Search Results (35,904)

Anticancer peptides (ACPs) offer a promising alternative to conventional chemotherapy but face challenges, including poor selectivity, limited tumor penetration, low cellular uptake, and rapid degradation in serum. To address these barriers, we developed synthetic mRNAs encoding chimeric ACPs designed for enhanced intracellular delivery and activity. mRNAs for constructs SAK6L9AS(1X), SAK6L9AS(4X), and WTAS-K6L9(4X) were transcribed in vitro and tested against 4T1 breast cancer cells. Cytotoxicity was assessed by cell confluence and MTT assays, while apoptosis was evaluated using caspase 3/7 activation, PI staining, and Annexin V flow cytometry. Our results demonstrate that all SAK6L9AS variants induced robust apoptosis and cellular toxicity in 4T1 cells. Importantly, this work provides the first demonstration of intracellular expression of an mRNA-encoded ACP fused to a cell-penetrating peptide, thereby validating a modular platform for RNA-based delivery of anticancer agents. This study highlights the feasibility of mRNA-encoded peptide therapeutics as a scalable and customizable strategy for cancer treatment. By combining the advantages of mRNA delivery with rational peptide design, ACP chimeras can be expressed directly inside tumor cells, overcoming the limitations of exogenous peptide administration. Our findings support further development of synthetic mRNA therapeutics to generate potent, selective anticancer peptides with reduced systemic toxicity and improved translational potential. Full article

Diagnostic testing of foot-and-mouth disease virus (FMDV) currently utilizes reverse transcription quantitative PCR (RT-qPCR) to detect the presence of viral RNA and double antibody sandwich ELISAs (DAS-ELISAs) to determine viral serotype. Serotype identification is critical to support informed vaccine selection to combat outbreaks. While DAS-ELISAs are capable of serotype identification, the test suffers from low sensitivity and requires a viral isolate for successful detection. In this study, we developed FMDV-ONTAPS: an Oxford Nanopore Technologies Amplicon P1 Sequencing protocol involving reverse transcription-PCR to amplify P1 of the FMDV genome, and Nanopore sequencing of the amplicons to provide genetic data for serotype and subtype/topotype identification. FMDV isolates representing all seven serotypes were successfully sequenced with this method. Additionally, the protocol successfully provided serotype identification from a variety of specimen matrices obtained from experimentally infected animals that included milk, serum, oral and nasal swabs, tissue suspensions, vesicular fluid, and oral fluid. The limit of detection for FMDV cell culture isolates was comparable for both sequencing and RT-qPCR detection. RT-qPCR Cq values for clinical samples evaluated ranged from 8 to 28.21. Sequencing was successful for all samples except for a single tissue suspension sample (Cq of 28.21). Identification of FMDV serotype in clinical samples is critical for effective outbreak response, and Nanopore sequencing offers a timelier and more sensitive alternative to DAS-ELISAs. Full article

Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a heterogeneous clinical entity encompassing multiple ischemic mechanisms, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction, coronary embolism, and spontaneous coronary artery dissection. Despite the absence of obstructive coronary disease, patients with MINOCA remain at substantial risk of adverse cardiovascular outcomes, underscoring the need for accurate early diagnosis and effective risk stratification. In this context, accumulating evidence indicates that circulating serum biomarkers may provide additional pathophysiological and prognostic insights in patients with a working diagnosis of MINOCA. Moreover, distinct biomarker profiles may help support the differential diagnostic evaluation between MINOCA and other causes of acute myocardial injury, such as myocardial infarction with obstructive coronary arteries, myocarditis, and Takotsubo syndrome. This narrative review summarizes current evidence on serum biomarkers in MINOCA, highlights their potential role in guiding tailored diagnostic strategies, and discusses future perspectives toward biomarker-driven precision medicine in patients presenting with acute myocardial injury. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health burden, yet effective therapeutic options remain limited. This study investigated the protective mechanisms of Astragalus membranous extract (AM) against high-fat diet (HFD)-induced MAFLD in mice using an integrated strategy combining network pharmacology, hepatic metabolomics, and 16S rRNA sequencing. UPLC–Q-Orbitrap–MS/MS identified 37 major constituents in AM, mainly phenolic acids and flavonoids. Iristectorin A, isorhamnetin, ononin, and rhamnocitrin were identified as key candidate compounds due to their relatively high abundance and confirmation as absorbed constituents in vivo. Network pharmacology and molecular docking indicated favorable interactions with hub targets (TNF, EGFR, and AKT1; binding energies < −5.0 kcal/mol) and highlighted the involvement of the AGE–RAGE signaling pathway and inflammation- and lipid metabolism-related processes. In vivo, AM significantly attenuated HFD-induced weight gain, decreased serum ALT and AST levels, and reduced hepatic lipid deposition. AM also alleviated oxidative stress by lowering malondialdehyde (MDA) and increasing superoxide dismutase (SOD) activity, while suppressing hepatic IL-1β and IL-6. Moreover, AM improved gut microbial homeostasis by restoring α-diversity and enriching beneficial genera, including Akkermansia and Bacteroides. Hepatic metabolomics further showed that AM partially normalized lipid metabolic disturbances, particularly glycerophospholipid and sphingolipid metabolism. Collectively, these results suggest that AM mitigates MASLD via a multi-component, multi-target mechanism, potentially through modulation of AGE–RAGE-associated inflammatory signaling and the gut–liver axis, supporting its development as a functional food-derived candidate for metabolic liver disorders. Full article

The objective of this study was to evaluate the physiological mechanisms and health resilience of Duroc pigs reared in an outdoor system compared to a conventional indoor system. A total of 24 Duroc pigs (approximately 3 months of age) were randomly assigned to either an indoor (IN, n = 12) or an outdoor (OUT, n = 12) rearing system for a 45-day trial. Growth performance (body weight and ADG) and spleen organ index were not significantly different between the two rearing systems (p > 0.05). Hematological profiles, including leukocyte and erythrocyte indices, showed no significant differences (p > 0.05), although plateletcrit tended to decrease in the OUT group (p = 0.08). For serum biochemical parameters, pigs in the OUT group exhibited significantly higher concentrations of total protein, triglycerides, calcium, and sodium compared to those in the IN group (p < 0.05). Additionally, serum albumin and glucose levels tended to be higher in the OUT group (p < 0.01). No significant differences were observed in liver and muscle enzyme activities (AST, ALP, GGT, CK) between the treatments (p > 0.05). In conclusion, outdoor rearing did not compromise growth performance or induce chronic physiological stress or tissue damage in Duroc pigs. Instead, it promoted active energy and lipid mobilization, enhanced protein metabolism, and improved mineral homeostasis, demonstrating the robust physiological adaptability of the Duroc breed to outdoor environments. Full article

Background: An unfavorable course of SARS-CoV-2 infection can lead to significant morbidity and mortality. The study aimed to develop a simple, accessible, and reliable tool to anticipate the poor results among COVID-19 pneumonia patients. Methods: This retrospective cohort study involves 306 individuals with severe COVID-19 pneumonia enrolled between March 2021 and June 2021. Each patient had confirmed SARS-CoV-2 infection and required oxygen therapy. Differential blood count and serum CRP were taken on admission day. Medical data were collected from the hospital’s information system. Results: Of 306 patients (133 females, 173 males, aged 66.3 ± 15.2 years), 105 (34.3%) died. Counts of neutrophils, lymphocytes, and eosinophils differed significantly between survivors and deceased (p < 0.001; p = 0.002; p = 0.009, respectively) and had substantially differentiating properties in ROC analysis. Built with the counts of neutrophils, lymphocytes, and eosinophils, the White Blood Cell Score (WBCS) was developed. WBCS robustly predicted mortality (OR = 2.821; CI: 2.037–3.906; p < 0.001) in the investigated population. Cumulative risk of death according to WBCS (ranging from 0 to 3 points) was as follows: 0 points—10.9%, 1 point—23.5%, 2 points—33.1%, 3 points—34.1%. Conclusions: Based on differential blood count, the proposed WBCS is easy to use and can be helpful in predicting mortality among severe COVID-19 patients. Full article

