Frontiers in bioscience (Landmark edition)最新文献

{"title":"Inflammatory Network Architecture Across Bone Marrow Failure: An Immune-Genetic Continuum.","authors":"Swarna Beesetti","doi":"10.31083/FBL50689","DOIUrl":"https://doi.org/10.31083/FBL50689","url":null,"abstract":"<p><p>Bone marrow failure (BMF) syndromes encompass inherited disorders, immune-mediated aplasia, and clonal myeloid neoplasms, which share overlapping biology but divergent clinical trajectories. Inflammation shapes hematopoietic stem and progenitor cell fate across this spectrum, yet its network organization, genetic conditioning, and therapeutic implications remain incompletely defined. An integrative, literature-based analysis of inflammatory cytokines, genetic contexts, and therapeutic targeting across major BMF disorders, including inherited BMF syndromes, aplastic anemia (AA), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and myelofibrosis (MF). Gene-inflammation-outcome networks and co-occurrence maps were constructed with stratification by germline and somatic alterations. Therapeutic activity was mapped across cytokine-directed and pathway-targeted agents. Inflammatory signaling emerged as a conserved feature across all BMF categories, with TNF-α, IFN-γ, and IL-6 forming a recurrent core module, and TGF-β linking inflammatory programs to fibrotic remodeling. <i>TP53</i>- and <i>JAK2</i>-associated pathways appeared as central nodes integrating multi-cytokine inputs. Germline lesions in <i>FANCA</i>, <i>TERC/TERT</i>, and <i>GATA2</i> were predominantly associated with apoptotic stem-cell attrition. In contrast, somatic drivers, including <i>TP53</i>, <i>JAK2</i>, <i>TET2</i>, <i>DNMT3A</i>, and <i>ASXL1</i>, were more frequently associated with clonal expansion. Multi-cytokine convergence on shared effectors was common, suggesting pathway redundancy. The therapeutic literature predominantly focused on TNF-α/IFN-γ/IL-6 pathways, with comparatively limited exploration of TGF-β, IL-8, and IL-17. These findings support a role for inflammation as a unifying, context-dependent modifier across the BMF spectrum, and highlight <i>TP53</i>- and <i>JAK2</i>-centered circuitry as potential nodes for rational combination strategies. TGF-β, IL-8, and IL-17 axes and inherited BMF entities represent underexplored opportunities for biomarker-guided cytokine-directed intervention.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"50689"},"PeriodicalIF":3.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E3 Ubiquitin Ligase RNF126 Promotes Ovarian Cancer Progression and Cisplatin Resistance Through Targeting Numb/Notch1 Axis.","authors":"Tianjiao Zheng, Han Wu, Li Niu, Xiaodong Wang, Hailiang Liu, Xinyan Jiang","doi":"10.31083/FBL54223","DOIUrl":"https://doi.org/10.31083/FBL54223","url":null,"abstract":"<p><strong>Background: </strong>RING finger protein 126 (RNF126) is an E3 ubiquitin ligase that is overexpressed in various malignancies. However, its role in ovarian cancer remains poorly understood.</p><p><strong>Methods: </strong>Ovarian cancer cell lines, including SKOV3, A2780, and cisplatin-resistant SKOV3/DDP, were utilized in this study. RNF126 expression was modulated via lentiviral transduction. Cell viability, colony formation, and migration were assessed by cell counting kit-8 (CCK-8), colony formation, and Transwell assays. Protein and mRNA levels were measured by Western blotting and real-time quantitative PCR (qPCR). Protein interaction was evaluated by co-immunoprecipitation and ubiquitination assays. <i>In vivo</i> tumor growth and cisplatin response were examined using a xenograft model.