Biomolecules & biomedicine最新文献

Pandoraea species are emerging multidrug-resistant pathogens increasingly associated with respiratory tract infections, particularly in cystic fibrosis patients. Despite their growing clinical relevance, these bacteria are underrepresented in the scientific literature. This review aims to consolidate existing evidence regarding Pandoraea species as emerging multidrug-resistant pathogens, with a focus on their taxonomy, diagnostic methodologies, antimicrobial resistance mechanisms, and treatment challenges. By identifying gaps in current therapeutic strategies and the limited clinical outcome data, this review underscores the necessity of advancing research into innovative interventions, such as bacteriophages, antimicrobial peptides, and combination therapies, to enhance patient management and infection control. A comprehensive literature search was conducted using PubMed and Google Scholar, employing relevant keywords to identify case reports, clinical studies, and in vitro research related to Pandoraea infections, resistance mechanisms, and therapeutic strategies. Our findings reveal a significant lack of comprehensive data on therapeutic approaches, particularly concerning bacteriophages, antimicrobial peptides, and combination antibiotic therapies. Furthermore, clinical data on treatment efficacy remain sparse, with the majority of evidence stemming from in vitro-studies rather than real-world clinical settings. This review emphasizes the urgent need for further research to address these knowledge deficits and to develop effective therapeutic interventions against Pandoraea infections.

Sclerostin is a key inhibitor of the Wnt signaling pathway, functioning by binding to the LRP5/6 receptor. This interaction inhibits beta-catenin expression, resulting in the downregulation of osteogenic markers, which contributes to the promotion of osteoporosis and an increase in osteoclast numbers. The primary objective of this research was to investigate the effects of sclerostin antibody (Scl-ab) on bone formation utilizing graft materials in tooth sockets, and to analyze the regulatory interaction between sclerostin and bone tissue through targeted sclerostin inhibition and stimulation of bone formation in tooth extraction sockets following local, single-dose administration. In this study, New Zealand male rabbits (3 months old, weighing 2.5-3 kg) were fully randomized to minimize bias. The experiments were conducted across five groups: a control group, a graft group, and three experimental groups receiving 100%, 75%, and 50% doses of Scl-ab. Calculated doses of Scl-ab were administered alongside the graft material in the extraction sockets, with results assessed at 2 and 4-week intervals. Cone-beam computed tomography indicated that the tooth extraction sockets treated with varying ratios of Scl-ab with graft material exhibited a statistically significant increase in the mean mandibular BV/TV ratio compared to the control and graft groups, with variations based on time and dosage. While bone volume improved over time, the most significant enhancement was observed in the 100% Scl-ab group. Additionally, the administration of different doses of Scl-ab significantly increased trabecular thickness of the alveolar bone compared to both the control (p < 0.001) and graft (p < 0.001) groups, with histological analysis corroborating these findings. The therapeutic application of Scl-ab facilitates early bone formation, and the localized inhibition of sclerostin secreted within the bone microenvironment targets potential bone regeneration.

Assessment of insulin resistance is increasingly emphasized in patients with systemic lupus erythematosus (SLE) due to its significant role in predicting kidney injury and cardiovascular risk. Given that sustained inflammation is a hallmark of SLE, the novel C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which comprehensively reflects insulin resistance and inflammation, has emerged as a valuable biomarker. This study aimed to investigate the association between the CTI and the risk of lupus nephritis (LN) risk and further explore its predictive potential in SLE patients. A cohort of 195 SLE patients stratified by renal involvement or CTI tertiles were included. Spearman's correlation analysis was performed to assess the relationship between the CTI and clinical parameters of lupus activity. Logistic regression analysis was utilized to identify the association between the CTI and risk of LN. The receiver operating characteristic (ROC) curve was employed to evaluate the CTI and the TyG index in predicting LN. The results demonstrated significantly elevated CTI levels in the LN group compared to the non-LN group. Multivariate-adjusted regression analysis indicated that a unit increase in CTI corresponded to enhanced risk of LN (adjusted OR =2.062; 95% CI: 1.208 - 3.522), particularly among patients in the third tertile compared to those in the first tertile (adjusted OR = 4.368; 95% CI: 1.411 - 13.520).  Subgroup analysis revealed that SLE patients with a SLEDAI-2K score greater than 6 exhibited an increased LN risk associated with higher CTI levels. ROC analysis illustrated the higher sensitivity of CTI (AUC = 0.6592; 95%CI, 0.576 - 0.742) compared to the TyG index (AUC = 0.6327; 95%CI, 0.546 - 0.719) in predicting LN risk. These findings indicate that elevated CTI is strongly associated with an increased risk of LN, suggesting its potential as a valuable predictor of LN risk in SLE patients.

