Biomolecules & biomedicine最新文献

Ischemia-reperfusion injury (IRI) presents a complex pathophysiology characterized by oxidative stress and inflammation. Arbutin, widely recognized for its use in skin whitening, also exhibits antioxidant, anti-inflammatory, and anticancer properties. This study aimed to assess the potential protective effects of arbutin at two different doses against IRI in the kidneys. Twenty-four male Wistar albino rats were randomly assigned to four equal groups: Control, IRI, 250 mg/kg arbutin + IRI (AR250+IRI), and 1000 mg/kg arbutin + IRI (AR1000+IRI). Arbutin was administered orally via gavage for 14 days to ensure sub-acute application. Following left kidney nephrectomy, ischemia was induced in the right kidney using a non-traumatic clamp for 45 minutes, succeeded by 60 minutes of reperfusion. Blood and tissue samples were subsequently collected for analysis. In the IRI group, levels of malondialdehyde, myeloperoxidase, interleukin-1 beta, and creatinine were significantly elevated; these levels decreased in the groups receiving arbutin supplementation. Notably, ischemia-modified albumin, urea, superoxide dismutase (inhibition ratio), and tumor necrosis factor alpha levels were reduced in the AR1000+IRI group. Additionally, decreased levels of catalase and glutathione peroxidase were observed in the AR1000+IRI group. Histopathological examination revealed flattening, necrosis, degeneration, dilation, glomerular necrosis, sclerosis, Bowman capsule dilation, and interstitial hemorrhage in the IRI group. The AR250+IRI group exhibited mild cortical-medullary congestion and a slight increase in glomerular size. Conversely, the AR1000+IRI group displayed a histological appearance resembling that of the control group. In conclusion, arbutin demonstrates potential protective effects against IRI. Its use may be recommended prophylactically for individuals at risk of developing IRI.

Nephrotic syndrome (NS) in children has been associated with an increased risk of early atherosclerosis, as indicated by carotid intima-media thickness (cIMT). However, the existing literature on the relationship between NS and cIMT in pediatric populations presents inconsistent findings. This meta-analysis aims to compare cIMT measurements between children with NS and healthy controls. A comprehensive search of PubMed, Embase, and Web of Science was conducted through May 22, 2025. Observational studies that compared cIMT in children under 18 years with NS against controls were included. Mean differences (MDs) with 95% confidence intervals (CIs) were aggregated using a random-effects model to account for potential heterogeneity. Thirteen case-control studies involving 578 children with NS and 741 controls were analyzed. The results indicated that children with NS had significantly higher cIMT compared to controls (MD: 0.06 mm; 95% CI: 0.04-0.08; p < 0.001; I² = 68%). Subgroup analyses revealed that the difference in cIMT was notably larger in studies with ≥ 60% male participants (MD: 0.09 mm) compared to those with < 60% males (MD: 0.03 mm; p for subgroup difference = 0.01). No significant differences were observed based on age, disease duration, or adjustments for body mass index, blood pressure, or lipid profile (all p > 0.05). Meta-regression analyses suggested that the proportion of male participants and the rate of steroid-resistant nephrotic syndrome (SRNS) may contribute to observed heterogeneity (adjusted R² = 29.8% and 22.5%, respectively), although the slopes for these meta-regressions were not statistically significant (p = 0.13 and 0.87). In conclusion, children with NS exhibit increased cIMT compared to controls, indicating early vascular changes. The predominance of males and the presence of SRNS may partially account for the heterogeneity observed across studies.

