Biomolecules & biomedicine最新文献

The endothelial activation and stress index (EASIX) is recognized as a prognostic indicator across various diseases; however, its utility in patients undergoing continuous renal replacement therapy (CRRT) is limited. This study aimed to investigate the relationship between EASIX and prognosis in individuals receiving CRRT. Data from patients receiving CRRT were extracted from the Medical Information Mart for Intensive Care IV database. EASIX was calculated and log2-transformed. Kaplan-Meier survival analysis was conducted based on log2(EASIX) quartiles. Cox proportional hazards regression was utilized to estimate the relationship between EASIX and 28-day all-cause mortality. Potential nonlinear associations were evaluated through restricted cubic splines (RCS) analysis, and subgroup analyses were performed to assess the robustness of EASIX's impact on all-cause mortality. A total of 2,873 ICU patients treated with CRRT were enrolled. Kaplan-Meier analysis revealed that higher EASIX scores were significantly associated with lower 28-day survival (log-rank p < 0.001). After adjusting for confounding factors, EASIX remained significantly associated with the risk of 28-day all-cause mortality among CRRT patients (HR: 1.066; 95% CI: 1.026-1.107; p = 0.001). The area under the curve (AUC) of the SOFA+EASIX model was 0.694 (95% CI: 0.673-0.714; p < 0.001), slightly higher than that of the SOFA scores alone. These results suggest that EASIX may enhance the predictive performance of SOFA scores. RCS analysis indicated a linear association between log2(EASIX) and 28-day all-cause mortality (p for overall = 0.001; p for nonlinear = 0.224). Subgroup analyses confirmed the robustness of this association across various patient groups. In conclusion, EASIX is independently associated with mortality in patients undergoing CRRT. Prospective studies are warranted to further explore its therapeutic and prognostic significance.

Thrombocytopenia and absolute neutropenia are recognized manifestations of Epstein-Barr virus infectious mononucleosis (EBV-IM). This study conducted a retrospective analysis of laboratory results from patients clinically suspected of having EBV-IM and tested over a two-year period (2018-2019) at a single testing center in Ireland, aiming to determine the prevalence of these hematological complications. A cohort of 51 confirmed acute EBV-IM cases was established, and the incidence of thrombocytopenia and absolute neutropenia within this group was assessed. These findings were then compared to the frequencies observed in non-acute EBV-IM patients, both with and without atypical lymphocytes. Among the 51 patients diagnosed with acute EBV-IM, 14% presented with thrombocytopenia and absolute neutropenia, including instances of severe cases. A comparable prevalence of these conditions was noted in non-acute EBV-IM patients with identifiable atypical lymphocytes; however, a significantly lower incidence was found in non-acute EBV-IM patients lacking atypical lymphocytes. These results suggest that thrombocytopenia and absolute neutropenia occur in patients with viral infections and are not exclusive to acute EBV-IM.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy of the head and neck that is often diagnosed at a locally advanced stage (LANPC). In such cases, intensity-modulated radiotherapy combined with concurrent chemoradiotherapy (CCRT) is the standard treatment; however, the occurrence of distant metastasis and treatment failure remains prevalent. This study evaluates the prognostic significance of a novel composite score that combines hemoglobin levels and the C-reactive protein-to-albumin ratio (HCAR) in LANPC patients undergoing CCRT. We conducted a retrospective analysis of 233 LANPC patients treated with intensity-modulated radiotherapy and platinum-based CCRT from 2011 to 2020. Receiver operating characteristic curve analysis determined pretreatment hemoglobin (Hb) and C-reactive protein-to-albumin ratio (CAR) cut-offs of 11.0 g/dL and 3.0, respectively, which were utilized to create a three-tiered HCAR score: HCAR-0 (Hb ≥11.0 g/dL and CAR <3.0), HCAR-1 (Hb ≥11.0 g/dL and CAR ≥3.0 or Hb <11.0 g/dL and CAR <3.0), and HCAR-2 (Hb <11.0 g/dL and CAR ≥3.0). The primary endpoint of the study was overall survival (OS), while progression-free survival (PFS) was the secondary endpoint. With a median follow-up of 85.7 months, the median PFS and OS were 66.0 months and 108.0 months, respectively, with 5-year PFS and OS rates of 52.8% and 75.9%. The HCAR score significantly stratified patient outcomes: median PFS was not reached for HCAR-0, 66.0 months for HCAR-1, and 25.0 months for HCAR-2. Median OS also varied significantly, being not reached for HCAR-0, 108.0 months for HCAR-1, and 55.0 months for HCAR-2 (all p < 0.001). Corresponding 10-year PFS rates were 50.2%, 34.4%, and 5.0%, while 10-year OS rates were 68.3%, 41.6%, and 11.1%. Multivariate analysis revealed that the HCAR score remained an independent predictor of both PFS and OS, alongside T and N stage. The HCAR score shows promising prognostic utility for predicting OS and PFS in LANPC; however, performance estimates may be overly optimistic due to the lack of internal validation.