The Braden score, a bedside assessment tool for evaluating the risk of pressure ulcers and frailty, may identify vulnerabilities pertinent to outcomes in acute pancreatitis (AP). However, its prognostic significance in this context remains uncertain. This study aimed to determine whether the Braden score at admission predicts all-cause mortality in intensive care unit (ICU) patients with AP and whether it provides additional value to existing clinical models. In a retrospective single-center cohort study utilizing data from MIMIC-IV v3.1 (2008-2022), we included 1,985 adults diagnosed with AP. We analyzed the Braden score as both a continuous variable and a dichotomous variable (high-risk: ≤15 vs. low-risk: >15), with 30-day mortality as the primary endpoint (with secondary endpoints at 90, 180, and 360 days). Our methodology encompassed Kaplan-Meier analysis, multivariable Cox regression, restricted cubic splines, receiver operating characteristic curves, and calibration assessments. By the 30-day mark, a total of 230 deaths were recorded (11.6%). Each 1-point increase in the Braden score correlated with a 7.7% reduction in mortality risk (HR 0.923, 95% CI 0.873-0.976; p=0.005). Furthermore, patients categorized as low-risk experienced lower mortality rates compared to high-risk patients (HR 0.688, 95% CI 0.501-0.945; p=0.021). The discrimination capability at 30 days was moderate (AUC 0.67, 95% CI 0.63-0.71), with an optimal cutoff score of 15 (sensitivity 61%, specificity 65%) and good calibration; however, performance diminished over longer durations. Incorporating the Braden score into a baseline clinical model enhanced predictive accuracy (AUC 0.712 vs. 0.647; NRI 0.235; IDI 0.040; all p<0.001). The Braden score at ICU admission is independently associated with 30-day mortality in patients with AP, providing moderate, well-calibrated predictions and significant incremental value. This supports its application as an early and straightforward tool for risk stratification, pending prospective validation.

Iliac vein stenting (IVS) is an endovascular revascularization procedure for iliac venous outflow obstruction. We aimed to synthesize the efficacy and safety of IVS across iliac vein disease phenotypes and follow-up horizons. Following a pre-registered protocol (PROSPERO CRD42024606701), we systematically searched Embase, Scopus, PubMed, Web of Science, and Cochrane Library on October 5, 2024. Without restricting study design, we included English-language reports with at least 10 patients that reported at least one prespecified outcome (or convertible data) and excluded studies with additional core therapies or duplicated cohorts. Diseases were classified as non-thrombotic iliac vein compression syndrome (NIVCS), post iliac vein thrombotic syndrome (PIVTS), chronic iliac vein obstruction (CIVO, that is, NIVCS or PIVTS), and acute thrombotic iliac vein obstruction (ATIVO, that is, a CIVO patient with acute ipsilateral thrombosis). The primary outcome was cumulative primary patency (CPP); secondary outcomes comprised ulcer healing, edema and pain relief, quality-of-life improvement, revised Venous Clinical Severity Score change, and adverse events. CPPs at prespecified intervals were extracted for each disease category and pooled in separate meta-analyses. Twenty-seven studies (4,782 patients) were included; demographic, intraoperative, and outcome data were systematically abstracted. Pooled CPPs were consistently high, particularly for NIVCS, and were lower when thrombotic components were present (PIVTS and ATIVO), while other efficacy outcomes generally improved and serious complications were uncommon. In conclusion, across diverse iliac vein diseases and follow-up periods, IVS demonstrates good efficacy and safety; this unfunded study supports IVS as a prominent treatment option.

