Biomedicines最新文献

{"title":"Evaluation of Spontaneous Pain in a Monosodium Iodoacetate-Induced Mouse Model of Osteoarthritis Using the Mouse Grimace Scale.","authors":"Mohammed Alnoud, Jose Rios, Megan W Szobody, Ayesha A Usman, Alma Rodriguez, Thao-April Nguyen, Seryna Ayala, Ayaan S Quraishi, Massimo Salinas, Khalid Benamar","doi":"10.3390/biomedicines14092114","DOIUrl":"10.3390/biomedicines14092114","url":null,"abstract":"<p><p>Animal models are critical for elucidating disease mechanisms and pathological outcomes, and for evaluating therapeutic interventions. Osteoarthritis (OA) is a leading cause of chronic pain and disability globally. Clinically, individuals with OA experience both sensory and ongoing pain. However, ongoing pain, as assessed by the Mouse Grimace Scale (MGS), has not yet been evaluated in animal models of OA. This study aims to address this significant knowledge gap. We induced OA by intra-articular injection of monosodium iodoacetate (MIA), while control mice received saline injections. We assessed pain behaviors using the MGS on days 1, 3, 7, and 14 after MIA administration. MIA-treated mice exhibited significantly higher MGS scores than saline-treated controls throughout the study period, indicating ongoing pain-related behavior in the MIA OA model. Furthermore, longitudinal studies showed that this pain is chronic, as seen in people with OA. These findings support the usefulness of the MGS test in the MIA model for studying ongoing pain.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057885","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":"Multi-Omics Integration Identifies Epithelial-Stromal-Immune Co-Regulators Bridging Ulcerative Colitis and Colorectal Cancer.","authors":"Wenhao Sun, Zhiwei Jiang","doi":"10.3390/biomedicines14092120","DOIUrl":"10.3390/biomedicines14092120","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives:&lt;/b&gt; Patients with ulcerative colitis (UC) carry a substantially elevated risk of developing colorectal cancer (CRC); yet, the transcriptional intermediates that bridge chronic mucosal inflammation and colorectal malignancy remain poorly characterized. A related question is whether any genes shared between the two conditions actually help drive transformation, or whether they represent downstream responders. &lt;b&gt;Methods:&lt;/b&gt; We integrated two UC microarray cohorts (totalling 227 samples) and the TCGA-COAD dataset (&lt;i&gt;n&lt;/i&gt; = 524), combining weighted gene co-expression network analysis (WGCNA) with directional differential expression to define shared candidate genes. Three machine-learning approaches-LASSO, random forest, and SVM-RFE-were applied to that candidate set, and the stability of their intersection was assessed by bootstrap resampling. The resulting panel was then examined by replication in an independent UC cohort, two-sample Mendelian randomization, immune deconvolution, survival modelling, and Visium spatial transcriptomics. &lt;b&gt;Results:&lt;/b&gt; WGCNA and directional differential expression together yielded 91 shared candidate genes, and the three algorithms converged on four: &lt;i&gt;CXCL1&lt;/i&gt;, &lt;i&gt;S100P&lt;/i&gt;, &lt;i&gt;THY1&lt;/i&gt;, and &lt;i&gt;TRIM29&lt;/i&gt;. Bootstrap resampling showed that this convergence is a property of one particular fit rather than a reproducible selector (all four recovered together in 0.3% of 1000 resamples), so we treated the ensemble as a hypothesis-generating step and made our case for the panel based on independent downstream evidence. This evidence was consistent, as, in an independent UC cohort (GSE92415, &lt;i&gt;n&lt;/i&gt; = 183), all four genes moved in the same direction as in discovery, and a four-gene model separated inflamed from control mucosa with a cross-validated AUC of 0.986 (95% CI 0.965-1.000). Two-sample Mendelian randomization using strong blood cis-eQTL instruments (&lt;i&gt;F&lt;/i&gt; = 345 for &lt;i&gt;CXCL1&lt;/i&gt;, &lt;i&gt;F&lt;/i&gt; = 2423 for &lt;i&gt;S100P&lt;/i&gt;) returned null estimates; for &lt;i&gt;S100P&lt;/i&gt;, the design had 80% power to detect an odds ratio of 1.07 per standard deviation, so this is an informative null rather than an absence of data, while &lt;i&gt;THY1&lt;/i&gt; and &lt;i&gt;TRIM29&lt;/i&gt; had no cis-eQTLs in eQTLGen and remain untestable. Each gene showed a distinct pattern of immune cell correlation in TCGA-COAD. LASSO-Cox retained only &lt;i&gt;CXCL1&lt;/i&gt;, whose higher expression was associated with a better rather than worse overall survival (HR 0.79 per SD, &lt;i&gt;p&lt;/i&gt; = 0.020); its discrimination was weak (optimism-corrected C-index 0.56 for the score alone) and did not