormone Reverses Cisplatin-Induced Ovarian Reserve Depletion in Mice: Transcriptomic Elucidation of Mitochondrial Metabolic Reprogramming and Protein Synthesis Regulation","authors":"Tianhong Huang,&nbsp;Niu Wang,&nbsp;Dongsheng Xiong,&nbsp;Yanan Zhang,&nbsp;Jiajing Wei,&nbsp;Furui Chen,&nbsp;Yu Qiu,&nbsp;Fangyi Long,&nbsp;Qianwen Luo,&nbsp;Jesse Li-Ling,&nbsp;Yan Gong","doi":"10.1096/fba.2026-00193","DOIUrl":"10.1096/fba.2026-00193","url":null,"abstract":"<p>Diminished ovarian reserve (DOR) presents a formidable challenge for assisted reproduction technology, as affected patients typically exhibit reduced oocytes and embryos during in vitro fertilization and embryo transfer (IVF-ET), which may ultimately lead to compromised clinical pregnancy rate. Although growth hormone (GH) supplementation has shown clinical efficacy in improving the outcomes of IVF-ET, the precise molecular mechanisms underlying its ability to enhance ovarian reserve have remained poorly characterized. In this study, a cisplatin-induced DOR mice model was established via intraperitoneal cisplatin administration. GH was subsequently evaluated at four dose levels over a 21-day intervention period. Comprehensive assessments included quantitative follicular histomorphometry, serum hormone profiling, and whole-transcriptome analysis of ovarian tissue. GH treatment significantly increased the number of primary and secondary follicles in a dose-dependent manner (<i>p</i> &lt; 0.05), while concurrently reducing atretic follicle counts in the medium- and high-dose GH groups compared to the DOR group (<i>p</i> &lt; 0.05). Furthermore, GH treatment restored hormonal balance, characterized by decreased follicle-stimulating hormone (FSH) and increased estradiol (E₂) and anti-müllerian hormone (AMH) levels (<i>p</i> &lt; 0.05). Transcriptomic analysis revealed that differentially expressed genes (DEGs) between the DOR and negative control (NC) groups were primarily associated with mitochondrial energy metabolism and the reproductive endocrine system, with functional enrichment in ribosome biogenesis, oxidative phosphorylation, and thermogenesis. In contrast, DEGs between the high-dose GH and DOR groups were predominantly enriched in pathways related to immunity, mitochondrial function, protein synthesis, and extracellular matrix-receptor interactions. In conclusion, GH can restore the ovarian reserve in cisplatin-induced DOR mice in a dose-dependent manner, potentially by modulating the genetic networks involved in energy metabolism, oxidative homeostasis, and protein synthesis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blue Light Exposure Induces Changes Associated With Senescence and Skin Aging in Human Dermal Fibroblasts","authors":"Helen McNish,&nbsp;Mruthyunjaya Swamy Mathapathi,&nbsp;Katarzyna Figlak,&nbsp;Anita Damodaran,&nbsp;Mark Birch-Machin","doi":"10.1096/fba.2026-00200","DOIUrl":"10.1096/fba.2026-00200","url":null,"abstract":"<p>Blue light is becoming increasingly prevalent in our daily lives. However, the possible deleterious effects of blue light exposure on the skin have been largely overlooked. We have previously shown that blue light has the ability to induce mitochondrial DNA (mtDNA) damage and dysfunction in human dermal fibroblasts (HDFn). However, whether blue light is able to induce senescence in skin has yet to be investigated. Cellular senescence is a key part of the aging process and is heavily associated with an aging phenotype. Our study involved exposing HDFn to varying doses of blue light before assessing the expression of known senescence markers using both immunofluorescence and gene expression qPCR. We also assessed beta-galactosidase activity using a senescence-associated beta-galactosidase (SA β-gal) staining kit. Blue light induces increased γH2AX expression (<i>p</i> = ≤ 0.0001), indicating its ability to induce DNA double-strand breaks. P21, a known marker of senescence, is increased in response to blue light, as seen in both immunofluorescence and gene expression, where a 15-fold increase is reported in cells exposed to 50 J/cm² blue light (<i>p</i> = ≤ 0.001). Importantly, NFκB also displayed a dose-dependent increase in expression following blue light exposure, with 25 J/cm² (<i>p</i> = ≤ 0.0001) and 50 J/cm² (<i>p</i> = ≤ 0.0001) inducing maximal nuclear translocation. SA β-gal activity also increased in response to blue light, with 25 J/cm² being the minimum dose required to induce statistical significance (<i>p</i> = ≤ 0.01) when compared to a non-irradiated control group. Taken together, we demonstrate that blue light may have the ability to induce not only mtDNA damage but also nuclear DNA (nDNA) damage. This, combined with the increased expression of senescent markers and SA-β-gal activity, suggests that blue light could induce cellular senescence while also eliciting the bystander effect in neighboring cells due to increased NFκB nuclear translocation and associated reactive oxygen species (ROS) production. These findings emphasize the need for further research into the potential deleterious effects of senescence in skin and for future interventions to attenuate these effects.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological Pitfalls in Endometriosis Biospecimen Research: Lessons From MAP4K4 Expression Studies","authors":"Dania Badran,&nbsp;Helen Clarke,&nbsp;Steven Salvini,&nbsp;Josephine Drury,&nbsp;Nicola Tempest,&nbsp;Alison Maclean,&nbsp;Christopher J. Hill,&nbsp;Dharani K. Hapangama","doi":"10.1096/fba.2026-00156","DOIUrl":"10.1096/fba.2026-00156","url":null,"abstract":"<p>Endometriosis is a chronic inflammatory condition affecting 10% of reproductive-age women. Current treatments remain limited and non-curative. While its biology is largely informed by human biospecimens, sample heterogeneity and methodological constraints often limit interpretability. Using mitogen-activated protein kinase 4 (MAP4K4), a cell motility and invasion regulator within the MAPK network, as a model molecule, we examined its expression in endometriosis to highlight challenges in biospecimen-based research. Public endometrial microarray datasets were re-analyzed using a standard limma pipeline to evaluate <i>MAP4K4</i> expression across tissue and disease states. MAP4K4 mRNA and protein were then assessed in eutopic endometrium from women with and without endometriosis and in surgically excised ectopic lesions using quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), RNA in situ hybridization (ISH), and laser capture microdissection (LCM) coupled with qPCR. <i>In silico</i> analyses revealed small effect sizes and inconsistent directional change in <i>MAP4K4</i> dysregulation across public datasets. <i>MAP4K4</i> mRNA levels differed significantly between pipelle and full-thickness eutopic biopsies. Bulk-qPCR showed no significant differences in the eutopic endometrium between groups, whereas IHC demonstrated increased MAP4K4 protein in mid-secretory eutopic endometrium from women with endometriosis. Whole-lesion qPCR suggested higher <i>MAP4K4</i> expression in ectopic versus matched eutopic tissue; however, LCM-qPCR and ISH did not identify consistent compartment-specific differences. Histology frequently revealed non-endometrial tissue in excised ectopic lesions. These findings highlight the methodological challenges in endometriosis biospecimen research and support the need for rigorous histological validation, spatially resolved approaches, and multi-modal analysis to improve the reliability and reproducibility of tissue-based studies in endometriosis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 9","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}