Background/Objectives: Sarcoidosis is a granulomatous disease with no widely accepted circulating biomarkers for routine diagnostics. Soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), identified through extracellular vesicle proteomics, have been proposed as candidates. We aimed to compare the diagnostic accuracy of serum sCD14 and LBP with the established biomarker soluble interleukin-2 receptor alpha chain (sCD25). Methods: A matched case–control study included 46 newly diagnosed, untreated sarcoidosis patients and 46 age- and sex-matched healthy controls. Serum sCD14, sCD25, and LBP were quantified by ELISA. BMI was included as a covariate in multivariable logistic regression. Diagnostic performance was evaluated by ROC analysis and stepwise AIC model selection. Longitudinal biomarker dynamics were assessed in 32 patients under treatment. Results: sCD25 demonstrated superior diagnostic discrimination (AUC 0.92, 95% CI 0.87–0.98), compared with LBP (AUC 0.71, 95% CI 0.60–0.82) and sCD14 (AUC 0.61, 95% CI 0.49–0.73). In multivariate analysis, only sCD25 (OR per +100 pg/mL: 1.53; p < 0.001) remained an independent predictor of sarcoidosis. Neither LBP nor sCD14 improved model fit. All biomarkers significantly decreased following therapy. Conclusions: Among routinely measurable serum markers, sCD25 outperformed sCD14 and LBP in sarcoidosis diagnosis. Further studies should explore immunometabolic interactions to refine diagnostic algorithms. Full article

Specific Learning Disability (SLD) describes persistent difficulties in academic skills in reading, writing, and mathematics, despite having normal intelligence. The exact origin of SLD is unknown. However, it is thought that biological factors and environmental conditions, along with genetic factors, contribute to the development of SLD. Agmatine, a neurotransmitter in the brain, plays a role in various biological processes. Agmatine has been reported to mediate antidepressant effects and neuroprotective effects, and it plays critical roles in learning and the processing of learned information into memory. Therefore, this study aimed to determine the relationship between SLD and agmatine metabolism by determining the enzyme levels of arginine decarboxylase (ADC) and agmatinase (AGMAT) in children with SLD. ADC and AGMAT levels in the blood serum of children with SLD and controls were analyzed using ELISA. When ADC levels in children with SLD (30.26 ± 5.06 ng/mL) were compared with those in the control group (29.82 ± 4.95 ng/mL), the difference was not statistically significant (p = 0.737). However, AGMAT levels in children with SLD (27.02 ± 4.46 ng/mL) were found to be statistically significantly higher than those in the control group (21.42 ± 3.98 ng/mL) (p < 0.001). In light of these findings, we can say that agmatine breakdown is significantly increased in children with SLD. Full article

Background and Objectives: Accurate assessment of liver fibrosis is essential for treatment decisions in patients with chronic hepatitis B (CHB). Although liver biopsy is considered the reference standard, its invasive nature limits routine use. Serum-based non-invasive fibrosis scores have been proposed as alternatives; however, their diagnostic performance in CHB remains variable. This study aimed to compare multiple serum-based non-invasive fibrosis scores with liver biopsy findings and to evaluate their association with histological activity. Materials and Methods: This retrospective cross-sectional study included 219 adult patients with CHB who underwent liver biopsy with simultaneous laboratory evaluation. Patients with viral co-infections (HIV, HCV, or HDV), metabolic syndrome, diabetes mellitus, hepatic steatosis, or incomplete data were excluded. Non-invasive fibrosis scores—including APRI, FIB-4, AST/ALT ratio (AAR), age–platelet index (API), GGT-to-platelet ratio (GPR), Lok index, modified Forns index, Albumin–Bilirubin (ALBI) score, and red cell distribution width (RDW)-based indices—were calculated using routine laboratory parameters. Histopathological fibrosis staging served as the reference standard. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, and areas under the curve (AUC) were compared using the DeLong test. Associations with histological activity index (HAI) were assessed using Spearman correlation. Results: For the prediction of significant fibrosis (≥F2), FIB-4 demonstrated the highest AUC, followed by ALBI and APRI. For advanced fibrosis (≥F3), FIB-4 again showed the highest AUC, followed by APRI and GPR. For significant fibrosis (≥F2), DeLong analysis revealed no statistically significant differences between FIB-4 and the other serum-based scores (p > 0.05). APRI (r = 0.556, p < 0.001) and FIB-4 (r = 0.463, p < 0.001) showed the strongest correlations with HAI. In ROC analysis for moderate-to-severe histological activity (HAI ≥ 4), APRI demonstrated the highest diagnostic accuracy (AUC = 0.677). Conclusions: Serum-based non-invasive fibrosis scores demonstrate comparable but overall modest diagnostic performance for biopsy-confirmed fibrosis in patients with chronic hepatitis B. Indices such as FIB-4 and APRI demonstrated relatively better discrimination and may be considered as screening or rule-out tools in selected clinical contexts. APRI and FIB-4 also show associations with histological activity; however, their clinical application should be interpreted with caution, given their moderate discriminatory capacity. Full article