Sleep-disordered breathing (SDB) is prevalent among patients undergoing renal dialysis, yet its prognostic implications for mortality and cardiovascular outcomes remain unclear. This meta-analysis investigates the relationship between SDB and all-cause mortality as well as major adverse cardiovascular events (MACEs) within this demographic. A systematic search of PubMed, Embase, and Web of Science was conducted from inception to May 29, 2025, focusing on longitudinal observational studies that assessed SDB in adult dialysis patients. The primary outcome analyzed was all-cause mortality, while the secondary outcome was MACEs. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using random-effects models to account for heterogeneity. A total of eleven cohort studies encompassing 656,328 dialysis patients, of which 23,725 had SDB, were included. The results indicated that SDB was significantly associated with an increased risk of all-cause mortality (HR: 1.79, 95% CI: 1.42-2.25; I² = 32%; p < 0.001). Notably, the association was more pronounced in Asian studies (HR: 2.07) compared to non-Asian studies (HR: 1.35; p for subgroup difference = 0.008) and in studies employing polysomnography or pulse oximetry versus those using ICD codes (HR: 2.57 and 2.00 vs. 1.35; p = 0.002). Furthermore, five studies indicated that SDB was linked to an elevated risk of MACEs (HR: 2.68, 95% CI: 1.86-3.85; I² = 0%; p < 0.001). In conclusion, SDB is associated with heightened mortality and cardiovascular risk in patients on renal dialysis. These findings underscore the necessity for increased awareness and management of SDB in this population. However, further interventional studies are required to ascertain whether systematic screening and treatment can enhance clinical outcomes.

Neuroendocrine bladder carcinoma (NEBC) is a rare but highly aggressive histologic subtype of bladder cancer with poor prognosis, often driven by delayed diagnosis and limited therapeutic options; despite widespread use of next-generation sequencing, its cellular origin remains unclear and controversial. We aimed to synthesize up-to-date molecular and immune features of NEBC and translate them into practical guidance for diagnosis and treatment. We performed a narrative review of English-language studies indexed in PubMed and Web of Science (January 2000-August 2025) using predefined keywords, integrating genomic, transcriptomic, immunohistochemical, and clinical outcome data. Key findings indicate frequent co-occurrence and probable common clonal origin with urothelial bladder carcinoma, with hallmark TP53 and RB1 alterations, prevalent APOBEC-driven mutagenesis, and recurrent TERT promoter mutations; tumor mutation burden is heterogeneous but can be high. Despite this, NEBC commonly exhibits an immune-cold or immune-excluded microenvironment characterized by low PD-L1 expression and T-cell dysfunction, which may blunt responses to immune checkpoint inhibitor monotherapy. Diagnostic practice still relies on morphology supported by immunohistochemistry (synaptophysin, chromogranin A, CD56, GATA3), with emerging tools such as INSM1 and a decision-tree model using synaptophysin, CD117, and GATA3 that improve accuracy. Therapeutically, neoadjuvant chemotherapy-most commonly EP or IA-followed by radical cystectomy improves outcomes compared with initial cystectomy alone, while metastatic disease is typically managed with EP chemotherapy and radiotherapy with limited durability. Early data support immunotherapy, particularly immune checkpoint inhibitors, and suggest potential benefit from chemoimmunotherapy; a prospective trial of neoadjuvant anti-PD-L1 plus EP is underway, and antibody-drug conjugates and bladder-sparing multimodality strategies are emerging. In conclusion, comprehensive molecular and immune characterization is critical to refine diagnosis, optimize patient selection, and accelerate prospective trials that evaluate neoadjuvant chemotherapy, chemoimmunotherapy, and targeted approaches in NEBC.

Hypertensive disorders of pregnancy are major causes of maternal and perinatal morbidity and mortality, and nutritional factors such as vitamin D and calcium have been proposed as modifiable risks; therefore, we investigated the association between maternal vitamin D and calcium status and pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) and explored the relation with supplementation. In this observational cross-sectional study, 84 third-trimester women were enrolled from two hospitals in Lublin, Poland (41 PIH/PE, 43 controls). Serum total and ionised calcium, 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D₃ were measured using standardised immunoassays, and group differences, correlations, and multivariable logistic regression were applied with adjustment for body mass index (BMI), maternal age, gestational age, calcium fractions, and gestational diabetes. PIH/PE cases had lower 25(OH)D than controls (27.8 vs 35.7 ng/mL; p = 0.012) and higher BMI (33.0 vs 27.5 kg/m²; p < 0.001), while total and ionised calcium and 1,25-dihydroxyvitamin D₃ were similar (all p ≥ 0.40); supplement use was more frequent among controls (84% vs 73%). In adjusted models, higher BMI increased the odds of PIH/PE (OR 1.19 per kg/m²) and higher 25(OH)D was protective (OR 0.92 per ng/mL); discrimination was fair (AUC 0.78). These findings support an association between vitamin D insufficiency and obesity with hypertensive pregnancy disorders and suggest preserved calcium homeostasis, but given the cross-sectional design, third-trimester sampling, small sample size, and non-standardised supplementation, causal inference and preventive recommendations cannot be made; larger prospective studies beginning in early pregnancy are warranted to test whether optimising vitamin D and calcium can reduce hypertensive complications.

