Biomedicines最新文献

Background/Objectives: Cardiac rehabilitation (CR) is known to improve clinical outcomes in cardiovascular disease, yet its benefits in patients with implantable cardioverter-defibrillators (ICD) are not well established. This meta-analysis evaluated the impact of CR on functional capacity and safety in ICD recipients. Methods: A systematic search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials (RCT) involving adults who underwent ICD implantation and were assigned to either CR or standard care. The primary outcome was the change in peak oxygen uptake (peak VO₂) from the baseline to the final follow-up. Random-effects models were applied, and subgroup analyses were conducted based on follow-up duration, supervision type, baseline peak VO₂, and ischemic vs. non-ischemic etiology. Results: Seven RCTs involving 1461 participants (784 CR; 677 control) met the inclusion criteria. CR was associated with a significant improvement peak VO₂ compared with usual care, expressed as the mean difference (MD) in change from the baseline to the last follow-up (MD 2 mL·kg^-1·min^-1; 95% CI 1.02-2.81; I² = 65.7%), with consistent effects across all subgroups. Quality of life improved in the CR group (MD 6.46; 95% CI 2.25-10.67; I² = 0%). A non-significant trend toward increased 6MWT distance was observed. CR did not increase adverse events, including ICD shocks, hospitalizations, or cardiac deaths. Conclusions: CR safely enhances exercise capacity and quality of life in ICD recipients without increasing arrhythmic events or mortality. Larger standardized trials are warranted to optimize CR delivery in this population.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritic eczematous lesions that significantly alter quality of life of patients. Dupilumab, a new biologic agent, has demonstrated efficacy and safety in the general adult population with AD. However, evidence on its use in elderly patients is limited. Objectives: The objective of this work was to systematically assess the effectiveness and safety of dupilumab in patients aged ≥60 years with AD, based on published data. Methods: A systematic review and meta-analysis were conducted following the PICO(S) framework. Articles written in English and published before 31 December 2024 that investigated patients ≥ 60 years with AD treated with dupilumab were included. Meta-analysis of the observational studies was performed using a random-effects model with subgroup and meta-regression analyses. Results: Twenty-one articles met the inclusion criteria. After 16 weeks of treatment, dupilumab significantly reduced disease severity (EASI: 21.8; 95% CI: 18.3-25.2), intensity of pruritus (P-NRS: 5.8; 95% CI: 4.2-7.3), and quality of life impairment (DLQI: 11.3; 95% CI: 6.1-16.5); all p < 0.001. Meta-regression revealed previous treatment with cyclosporin A as a predictor of a poorer response to treatment. The generalized-prurigo phenotype was associated with worse control of pruritus. The most common adverse events were conjunctivitis, injection site reactions, and facial flushing. Conclusions: Dupilumab appears to be an effective and well-tolerated treatment for AD in elderly patients. More research is warranted to evaluate its long-term effectiveness and safety in this age group.

Background: Metabolic reprogramming is increasingly recognized as a hallmark of endometrial cancer, yet tissue-based metabolic signatures remain insufficiently defined. Methods: Untargeted metabolomics was performed on paired endometrial cancer (n = 10) and adjacent normal tissues (n = 10). Differential metabolites were identified through multivariate and univariate analyses. KEGG enrichment characterized altered pathways, while Random Forest and SVM were used for machine-learning-based feature prioritization. ROC analyses were conducted to evaluate the discriminative potential of selected metabolites. Results: 300 metabolites were significantly altered. Tumor tissues showed increased sphingolipid metabolism, glutathione metabolism, and arachidonic acid metabolism, alongside decreased bile acid, phenylalanine, and steroid biosynthesis. Machine learning converged on six key metabolites that demonstrate strong tissue-discriminative capacity. Conclusions: Endometrial cancer exhibits a distinct metabolic profile characterized by lipid remodeling and redox adaptation. The six metabolites identified through machine-learning-based analyses represent candidate metabolic features associated with endometrial cancer and provide a foundation for future mechanistic studies and validation in larger, independent cohorts.