</p><p><strong>Results: </strong>In SKOV3 and A2780 cells, RNF126 overexpression promoted proliferation, colony formation, and migration, while its knockdown produced the opposite effects. Notably, elevated RNF126 expression was observed in the cisplatin-resistant SKOV3/DDP line. Silencing RNF126 in these cells increased cisplatin sensitivity while concurrently reducing proliferative capacity, clonogenicity, and migratory potential. RNF126 depletion in SKOV3/DDP cells led to decreased mRNA and protein expression of Notch1 and its downstream targets Myc, Cyclin D3, and Hes1. Meanwhile, Numb mRNA levels remained unchanged, whereas its protein levels increased, indicating post-transcriptional regulation. Furthermore, Numb silencing increased cell viability, clonality, migration, and Notch signaling activation in RNF126 knockdown SKOV3/DDP cells. <i>In vivo</i>, silencing RNF126 markedly enhanced the sensitivity of cells to cisplatin, suppressed tumor growth, and inhibited Myc, Cyclin D3, Hes1, and Notch1 protein expression. Silencing Numb can reverse the inhibitory effects of RNF126 knockdown. Mechanistic studies showed that RNF126 directly binds to the Notch signaling inhibitor Numb and mediates its ubiquitination and proteasomal degradation, thereby activating the Notch1 signaling pathway and upregulating its downstream genes. In addition, analysis of the TCGA dataset revealed that elevated RNF126 expression is a significant prognostic factor associated with increased mortality risk in ovarian cancer.</p><p><strong>Conclusions: </strong>These findings establish RNF126 as a critical contributor to cisplatin resistance in ovarian cancer via regulation of the Numb/Notch1 pathway and highlight its potential as a therapeutic target to counteract chemoresistance.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"54223"},"PeriodicalIF":3.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Resveratrol on Cardiac Remodeling in Female Rats: Emphasizing the Need for Sex-Specific Research.","authors":"Elizabeth Romero-Monter, Jazmín Flores-Monroy, Diego Lezama-Martínez, German-Isauro Garrido-Fariña, Andrés Aragón-Martínez, Ruth-Mery Lopez-Mayorga, Karla Reyes-Alvarado, Cesar-Froylan Ramirez-Hernandez, Diana Ramirez-Hernandez","doi":"10.31083/FBL54167","DOIUrl":"https://doi.org/10.31083/FBL54167","url":null,"abstract":"<p><strong>Background: </strong>Menopause induces estrogen deficiency and promotes a pro-inflammatory and pro-fibrotic cardiovascular environment that increases susceptibility to adverse remodeling after myocardial infarction (MI). This study evaluated resveratrol as an inflammatory modulator and assessed its effects on cardiac fibrosis and hypertrophy in aged ovariectomized Wistar rats with chronic MI.</p><p><strong>Methods: </strong>Thirty-six, one-year-old female Wistar rats (450-500 g) were allocated to six groups (n = 6 per group), with or without resveratrol treatment: (1) Sham, (2) Sham-R, (3) Bilateral ovariectomy (OVX), (4) OVX-R, (5) OVX + left anterior descending coronary artery ligation (LADL); OVX-LADL, and (6) OVX-LADL-R. Structural alterations, collagen deposition, and inflammatory profiles were assessed using histological analysis, morphometric measurements, and correlation-based heatmap. LADL in ovariectomized rats resulted in marked structural disorganization, increased cardiac fibrosis, and a predominance of pro-inflammatory mediators.</p><p><strong>Results: </strong>Resveratrol treatment attenuated collagen deposition, partially preserved tissue architecture, and shifted the inflammatory profile towards a less pro-fibrotic pattern. Heatmap analysis showed that resveratrol reduced the strength of correlations between inflammatory markers and fibrotic remodeling, particularly in estrogen-deficient animals.</p><p><strong>Conclusion: </strong>These findings suggest that resveratrol attenuates adverse cardiac remodeling after MI in ovariectomized rats by modulating inflammation-driven fibrosis under estrogen-deficient conditions a response associated with increased IFN-γ.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"54167"},"PeriodicalIF":3.