Biomedicines最新文献

{"title":"Engineering Bone-Mimetic Microspheres to Recapitulate the Tumor Microenvironment for In Vitro Osteosarcoma Modeling.","authors":"Fangqiao Zheng, Zhengyi Lan, Hangrong Chen, Ming Ma","doi":"10.3390/biomedicines14040868","DOIUrl":"10.3390/biomedicines14040868","url":null,"abstract":"<p><p><b>Background:</b> Osteosarcoma (OS) is an aggressive bone tumor. The lack of physiologically relevant three-dimensional models that recapitulate the native tumor microenvironment hampers drug development and mechanistic studies. The study aimed to develop bone-mimetic microspheres for the construction of an OS model. <b>Materials and Methods:</b> We employed droplet microfluidics to fabricate bone-mimetic microspheres (named MSHA) from a composite of gelatin methacryloyl, polyethylene glycol diacrylate, and nano-hydroxyapatite (nHA). MNNG/HOS cells were cultured on MSHA microspheres and subsequently evaluated for their bioactivity and capabilities of stemness, migration, and invasion. <b>Results:</b> The microfluidic platform enabled efficient and scalable production of highly uniform MSHA microspheres with controlled sizes. MNNG/HOS cells cultured on MSHA maintained high viability and spontaneously formed compact tumor spheroids after 7 days. Compared with two-dimensional cultures, cells cultured on these microsphere-based platforms exhibited enhanced migration and invasion capacities, along with increased expression of relevant biomarkers. RNA sequencing further revealed the activation of cancer-related pathways. Notably, the incorporation of nHA into microspheres amplified these malignant phenotypes, potentially through the activation of ECM-receptor interaction and calcium signaling pathways. <b>Conclusions:</b> The microfluidics-fabricated MSHA microspheres, as biomimetic three-dimensional culture scaffolds, offer a promising platform for applications in mechanistic studies of osteosarcoma progression and drug screening.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810613","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":"Effect of Knee Joint Meniscus Tears on Joint Cartilage Contact and Pressure with Finite Element Analysis.","authors":"Cengizhan Kurt, Arif Gök","doi":"10.3390/biomedicines14040869","DOIUrl":"10.3390/biomedicines14040869","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The medial meniscus is crucial for load transmission and knee stability. Meniscal tears disrupt joint biomechanics, increasing the risk of cartilage degeneration. However, few studies have quantitatively compared how different tear types affect stress and contact mechanics using finite element analysis (FEA). This study aims to analyze stress distributions for various meniscal tear types and develop a predictive model for meniscal stress behavior. This study investigates how stress distributions differ between healthy and torn medial menisci under identical loading conditions. The study examines which meniscal tear type produces the highest stress concentrations. The effects of different tear types on penetration, gap formation, pressure distribution, and sliding distance at the meniscus interface are also analysed. <b>Materials and Methods:</b> The FEA model of the knee joint, including femoral and tibial cartilage and the medial meniscus, was developed. Simulations were conducted for a healthy meniscus and for menisci with radial, horizontal and complex tears. Stress, penetration, gap, pressure, and sliding distance were calculated, and a mathematical model describing their relationships was established. <b>Results:</b> All torn menisci exhibited significantly higher stresses than the healthy meniscus (<i>p</i> < 0.001). Radial tears generated the highest stress concentrations (<i>p</i> < 0.001). Pressure was mainly influenced by meniscal geometry, while the gap remained nearly constant. Penetration increased slightly (<i>p</i> < 0.05). The predictive model demonstrated a strong correlation between meniscal stress and interface parameters (R² > 0.9). In a healthy meniscus, stress distribution is homogeneous (≈26 MPa). Stress concentration increases depending on the tear type: limited in a horizontal tear (≈26.5 MPa), significant in a vertical tear (≈30.8 MPa), and highest in a radial tear (≈40.6 MPa). These results indicate that as the tear progresses, the load-bearing capacity of the meniscus decreases, and stresses concentrate at the tear edges. <b>Conclusions:</b> Meniscal tears, especially radial ones, substantially alter knee biomechanics and elevate tissue stress. These biomechanical insights highlight the importance of early diagnosis and targeted rehabilitation strategies to prevent further cartilage damage and osteoarthritis progression.