Biomedicines最新文献

{"title":"Topical 7% Ectoine Modulates Cutaneous Response During Serial Vascular 1064-nm Nd:YAG Laser Therapy: A Randomized, Vehicle-Controlled Split-Face Study.","authors":"Izabela Załęska, Urszula Goik, Anna Smuda","doi":"10.3390/biomedicines14092068","DOIUrl":"10.3390/biomedicines14092068","url":null,"abstract":"<p><p><b>Background</b>: Repeated vascular laser exposure induces not only selective photothermal effects within blood vessels but also secondary responses in the surrounding skin. This study investigated whether topical 7% ectoine modifies the trajectory of cutaneous response during a series of 1064-nm Nd:YAG laser treatments. <b>Methods</b>: Thirty participants underwent four 1064-nm Nd:YAG laser treatments in a prospective, randomized, vehicle-controlled split-face study. Following each treatment, one side of the face received a formulation containing 7% ectoine (ECT), whereas the contralateral side received an identical vehicle without ectoine (vehicle control). Skin erythema, stratum corneum hydration, transepidermal water loss (TEWL), melanin index, and skin surface pH were assessed longitudinally. Redness was independently quantified using the CIELAB a* coordinate, while high-frequency ultrasonography was used to determine the proportion of low-echogenic pixels (LEPs). An untreated internal reference area (UIRA) was additionally assessed to characterize spontaneous temporal and environmental variability in skin parameters. The study was retrospectively registered in the ISRCTN registry (ISRCTN69645337). <b>Results</b>: Compared with the vehicle, ECT produced a significantly greater overall reduction in skin erythema (ΔΔ = -35.44 AU; 95% CI: -44.88 to -26.01; <i>p</i> < 0.001), accompanied by a greater reduction in CIELAB a* (ΔΔ = -1.18; 95% CI: -1.58 to -0.78; <i>p</i> < 0.001). ECT was also associated with a greater overall improvement in stratum corneum hydration assessed by corneometry (ΔΔ = +5.96 AU; <i>p</i> < 0.001), a greater reduction in TEWL (ΔΔ = -0.73 g/m²/h; <i>p</i> = 0.0012), and a greater decrease in LEPs (ΔΔ = -0.55 percentage points; <i>p</i> < 0.001). No significant between-treatment advantage was observed for the melanin index or skin surface pH. <b>Conclusions</b>: Topical application of 7% ectoine during serial vascular 1064-nm Nd:YAG laser therapy was associated with a distinct trajectory of cutaneous response compared with the vehicle alone. The effect was characterized by a greater reduction in the erythematous component, improvement in barrier-related parameters, and changes in dermal echogenic properties. These short-term instrumental findings support further investigation of ectoine as an adjunctive topical strategy during repeated photothermal procedures; their clinical significance requires confirmation using standardized clinical and patient-reported outcomes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-Inflammation Crosstalk in Myeloproliferative Neoplasms: MPN-Specific Human Data, Mechanistic Plausibility and Translational Priorities.","authors":"Laura-Gabriela Țîrlea, Lavinia Lipan, Alina Daniela Tănase","doi":"10.3390/biomedicines14092074","DOIUrl":"10.3390/biomedicines14092074","url":null,"abstract":"<p><p>Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders driven mainly by somatic mutations in <i>JAK2</i>, <i>CALR</i> or <i>MPL</i>, but their clinical phenotype is also shaped by chronic inflammation, immune dysregulation, vascular complications and microenvironmental remodeling. Emerging evidence suggests that the gut microbiota may contribute to this inflammatory and immunometabolic landscape; however, the current literature remains heterogeneous and its translational relevance is still insufficiently defined. This critical narrative review maps the available evidence linking the gut microbiota, microbial metabolites and systemic microbial signatures to MPN biology. We distinguish direct human MPN data from indirect mechanistic evidence derived from studies of intestinal barrier dysfunction, thrombo-inflammation, hematopoietic regulation, allogeneic hematopoietic cell transplantation and infection risk. Across human MPN cohorts, the most consistent findings are not uniform changes in global microbial diversity, but rather alterations in specific immunoregulatory taxa, particularly reduced <i>Firmicutes</i>/<i>Faecalibacterium</i>-related communities and dysbiotic signatures associated with <i>JAK2V617F</i> status. Mechanistically, dysbiosis and impaired intestinal barrier integrity may facilitate low-grade endotoxemia, TLR4/NF-κB activation, cytokine amplification, endothelial activation and platelet priming. In parallel, microbial metabolites may influence