reach significance in an external cohort (GSE39582, &lt;i&gt;n&lt;/i&gt; = 573; &lt;i&gt;p&lt;/i&gt; = 0.11), so we reported no prognostic model. In Visium spatial data from four colonic sections, a three-compartment structure was reproducible between UC sections-&lt;i&gt;CXCL1&lt;/i&gt; near the neutrophil and interferon signals, &lt;i&gt;THY1&lt;/i&gt; within the stroma and anticorrelated with the epithelium, and &lt;i&gt;S1","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057888","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":"Decisions in Diuretic Resistance: Oral or Subcutaneous Furosemide in Advanced Ambulatory Heart Failure?","authors":"Raquel López-Vilella, Borja Guerrero Cervera, Emilio Monte Boquet, Víctor Donoso Trenado, Julia Martínez-Solé, Luis Martínez Dolz, Luis Almenar-Bonet","doi":"10.3390/biomedicines14092112","DOIUrl":"10.3390/biomedicines14092112","url":null,"abstract":"<p><p><b>Objectives</b>: The objective of this study was to explore differences in short-term clinical response, renal outcomes, and healthcare resource utilization between two non-equivalent outpatient furosemide strategies: high-dose oral solution and subcutaneous administration. <b>Methods</b>: This retrospective observational study included 108 consecutive outpatients with advanced heart failure (HF) and diuretic resistance treated between January 2018 and December 2024. Patients received furosemide for 5 days as oral solution (250 mg/day; <i>n</i> = 81) or subcutaneous infusion via elastomeric pump (100 mg/day; <i>n</i> = 27). Primary endpoints were changes in functional status (NYHA [New York Heart Association] class), body weight, and renal function, assessed by changes in serum creatinine and estimated glomerular filtration rate and by clinically relevant worsening renal function criteria. Secondary endpoints included NT-proBNP changes and unplanned healthcare utilization at 30 days. <b>Results</b>: Both strategies were associated with short-term decongestion. Weight decreased similarly in both groups, with no difference in the proportion of patients achieving weight loss (oral 90% vs. subcutaneous 89%; <i>p</i> = 0.854). Functional improvement was more frequently observed in the oral-solution group (99% vs. 89%; <i>p</i> = 0.019). Renal outcomes were comparable between strategies, with no significant changes in eGFR and a similar proportion of patients experiencing a serum creatinine increase ≥0.3 mg/dL (25.9% vs. 22.2%; <i>p</i> = 0.85). No significant differences were observed in NT-proBNP changes. HF-related healthcare encounters decreased during the 30 days following treatment compared with the preceding 30-day period in the oral-solution group, whereas no significant within-group change was observed in the subcutaneous group. <b>Conclusions</b>: In this exploratory real-world cohort of patients with advanced HF and refractory congestion, both outpatient strategies were associated with short-term decongestion, with differences observed in symptomatic response. These findings are hypothesis-generating and warrant confirmation in prospective studies using comparable dosing strategies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057818","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":"Gut Microbiota in Heart Failure with Preserved Ejection Fraction: Clinical Phenotyping and Therapeutic Opportunities.","authors":"Goran Loncar, Milovan Bojic, Jelena Repac, Natasa Cvetinovic, Marija Rakic, Tamara Nedeljkovic, Tanja Lunic, Danilo Obradovic, Stephan von Haehling, Mitja Lainscak, Petar Otasevic, Masa Petrovic, Nikola Blagojevic, Danka Vukasinovic, Bojan Bozic, Biljana Bozic Nedeljkovic","doi":"10.3390/biomedicines14092123","DOIUrl":"10.3390/biomedicines14092123","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In heart failure with preserved ejection fraction (HFpEF), the gut-heart axis has emerged as a potential contributor to inflammation and cardiometabolic stress. We characterised gut microbiota composition, diversity, and predicted metabolic potential in HFpEF to assess their associations with disease status and clinical heterogeneity. <b>Methods and Results</b>: Faecal samples from 30 HFpEF patients and 28 healthy controls were profiled by means of bacterial ribosomal RNA gene sequencing. The groups were comparable in age (74 years in both groups) and sex (female: 60% vs. 60.7%). HFpEF patients exhibited lower community evenness (<i>p</i> = 0.04) and a trend toward lower diversity (<i>p</i> = 0.08), but no detectable shift in global community structure. The tested clinical and demographic variables explained only a modest proportion of the observed variation in community structure, with