Biomolecules & biomedicine最新文献

Probiotic efficacy is contingent upon delivering a sufficient number of viable cells to the site of action. However, industrial processing, storage, and gastrointestinal stresses frequently diminish survival rates below the ~10⁶-10⁷ CFU/g or mL typically required at the time of consumption. This review aims to provide a comprehensive overview of probiotic encapsulation-particularly micro- and nanoencapsulation-as a strategy to enhance viability and facilitate timely, site-specific release. We synthesized and analyzed existing literature on key encapsulating materials, including natural polysaccharides and proteins such as alginate, chitosan, pectin, starch, casein/whey, and selected synthetic pH-responsive polymers. We also examined major encapsulation techniques, including extrusion, emulsification, spray-drying, freeze-drying, electrospinning, and coacervation, with a focus on release mechanisms and compatibility with food matrices. Overall, encapsulation consistently improved resistance to acid, bile, oxygen, heat, and dehydration, often resulting in reduced viability losses compared to free cells, enhanced storage stability, and expanded applications in functional foods and novel biomedical delivery systems. Multilayer and nanoscale systems frequently provided additional protection and targeted release in the intestinal and colonic regions. However, performance is still dependent on specific strains and matrices, and challenges persist regarding process-induced damage, premature release, sensory and textural alterations, cost and scalability, and safety and regulatory standardization, particularly for nano-enabled formats. In conclusion, encapsulated probiotics represent a promising platform; however, future advancements should focus on the development of smart, stimuli-responsive materials, scalable automated manufacturing processes, and functional validation that extends beyond viable cell counts.

Osteoporosis is a degenerative skeletal disorder characterized by reduced bone mass and the deterioration of bone microarchitecture, resulting in an increased risk of fractures. Its development is driven by an imbalance in bone remodeling, where osteoclastic bone resorption surpasses osteoblastic bone formation. Factors such as oxidative stress, chronic inflammation, ferroptosis, and hormonal changes, particularly estrogen deficiency in postmenopausal women, contribute to this imbalance. Metabolites derived from phenolic compounds have emerged as promising natural agents for osteoporosis prevention due to their antioxidant, anti-inflammatory, and hormone-modulating properties. Key phenolic groups, including flavonoids (quercetin), isoflavones (genistein and daidzein), and stilbenes (resveratrol), have demonstrated significant osteoprotective effects by regulating receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) signaling, activating Wnt and β-catenin pathways, and suppressing inflammatory cytokines. Clinical findings indicate that these compounds may enhance bone mineral density and modulate bone turnover markers in populations at risk for osteoporosis. However, their clinical application is limited by low bioavailability and rapid metabolism. Advances in drug delivery systems, including nanoencapsulation, liposomal formulations, and prodrug design, have improved stability, absorption, and targeted delivery to bone, thereby enhancing therapeutic potential while minimizing systemic effects. This review discusses the molecular mechanisms underlying osteoporosis, emphasizing oxidative and hormonal dysregulation, and highlights the therapeutic relevance of phenolic compounds. Additionally, it summarizes recent clinical observations and formulation strategies aimed at enhancing therapeutic efficacy. Overall, phenolic compounds represent promising plant-based strategies for the prevention and management of osteoporosis.

Visit-to-visit variability in glycated hemoglobin (HbA1c) reflects long-term instability in glycemic control, potentially contributing to cardiovascular complications. However, the association between HbA1c variability and heart failure (HF) risk remains unclear. This meta-analysis aimed to quantify the relationship between HbA1c variability and the risk of incident HF in adults. A systematic search of PubMed, Embase, and Web of Science was conducted to identify relevant studies. Observational studies and post-hoc analyses of clinical trials evaluating the association between visit-to-visit HbA1c variability and incident HF were included. Random-effects models were employed to pool hazard ratios (HRs) with 95% confidence intervals (CIs), accounting for potential heterogeneity. A total of nine studies (n = 342,123) were included in the analysis. Overall, high HbA1c variability was associated with an increased risk of HF (pooled HR = 1.78, 95% CI: 1.39-2.27, p < 0.001; I² = 87%). Sensitivity analyses restricted to patients with type 2 diabetes (HR = 1.73, 95% CI: 1.35-2.22), high-quality studies (HR = 1.82, 95% CI: 1.32-2.50), or studies adjusting for mean HbA1c (HR = 1.68, 95% CI: 1.31-2.16) produced consistent results. Subgroup analyses indicated a stronger association in prospective cohorts (HR = 2.51) compared to retrospective or post-hoc studies (p for subgroup difference < 0.001). Meta-regression analysis revealed no significant modifying effects of age, sex, follow-up duration, or study quality (p all > 0.05). In conclusion, greater visit-to-visit HbA1c variability may be associated with an increased risk of incident HF, underscoring the prognostic importance of maintaining stable long-term glycemic control in patients with type 2 diabetes.