Prostate cancer (PC) is a common malignancy driven by interacting genetic, environmental, and lifestyle factors, including hereditary mutations (BRCA1/2, HPC1, AR variants), premalignant lesions [proliferative inflammatory atrophy (PIA), prostatic intraepithelial neoplasia (PIN)], and Western dietary patterns. This narrative review aims to synthesize evidence on the role of microRNAs (miRNAs) in PC pathogenesis and clinical management across diagnosis, prognosis, therapy, and recurrence prediction. We searched PubMed/MEDLINE (2004-present) using predefined terms, screened reference lists, excluded outdated records, and prioritized biomarker studies with AUC ≥ 0.85. Current diagnostic pathways-digital rectal examination, prostate-specific antigen (PSA) testing, multiparametric MRI, and Gleason-based International Society of Urological Pathology (ISUP) grading-are complemented by molecular tools (4Kscore, PHI, SelectMDx, TMPRSS2-ERG, PCA3, ConfirmMDx). MiRNAs, key post-transcriptional regulators, contribute to PC via dysregulated biogenesis and modulation of androgen receptor signaling within an inflamed, remodeled tumor microenvironment. Circulating and exosomal miRNAs (notably miR-21, miR-375, and miR-182-5p) exhibit greater specificity and stability than PSA, enabling non-invasive diagnosis, risk stratification, treatment monitoring, and recurrence prediction. Therapeutic approaches-antagomirs, sponges, miRNA masks, and CRISPR editing-show preclinical promise, while chemical modifications [peptide nucleic acids (PNAs), locked nucleic acids (LNAs), C2' modifications] improve stability and delivery but remain limited by biodistribution, tissue penetration, off-target effects, and immunogenicity. In conclusion, standardized workflows and multicenter validation, integrated with clinical and imaging data, are essential to translate miRNA-based tools into precision PC management.

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are a clinically attractive regenerative and immunomodulatory platform that combines ethical accessibility, low immunogenicity, rapid expansion, genetic stability, and a potent paracrine secretome. This study aimed to synthesize evidence on safety, efficacy, and translational readiness by conducting a focused PubMed review (2014-2024) restricted to clinical studies and trials, using predefined inclusion and exclusion criteria and structured data extraction. Across indications, UC-MSCs show a consistent safety profile and signals of benefit mediated by tissue repair and immune regulation: in musculoskeletal disease they improve osteoarthritis pain and function and may slow osteonecrosis; in hepatology they sustain gains in decompensated cirrhosis, mitigate acute allograft rejection, and aid recovery from ischemic-type biliary lesions; as induction in renal transplantation they are feasible with early graft benefits; in type 2 diabetes responders improve glycemic control and inflammation, while maternal and obstetric factors can shape intrinsic cell properties; in neurology, studies in cerebral palsy, chronic spinal cord injury, and traumatic optic neuropathy report motor, sensory, and visual improvements; in COVID-19-related acute respiratory distress syndrome (ARDS) trials show better oxygenation, radiological recovery, quality of life, and modulation of the TNF-sTNFR2 axis; in immune-mediated and transplant settings they reduce graft-versus-host disease, with signals in systemic lupus erythematosus, refractory immune thrombocytopenia, Crohn's fistulas, and as cotransplant support in aplastic anemia. The limitations of this study encompass small sample sizes, single-center designs, and short-duration trials. Additionally, there is significant heterogeneity concerning the source, manufacturing processes, dosage, administration routes, and endpoints. Other challenges include adherence to good manufacturing practices (GMP), issues related to potency, biobanking, logistical constraints, cost factors, and regulatory obstacles. Large multicenter randomized trials with standardized protocols and long-term follow-up, and combination strategies with biomaterials, gene engineering, and extracellular vesicle or exosome products, are needed to confirm durable benefit and enable routine clinical integration.