substantial residual variation across the beta-diversity analyses. No taxa were differentially abundant between groups at the predefined thresholds. Among clinical stratifications, New York Heart Association (NYHA) class showed the most consistent family-level associations, including stepwise depletion of <i>Lachnospiraceae</i>, <i>Butyricicoccaceae</i>, and <i>Ruminococcaceae</i> and enrichment of <i>Akkermansiaceae</i>; <i>Enterobacteriaceae</i> peaked in milder disease. These severity-associated taxonomic trajectories were accompanied by predicted functional shifts consistent with microbial adaptation to increasing metabolic constraints, including enrichment of stress-adaptation traits and, with increasing functional limitation, depletion of core metabolic and fermentative pathways and relative enrichment of oxidative stress-response pathways. <b>Conclusions</b>: HFpEF is associated with subtle gut microbiota alterations that appear to reflect severity- and context-dependent ecological reorganisation rather than uniform dysbiosis. These findings support severity-informed approaches targeting microbial metabolic function and ecological context rather than broad compositional changes.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057866","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":"End-of-Surgery Remimazolam Bolus Reduces Emergence Delirium in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized, Triple-Blind, Placebo-Controlled Trial.","authors":"Grgur Prižmić, Filip Periš, Ana Maria Mitar, Ana Bego, Ana Šarić Jadrijev, Toni Kljaković-Gašpić","doi":"10.3390/biomedicines14092115","DOIUrl":"10.3390/biomedicines14092115","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Emergence delirium (ED) is common after sevoflurane anesthesia in children undergoing otolaryngologic surgery. Remimazolam is an ultra-short-acting benzodiazepine that may reduce ED without delaying recovery. This study evaluated the effect of a single remimazolam bolus administered at the end of surgery on ED in children undergoing tonsillectomy and/or adenoidectomy. <b>Methods</b>: In this prospective, randomized, triple-blind, placebo-controlled trial, 110 children aged 3-9 years with American Society of Anesthesiologists physical status I received remimazolam 0.1 mg/kg (<i>n</i> = 57) or an equal volume of normal saline (<i>n</i> = 53) immediately after discontinuation of sevoflurane and before extubation. The primary outcome was ED at extubation, defined as a Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Secondary outcomes included Face, Legs, Activity, Cry, and Consolability (FLACC) scores, emergence time, early recovery, postoperative vomiting, and airway complications. <b>Results</b>: ED occurred in 1 of 57 children (1.8%) receiving remimazolam and in 11 of 53 children (20.8%) receiving placebo (<i>p</i> = 0.002). The absolute risk reduction was 19.0% (95% confidence interval [CI], 7.5-31.8), the relative risk was 0.08 (95% CI, 0.01-0.63), and the number needed to treat was 6. The overall distribution of FLACC scores at extubation differed between groups (<i>p</i> = 0.047), with FLACC scores of 0 occurring more frequently in the remimazolam group. Median emergence time was 10 min in both groups, and all children achieved a modified Aldrete score > 8 within 15 min. Postoperative vomiting was assessed through 30 min; the comparison at 5 min showed no significant between-group difference. Airway complications also did not differ significantly between groups. <b>Conclusions</b>: A single intravenous bolus of remimazolam 0.1 mg/kg administered at the end of surgery significantly reduced PAED-defined ED without prolonging emergence or delaying early postoperative recovery.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057913","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":"Reply to Dal, Z.; Erkan, M. Comment on \"Lai et al. Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence. <i>Biomedicines</i> 2024, <i>12</i>, 2419\".","authors":"Quirino Lai, Alessandro Coppola, Anna Mrzljak, Maja Cigrovski Berkovic","doi":"10.3390/biomedicines14092110","DOIUrl":"10.3390/biomedicines14092110","url":null,"abstract":"<p><p>We would like to sincerely thank the Authors for their thoughtful and well-argued commentary on our systematic review addressing liver transplantation (LT) for neuroendocrine neoplasm liver metastases (NEN-LMs) [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057979","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 BDNF-TrkB Expression and Vitamin D Status in Depression, Prediabetes and Type 2 Diabetes: A Cross-Sectional Biomarker Study.","authors":"Oleksandr Pavlovych, Iryna Kamyshna, Larysa