Procalcitonin (PCT) is classically a biomarker of bacterial infection, but its role in cardiovascular inflammation-particularly in coronary artery disease (CAD)-is less well defined. Evidence linking PCT with disease extent and outcomes across acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) remains limited. We compared PCT levels among ACS, CCS, and angiographic controls; examined associations with inflammatory burden and anatomic complexity (SYNTAX score); and evaluated diagnostic performance and short- and intermediate-term prognostic value. In this single-center retrospective study, 477 consecutive adults undergoing diagnostic coronary angiography (December 2019-March 2020) were categorized as ACS (n=190), CCS (n=202), or controls with normal epicardial arteries (n=85). Demographic, laboratory, and angiographic data were collected. PCT was measured within 24 hours of admission. Multivariable logistic regression (using log10-transformed PCT) assessed independent associations with ACS and CCS. Correlations tested relationships with SYNTAX, C-reactive protein (CRP), and troponin-I. Receiver operating characteristic (ROC) analyses quantified discrimination. In ACS, outcomes were compared by PCT ≥0.25 ng/mL. Median PCT was higher in ACS and CCS than in controls (both p<0.001). Log10-PCT independently predicted disease presence in ACS (OR 4.30, 95% CI 2.00-9.20, p<0.001) and CCS (OR 2.81, 95% CI 1.43-5.54, p=0.003). In CCS, PCT correlated weakly but significantly with SYNTAX score (r=0.274, p=0.002); no meaningful correlations with SYNTAX, CRP, or troponin-I were observed in ACS. PCT showed moderate diagnostic accuracy (AUC 0.791 for ACS; optimal cut-off 0.25 ng/mL, sensitivity 82.4%, specificity 65.3%; and AUC 0.763 for CCS; optimal cut-off 0.30 ng/mL, sensitivity 89.4%, specificity 54.0%; all p<0.001). In ACS, PCT ≥0.25 ng/mL was not associated with higher in-hospital mortality, 1-year all-cause mortality, or major adverse cardiovascular events. PCT reflects inflammatory burden and the presence of CAD in both ACS and CCS and remains an independent predictor of disease presence, but its prognostic utility-particularly in ACS-is limited. PCT should complement, not replace, established biomarkers and anatomical scoring systems in clinical decision-making. Prospective, multicenter studies with serial PCT measurements are warranted to refine its clinical role.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease for which reliable early diagnostic biomarkers are still lacking. This study aimed to evaluate the diagnostic and monitoring value of induced sputum Krebs von den Lungen-6 (KL-6) levels in patients with IPF and to investigate their relationship with pulmonary function parameters and high-resolution computed tomography (HRCT) scoring. In this prospective observational study, 20 patients with IPF and 20 age-matched healthy subjects (HS) were enrolled between October 2021 and April 2023. Induced sputum samples were collected for KL-6 measurement using enzyme-linked immunosorbent assay, while all participants underwent pulmonary function testing and HRCT scoring. KL-6 levels were significantly higher in the IPF group compared with the HS group [776.29 (interquartile range, IQR: 681.98-858.57) vs. 322.21 (IQR: 253.67-338.64) U/mL, p<0.001]. In IPF patients, induced sputum KL-6 levels showed strong negative correlations with multiple lung function indices, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO) (all p<0.05), and a strong positive correlation with HRCT scores (r=0.908, p<0.001). Receiver operating characteristic (ROC) analysis demonstrated that combining KL-6 levels with HRCT scores yielded an area under the curve (AUC) of 0.936 (95% confidence interval, CI: 0.914-0.944), with specificity of 97.5% and sensitivity of 80.0%. In conclusion, induced sputum KL-6 levels reflect the degree of pulmonary fibrosis and are closely associated with functional and imaging indicators in IPF. The combination of KL-6 with HRCT scoring enhances diagnostic accuracy, underscoring its potential clinical utility as a noninvasive biomarker for early detection and monitoring of IPF.