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Attenuates Gemcitabine Resistance in Hepatocellular Carcinoma Cells by Inhibiting Thymidylate Synthase.","authors":"You Tang, Chuang Peng, Sulai Liu, Yunfeng Li, Siwei Zhu, Ya Zhu, Zhiguo Tan, Xu Chen, Ou Li","doi":"10.31083/FBL52448","DOIUrl":"https://doi.org/10.31083/FBL52448","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Gemcitabine (Gem) is a commonly used drug against HCC, but its efficacy is limited by the development of resistance. Resveratrol (Res), a natural polyphenol with antitumor activity, may reverse Gem resistance in HCC, although the mechanism remains unclear.</p><p><strong>Methods: </strong>The effects of Res on the proliferation, apoptosis, cell cycle, and invasion of Hep3B and HuH-7 cells were assessed via cell counting kit-8 (CCK-8), clonogenic, flow cytometry, and Transwell assays, respectively. Potential Res targets were predicted by network pharmacology, and markers of HCC prognosis were identified from the cancer genome atlas (TCGA) data. The interaction between Res and thymidylate synthase (TYMS) was validated by molecular docking and dynamics simulation. A Gem-resistant HuH-7 cell line (HuH-7/GR) was established, and when these cells were treated with Res combined with Gem, the effect on Gem sensitivity was detected by CCK-8 assay, clonogenic assay, and flow cytometry. Finally, a subcutaneous nude mouse model of HCC was used to evaluate the <i>in vivo</i> effects of Res combined with Gem.</p><p><strong>Results: </strong>Res inhibited HCC cell proliferation, induced apoptosis and G2/M arrest, and suppressed invasion in a concentration-dependent manner. Network pharmacology and TCGA analysis identified TYMS as an important target gene for Res. TYMS was highly expressed in HCC tissues and correlated with poor prognosis. Res treatment reduced TYMS expression, while molecular docking and simulation showed stable binding of Res to TYMS. TYMS levels were elevated in HuH-7/GR resistant cells. Res combined with Gem was found to reverse drug resistance, inhibit proliferation and colony formation, and induce apoptosis. The Res + Gem combination group showed the smallest tumor volume in the <i>in vivo</i> model.</p><p><strong>Conclusion: </strong>By attenuating Gem resistance through TYMS inhibition, Res holds promise as a clinically viable adjunct to Gem-based chemotherapy, offering a potential strategy to improve outcomes in HCC patients.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"52448"},"PeriodicalIF":3.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tazarotene-Induced Gene 2 Promotes Melanoma Cell Death via the Activation of Endoplasmic Reticulum Stress.","authors":"Chun-Hua Wang, Lu-Kai Wang, Fu-Ming Tsai","doi":"10.31083/FBL54095","DOIUrl":"https://doi.org/10.31083/FBL54095","url":null,"abstract":"<p><strong>Background: </strong>Tazarotene-induced gene 2 (<i>TIG2</i>), also known as retinoic acid receptor responder 2 (<i>RARRES2</i>), encodes the secreted protein TIG2, also known as chemerin, which is involved in immune regulation and metabolism. However, its role in melanoma remains unclear.</p><p><strong>Methods: </strong><i>TIG2</i> expression was analyzed using The Cancer Genome Atlas, Genotype-Tissue Expression, OncoDB, and melanoma tissue cDNA arrays. To evaluate its effects on cell viability and death, TIG2 was overexpressed in A2058 and A375 melanoma cells. RNA sequencing (RNA-seq), qPCR, and Western blotting were performed to identify TIG2-regulated genes and signaling pathways. The involvement of chemokines and endoplasmic reticulum (ER) stress was further examined using the C-X-C motif chemokine ligand 10 (CXCL 10)/CXCL11 and the ER stress inhibitor tauroursodeoxycholic acid (TUDCA).</p><p><strong>Results: </strong><i>TIG2</i> expression was reduced in melanoma and other skin cancers. TIG2 overexpression significantly reduced cell viability and induced cell death. RNA-seq analysis showed that TIG2 downregulated <i>CXCL10</i>, <i>CXCL11</i>, and <i>CCL2</i> while upregulating ER stress-related genes such as <i>HERPUD1</i> and <i>DDIT3</i>. Exogenous CXCL10 or CXCL11 did not reverse TIG2-mediated effects, whereas TUDCA partially restored cell viability and reduced cell death.