This study investigated the effects of dietary lysophospholipids on growth performance, hepatic lipid metabolism, intestinal health, and dietary lipid levels of largemouth bass. The 56-day experiment included five groups: CON (0% lysophospholipids), LL50 (0.05% lysophospholipids), LP50 (0.05% lysophospholipids—0.5% oil), LP100 (0.1% lysophospholipids—1.0% oil), and LP200 (0.1% lysophospholipids—2.0% oil), with 3 replicates (30 fish/replicate) per group. The results showed that compared with the CON group, dietary supplementation of 0.05% lysophospholipid had no significant effect on the growth performance of largemouth bass, but increased the crude protein content and decreased the crude lipid content in the whole body. An amount of 0.05% lysophospholipid improved hepatic lipid utilization efficiency. Specifically, this supplementation level promoted serum lipid transport (increased serum HDL-C content and decreased triglyceride and LDL-C contents), and enhanced hepatic lipid metabolism by regulating the expression of lipid metabolism-related genes (fas, hsl, and acc) and the levels of lipid metabolites (phosphatidylcholine and fatty acids), thereby reducing hepatic triglyceride content. In addition, 0.05% lysophospholipid improved intestinal health by increasing lipase activity and intestinal villus height, up-regulating the expression of the anti-inflammatory gene (tgf-β1) and tight junction protein genes (claudin-1, claudin-4, and zo-1), and down-regulating the expression of the pro-inflammatory gene (tnf-α). In terms of dietary lipid reduction, supplementation with 0.1% lysophospholipid allowed a 1% reduction in dietary lipid level without affecting the growth performance of largemouth bass, whereas at the same level of lysophospholipid supplementation, a 2% reduction in dietary lipid level resulted in decreased growth performance of largemouth bass. These findings provide theoretical support for the practical application of lysophospholipids, and demonstrate that reducing dietary lipid inclusion by adding lysophospholipids helps to reduce feed costs and improve aquaculture economic benefits. Full article