Background/Objectives: Vedolizumab (VDZ), a monoclonal antibody targeting α4β7 integrin, is used in Crohn's disease (CD) management, yet patients' responses vary, underscoring the need for pharmacogenomic (PGx) markers. This study aimed to identify PGx pathways associated with suboptimal VDZ response using a rare-variant analytical framework. Methods: DNA from 63 CD patients treated with VDZ as first-line advanced therapy underwent whole-exome sequencing. Clinical response at week 14 classified patients as optimal responders (ORs) or suboptimal responders (SRs). Sequencing data were processed using GATK Best Practices, annotated with variant effect predictors, and filtered for rare damaging variants (damaging missense and high-confidence loss-of-function; minor allele frequency < 0.05). Variants were mapped to genes specific for SRs and ORs, and analyzed for pathway enrichment using the Reactome database. Rare-variant burden and composition differences were assessed with Fisher's exact test and SKAT-O gene-set association analysis. Results: Suboptimal VDZ response was associated with pathways related to membrane transport (ABC-family proteins, ion channels), L1-ankyrin interactions, and bile acid recycling, while optimal response was associated with pathways involving MET signaling. SKAT-O identified lipid metabolism-related pathways as significantly different-SRs harbored variants in pro-inflammatory lipid signaling and immune cell trafficking genes (e.g., PIK3CG, CYP4F2, PLA2R1), whereas ORs carried variants in fatty acid oxidation and detoxification genes (e.g., ACADM, CYP1A1, ALDH3A2, DECR1, MMUT). Conclusions: This study underscores the potential of exome-based rare-variant analysis to stratify CD patients and guide precision medicine approaches. The identified genes and pathways are potential PGx markers for CD patients treated with VDZ.

The brain's extracellular matrix (ECM) serves as a dynamic and instructive regulator of glioma progression. The ECM provides structural support while integrating pharmacological and mechanical signals that influence glioma initiation, progression, and treatment resistance. Deviant ECM remodeling fosters tumor heterogeneity, invasion, and immune evasion by altering stiffness, composition, and cellular matrix signaling. We proposed that ECM remodeling in gliomas not only facilitates tumor growth and heterogeneity but also establishes advantageous biophysical and metabolic conditions that foster treatment resistance and recurrence. Our objective is to analyze current findings regarding the structural, biochemical, and mechanical roles of the brain ECM in glioma growth, emphasizing its contribution to tumor heterogeneity, mechanotransduction, immunological modulation, and its potential as a therapeutic target.

Method: A comprehensive literature review was conducted using scientific databases including PubMed, Web of Science, and Scopus. Peer-reviewed literature published between 2000 and 2025 was selected for its relevance to ECM composition, stiffness, remodeling enzymes, extracellular vesicles, and mechanobiological processes in gliomas.

Results: Recent investigations demonstrate that glioma cells actively alter the ECM by secreting collagens, laminins, and metalloproteinases, establishing a feedback loop that facilitates invasion and resistance.

Discussion: Mechanical variables, such as ECM stiffness and solid stress, influence glioma growth, metabolism, and immune exclusion. Moreover, extracellular vesicles facilitate significant extracellular matrix remodeling and improve communication between tumors and stromal cells. The disruption of ependymal and subventricular extracellular matrix niches enhances invasion and cerebrospinal fluid-mediated signaling. The remodeling of the ECM influences glioma growth through interconnected biochemical, mechanical, and immunological mechanisms. Examining ECM stiffness, crosslinking enzymes, and vesicle-mediated signaling represents a potential therapeutic approach. Integrative methodologies that combine mechanobiology, imaging, and multiomics analysis could uncover ECM-related vulnerabilities to improve glioma treatment.