hematopoietic stem cell programs, the bone marrow niche, megakaryopoiesis and thrombopoiesis. Treatment exposure and diet are relevant modifiers of the microbiota-inflammation axis, although available interventional data remain preliminary. Mendelian randomization and multi-omics studies provide hypothesis-generating evidence for microbiota-metabolome-MPN interactions, but require longitudinal validation, functional studies and contamination-aware analytical pipelines, especially for low-biomass blood and bone marrow samples. Microbiota-targeted strategies, including nutritional interventions and fecal or washed microbiota transplantation, represent promising but still investigational approaches, particularly in immunocompromised or post-transplant settings. Future studies should integrate microbiome, metabolome, genome, proteome, inflammatory biomarkers and clinical outcomes while controlling for diet, antibiotics, treatment exposure and driver mutation status. Such an approach may clarify whether the microbiota is a biomarker, mediator or therapeutic target in MPNs.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism and Component Study of Scorpion Peptides Regulation of Macrophage Polarization in Diabetic Wounds.","authors":"Si Shi, Yarong Ding, Shuangxi Yang, Furong Zhu, Li Chen, Xinling Huang, Zhongzhi Zhou","doi":"10.3390/biomedicines14092071","DOIUrl":"10.3390/biomedicines14092071","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The incidence of diabetes-related chronic wounds has been increasing annually, characterized by delayed wound healing due to persistent inflammatory responses. To alleviate patient suffering, there is an urgent need to discover novel wound-healing agents that reduce local inflammatory reactions. Animal peptides emerge as promising candidates due to their low molecular weight, low toxicity, low resistance potential, high sensitivity, potent activity, and ease of transmembrane absorption. However, the precise mechanism by which animal peptides accelerate skin wound healing remains unclear. &lt;b&gt;Method:&lt;/b&gt; Scorpion peptides were extracted using ultrafiltration, followed by de novo analysis after library searching with Peaks 8 software and combined LC-MS/MS detection to identify peptide components in scorpions. A full-thickness skin defect model in diabetic mice was established to evaluate the wound-healing promotion capacity of scorpion peptides. In vitro experiments were conducted using mouse monocyte-macrophage leukemia cells (RAW264.7 cells). Enzyme-linked immunosorbent assay (ELISA) evaluated inflammatory cytokine expression, flow cytometry analyzed macrophage phenotypes, Western blotting (WB) measured P-P65 and P65 protein levels, immunofluorescence to observe P-P65 nuclear translocation, molecular docking and molecular dynamics simulations, and the Cellular Thermal Shift Assay (CETSA) to evaluate the binding capacity of scorpion peptides to target proteins, and the TUNEL assay to detect apoptosis, among other methods, to investigate the mechanisms by which scorpion peptides promote wound healing. &lt;b&gt;Result:&lt;/b&gt; This study successfully identified 2331 peptides from a scorpion peptide extract. In a full-thickness skin defect model in diabetic mice, treatment with scorpion peptides significantly promoted wound healing and induced M2 polarization of macrophages at the wound site. Further in vitro mechanism studies were conducted using a RAW264.7 cell inflammation model established by combining lipopolysaccharide (LPS) with high glucose. The results showed that scorpion peptide reduced the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), increased the anti-inflammatory cytokine interleukin-10 (IL-10), downregulate the P-P65/P65 protein expression ratio, and reduce the number of TUNEL-positive apoptotic cells, suggesting that the NF-κB pathway may be involved in mediating its anti-inflammatory and anti-apoptotic effects. To further identify the target, molecular docking and molecular dynamics simulations showed that the active peptide segments PPPPPP and GPPPPP adopt stable binding conformations with the P65 protein; CETSA further validated that they enhance the thermal stability of the P-P65 protein. Through repeated validation using active peptide fragments, ELISA, flow cytometry, Western blot, and immunofluorescence assays consistently confirmed that scorpion peptide, PPPPPPP, and GPPPPP not only inhibit P65 phos","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Association Between Polyamine Metabolism and Lipid Peroxidation in Different Pathological Regions of Glioblastoma.","authors":"Zheng Qu, Kaijing Guo, Xin Xiang, Yuhan An, Ting Lei, Angsi Liu, Yulin Wang, Dongting Chen, Hong