Hypochlorite (ClO⁻), a major reactive oxygen species generated in inflammation, is a potent biological oxidant involved in diverse physiological and pathological processes; therefore, sensitive detection of ClO⁻ is important for understanding disease pathophysiology and supporting early diagnosis and prevention. Here, we aimed to develop a physiologically compatible fluorescent tool for specific ClO⁻ sensing and imaging. We designed and synthesized a novel A-D-A type molecular fluorescent probe, XY-01, and characterized it by NMR, HRMS, UV-Vis and fluorescence spectroscopy. XY-01 operates through ClO⁻-triggered oxidation of a thioformyl group (C=S) to a carbonyl (C=O), which restores intramolecular charge transfer and produces a prominent fluorescence turn-on signal. In PBS (pH 7.4), XY-01 responded to ClO⁻ within 1 min with strong red emission at 666 nm and a large Stokes shift (~167 nm), showed high selectivity against common ions and reactive species, and achieved a detection limit of 3.39 µM within the biologically relevant range. Cytotoxicity assays indicated negligible toxicity, enabling real-time confocal imaging of ClO⁻ distribution in HCT-116 cells and colorectal cancer organoids. Collectively, XY-01 is a simple, sensitive, and low-toxicity probe that provides a promising platform for optical sensing and imaging of hypochlorite in living cells and organoids.

Complementary therapies are increasingly integrated into the framework of integrative oncology. While numerous complementary therapies provide potential benefits, some may also carry risks, including interactions with conventional cancer treatments. The degree to which oncologists' real-world decisions regarding complementary therapies align with evidence-based guidelines remains uncertain. This study aimed to evaluate oncologists' evidence-based decisions on whether specific complementary therapies should be prohibited, permitted, or recommended for early breast cancer treatment. We conducted a cross-sectional online survey that included a randomized vignette experiment involving oncology specialists and residents from seven Southeast European countries. The primary outcome was the percentage of accurate classifications of 28 therapy-indication pairs in neoadjuvant and adjuvant settings, benchmarked against published evidence. Correctness was assessed using both a strict definition (one correct option) and an expanded definition (accepting "allow" or "recommend" when supported by evidence). A total of 136 respondents met the inclusion criteria and provided paired responses. Median accuracy was found to be 52% (95% CI 48-55) under the strict definition and 70% (95% CI 67-72) under the expanded definition, with no significant differences observed between neoadjuvant and adjuvant settings. Evidence-based therapies, such as physical exercise and cognitive behavioral therapy, were most frequently recommended, whereas most other therapies received endorsement from fewer than 25% of respondents. Overall, oncologists exhibited moderate alignment with evidence, demonstrating a tendency to permit rather than actively recommend complementary therapies, even when evidence indicated potential benefits and safety. These findings underscore the necessity for targeted educational interventions aimed at enhancing oncologists' understanding and ensuring the safe and informed integration of complementary therapies into clinical practice.

A minority of individuals who consume excessive alcohol develop cirrhosis. Variants in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) and the transmembrane 6 superfamily member 2 gene (TM6SF2) have been previously identified as associated with alcohol-related cirrhosis (ALC). This study aimed to examine the variants of PNPLA3 and TM6SF2 and to develop and assess a polygenic risk score (PRS) for ALC. We enrolled 118 patients diagnosed with ALC and 131 control subjects, who were either abstainers or low-level alcohol consumers without evidence of liver disease. Genotyping of risk variants was performed using PCR-RFLP methodology. PRS, based on independent allelic effect size estimates from genotyped genetic loci, were computed and compared across groups. The development of ALC was significantly associated with CG and GG genotypes of PNPLA3 (CG: OR: 1.82; 95% CI: 1.05-3.17; p=0.033; GG: OR: 7.64; 95% CI: 3.06-19.07; p<0.001) and the CT genotype of TM6SF2 (OR: 2.43; 95% CI: 1.27-4.63; p=0.007), controlling for age and sex. Patients with cirrhosis exhibited a significantly higher mean PRS compared to controls (0.32 vs. 0.167, p = 1.8e-07). The odds ratios (ORs) and 95% confidence intervals for the group with the highest PRS score compared to the reference group were 6.707; 95% CI: 3.313-13.581, p<0.001. In our ALC patient cohort, the PNPLA3 rs738409 and TM6SF2 rs58542926 variants were associated with an increased risk of ALC development. Moreover, the PRS derived from these two variants effectively identified the genetic components linked to cirrhosis within the study population.