This study aimed to investigate the effects of feeding high-moisture corn (HMC) on weight performance, serum immune and antioxidant indices, rumen fermentation, microbial community, and metabolomics in Kazakh rams. A total of 32 healthy Kazakh rams were randomly divided into a control group (CT, diet with only ordinary crushed corn) and an experimental group (GS, diet with 50% ordinary crushed corn + 50% HMC), following a 7-day adaptation period and a 120-day trial period. Results showed that the F/G was significantly lower in the GS group than in the CT group (p < 0.05). FBW, net weight gain and ADG increased by 4.58%, 8.69%, and 8.70%, respectively, while ADFI decreased by 7.04% (p > 0.05). Regarding serum immune indices, IgA in the GS group was significantly higher at 40 d (p < 0.01), and IgM was significantly higher at 40, 80, and 120 d (p < 0.05). For antioxidant indices, the SOD activity in the GS group was significantly higher than that in the CT group at 120 d (p < 0.01). The CAT activity in the GS group was significantly higher at 40, 80, and 120 d (p < 0.01). Among rumen fermentation parameters, the concentration of butyric acid in the GS group was significantly lower than in the CT group (p < 0.01). Microbial diversity analysis indicated no significant differences in Alpha- and Beta-diversity of rumen microorganisms between the two groups. However, the relative abundance of Firmicutes_A at the phylum level was significantly higher in the GS group (p < 0.05), and the abundance of Cryptobacteroides was significantly higher than in the CT group (p < 0.01). Rumen metabolomic analysis identified a total of 1357 differential metabolites, among which 1130 showed significant differences, with 459 upregulated and 671 downregulated. These were mainly enriched in pathways such as Glutathione metabolism, Beta-alanine metabolism, Sphingolipid metabolism, and lysine degradation. In conclusion, feeding HMC can improve feed conversion efficiency and weight performance in Kazakh rams, regulate the structure of dominant rumen microorganisms, and enhance immune and antioxidant capacities. Full article

Background/Objectives: Population aging has been accompanied by increased institutionalization of older adults and a high prevalence of vitamin D deficiency in this group. Although the literature suggests a possible relationship between vitamin D and cognition, findings remain inconsistent, particularly in institutional settings. This cross-sectional study aimed to investigate factors associated with vitamin D deficiency in institutionalized older adults, emphasizing the role of vitamin D supplementation and length of institutionalization, as well as to evaluate the association between serum vitamin D levels, cognitive decline, and dementia. Methods: A total of 104 older adults living in different long-term care institutions (LTCFs) in the city of Pelotas, RS, Brazil, were evaluated. Sociodemographic, clinical, and nutritional data were collected via interviews and medical record review. Serum 25-hydroxyvitamin D levels were categorized according to the Institute of Medicine cutoffs (<20 ng/mL and ≥20 ng/mL). Cognitive decline was assessed using the Mini-Mental State Examination, and dementia was evaluated with the Clinical Dementia Rating scale. Analyses included bivariate tests and binary logistic regression. Results: A high prevalence of vitamin D deficiency (52.9%), cognitive decline (83.6%), and questionable or mild dementia (79.4%) was observed. In multivariate analysis, vitamin D supplementation remained independently associated with vitamin D deficiency, whereas no significant association was observed between vitamin D levels and cognitive decline or dementia. Conclusions: Vitamin D deficiency in institutionalized older adults is predominantly associated with contextual and care-related factors rather than cognitive impairment, highlighting the importance of systematic nutritional monitoring and vitamin D supplementation strategies in institutional settings. Full article

Background: Short-chain fatty acids (SCFAs) support mucosal integrity and reduce inflammation, while nesfatin-1 is a neuropeptide with antiapoptotic, anti-inflammatory, antioxidant, and anorexigenic actions. Their roles in inflammatory bowel disease (IBD) and links to quality of life (QoL) are unclear. Methods: We conducted a cross-sectional study including adults with Crohn’s disease (CD), ulcerative colitis (UC), and healthy controls (HC). Serum total short-chain fatty acids and nesfatin-1 were measured using enzyme-linked immunosorbent assays (ELISA). Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Group comparisons and correlation analyses were performed using non-parametric statistical methods. Results: Serum total SCFA concentrations did not differ significantly between patients with CD, UC, and HC (p = 0.29). Nesfatin-1 levels showed between-group variability, with lower values in CD compared with healthy controls, while patients with UC showed intermediate and variable levels (p = 0.064). An inverse correlation between SCFAs and nesfatin-1 was observed in UC and in the combined IBD cohort, but not in CD. Quality of life was comparably impaired in CD and UC. No statistically significant associations were observed between serum SCFAs or nesfatin-1 and IBDQ scores. Conclusions: In this pilot exploratory study, circulating SCFAs and nesfatin-1 showed distinct patterns across IBD subtypes, with evidence of subtype-specific associations between these biomarkers. However, no relationship with quality of life was demonstrated. Larger longitudinal studies are required to confirm these findings and clarify their clinical relevance. Full article