</p><p><strong>Conclusions: </strong>These findings suggest that TIG2 suppresses melanoma cell growth by activating ER stress and modulating immune-related chemokines, highlighting its potential therapeutic relevance.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"54095"},"PeriodicalIF":3.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fungal Esophagitis: Molecular Insights Into Pathogenesis and Emerging Antifungal Strategies.","authors":"Konstantinos Papantoniou, Ploutarchos Pastras, Ioanna Aggeletopoulou, Christos Triantos","doi":"10.31083/FBL50241","DOIUrl":"https://doi.org/10.31083/FBL50241","url":null,"abstract":"<p><p>Fungal esophagitis, predominantly caused by <i>Candida</i> species, remains the leading form of infectious esophagitis worldwide. Although historically linked to human immunodeficiency virus infection, its epidemiology has shifted over recent decades, with a growing incidence among oncology patients receiving immune checkpoint inhibitors, individuals with eosinophilic esophagitis on oral corticosteroids, and solid-organ transplant recipients. Increasing evidence highlights that disease pathogenesis extends beyond simple fungal overgrowth and involves intricate host-pathogen interactions. Pathogenic mechanisms such as adhesion, hyphal transition, and biofilm formation enhance fungal virulence, while mucosal immune dysfunction, particularly impaired T helper 17/interleukin 17 signaling and reduced antimicrobial peptide activity, predisposes to persistent infection. Antifungal resistance represents an emerging challenge, driven by efflux pump overexpression, <i>ERG11</i> mutations conferring azole resistance, and mutations of <i>FKS</i> genes leading to reduced echinocandin susceptibility. These molecular mechanisms underscore the complexity of treatment and have important implications for antifungal selection and clinical management. While fluconazole remains the first-line agent for most cases, the increasing prevalence of non-<i>albicans Candida</i> species and drug resistance underscore the importance of alternative medications with different molecular targets. Agents such as the recently approved rezafungin as well as compounds such as ibrexafungerp and fosmanogepix, represent promising options for the treatment of refractory disease. This review synthesizes current advances in the molecular pathogenesis of fungal esophagitis, with particular emphasis on host-fungal interactions, antifungal resistance mechanisms, and novel treatment strategies. A deeper understanding of these processes is essential to improve management and to guide the development of innovative immunomodulatory and antifungal therapies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"50241"},"PeriodicalIF":3.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Ma et al. Qi-dan-di-huang decoction alleviates diabetic nephropathy by inhibiting the NF-kappaB pathway. Frontiers in Bioscience (Landmark Edition). 2019; 24: 1477-1486.","authors":"","doi":"10.31083/FBL57288","DOIUrl":"https://doi.org/10.31083/FBL57288","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"57288"},"PeriodicalIF":3.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the HIF-1α/IL-1β Axis in Macrophages With the Novel Inhibitor LJ-6 Mitigates Adipose Tissue Inflammation in Cellular and <i>Ex Vivo</i> Models.","authors":"Min Gao, Mengyuan Liu, Anran Chu, Sisi Deng, Jingsong Gao, Shasha Li, Dongsheng Jiang, Yuqing Shen, Xinyue Wang, Saifei Lei, Rui Wu, Haowen Jiang, Jia Li, Jinlong Li, Xinyi Wang, Chang Peng","doi":"10.31083/FBL53391","DOIUrl":"https://doi.org/10.31083/FBL53391","url":null,"abstract":"<p><strong>Background: </strong>Sustained activation of adipose tissue macrophages (ATMs) drives metabolic dysfunction in obesity, with the hypoxia-inducible factor-1α (HIF-1α)/interleukin-1β (IL-1β) axis being a core signaling pathway. However, specific strategies targeting this axis are still lacking. Here, we aimed to identify novel compounds capable of disrupting this pathway.