Background: Advanced glycation end-products (AGEs) are formed and deposited in tissues, contributing to various disorders, including diabetes, other metabolic diseases, and aging. A new epitope, AGE10, was identified in human and animal tissues using a monoclonal antibody raised against synthetic melibiose-derived glycation end-products (MAGE), which were synthesized under anhydrous conditions with bovine serum albumin or myoglobin. The biology of the AGE10 epitope, particularly its role in diseases and in cancer tissues, is not well understood. Methods: The study was aimed at investigating the immunohistochemical recognition of AGE10 with the MoAb-anti-MAGE antibody. Results: Data obtained show that AGE10 is recognized in striated muscles but not in tumors of muscular origin. AGE10 is also stained in both normal and cancerous salivary glands and in adenomas of the large intestine. The staining is cytoplasmic. Discussion: Our approach may provide a methodology for cell biology research; AGE10 may be related to an advanced lipoxidation end-product; further investigation of MAGE may clarify disease mechanisms, support the development of novel therapeutic strategies. Conclusions: The key finding is that antibodies recognize mainly the epitope in epithelial and some mesenchymal tissues. Thus, the potential for AGE10 as a diagnostic marker is limited. The implications concern the biology of this epitope, the unique tissue distribution, and a role in cellular metabolism.

Atherosclerosis (AS) is a disease characterized by chronic vascular wall inflammation and lipid deposition. Although lipid-lowering drugs such as statins have significantly reduced cardiovascular event rates, "residual inflammatory risk" remains a key factor driving disease progression and plaque rupture. As a central regulator of the inflammatory response, the nuclear factor-κappaB (NF-κB) signaling network comprises both canonical pro-inflammatory pathways and functionally more complex non-canonical pathways. Increasing evidence in recent years indicates that abnormal and sustained activation of the non-canonical NF-κB signaling pathway plays a pivotal role in driving plaque rupture. This review first elaborates on the shift in AS strategies from "lipid-lowering" to "anti-inflammatory" approaches, followed by an in-depth analysis of the molecular activation mechanisms of the NF-κB signaling pathway and its distinctiveness in the AS pathological process, along with its epigenetic regulation. It emphasizes how this pathway drives pathological angiogenesis and regulates vascular smooth muscle cell (VSMC) phenotypic switching and macrophage function, thereby forming a vicious cycle that amplifies inflammation and structural damage, ultimately leading to acute cardiovascular events. Finally, we systematically summarize current progress and challenges in drug development targeting the NF-κB pathway (e.g., targeting key kinases like NIK and IKKα), aiming to provide theoretical foundations and future directions for novel therapeutic strategies to stabilize coronary plaques and prevent acute coronary syndromes.

Background: The aim of this study was to evaluate the diagnostic and prognostic performance of albumin-based inflammatory-nutritional indices in hyperemesis gravidarum (HG) and to determine their associations with disease severity and risk of re-hospitalization. Methods: This retrospective case-control study included 246 women with HG and 246 gestational-age-matched healthy pregnant controls at 6-16 weeks of gestation. Disease severity was classified as mild, moderate, or severe using the Pregnancy-Unique Quantification of Emesis (24 h scale) (PUQE-24) score. A comprehensive panel of albumin-based inflammatory indices-including C-reactive protein-to-albumin ratio (CAR), fibrinogen-to-albumin ratio (FAR), neutrophil-to-albumin ratio (NAR), leukocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), monocyte-to-albumin ratio (MAR), hemoglobin-albumin-lymphocyte-platelet (HALP) score, modified HALP (m-HALP) score, prognostic nutritional index (PNI) score, systemic immune-inflammation index-to-albumin (SII/Alb), and systemic inflammatory response index-to-albumin (SIRI/Alb)-was calculated from routine complete blood count and serum biochemistry results obtained at diagnosis. Receiver operating characteristic analysis, along with univariate and multivariate logistic regression models, was performed to evaluate diagnostic performance and identify predictors of severe HG and re-hospitalization. Results: Albumin-based indices exhibited severity-associated alterations, with an overall trend toward worsening immuno-nutritional status across increasing HG severity. Among these, m-HALP score demonstrated the strongest inverse correlations with PUQE-24 score, ketonuria grade, length of hospital stay, and re-hospitalization risk (r = -0.74 to -0.52; all p < 0.001) and achieved the highest discriminative accuracy for both severe HG (AUC 0.864, 95% CI 0.836-0.892, p < 0.001) and re-hospitalization (AUC 0.722, 95% CI 0.675-0.766, p < 0.001). In multivariable analysis, higher HALP, m-HALP, and PNI were independently associated with a lower likelihood of severe HG. For re-hospitalization, higher m-HALP and HALP were independently associated with a lower risk, whereas higher NPAR, higher ketonuria grade, and higher PUQE-24 score were independently associated with an increased risk of re-hospitalization. Conclusions: Albumin-based indices, particularly m-HALP, demonstrated robust diagnostic and prognostic performance in HG compared with conventional biomarkers. These readily available, cost-neutral composite biomarkers enable objective severity stratification and accurate identification of patients at elevated risk of recurrent hospitalization, offering immediate potential to guide personalized, evidence-based clinical management.