Second-generation antipsychotics (SGAs) are frequently prescribed in psychiatry due to their efficacy and improved tolerability compared to first-generation agents. However, these medications are associated with significant cardiac adverse effects, particularly QT interval prolongation and torsades de pointes (TdP). This review aims to summarize the mechanisms by which SGAs affect cardiac ion channels and how these actions contribute to QT interval disturbances and increased arrhythmia risk. A narrative literature review was conducted using PubMed, Web of Science, and Google Scholar, without year restrictions, focusing on English-language experimental and clinical studies related to clozapine, olanzapine, risperidone, quetiapine, and ziprasidone. The findings indicate that all five SGAs inhibit the rapid delayed rectifier potassium current (IKr) mediated by the human ether-a-go-go-related gene (hERG) potassium channel. Notably, the observed variability in the ratio of half-maximal inhibitory concentration to maximum free plasma concentration (IC₅₀/Cmax,free) reflects its dependence on both the degree of hERG inhibition and the pharmacokinetic properties specific to each SGA. Additionally, several SGAs affect other potassium, sodium, and calcium currents, which may either mitigate or exacerbate the consequences of IKr inhibition. In conclusion, QT interval prolongation associated with SGAs is primarily driven by hERG potassium channel blockade, although the degree of this effect varies significantly among different agents. This variability highlights the necessity for electrocardiogram (ECG) monitoring and individualized cardiac risk assessments, especially for vulnerable patient populations.

Crohn's disease (CD) is a complex chronic inflammatory bowel disorder characterized by the absence of reliable biomarkers and effective targeted treatments. Recent evidence has suggested a role for S-palmitoylation, a reversible post-translational modification, in immune regulation and intestinal inflammation. However, a systematic, gene-centric investigation explicitly linking S-palmitoylation to the pathogenesis and diagnosis of CD has not been conducted. To address this gap, our study employs a comprehensive bioinformatic analysis to identify and validate key genes associated with both CD and S-palmitoylation, assessing their potential as diagnostic biomarkers and therapeutic targets. Utilizing data from the Gene Expression Omnibus (GEO, GSE83448) and GeneCards, we identified 23 S-palmitoylation-associated differentially expressed genes (SP-DEGs) in CD. Functional enrichment analysis indicated their significant roles in cysteine-specific S-palmitoylation and immunometabolic regulation. We applied machine learning algorithms, including least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), to select nine hub genes. Validation in two independent cohorts (GSE16879 and GSE59071) and ROC analysis confirmed ZDHHC23 and IFITM1 as biomarkers with high diagnostic value. These genes also exhibited correlations with immune infiltration patterns, as determined by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), MCPcounter, and QuanTIseq. In vitro experiments corroborated consistent changes in mRNA and protein expression for both ZDHHC23 and IFITM1, reinforcing their involvement in CD. This study offers systematic insights into the functional roles of S-palmitoylation-related genes in CD, providing a novel theoretical foundation for the development of diagnostic and targeted therapeutic strategies.

Doxorubicin-induced cardiotoxicity is closely associated with oxidative stress (OS), and apelin-13 has been proposed as a potential cardioprotective peptide. However, its effects on specific oxidative stress (OS) markers remain poorly understood. This preliminary study aimed to evaluate the impact of apelin-13 on oxidative stress markers in rats chronically treated with doxorubicin (DOX). Male rats received DOX with or without apelin-13 (40 µg/kg body weight/day). The levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. The DOX treatment resulted in increased MDA levels, which were unaffected by apelin-13. Conversely, 8-OHdG levels decreased with DOX alone but returned to baseline levels in the presence of DOX and apelin-13. In conclusion, while apelin-13 did not mitigate DOX-induced lipid oxidative damage, it may selectively influence nuclear OS markers. This suggests a complex and context-dependent role of apelin-13 in modulating oxidative stress associated with DOX treatment.

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.