Aim: We aimed to evaluate the clinical efficacy and safety of Shenqu Xiaoshi Oral Liquid in the treatment of functional constipation in children. Methods: A comprehensive literature search was conducted from inception to 20 October 2025, across PubMed, Embase, Scopus, Web of Science, the Cochrane Library, Chinese VIP Information Database, China National Knowledge Infrastructure (CNKI), and Wan Fang Med Database. For quantitative analysis, the mean difference (MD) was used for continuous outcomes and the risk ratio (RR) for dichotomous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Statistical analyses were performed using RevMan 5.3 and Stata 13 software. Results: Eight studies involving 692 pediatric patients were included (Shenqu Xiaoshi Oral Liquid group: 345; control group: 347). Compared to the control group, Shenqu Xiaoshi Oral Liquid demonstrated superior clinical effectiveness [RR = 1.36, 95% CI: (1.25, 1.47); z = 7.11, p < 0.00001] and a lower recurrence rate [RR = 0.49, 95% CI: (0.26, 0.93); z = 2.18, p = 0.03]. Both the post-treatment [WMD = −0.91, 95% CI: (−0.97, −0.86); z = 31.94, p < 0.00001] and post-recurrence [WMD = −1.49, 95% CI: (−1.56, −1.41); z = 40.12, p < 0.00001] defecation intervals were shorter in the Shenqu Xiaoshi Oral Liquid group. No significant difference was observed in the incidence of adverse reactions between the two groups [RR = 0.67, 95% CI: (0.35, 1.29); z = 1.20, p = 0.23]. Furthermore, serum levels of motilin [WMD = 41.66, 95% CI: (34.17, 49.16); z = 10.90, p < 0.00001] and gastrin [WMD = 23.74, 95% CI: (7.30, 40.19); z = 2.83, p = 0.005] were significantly higher in the Shenqu Xiaoshi Oral Liquid group. Conclusions: Shenqu Xiaoshi Oral Liquid shows favorable clinical efficacy and an acceptable safety profile for treating functional constipation in children. However, these outcome measures are influenced by the limited sample size and potential heterogeneity of the included studies, warranting cautious interpretation of the results. Full article

Background and Objectives: Sclerostin or dickkopf-1 (DKK1) inhibits the canonical Wnt/β-catenin signaling pathway, which regulates vascular calcification and may contribute to the development of arterial stiffness. The brachial–ankle pulse wave velocity (baPWV) measures peripheral arterial stiffness (PAS). This study aimed to investigate the correlation between sclerostin and DKK1 levels and PAS in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Biochemical data and sclerostin and DKK1 levels were analyzed in the fasting blood samples of 125 patients with T2DM. baPWV measurements using the VaSera VS-1000 automatic pulse wave analyzer classified patients with values > 18.0 m/s on either side into the PAS group. Results: Among patients with T2DM, 47 (37.6%) were classified as having PAS. These patients exhibited higher hypertension prevalence (p = 0.002); greater age (p < 0.001); elevated systolic (p < 0.001) and diastolic blood (p = 0.012) pressures; and increased fasting glucose (p = 0.001), glycated hemoglobin (p = 0.008), triglyceride (p = 0.001), blood urea nitrogen (p < 0.001), and creatinine (p = 0.001) levels, urine albumin-to-creatinine ratio (p = 0.039), and C-reactive protein (p = 0.024) and serum sclerostin (p < 0.001) levels, but decreased estimated glomerular filtration rate (p < 0.001). Multivariate logistic regression analysis identified serum sclerostin level (odds ratio, 1.127; 95% confidence interval, 1.058–1.200; p < 0.001) as an independent PAS predictor in patients with T2DM. Serum log-transformed sclerostin levels were positively correlated with left (p = 0.005) and right (p = 0.001) baPWV via Spearman’s rank-order correlation coefficient analysis. Conclusions: Serum sclerostin levels, but not DKK1 levels, are positively correlated with PAS in patients with T2DM. Full article