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810633","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":"Evaluation of MassFrontier, MetFrag, MS-FINDER, and SIRIUS for Metabolite Annotation Using an Experimental LC-HRMS Dataset.","authors":"Dmitrii A Leonov, Irina A Mednova, Alexander A Chernonosov","doi":"10.3390/biomedicines14040872","DOIUrl":"10.3390/biomedicines14040872","url":null,"abstract":"<p><p><b>Background</b>: Untargeted metabolomics enables comprehensive profiling of biological systems, but accurate metabolite annotation remains a critical bottleneck due to incomplete spectral libraries and structural isomerism. The use of in silico annotation tools can increase the coverage of annotated compounds, but it remains unclear whether these tools, in the absence of reference standards, can reliably annotate real-world experimental LC-HRMS data and whether they are sufficient for this task. <b>Methods</b>: This study assesses the performance and limitations of four widely used in silico structure prediction tools (MassFrontier, MetFrag, MS-FINDER, and SIRIUS/CSI:FingerID) when applied to an experimentally acquired feature set previously used to differentiate patients with depressive disorders from healthy controls. To ensure uniform evaluation across tools under realistic but optimized conditions, the quality of MS/MS data was improved using a parallel reaction monitoring method, allowing acquisition of interpretable fragmentation spectra for 26 of the 28 detected features. <b>Results</b>: For most features, all tools were able to suggest structure candidates. However, none of the tools proved sufficient as a standalone solution for reliable metabolite annotation. Due to their different algorithms, each tool had strengths and weaknesses in fragmentation interpretation, candidate generation, and ranking, resulting in incomplete or inconsistent annotations. While the combined application of all four tools provided a substantial improvement in putative annotation over conventional spectral library matching, the in silico structure prediction tools often prioritized chemically implausible, biologically irrelevant, or artifactual candidates. Consequently, manual expert evaluation was required to assess the chemical plausibility and biological relevance of the proposed structures. This ultimately reduced the number of biologically plausible metabolites putatively associated with disease to ten. <b>Conclusions</b>: Overall, these results demonstrate that existing in silico annotation tools can substantially support the annotation of experimental metabolomics data, but are insufficient on their own. Reliable identification of metabolites in complex biological matrices still depends on high-quality MS/MS data acquisition, the combined use of complementary tools, and mandatory post-annotation expert curation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810679","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":"A Personalized Medicine Approach: Psychosocial and Genetic Risk Assessments Predictors of Bariatric Surgery Outcomes After 3 Years.","authors":"Panayotis K Thanos, Shtakshe Chatrath, Colin Hanna, Fiona Comstock, John Butsch, Kenneth Blum, Albert Pinhasov, Lucy Mastrandrea, Teresa Quattrin, Lesley Georger, Alan Posner","doi":"10.3390/biomedicines14040870","DOIUrl":"10.3390/biomedicines14040870","url":null,"abstract":"<p><p><b>Background:</b> This study aimed to further explore the application of genetic risk assessments in 24 metabolic bariatric surgery (MBS) patients to predict weight loss outcomes three years after the procedure. <b>Methods:</b> Participants were assessed using the Genetic Addiction Risk Severity (GARS) test, which evaluates neurogenic polymorphisms linked to addiction and reward deficiency. Genetic and psychosocial data collected prior to surgery were analyzed in relation to post-operative weight loss measures, including weight