Chen, Ziqian Zhang, Jiangjia Qin, Jiuming He, Xueji Li, Fangjun Liu, Yan Li","doi":"10.3390/biomedicines14092067","DOIUrl":"10.3390/biomedicines14092067","url":null,"abstract":"<p><p><b>Background</b>: Glioblastoma is highly heterogeneous, highly invasive, and resistant to temozolomide, with an extremely low 5-year survival rate. The spatial association between polyamine metabolism and ferroptosis remains unclear. Spatial metabolic heterogeneity is a core challenge in glioblastoma treatment. <b>Methods</b>: In this study, 17 patients with primary or recurrent high-grade glioma were included. Spatial metabolomics (<i>n</i> = 9), multiplex immunofluorescence (exploratory experiment <i>n</i> = 10, observational experiment <i>n</i> = 1), flow cytometry (<i>n</i> = 13), and mouse orthotopic models (<i>n</i> = 3) were combined to analyze the characteristics of the polyamine-ferroptosis axis in the para-carcinoma, tumor, and necrotic regions. <b>Results</b>: Differences in the polyamine-metabolism-ferroptosis axis were observed across distinct pathological regions of glioblastoma. Regional differences in polyamine distribution were associated with regional differences that lower lipid-peroxidation signals in the tumor region and higher lipid-peroxidation signals in the necrotic region. Moreover, in glioblastoma patient specimens, lipid-peroxidation-associated signals were detected in immune-cell compartments, alongside immune-cell phenotypic features suggestive of dysfunction, which show correlation with an immunosuppressive microenvironment. At the regional level, enzymes related to polyamine metabolism, namely GLS and SMS, exhibited spatial co-localization trends with lipid-peroxidation markers. Alterations in markers of the GSH-GPX4 and FSP1 antioxidant systems were spatially associated with the tumor-region-specific lipid-peroxidation profile. Partial spatial patterns of polyamine metabolism observed in human samples were partially recapitulated in mouse orthotopic tumor models. <b>Conclusions</b>: Glioblastoma exhibits spatially distinct distribution of the polyamine-ferroptosis-associated molecular signature. Notable correlative spatial features include spermidine and spermine enrichment, altered regional abundance within the glutamine-glutamate metabolic axis, immune-cell lipid-peroxidation-associated signals and immune-cell-dysfunction-related phenotypes, and regional shifts in GSH-GPX4/FSP1-related markers. This study identifies potential targets and provides a correlative spatial framework for region-specific therapeutic investigation, but the establishment of the causal relationship still requires further functional verification.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FABP4/5-Mediated Lipid Reprogramming Is Associated with Immunosuppressive T Cell Crosstalk in Cervical Cancer After Chemoradiotherapy.","authors":"Tianhan Xu, Mingjun Ma, Jiawen Zhang, Yanan Wang, Xiaoxia Tang, Sufang Wu","doi":"10.3390/biomedicines14092072","DOIUrl":"10.3390/biomedicines14092072","url":null,"abstract":"<p><p><b>Background:</b> Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer, but resistance and recurrence remain major clinical challenges. Tumor immune-metabolic reprogramming profoundly affects treatment response and immune evasion; however, the molecular mechanisms of lipid metabolism remodeling and its interaction with T cells after CCRT in cervical cancer are still unclear. This study aimed to investigate how CCRT-induced metabolic changes in cervical cancer cells influence T cell function and immune evasion. <b>Methods:</b> We performed metabolic pathway activity analysis, cell-cell communication prediction, and transcriptomic analysis on paired single-cell transcriptomic data from three cervical cancer patients before and after CCRT (<i>n</i> = 3 paired). Validation was conducted using multiple independent GEO cohorts, in vitro cell culture experiments, and multi-sample immunofluorescence staining. <b>Results:</b> CCRT was associated with upregulation of <i>FABP4/5</i> in malignant epithelial cells and activation of the PPAR and adipocytokine signaling pathways, leading to lipid metabolic reprogramming. Epithelial cells with high <i>FABP4/5</i> expression showed enhanced predicted intercellular communication with T cells via the computationally inferred ligand-receptor axes <i>PTGER4</i> and <i>CXCR4</i>. T cells with high communication intensity exhibited an immunosuppressive phenotype signature, accompanied by metabolic alterations in lipid and carbohydrate pathways and enrichment of regulatory T cell subsets. Validation experiments confirmed the association between <i>FABP4/5</i> and inhibitory T cells. <b>Conclusions:</b> This study suggests that <i>FABP4/5</i>-mediated lipid metabolism reprogramming may represent a key mechanism contributing to the immunosuppressive crosstalk between cervical cancer epithelial cells and T cells after CCRT. Targeting this axis may reverse T cell dysfunction and provide a potential immunometabolic strategy to reduce post-CCRT recurrence.