</p><p><strong>Methods: </strong>We screened a natural product library for inhibitors of IL-1β expression in macrophages. The hit compound LJ-6 was then evaluated in lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and in a physiologically relevant model using conditioned medium from obese adipose tissue. Mechanism of action was investigated <i>via</i> Western blotting, molecular docking, dynamics simulations, and hypoxia-response element (HRE)-luciferase reporter assays with site-directed mutagenesis.</p><p><strong>Results: </strong>LJ-6 was identified as a potent inhibitor of IL-1β. It dose-dependently suppressed IL-1β in both LPS-induced and obese adipose tissue-conditioned medium-induced macrophage inflammation. Mechanistically, LJ-6 reduced HIF-1α protein stability. Molecular docking and mutagenesis studies supported an interaction involving the Tyr92 and His197 residues of HIF-1α, and suggested that this interaction is critical for its inhibitory function on the HIF-1α/IL-1β axis.</p><p><strong>Conclusions: </strong>This study identifies the natural compound LJ-6 as a novel direct inhibitor of HIF-1α. By binding to HIF-1α, LJ-6 effectively suppresses the HIF-1α/IL-1β axis in macrophages, thereby reducing IL-1β-driven inflammatory responses in cellular and <i>ex vivo</i> models of obesity-associated adipose tissue inflammation, and thus represents a promising lead compound for therapeutic development.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"53391"},"PeriodicalIF":3.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PF-127 Hydrogel-Delivered hUCMSC-Exosomes Attenuate Endometrial Injury by Inhibiting Epithelial-Mesenchymal Transition.","authors":"Liwei Bao, Li Li, Shengbin Tang, Yezi Tang, Zihan Wang, Jiaxi Tan, Huihui Zhang, Rushi Liu, Xia Zhang","doi":"10.31083/FBL53953","DOIUrl":"https://doi.org/10.31083/FBL53953","url":null,"abstract":"<p><strong>Background: </strong>Endometrial injury, often resulting from iatrogenic procedures or infections, can lead to fibrosis, adhesions, and infertility. Current therapies are inadequate for reversing fibrosis or restoring normal function. Mesenchymal stem cell-derived exosomes (MSC-exos) present therapeutic potential; however, their rapid clearance poses a challenge. The purpose of this study was to develop a thermosensitive Pluronic F-127 (PF-127) hydrogel for sustained intrauterine delivery of human umbilical cord MSC-derived exosomes (PF-127-hUCMSC-exos) and to evaluate its efficacy and underlying mechanisms in a rat model of ethanol-induced endometrial injury.</p><p><strong>Methods: </strong>A thermosensitive PF-127 hydrogel loaded with hUCMSC-exos was developed. Its retention and therapeutic effects were evaluated in a rat model of ethanol-induced endometrial injury. Comparisons were made among control, model, hydrogel treatment alone, and PF-127-hUCMSC-exos treatment. Mechanistic assessments included histological analysis, collagen deposition measurement, fertility testing, expression analysis of epithelial-mesenchymal transition (EMT) markers (E-cadherin, vimentin, β-catenin), transcriptomic analysis of exosome-treated primary rat endometrial stromal cells, and measurement of early growth response 2 (EGR2) mRNA and protein levels.</p><p><strong>Results: </strong>PF-127-hUCMSC-exos were detectable in the uterine cavity up to day 12, and this treatment significantly improved endometrial morphology, increased thickness and gland number, reduced collagen deposition, and partially restored fertility. Mechanistically, exosomes inhibited EMT by upregulating E-cadherin and downregulating vimentin and β-catenin. RNA-seq of exosome-treated rESCs identified 1173 differentially expressed genes, with enrichment in EMT-related pathways. EGR2, a pro-fibrotic transcription factor, was significantly downregulated at both mRNA and protein levels. EGR2 overexpression promoted cell migration, which was reversed by exosome treatment.