Pavlovych, Oleh Lushchak, Iryna Halabitska, Pavlo Petakh, Oleksandr Kamyshnyi","doi":"10.3390/biomedicines14092106","DOIUrl":"10.3390/biomedicines14092106","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Depression and anxiety cluster with dysglycaemia along a prediabetes-type 2 diabetes continuum, but the signatures of affective and metabolic burden are unclear. We examined whether neurotrophin-related gene expression and 25(OH)D status track symptoms, parameters, or both. <b>Methods</b>: A cross-sectional study of 200 adults (<i>n</i> = 50 each: type 2 diabetes, prediabetes, depressive-anxiety, apparently healthy controls) was conducted. Anthropometry, glycaemic and lipid indices, PHQ-9, GAD-7, serum 25(OH)D and RT-qPCR expression of BDNF, NGF, NTRK1 and NTRK2 in whole peripheral blood were assessed. Multivariable regression, dominance analysis and pre-specified sensitivity analyses were applied. <b>Results</b>: BDNF, NGF and NTRK2 expression progressively decreased from controls to prediabetes and type 2 diabetes and was lowest in the depressive-anxiety group (<i>p</i> < 0.001); NTRK1 expression did not differ. Peripheral BDNF was more closely associated with PHQ-9 and 25(OH)D than with glycaemic or anthropometric indices. Psychiatric variables accounted for approximately 81% of the variance explained by the multivariable model (apparent R² = 0.257), corresponding to approximately 21% of the total observed variance in log(BDNF). <b>Conclusions</b>: Peripheral BDNF and NTRK2 mRNA and 25(OH)D status were associated with depressive symptom burden more strongly than with metabolic parameters across a prediabetes-type 2 diabetes continuum. These associations describe an exploratory biomarker pattern; they do not establish altered signalling activity, causality or clinical utility, which require prospective validation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057992","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":"Comment on Lai et al. Liver Transplantation for the Cure of Neuroendocrine Liver Metastasis: A Systematic Review with Particular Attention to the Risk Factors of Death and Recurrence. <i>Biomedicines</i> 2024, <i>12</i>, 2419.","authors":"Zeynep Dal, Mert Erkan","doi":"10.3390/biomedicines14092109","DOIUrl":"10.3390/biomedicines14092109","url":null,"abstract":"<p><p>Gastrointestinal neuroendocrine tumors (GI-NETs) are being diagnosed with increasing frequency and often manifest with liver metastases, presenting considerable therapeutic challenges. This commentary addresses the systematic review by Lai et al., which evaluated liver transplantation (LT) for NET-associated liver metastases (NEN-LM). Although Lai et al. identified LT as a promising intervention for unresectable or liver-confined NETs, we believe that certain aspects warrant further discussion. To begin with, approximately 16% of reported cases had an unknown primary tumor. This not only complicates patient selection and potentially introduces confounding outcomes but also contradicts the notion of \"liver-limited disease\". Furthermore, elevated proliferative activity, as indicated by a Ki-67 index of >2%, has been correlated with reduced survival rates. Therefore, LT should ideally be offered to patients with GI-NETs with a Ki-67 index of <2%. This subgroup of patients may also benefit from alternative therapy options, such as cytoreductive surgery/tumor debulking combined with peptide receptor radionuclide therapy (PRRT), which has demonstrated favorable outcomes and deserves greater attention. Finally, advocating LT for patients with NEN-LM based on retrospective data might facilitate its overuse, especially in countries/regions where living donor LT is employed. We believe that this important yet missing point merits an in-depth examination of its advantages and disadvantages.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057941","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":"The Molecular Basis and Biomarker Potential of the HIF-1α-VEGF-GLUT1 Hypoxia Axis in Laryngeal Squamous Cell Carcinoma.","authors":"Wojciech Domka, Maciej Misiołek, Daniel Roshan Justin Raj, Dorota Bartusik-Aebisher, Angelika Myśliwiec, David Aebisher","doi":"10.3390/biomedicines14092103","DOIUrl":"10.3390/biomedicines14092103","url":null,"abstract":"<p><p>In laryngeal squamous cell carcinoma, hypoxia plays a major role in growth, spread, and treatment resistance. HIF-1α, VEGF, and GLUT1 are three linked biomarkers that show different aspects of this response. Low oxygen can be sensed by HIF-1α, and it follows up by activating genes that help with the survival of the tumour cells. VEGF helps to form new blood vessels, while GLUT1 increases