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcineurin Inhibitor-Based Triple Immunosuppressive Therapy Induces Profibrotic Changes in the Jejunal Mucosa of Male Rats: A Digital Image Analysis of Collagen Fibers.","authors":"Kamila Szumilas, Aleksandra Wilk, Paweł Szumilas, Karolina Klimek, Karolina Kędzierska-Kapuza","doi":"10.3390/biomedicines14092064","DOIUrl":"10.3390/biomedicines14092064","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Long-term immunosuppressive therapy administered to solid organ transplant recipients may induce adverse effects in various tissues, including the gastrointestinal tract. The aim of the present study was to evaluate the influence of prolonged treatment with calcineurin inhibitor (CNI)-based triple immunosuppressive regimens on the morphology of the jejunal mucosa in male rats. Particular attention was paid to fibrotic changes occurring within the mucosal connective tissue, including the intestinal villi and lamina propria. <b>Methods</b>: Animals were treated for six months with regimens containing either cyclosporine A (CyA) or tacrolimus (TAC) in combination with rapamycin and prednisone. To assess the content of collagen fibers, jejunal sections were stained using the Mallory trichrome method and subsequently subjected to quantitative digital image analysis. <b>Results</b>: Histological examination demonstrated increased collagen deposition in the jejunal mucosa of rats receiving immunosuppressive treatment compared with the control group. Quantitative analysis confirmed an increase in collagen fiber content, indicating enhanced extracellular matrix accumulation and changes consistent with fibrotic remodeling of the mucosal connective tissue. The highest collagen fiber content was observed in animals treated with the cyclosporine-based regimen. <b>Conclusions</b>: These findings suggest that long-term administration of CNI-based triple immunosuppressive therapy may be associated with changes consistent with fibrotic remodeling of the jejunal mucosa. The present study provides novel data on the effects of clinically relevant multidrug immunosuppressive protocols, whereas most previous experimental studies investigating the effects of immunosuppressive agents have focused on single-drug exposure in animal models or in vitro systems.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Nerve Block with Ropivacaine Ameliorates Acute Compartment Syndrome by Promoting Macrophage M2 Polarization via JAK-STAT Signaling.","authors":"Yingying Deng, Yuan Pan, Tao Wang, Chaoran Hu, Kunzhi Zhu, Chao Xie, Chao Feng","doi":"10.3390/biomedicines14092065","DOIUrl":"10.3390/biomedicines14092065","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Acute compartment syndrome (ACS) is a critical orthopedic emergency where increased pressure in a limb compartment leads to muscle ischemia, necrosis, and lasting dysfunction. While fasciotomy is the standard treatment, it often results in complications like infection and nerve damage, underscoring the need for effective non-surgical therapies to manage the inflammation causing tissue damage. Peripheral nerve block (PNB) with ropivacaine is clinically used for analgesia, but whether it can serve as a disease-modifying adjunct intervention for ACS beyond pain control remains unexplored. &lt;b&gt;Objective:&lt;/b&gt; This study examined the potential of PNB utilizing ropivacaine to enhance outcomes in ACS and explored the underlying mechanisms related to macrophage polarization. We aimed to distinguish two unresolved questions: (1) whether ropivacaine-based PNB confers tissue-protective effects in ACS independent of analgesia; (2) what signaling pathway mediates ropivacaine-driven macrophage phenotypic switch under ACS-relevant inflammatory conditions. &lt;b&gt;Methods:&lt;/b&gt; Using rats, an ACS model was established, with the animals being randomly allocated to five different groups: Control, ACS, sciatic PNB, femoral PNB, and combined PNB. The study assessed functional outcomes, histopathological changes, levels of inflammatory markers (interleukin-6 (IL-6), C-reactive protein (CRP), and markers of macrophage polarization (CD86, CD206). In parallel, RAW264.7 macrophages stimulated with LPS and IFN-γ were treated with ropivacaine (1-10 μg/mL), and M1/M2 markers, pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), migratory capacity, and