</p><p><strong>Conclusions: </strong>PF-127-hUCMSC-exos hydrogel effectively repairs endometrial injury and restores fertility by inhibiting EMT, potentially via EGR2 downregulation. This cell-free strategy offers a promising approach for endometrial regeneration.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"53953"},"PeriodicalIF":3.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental Study on Anti-Infection and Promotion of Macrophage Polarization for the Treatment of Traumatic Bone Infection Using Rifampicin/Moxifloxacin-Loaded PLGA Microspheres.","authors":"Jing An, Yafeng Zhang, Peijie Zhao, Tao Ding, Huanhuan Sun, Zhipeng Yang, Huanxiang Guan, Yaodong Wang, Hairui Fang, Zewen Qiao","doi":"10.31083/FBL52014","DOIUrl":"https://doi.org/10.31083/FBL52014","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Traumatic osteomyelitis remains a prevalent and intractable clinical disorder in orthopedics. Treatment of this condition is severely hindered by multiple factors, including multidrug-resistant bacterial infections (predominantly methicillin-resistant Staphylococcus aureus, MRSA), the blood-bone barrier, infection-induced bone necrosis, and the internalization capacity of bone cells. Current therapeutic strategies mainly consist of debridement, systemic antibiotic administration, and local sustained-release antibiotic delivery. Local biodegradable materials with sustained antibiotic release may help maintain effective antibacterial exposure at infectious sites and may be associated with favorable changes in the inflammatory microenvironment during infection resolution and tissue repair.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Our research team has previously constructed rifampicin/moxifloxacin-loaded Poly(lactic-co-glycolic acid) (PLGA) sustained-release microspheres and validated their favorable sustained-release characteristics and antibacterial properties &lt;i&gt;in vitro&lt;/i&gt;. In the present study, we further investigated their therapeutic efficacy against traumatic osteomyelitis, with a focus on infection-related pathological changes and macrophage polarization-associated inflammatory responses. A murine femoral traumatic osteomyelitis model was established, and animals were assigned to three groups (control, model, and rifampicin-moxifloxacin (RM)-PLGA treatment) for comparative intervention. General observation, X-ray examination, and histopathological staining were performed for evaluation. Additionally, serological analysis, histopathological assessment, western blotting, and immunofluorescence were used to detect relevant indicators. &lt;i&gt;In vitro&lt;/i&gt; experiments using infected RAW264.7 macrophages co-cultured with microspheres were conducted to further verify the effects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;General observation, X-ray examination, and histopathological staining revealed that local infection was markedly alleviated in the microsphere group, whereas persistent infection-related changes were observed in the model group, and the control group remained largely normal. Serological analysis, histopathological assessment, Western blot, and immunofluorescence showed that RM-PLGA treatment attenuated inflammatory responses and was associated with changes in macrophage polarization-associated markers. &lt;i&gt;In vitro&lt;/i&gt;, RM-PLGA treatment reduced IL-6 and IL-1β levels, increased IL-10 levels, and significantly decreased the fluorescence intensities of both CD38 and CD206. &lt;i&gt;In vivo&lt;/i&gt;, RM-PLGA treatment reduced serum pro-inflammatory cytokine levels and CD38 fluorescence intensity. CD206 fluorescence intensity was comparable to that in the model group on day 7 but was significantly lower on days 14 and 28; serum IL-10 levels were significantly lower on days 7 and 28 and did not differ significantly on day ","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"31 8","pages":"52014"},"PeriodicalIF":3.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}