Coronary heart disease (CHD) is a leading cause of morbidity and mortality; patients with type 2 diabetes mellitus (T2DM) are at particularly high risk, highlighting the need for reliable biomarkers for early detection and risk stratification. We investigated whether combining the stress hyperglycemia ratio (SHR) and systemic inflammation response index (SIRI) improves CHD detection in T2DM. In this retrospective cohort of 943 T2DM patients undergoing coronary angiography, associations of SHR and SIRI with CHD were evaluated using multivariable logistic regression and restricted cubic splines; robustness was examined with subgroup and sensitivity analyses. Discriminative performance was assessed by receiver operating characteristic (ROC) analysis and reclassification metrics (integrated discrimination improvement [IDI], net reclassification improvement [NRI]). Internal validation used bootstrapping, with calibration and discrimination yielding apparent and bias-corrected estimates. Of 943 patients, 600 had CHD. Multivariable models showed SHR (OR=1.68; 95% CI, 1.14-2.46; p=0.008) and SIRI (OR=2.17; 95% CI, 1.54-3.05; p<0.001) were independently associated with CHD, with nonlinear relationships (p for nonlinearity <0.05). Findings were consistent across subgroups and sensitivity analyses. The combined SHR-SIRI model achieved an AUC of 0.813 (95% CI, 0.783-0.843), outperforming SHR alone (AUC=0.773; 95% CI, 0.740-0.805) and SIRI alone (AUC=0.745; 95% CI, 0.713-0.778), and significantly improved NRI and IDI (p <0.05). All models showed strong discrimination and calibration. In conclusion, SHR and SIRI are independently associated with CHD in T2DM, and their combination enhances early identification of high-risk individuals.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which dysregulated interferon regulatory factor 5 (IRF5) may amplify pro-inflammatory pathways; prior genetic studies of IRF5 single-nucleotide variants (SNVs) in RA are inconsistent across populations and have not included mestizo Mexicans or evaluated rs59110799 in RA. We aimed to test whether four IRF5 SNVs (rs2004640G/T, rs2070197T/C, rs10954213G/A, rs59110799G/T) confer susceptibility to RA in women from Central Mexico. In a case-control study of 239 women with RA and 231 female controls (all self-identified Mexican-Mestizos, ≥3 generations), genotyping was performed by real-time PCR with TaqMan® probes; 80% of samples were duplicated (100% concordance) and control genotypes conformed to Hardy-Weinberg equilibrium. Association was assessed under allelic and multiple genetic models using logistic regression adjusted for age and birthplace, with Bonferroni correction for 23 tests (α=0.0022). Haplotype and linkage disequilibrium (LD) were analyzed with Haploview; putative functional effects were explored in silico (SNPinfo; GTEx). The minor alleles rs2004640T [OR=1.69, 95% CI 1.29-2.21; p=1.2×10⁻⁴], rs2070197C [OR=1.85, 1.39-2.46; p=2.0×10⁻⁵], and rs10954213A [OR=1.47, 1.12-1.93; p=0.002] were associated with increased RA risk after correction. Genotype-based associations were observed for rs2004640 (codominant and recessive) and rs2070197 (codominant, dominant, recessive). rs59110799G/T showed no significant association after correction (dominant model OR=1.69, 1.15-2.48; p=0.007). Nine haplotypes were identified; the haplotype carrying all four risk alleles (TCAT) was not associated, and two haplotypes with nominal signals (GCAG, TTGT) had control frequencies <1% and were excluded; variants were not in strong LD (r²<0.80). Our findings-providing the first evaluation of these IRF5 variants in Mexican women and the first report of rs59110799 in RA-support a role for IRF5 (rs2004640, rs2070197, rs10954213) in RA susceptibility in this Latin American population. Given the female-only design and moderate statistical power, replication and functional studies are warranted.

Neoadjuvant stereotactic radiosurgery (SRS) has emerged as a promising strategy for managing brain metastases, offering several advantages over traditional postoperative approaches. By delivering targeted radiation prior to surgical resection, neoadjuvant SRS aims to enhance local tumor control, reduce the risk of leptomeningeal dissemination, and optimize treatment efficiency. Recent findings suggest that neoadjuvant SRS provides comparable, if not superior, local control compared to postoperative SRS, while exhibiting lower rates of radiation necrosis and leptomeningeal disease. However, uncertainties persist regarding optimal dosing regimens, treatment timing, and patient selection criteria, as factors such as tumor size, volume, and histology may significantly influence clinical outcomes. Additionally, while neoadjuvant SRS addresses challenges related to target delineation and delays associated with postoperative treatment, its long-term efficacy and integration with systemic therapies require further investigation. This review consolidates evidence from recent retrospective and prospective studies, focusing on key outcomes such as local control rates, radiation toxicity profiles, and overall survival.

Sepsis is a complex systemic disease in which systemic toxicity-arising from inflammation-immune dysregulation, oxidative stress, programmed cell death (apoptosis, pyroptosis, ferroptosis), and metabolic reprogramming-drives multi-organ injury. The aim of this review was to synthesize how signaling pathways evolve within and between key organs (lungs, liver, kidneys, heart) and to evaluate whether multi-omics integration and network modeling can identify critical toxic nodes and predict disease progression. We conducted a narrative review of English-language mechanistic studies published between 2015 and 2025 in PubMed, Web of Science, and Scopus, supplemented by bibliography screening, while excluding case reports, conference abstracts, and non-mechanistic work. The evidence depicts a high-dimensional systemic network that remodels over time, with early pro-inflammatory modules transitioning toward immunosuppression and organ-specific injury patterns, while inter-organ propagation is mediated by damage-associated molecular patterns (DAMPs), exosomes, and metabolites. Oxidative stress and mitochondrial dysfunction, via reactive oxygen species (ROS), couple to pyroptosis and ferroptosis to reinforce toxicity loops, and computational approaches such as dynamic Bayesian networks (DBN) and graph neural networks (GNN) delineate regulatory hubs and support forecasting. Therapeutic progress has concentrated on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the NOD-, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome, and glutathione peroxidase 4 (GPX4), alongside artificial intelligence (AI)-assisted personalized toxicity maps and dynamic early-warning systems, though challenges remain in specificity, safety, and resistance. In conclusion, sepsis can be conceived as a temporally staged systemic toxicity network, and when combined with multi-omics, DBN/GNN modeling, and AI-enabled decision support, this framework offers a path toward individualized, mechanism-based care, while requiring rigorous validation to ensure clinical durability.