cytotoxicity were assessed. Differentially expressed genes and enriched pathways were identified through RNA sequencing, followed by mechanistic validation of JAK-STAT signaling using Western blotting, immunofluorescence, immunohistochemistry, and rescue experiments with the JAK2 inhibitor AG490. &lt;b&gt;Results:&lt;/b&gt; PNB significantly improved all functional and histological parameters in ACS rats, with combined blockade demonstrating the greatest efficacy. Ropivacaine at 5 μg/mL promoted M2 macrophage polarization, evidenced by upregulated CD206 and arginase-1 alongside downregulated CD86 and iNOS, while reducing pro-inflammatory cytokine production without cytotoxicity. Ropivacaine also suppressed macrophage migration. Among 83 differentially expressed genes, RNA sequencing pinpointed JAK-STAT as the pathway with the highest level of enrichment. Mechanistically, ropivacaine activated JAK2-STAT3, reflected by increased p-JAK2/JAK2 and p-STAT3/STAT3 ratios. AG490 completely reversed ropivacaine-induced JAK-STAT activation, M2 polarization, cytokine suppression, and migratory inhibition in vitro, and similarly abrogated PNB-mediated functional recovery and histological protection in vivo. &lt;b&gt;Conclusions:&lt;/b&gt; In vitro, ropivacaine directly promoted macrophage M2 polarization via JAK-STAT activation. In vivo, ropivacaine-","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic CD4+ T Cell Genetics Identifies Candidate Therapeutic Targets for Allergic Rhinitis: Mendelian Randomization with Exploratory Single-Cell Contextualization.","authors":"Wei Gu, Jinglei Li, Chuan Liu, Chuan Chen, Jian Wang","doi":"10.3390/biomedicines14092077","DOIUrl":"10.3390/biomedicines14092077","url":null,"abstract":"<p><p><b>Background</b>: Allergic rhinitis is common and clinically heterogeneous, but the genes whose genetically regulated immune-state expression influences susceptibility remain incompletely resolved. <b>Methods</b>: We integrated dynamic CD4+ T cell eQTL data (46 activation-state profiles) with allergic rhinitis GWAS summary statistics, applying transcriptome-wide Mendelian randomization (MR), colocalization, SMR/HEIDI, metabolite screening, paired single-cell RNA-seq and TCR analysis, and computational follow-up. Colocalization support was prespecified as conditional ratio PP.H4/(PP.H3 + PP.H4) > 0.7; HEIDI at <i>p</i> > 0.05. <b>Results</b>: After MHC-region exclusion, 50,654 gene-profile pairs were tested and 129 MR-significant genes were identified. Colocalization supported 418 pairs (111 genes); 70 genes passed both SMR and HEIDI; and cross-database comparison yielded a nine-gene overlap set. In GSE200107, baseline good-versus-poor responder differences were larger than treatment-induced transcriptional change; patient-level reanalysis found no pair surviving multiple-testing correction (<i>n</i> = 4 vs. 3); these findings are hypothesis-generating. Paired TCR analysis suggested greater clonotype renewal in good responders (descriptive). Structure-guided screening prioritized unvalidated binder candidates for SLC25A46 and TLR1 (TLR1 TIR docking -5.86 kcal/mol; MD RMSD 0.20 nm). <b>Conclusions</b>: An exploratory metabolite screen yielded nominally significant indirect-effect signals, but the candidate metabolite did not colocalize with the disease locus. This framework prioritizes candidate therapeutic targets for allergic rhinitis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a Cytological Classification of Nasal Biofilms in Upper Airway Inflammation: Microscopic Patterns, Clinical Meaning, and Therapeutic Implications.","authors":"Matteo Gelardi","doi":"10.3390/biomedicines14092076","DOIUrl":"10.3390/biomedicines14092076","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Nasal biofilms are increasingly recognized as contributors to chronic and recurrent upper airway inflammation, yet their cytological interpretation is still often reduced to a binary presence/absence judgment, underestimating their morphological, microbial, and inflammatory heterogeneity. This Perspective proposes a cytological classification framework for nasal biofilms based on microscopic morphology, degree of organization, bacterial and fungal composition, host inflammatory response, and therapeutic implications. <b>Methods:</b> This conceptual framework integrates standardized nasal cytology, microscopic observation of bacterial aggregates and biofilm-like structures, May-Grünwald-Giemsa staining features, and current knowledge of biofilm behavior in upper airway inflammatory disorders, focusing on relationships among bacteria, fungal elements, mucus, epithelial cells, and inflammatory infiltrates. <b>Results:</b> Five cytological patterns are