change, body mass index (BMI), percentage of total weight loss (%TWL), and percentage of expected weight loss (%EWL). The analysis examined associations between specific genetic risk alleles, weight-related outcomes at three to four years post-surgery, and psychosocial trait scores. <b>Results:</b> Spearman's correlations revealed that the DRD2 risk allele is negatively correlated with 3-year BMI (r_s = -0.481, <i>p</i> < 0.05, 95% CI: -0.746 to -0.083). One-way ANOVA indicated that there is a significant difference in 3-year BMI (<i>p</i> = 0.018) between 0 and 1 DRD2 risk allele copy. There is also a significant difference in ∆weight (<i>p</i> = 0.022), ∆BMI (<i>p</i> = 0.014), and %EWL (<i>p</i> = 0.032) among the different SNP expression values of the MAOA risk allele. In addition, Spearman's correlation revealed that FCQ scores are negatively correlated with ∆BMI (r_s = -0.470, <i>p</i> < 0.05, 95% CI: -0.767, -0.005), %TWL (r_s = -0.561, <i>p</i> < 0.05, 95% CI: -0.814, -0.129), and %EWL (r_s = -0.533, <i>p</i> < 0.05, 95% CI: -0.800, -0.090) at 3 years post-surgery and positively correlated with 3-year weight (r_s = 0.576, <i>p</i> < 0.05, 95% CI: 0.151, 0.821) and 3-year BMI (r_s = 0.552, <i>p</i> < 0.05, 95% CI: 0.117, 0.810). Lastly, GARS scores are positively correlated with 3-year ∆weight (r_s = 0.422, <i>p</i> < 0.05, 95% CI: 0.010, 0.712).</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810657","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":"Effectiveness of an Oral Supplementation of Phycocyanin and Palmitoylethanolamide for a Short-Term Prophylaxis of Menstrual Migraine: A Retrospective Observational Study.","authors":"Gianni Allais, Massimo Autunno, Florindo D'Onofrio, Luisa Fofi, Maria Gabriella Saracco, Fabiola Bergandi, Chiara Benedetto, Francesca Silvagno, Loredana Bergandi","doi":"10.3390/biomedicines14040865","DOIUrl":"10.3390/biomedicines14040865","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background&lt;/b&gt;: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. &lt;b&gt;Objectives&lt;/b&gt;: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. &lt;b&gt;Methods&lt;/b&gt;: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. &lt;b&gt;Results&lt;/b&gt;: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. &lt;b&gt;Conclusions&lt;/b&gt;: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual m","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810645","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":"Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics.","authors":"Yujia Lin, Panpan Lu, Qiang Ding, Mei Liu","doi":"10.3390/biomedicines14040859","DOIUrl":"10.3390/biomedicines14040859","url":null,"abstract":"<p><p>The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis-reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts-collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift-from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation-thereby advancing the goal of precision medicine in IBD.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810594","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 T Allele of the HNMT C314T Polymorphism Is Associated with a Reduced Risk of Idiopathic Parkinson's Disease in Mexican Patients.","authors":"Antonio Bueno-Nava, Diana-Karina Díaz-Hernández, Rogelio Paniagua-Pérez, Paul Carrillo-Mora, José-Antonio Martínez-Cortez, Claudia Hernández-Arenas, Saúl-Renán León-Hernández, Adriana Olmos-Hernández, Antonio Verduzco-Mendoza, Alberto Avila-Luna, Arturo Gálvez-Rosas","doi":"10.3390/biomedicines14040861","DOIUrl":"10.3390/biomedicines14040861","url":null,"abstract":"<p><p><b>Introduction:</b> The histaminergic pathway has been implicated in Parkinson's disease (PD). Histamine is metabolized by histamine N-methyltransferase (HNMT), and the gene encoding this enzyme has a C314T polymorphism, in which cytosine is replaced by thymine. This results in reduced enzymatic activity. <b>Objective:</b> To analyze the C314T polymorphism of the HNMT gene in Mexican patients with idiopathic PD. <b>Materials and Methods:</b> In this study, peripheral blood samples were collected from patients with PD and healthy controls for genomic DNA extraction. HNMT genotyping was performed using the restriction fragment length polymorphism (RFLP) technique. Quantitative variables