Thrombophilia is considered one of the key mechanisms underlying reproductive disorders. Clinical heterogeneity of reproductive disorders and a lack of stratification by phenotype often limit interpretation. Therefore, evaluating thrombophilia-associated genetic markers separately in fetal loss syndrome, postpartum hemorrhage (PPH), and hypertensive disorders of pregnancy is essential. Background/Objectives: To assess the frequency of thrombophilia-related genetic polymorphisms in women with various reproductive disorders and evaluate their association with clinical-anamnestic characteristics and obstetric antiphospholipid syndrome. Methods: A total of 132 women with reproductive disorders (fetal loss syndrome, postpartum hemorrhage, preeclampsia). Results: Statistically significant differences were found when comparing between the groups. Thus, heterozygous F13 genetic polymorphisms were statistically more common in the group with a history of preeclampsia compared to the group with PPH (the G/A genotype was detected in 22.2% versus 10.7%, p = 0.045), and heterozygous ITGA2 gene genetic polymorphisms were also more common (the C/T genotype was detected in 66.7% versus 42.9%, p = 0.023). In women with a history of PPH, homozygous ITGA2 genetic polymorphisms were statistically more common (the T/T genotype was detected 2.6 times more often-21.4% versus 8.8% compared to the group with fetal loss syndrome, p = 0.022; and 3.8 times more often-21.4% versus 5.6% compared to the group with PE, p = 0.022). Conclusions: A study of thrombophilia gene polymorphisms in women with reproductive disorders showed that the G/A genotype of F13, the C/T genotype of ITGA2, and the A/G genotype of MTR:2756 were significantly more common in women with preeclampsia than in the group with postpartum hemorrhage; the T/T genotype of the ITGA2 gene was detected in postpartum hemorrhage. The MTHFR 1286A > C (A/C) polymorphism was associated with a reduced risk of postpartum hemorrhage. In contrast, the MTR 2756A > G (A/G) genotype was associated with an increased risk of preeclampsia.

The prevalence and incidence of prediabetes in children and youth continue to increase in parallel with the obesity epidemic. While prediabetes is defined by elevated HbA1c and/or impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG), the risk of clinical disease is a continuum. Individuals with prediabetes are at a higher risk of developing youth-onset type 2 diabetes, which is considered a more aggressive form of the disease. This condition is associated with increased cardiovascular and metabolic risks and leads to an earlier onset of complications compared to adults with type 2 diabetes. Additionally, significant damage to beta cells may occur even before dysglycemia develops. Recent data indicate that mortality rates are higher in youths with type 2 diabetes compared to those with type 1 diabetes. Childhood prediabetes and cardiovascular complications associated with it are a significant health concern. This review provides the latest insights into this complex issue. We will present an overview of pathophysiology, screening methods, and therapeutic options to prevent the progression from prediabetes to type 2 diabetes in children. In summary, it is crucial to identify prediabetes in children, as this underscores the importance of appropriate screening and timely intervention.