Secreted Frizzled-Related Protein 4 (sFRP4), the largest member of the Secreted Frizzled-Related Protein (sFRP) family, contains two functional domains: a cysteine-rich domain (CRD) homologous to the Wnt-binding region of Frizzled (FZD) receptors and a netrin-like (NTR) domain structurally similar to axonal guidance proteins. By modulating the Wingless/Integrated (Wnt) signaling pathway, sFRP4 regulates essential cellular processes including proliferation, differentiation, apoptosis, and tissue homeostasis. This review aims to provide a comprehensive overview of the dualistic roles of sFRP4 in cancer, highlighting its tumor-suppressive and tumor-promoting functions, underlying molecular mechanisms, and therapeutic potential. A systematic literature search was conducted in PubMed and Web of Science databases (1996-2025) using predefined keywords, and from 277 identified publications, 47 studies were included that comprised clinical data, in vitro cell models, and in vivo experimental systems. Findings demonstrate that sFRP4 frequently acts as a tumor suppressor by sequestering Wnt ligands, suppressing cancer stem cell-like properties, reprogramming tumor metabolism, inhibiting angiogenesis, and enhancing chemosensitivity. Its downregulation is often driven by promoter hypermethylation or repression mediated by microRNAs (miRNAs). Conversely, in gastrointestinal and prostate cancers, sFRP4 is frequently upregulated, where it promotes Wnt pathway activation, invasion, stemness, chemoresistance, and reshaping of the tumor immune microenvironment. Mechanistic insights indicate that post-translational modifications and nuclear localization of sFRP4 further contribute to its paradoxical context-dependent functions. In conclusion, sFRP4 exerts dual roles in tumorigenesis, acting either as a tumor suppressor or promoter depending on tissue type, tumor microenvironment, and regulatory mechanisms. This complexity underscores both the challenges and opportunities of targeting sFRP4 in oncology, and future therapeutic strategies incorporating recombinant proteins, synthetic peptides, and nanoparticle-based delivery systems hold promise for harnessing its anti-tumor potential while overcoming resistance mechanisms.

Prediabetes, characterized by intermediate hyperglycemia, is increasingly prevalent worldwide. While diabetes has been associated with a heightened risk of various cancers, the relationship between prediabetes and thyroid cancer remains ambiguous. This meta-analysis sought to assess whether prediabetes correlates with an elevated incidence of thyroid cancer. A systematic literature search was conducted across PubMed, Embase, Web of Science, Wanfang, and CNKI to identify longitudinal studies that compared the incidence of thyroid cancer in individuals with prediabetes to those with normoglycemia. Risk ratios (RRs) with 95% confidence intervals (CIs) were aggregated using a random-effects model. Subgroup and sensitivity analyses were performed to identify potential effect modifiers. Six prospective cohort studies, encompassing 5,743,849 participants, were included in the analysis. Overall, prediabetes was not significantly correlated with thyroid cancer incidence (RR = 1.04; 95% CI: 0.98-1.11; p = 0.23; I² = 53%). Subgroup analyses revealed no significant variations based on age, sex, region, follow-up duration, or definition of prediabetes. Notably, a significant association was identified in studies utilizing cancer registries or validated clinical diagnoses (RR = 1.29; 95% CI: 1.04-1.60), in contrast to studies relying solely on ICD-10 codes (RR = 1.01; 95% CI: 0.98-1.05; p for subgroup difference = 0.03). In conclusion, prediabetes was not linked to a significantly increased risk of thyroid cancer overall. However, a potential association was noted in studies employing clinically validated cancer diagnoses. These findings, derived from observational cohorts, should be interpreted cautiously, and further prospective research is necessary to elucidate any causal relationship.