Periodontitis is an inflammatory disease characterized by the destruction of the periodontal attachment apparatus, which includes alveolar bone, periodontal ligament, and cementum. This destruction is driven by a dysregulated host immune response to pathogenic subgingival biofilm. The present preliminary study aimed to evaluate immune-related gene expression patterns in patients with stage III/IV periodontitis utilizing the NanoString nCounter® platform. Unstimulated saliva samples were collected from twelve individuals: ten with severe periodontitis (stage III/IV) and two periodontally healthy controls. Total RNA was isolated and analyzed using the nCounter® Human Inflammation Panel, which profiles 249 inflammation-associated human genes. Data normalization and differential expression analysis were performed with nSolver™ software. Following quality control, genes with low expression (mean normalized counts < 20) were excluded, resulting in 89 genes available for comparison. Among these, 26 genes (29.2%) met a predefined effect-size threshold (|log2FC| ≥ 1), comprising 23 upregulated and 3 downregulated transcripts in the periodontitis group. Notably, the upregulated genes HLA-DRB1 (p = 0.003; FDR = 0.267) and CCR1 (p = 0.007; FDR = 0.312) exhibited relatively large log2 fold changes and the lowest unadjusted p-values; however, neither retained significance after FDR correction. These findings underscore the feasibility of salivary gene expression profiling as a method for identifying molecular markers associated with disease severity. Given their roles in immune activation and leukocyte recruitment, HLA-DRB1 and CCR1 emerge as potential biomarker candidates for detection, risk stratification, and therapeutic monitoring in periodontitis, necessitating validation in larger, well-characterized cohorts.

Atherosclerotic cardiovascular diseases continue to be the leading causes of morbidity and mortality globally. Disorders of lipoprotein metabolism contribute significantly to the development of atherosclerosis, which begins with the subendothelial retention of plasma-derived apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein (LDL) and its remnants. Elevated LDL cholesterol levels and triglycerides, coupled with low high-density lipoprotein (HDL) cholesterol levels, are critical risk factors for atherosclerotic cardiovascular diseases. Landmark epidemiological studies have identified dyslipidemia as a key modifiable risk factor for these diseases, elucidating the essential role of lipid abnormalities in atherogenesis and highlighting significant opportunities for cardiovascular disease prevention and risk stratification. Genetic epidemiology studies have shown that lifelong low levels of LDL due to genetic variations markedly reduce the risk of atherosclerotic cardiovascular diseases. Recent advancements in lipid-lowering pharmacology are increasingly informed by genetic studies that reveal naturally occurring mutations offering lifelong cardioprotection. Furthermore, these genetic studies have facilitated the development of novel therapeutics and enhanced the prediction of potential side effects, variability in individual drug responses, and improved risk stratification. This narrative review article aims to summarize key genetic variants that influence lipid metabolism and examine their therapeutic potential in cardiovascular therapy. Given the central role of atherosclerosis in determining cardiovascular risk, it is vital to consider lipid metabolism in the context of genetic factors that affect individual susceptibility to hyperlipidemia. Defining cardioprotective genetic determinants is equally important, as it may provide a foundation for therapeutic strategies by emphasizing protective mechanisms.