were compared using Student's <i>t</i> test, and categorical variables were compared using Pearson's χ² test. The risk of PD was estimated using odds ratios (ORs) and 95% confidence intervals (CIs). <b>Results:</b> According to the results of the bivariate analysis, compared with the controls, the patients were significantly older (<i>p</i> = 0.001) and had a higher incidence of hypertension (<i>p</i> = 0.020). HNMT RFLP analysis suggested an association between the C allele and PD development, with an OR (95% CI) of 7.424 (0.866-63.646). In contrast, the T allele appeared to confer a protective effect, with an OR of 0.134. In the age-adjusted Mantel-Haenszel stratified analysis of the HNMT C314T polymorphism, the C allele was identified as a risk factor for PD development in this small cohort, with an OR (95% CI) of 12.0 (0.8-160.4; <i>p</i> = 0.041). <b>Conclusions:</b> Advanced age, hypertension, and the C allele of the HNMT gene were associated with an increased risk of PD, whereas the T allele appeared to be associated with a protective role.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810661","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":"Systemic Immune-Inflammation Index and Clinical Predictors of Atypical PRES in Eclampsia: Higher Blood Pressure and Inflammatory Burden Drive Multi-Regional Involvement.","authors":"Mehmet İncebıyık, Adalet Göçmen","doi":"10.3390/biomedicines14040862","DOIUrl":"10.3390/biomedicines14040862","url":null,"abstract":"<p><p><b>Objective</b>: To identify clinical and neuroimaging predictors of atypical Posterior Reversible Encephalopathy Syndrome (PRES) in eclampsia and evaluate the role of multi-regional cerebral involvement (neuroimaging burden). <b>Methods</b>: This retrospective cohort study included 266 patients with eclampsia and radiologically confirmed PRES (2018-2025). Patients were classified as typical (<i>n</i> = 234, 88.0%) or atypical (<i>n</i> = 32, 12.0%). A two-stage multivariable logistic regression was performed to identify independent predictors, sequentially incorporating clinical and neuroimaging variables. <b>Results</b>: Peak systolic blood pressure was significantly higher in atypical vs. typical groups (191.6 ± 20.4 vs. 172.4 ± 18.5 mmHg, <i>p</i> < 0.001). Furthermore, atypical cases exhibited a significantly higher systemic inflammatory burden, characterized by markedly elevated Systemic Immune-Inflammation Index (SII) and CRP levels (<i>p</i> < 0.001). Atypical cases exhibited a markedly greater neuroimaging burden, with a higher mean number of involved brain regions (4.4 ± 1.2 vs. 2.1 ± 0.6, <i>p</i> < 0.001). In Model 1 (clinical variables only), systolic blood pressure was a strong predictor of atypicality (OR: 1.24 per 10 mmHg increase, 95% CI: 1.12-1.38, <i>p</i> < 0.001). After incorporating neuroimaging features in Model 2, the total number of involved brain regions emerged as the strongest independent predictor (OR: 2.08, 95% CI: 1.52-2.85, <i>p</i> < 0.001), while the independent effect of blood pressure was attenuated. <b>Conclusions</b>: Atypical PRES in eclampsia reflects extensive, high-burden cerebral vasogenic edema rather than a distinct radiological subtype. While hypertension initiates the process, the total regional burden determines the atypical signature. This burden-focused perspective improves risk stratification and diagnostic vigilance in high-risk obstetrics.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810811","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":"Modulation Effects of Reproductive Hormones on Oogenesis in a Collagenase-Induced Osteoarthritis Mouse Model.","authors":"Anton Kolarov, Irina Chakarova, Valentina Hadzhinesheva, Venera Nikolova, Stefka Delimitreva, Maya Markova, Ralitsa Zhivkova","doi":"10.3390/biomedicines14040857","DOIUrl":"10.3390/biomedicines14040857","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Osteoarthritis has been increasingly described as associated with systemic inflammation, raising the question of how it would affect fertility in young women with or without reproductive hormone administration. We studied oogenesis in mice with collagenase-induced osteoarthritis (CIOA) as a model system with fewer ethical limitations after estradiol (E2) or follicle-stimulating hormone (FSH) treatment. <b>Methods</b>: Oocytes have been isolated from mice subjected to various treatment regimens. The meiotic spindle, the chromatin, and the actin cap were fluorescently labeled and analyzed. <b>Results</b>: In addition to reduced maturation rates, specific oocyte abnormalities were registered when CIOA, FSH, or E2 were applied in isolation. Combined treatments showed that the spindle, chromatin, and actin cytoskeleton parameters were differently affected in oocytes from groups with CIOA treated by estradiol and those treated with FSH. Enlarged spindles, ooplasmic tubulin asters, aligned metaphases, and predominantly normal actin caps, often with an actin halo, were typical for groups with CIOA combined with estradiol. The groups with CIOA and FSH had slightly enlarged spindles, unaligned metaphases with degenerated chromatin surrounded by a cloud of depolymerized tubulin, and small actin caps. <b>Conclusions</b>: Our results show that experimental osteoarthritis with or without exogenous reproductive hormones negatively affects oogenesis, presumably due to systemic inflammatory factors making the ovarian microenvironment less capable of supporting oocyte maturation. Estradiol supplementation does not benefit oogenesis. FSH treatment induced cytoskeletal and chromatin abnormalities that presumably disturb the fertilization and development potential of affected oocytes. These data can have implications for assisted reproduction in cases of patients with osteoarthritis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810556","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":"Metabolic Amplification in Endometrial Carcinogenesis: Biological Rationale and Translational Limits of Precision Chemoprevention.","authors":"Weronika Rzeska, Aneta Adamiak-Godlewska","doi":"10.3390/biomedicines14040863","DOIUrl":"10.3390/biomedicines14040863","url":null,"abstract":"<p><strong>Background: </strong>Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and one of the few solid tumors with a steadily rising incidence, paralleling global trends in obesity and insulin resistance. Its strong epidemiologic association with systemic metabolic dysfunction positions EC as a uniquely accessible model for metabolically informed chemoprevention.</p><p><strong>Methods: </strong>This narrative review was conducted through a systematic search of PubMed/MEDLINE and Embase using the following terms: \"endometrial cancer\" AND (\"insulin resistance\" OR \"metabolic syndrome\" OR \"PI3K\" OR \"chemoprevention\" OR \"bariatric surgery\" OR \"metformin\" OR \"cellular senescence\"). Searches were limited to English-language publications; no date restriction was applied for foundational molecular studies, while clinical and translational evidence was reviewed from 2000 to 2025. Additional references were identified through manual review of reference lists of included articles.</p><p><strong>Results: </strong>We examine metabolic amplification as a conceptual framework in which hyperinsulinemia, inflammatory reinforcement, and redox-epigenetic modulation intensify proliferative signaling in biologically susceptible endometrial tissue, particularly within molecular subtypes enriched for PI3K pathway activation such as tumors lacking a specific molecular profile (NSMP). Bariatric surgery offers the strongest human evidence supporting the principle that durable metabolic correction can substantially reduce EC incidence. In contrast, pharmacologic interventions including metformin, anti-inflammatory agents, and nutraceutical compounds demonstrate variable or limited preventive efficacy, and short-term biomarker modulation cannot substitute for validated reduction in cancer risk. The endometrial intraepithelial neoplasia (EIN) model provides a uniquely accessible platform for biomarker-guided intervention.</p><p><strong>Conclusions: </strong>Integration of genomic subtype classification with metabolic profiling may enable precision prevention strategies in clearly defined high-risk populations. Effective chemoprevention will require molecular enrichment, confirmation of tissue-level target engagement, and clinically meaningful endpoints, while acknowledging the translational limits of pathway-directed approaches.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810469","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}