the uptake of glucose and maintains the production of energy even when there is a lack of oxygen. Tissue and serum studies have reported higher levels of these biomarkers in malignant than in benign or normal samples, together with associations with adverse clinicopathological features. However, their diagnostic and prognostic utility remains exploratory because clinically validated thresholds, diagnostic performance measures, and independent prospective validation remain limited. Combined assessment of these biomarkers may provide complementary information on hypoxic signalling, angiogenesis and metabolic adaptation, although its diagnostic or prognostic superiority over individual biomarkers has not yet been established. However, serum measurements can be influenced by pre-analytical and systemic factors. So, in order for these biomarkers to advance enough to be used in clinical laryngology, large multicenter studies and a standardized set of testing methods will be necessary.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058051","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":"Reduced Granulosa Cell AKT2 mRNA Expression in Women with Unexplained Infertility: A Prospective Case-Control Study of ICSI Cycles.","authors":"Özgür Uzun, Belgin Devranoğlu, Enis Özkaya, Huri Demirci, Gülden Tunalı, Zehra Sezer, Fatma Beyza Sağ, Emine Elif Güzel Meydanlı","doi":"10.3390/biomedicines14092108","DOIUrl":"10.3390/biomedicines14092108","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: Unexplained infertility (UI) is defined by the absence of detectable abnormality on standard evaluation, which raises the possibility that the causative defect lies at the level of intracellular signaling rather than at the level of gamete number or hormone concentration. The PI3K/Akt pathway governs primordial follicle activation, granulosa cell survival, and the acquisition of oocyte competence, but AKT2 transcript abundance in the somatic follicular compartment has not been characterized clinically in UI. We compared cumulus/granulosa cell AKT2 transcript levels and follicular fluid Akt and phospho-Akt (Ser473) protein levels between women with UI and women undergoing intracytoplasmic sperm injection (ICSI) for isolated male factor infertility. &lt;b&gt;Methods&lt;/b&gt;: This was a prospective case-control study of 128 women (64 UI, 64 male factor) aged 23-35 years, all stimulated with a GnRH antagonist protocol and recruited December 2020-May 2021. AKT2 expression in cumulus/granulosa cells recovered at denudation was quantified using RT-qPCR (ΔΔCt, GAPDH reference). Total Akt and phospho-Akt (Ser473) were measured in follicular fluid using ELISA and normalized to the number of oocytes retrieved. Oocyte maturation, fertilization, day 3 embryo quality, and day 5 blastocyst quality were assessed using Alpha/ESHRE Istanbul consensus criteria. Correlation analyses were exploratory and reported with Benjamini-Hochberg false discovery rate (FDR) adjustment. &lt;b&gt;Results&lt;/b&gt;: Baseline characteristics, including age, body mass index, antral follicle count, AMH, FSH, LH, oocytes retrieved, and duration of infertility, were comparable between groups. Granulosa cell AKT2 ΔCt was higher in the UI group (3.46 ± 1.47 versus 2.68 ± 1.18; &lt;i&gt;p&lt;/i&gt; = 0.001), corresponding to a 1.72-fold lower AKT2 transcript level (ΔΔCt 0.78; Cohen's d = 0.59); the difference persisted after adjustment for age, body mass index, AMH, basal estradiol levels, and previous IVF attempts (adjusted ΔCt difference 0.74, 95% CI 0.25-1.24; &lt;i&gt;p&lt;/i&gt; = 0.004). Follicular fluid total Akt (11.55 ± 4.08 versus 11.75 ± 3.60 relative units; &lt;i&gt;p&lt;/i&gt; = 0.78) and phospho-Akt (21.05 ± 7.14 versus 19.81 ± 7.24; &lt;i&gt;p&lt;/i&gt; = 0.34) did not differ, nor did values normalized per oocyte. Oocyte maturation rate (0.72 ± 0.25 versus 0.76 ± 0.18), fertilization rate (44.6 ± 29.5% versus 42.2 ± 25.6%), day 3 good-quality embryo rate (25.0 ± 25.8% versus 26.6 ± 23.8%), and good-quality blastocyst rate (30.2 ± 25.8% versus 20.5 ± 18.5%) were all comparable. Of 24 exploratory correlations, only two survived FDR adjustment. Both correlations were in the male factor comparison group and both involved the small blastocyst subgroup: total Akt per oocyte (ρ = 0.738) and phospho-Akt per oocyte (ρ = 0.728) versus good-quality blastocyst rate (&lt;i&gt;n&lt;/i&gt; = 17; FDR &lt;i&gt;p&lt;/i&gt; = 0.011). AKT2 ΔCt did not correlate with any embryological endpoint in either group. &lt;b&gt;Conclusions&lt;/b&gt;: Cumulus and granulosa","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058003","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}