Sestrin2, a stress-inducible protein with antioxidant properties, is upregulated in response to various stressors, including oxidative and energetic stress. This study examines the relationship between plasma Sestrin2 levels, total antioxidant capacity (TAC), total nitric oxide (NO), and the likelihood of experiencing an acute ischemic stroke (AIS) within the Qatari population. The cohort consisted of 187 AIS patients and 30 healthy controls. Plasma concentrations of Sestrin2, TAC, and nitrite/nitrate (an indirect measure of NO) were evaluated at four intervals: within 48 hours of stroke onset, and at 5 days, 30 days, and 1 year post-stroke. At stroke onset, AIS patients exhibited significantly lower plasma levels of Sestrin2 (1.434±3.57 vs. 8.383±7.39; p <0.001), TAC (1.88±0.42 vs. 2.279±0.326; p <0.001), and nitrite/nitrate (53.5±47.9 vs. 65.951±44.07; p = 0.04) compared to controls. Sestrin2 levels remained diminished at 5 and 30 days post-stroke, while NO levels increased by day 5 (p = 0.01). Multiple logistic regression analysis revealed that male sex, diabetes, high National Institutes of Health Stroke Scale (NIHSS) scores, and small vessel disease (SVD) were associated with increased odds of AIS, whereas Middle Eastern ethnicity correlated with reduced odds. Notably, higher tertiles of Sestrin2, TAC, and NO were linked to decreased odds of AIS, with adjusted odds ratios of 0.123 (p < 0.001), 0.327 (p = 0.01), and 0.063 (p = 0.01), respectively. The observed lower plasma levels of Sestrin2, TAC, and NO at stroke onset and up to 30 days post-event suggest their potential role as biomarkers in stroke occurrence and recovery, with elevated levels associated with a decreased likelihood of AIS.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that poses a growing global health challenge. Beyond traditional hallmarks such as amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation, the gut-brain axis (GBA) has emerged as a significant modulator of AD pathogenesis. Among gut-derived mediators, microbiota-derived extracellular vesicles (mEVs) transport bioactive cargo across epithelial and vascular barriers, thereby linking intestinal dysbiosis to neurodegeneration. This narrative review synthesizes experimental, translational, and early clinical evidence regarding the immunomodulatory roles of gut mEVs in AD. We examine how mEVs may traverse compromised intestinal and blood-brain barriers, activate microglia and astrocytes, and influence Aβ and tau metabolism, thereby integrating peripheral and central immune interactions. Based on this evidence, we propose the "microbiota-EV-immune-neuro axis" as a conceptual framework that connects gut dysbiosis with AD-related neurodegeneration. The review also highlights emerging data on mEV signatures as minimally invasive biomarkers and explores their potential as therapeutic targets or delivery vectors. While current evidence is preliminary and methodologically heterogeneous, mEVs are increasingly recognized as both indicators and potential modulators of AD pathophysiology, emphasizing the need for standardized, longitudinal, and interventional studies.