proposed: free bacterial colonization, microaggregate biofilm-like pattern, structured/mature biofilm pattern, inflammatory biofilm-associated pattern, and dispersal/disrupted biofilm pattern, reflecting different degrees of microbial organization and host-microbe interaction and possibly coexisting within the same smear. Nasal cytology may also reveal fungal-predominant or mixed bacterial-fungal patterns, supporting an \"infectious condominium\" concept, and should distinguish isolated fungal spores from the rarer, clinically more significant vegetative forms such as hyphae. <b>Conclusions:</b> Moving from a presence/absence approach to pattern-based interpretation may improve the diagnostic and clinical value of nasal cytology. Although prospective validation is required, this classification offers a shared descriptive language that may support more precise phenotyping of upper airway inflammation, avoid overinterpretation of simple colonization, and inform personalized diagnostic and therapeutic strategies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6, Proteinuria, and Arterial Stiffness in Preeclampsia: Distinct Inflammatory, Renal, and Vascular Associations.","authors":"Izabella Petre, Mircea Iurciuc, Florina Buleu, Daian Popa, Luciana Marc, Tiberiu Buleu, Ioana Marin, Ramona Dragomir, Narcisa Carmen Mladin, Marina Adriana Mercioni, Ion Petre","doi":"10.3390/biomedicines14092069","DOIUrl":"10.3390/biomedicines14092069","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt;: Preeclampsia is characterized by systemic inflammation, endothelial dysfunction, and progressive abnormalities in the maternal vasculature. Interleukin-6 (IL-6) may indicate inflammatory activity, while aortic pulse wave velocity (PWVao) and augmentation index (AIx) offer complementary assessments of arterial stiffness and vascular function. This study examined the relationships among IL-6, proteinuria, and arterial stiffness in women with preeclampsia. &lt;b&gt;Methods&lt;/b&gt;: This observational study involved 87 pregnant women with preeclampsia who were evaluated at the Emergency Clinical Hospital \"Pius Brînzeu\" in Timișoara, Romania. Arterial stiffness was measured non-invasively with the Arteriograph system during the second trimester (20-24 weeks) and the third trimester (32-36 weeks). PWVao served as the primary marker of arterial stiffness, whereas AIx provided a complementary measure of arterial wave reflection. Serum IL-6 levels were quantified by enzyme-linked immunosorbent assay, and 24 h proteinuria was recorded. Associations among inflammatory, renal, and vascular parameters were examined using Spearman correlation analyses. Multivariable linear regression then identified independent predictors of third-trimester PWVao. &lt;b&gt;Results&lt;/b&gt;: The mothers had a mean age of 37.59 ± 2.65 years, and the mean BMI was 30.41 ± 2.70 kg/m&lt;sup&gt;2&lt;/sup&gt;. PWVao rose significantly between the second and third trimesters, from 10.94 ± 1.36 m/s to 12.46 ± 1.70 m/s (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). AIx also increased, from 1.26 ± 0.85% to 3.66 ± 1.32% (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). The mean serum IL-6 concentration was 31.01 ± 35.61 pg/mL. No significant correlation was found between IL-6 and PWVao in either the second trimester (ρ = -0.100, &lt;i&gt;p&lt;/i&gt; = 0.356) or the third trimester (ρ = -0.100, &lt;i&gt;p&lt;/i&gt; = 0.358), and IL-6 was not significantly correlated with AIx. A significant positive correlation was observed between IL-6 and 24 h proteinuria (ρ = 0.337, &lt;i&gt;p&lt;/i&gt; = 0.0014). Proteinuria itself showed no significant association with PWVao or AIx. In the multivariable analysis, only BMI independently predicted third-trimester PWVao (β = 0.634, 95% CI: 0.469-0.799, &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Age, systolic blood pressure, proteinuria, and IL-6 showed no independent association with PWVao. Nor were IL-6, proteinuria, or third-trimester PWVao significantly associated with birth weight or the 1 min Apgar score. &lt;b&gt;Conclusions&lt;/b&gt;: Among women with preeclampsia, arterial stiffness increased progressively throughout pregnancy. Systemic inflammation, measured by IL-6, was more strongly associated with renal involvement than with mechanical arterial stiffness. BMI was the main independent determinant of third-trimester PWVao. Together, these results support a multidimensional view of preeclampsia, in which inflammatory, renal, metabolic, and vascular abnormalities form related yet partly distinct pathways. Assessing IL-6, proteinuria, BMI, and arterial stiffness together may improve ","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}