Ankle sprains are prevalent musculoskeletal injuries commonly encountered in the general population, particularly among athletes. While conventional treatments are widely practiced, regenerative therapies have emerged as potential adjunctive options. This narrative review aims to assess the role of regenerative therapy in the management of acute ankle sprains and evaluate its efficacy through an analysis of the literature. We focused on studies available in PubMed, restricting our search to English-language articles published between January 2005 and December 2024. Our review identified five studies on platelet-rich plasma (PRP) and one on hyaluronic acid (HA). The PRP studies included four clinical trials and one case report. PRP injections demonstrated short-term benefits in pain reduction and functional recovery, particularly when administered early and in multiple doses. However, long-term outcomes were often comparable to standard treatments or placebo. The study on HA indicated consistent and sustained advantages over placebo in alleviating pain, expediting the return to sport, and reducing recurrence rates. Based on the current evidence, PRP and HA may function as adjunctive therapies for acute ankle sprains, especially for short-term symptom relief and functional recovery. Treatment efficacy appears to be influenced by factors such as injection timing, volume, immobilization protocols, and the concurrent use of nonsteroidal anti-inflammatory drugs. Nonetheless, the evidence base remains constrained by small sample sizes, heterogeneous protocols, and a lack of long-term follow-up. Therefore, further high-quality randomized controlled trials are essential to establish standardized protocols and ascertain the long-term efficacy of these regenerative therapies.

Esophageal cancer is recognized as one of the most aggressive malignancies within the digestive system, with global survival rates typically falling below 20%. Malnutrition impacts up to 80% of patients, significantly affecting treatment tolerance, postoperative outcomes, and overall quality of life. Recent advancements in clinical nutrition and immunometabolism have transformed the perception of nutrition from a mere supportive measure to a vital therapeutic component in cancer care. This review synthesizes evidence from studies published between 2010 and 2025, exploring the effects of various nutritional strategies-including enteral, elemental, parenteral, immuno-nutritional, behavioral, and prehabilitative interventions-on metabolism, immune response, and clinical outcomes in patients with esophageal cancer. The findings demonstrate that targeted approaches such as immune-enhancing enteral formulations, omega-3-enriched parenteral nutrition, and structured dietary counseling can mitigate inflammation, preserve muscle mass, enhance treatment adherence, and improve psychological well-being. Overall, the literature supports the perspective of nutrition as a precision-based, integral component of multidisciplinary cancer management. Incorporating nutritional optimization throughout all stages of care-ranging from prehabilitation and perioperative support to survivorship and palliative management-can enhance metabolic resilience, promote faster recovery, and significantly improve the quality of life for individuals diagnosed with esophageal cancer.

Acid ceramidase (AC), a pivotal enzyme in sphingolipid metabolism, has been associated with various cancers; however, its specific role in rectal cancer remains poorly understood. This study aimed to explore the clinical significance of AC gene and protein expression in rectal cancer. We analyzed the expression of ASAH1, BAX, and BCL2 through quantitative Real-Time PCR in paired tumor and non-tumor tissue samples obtained from patients with locally advanced rectal cancer (LARC) prior to neoadjuvant chemoradiotherapy. Additionally, serum AC levels and standard biochemical parameters were assessed. We further evaluated ASAH1 expression using RNA-seq data from publicly available TCGA-READ datasets accessed via the UCSC Xena Browser. Two approaches indicated a significant reduction in ASAH1 expression in tumor tissue (p=0.004 and p<0.001, respectively). Receiver operating characteristic curve analysis revealed a modest capacity for ASAH1 expression to differentiate between tumor and non-tumor tissue in LARC patients (AUC=0.652, p=0.042). No correlation was observed between ASAH1 expression and the BAX/BCL2 ratio in tumor tissue, nor with serum AC levels or the CRP-albumin-lymphocyte (CALLY) index. Conversely, serum AC levels exhibited a negative correlation with the BAX/BCL2 ratio (rs=-0.536, p=0.002, FDR-adjusted q=0.021). Furthermore, ASAH1 expression, AC levels, and the CALLY index were not linked to overall survival or treatment response. A key finding of this study is the inverse relationship between serum AC levels and the pro-apoptotic status of tumor tissue, suggesting that circulating AC may provide valuable insights into tumor apoptotic activity. Further large-scale studies are necessary to validate these preliminary findings and elucidate the biomarker potential of AC in rectal cancer.