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19 pages, 3743 KB  
Article
Phylogenetic Groups, Virulence Factors, and Antimicrobial Susceptibility of Escherichia coli Associated with Urinary Tract Infections from a Metropolitan Area of Buenos Aires, Argentina
by Nora B. Molina, Ramón A. González Pasayo, Marisa A. López and Mónica D. Sparo
Antibiotics 2026, 15(4), 350; https://doi.org/10.3390/antibiotics15040350 (registering DOI) - 29 Mar 2026
Abstract
Background: Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of urinary tract infections (UTIs) worldwide. The emergence of strains combining high virulence with multidrug resistance (MDR) poses a significant challenge to public health. This study aimed to characterize the phylogenetic distribution, virulence [...] Read more.
Background: Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of urinary tract infections (UTIs) worldwide. The emergence of strains combining high virulence with multidrug resistance (MDR) poses a significant challenge to public health. This study aimed to characterize the phylogenetic distribution, virulence profiles, and antimicrobial susceptibility of UPEC isolates recovered from patients in the metropolitan area of Buenos Aires (AMBA), Argentina. Methodology: Phylogenetic groups, the ST131 lineage, and virulence-associated genes were identified using PCR-based assays. Antimicrobial susceptibility testing (AST) was performed using automated methods and extended-spectrum beta-lactamase (ESBL) production was confirmed using the double-disk synergy test. Colistin (COL) resistance was evaluated by Colistin Drop Test and PCR screening for the mcr-1 (mobile colistin resistance gene 1). Biofilm formation was detected by the Tissue Culture Plate (TCP) method, whereas phenotypic virulence factors (VF) were assessed with Congo Red agar, hemagglutination, and hemolysis assays. Results: Phylogenetic groups B2 (43.8%) and D (26.7%), typically associated with extraintestinal infections, were the most frequent. The high-risk clone B2-ST131 was detected in 6.7% of isolates. Biofilm production was observed in 92.4% of the isolates, with curli fimbriae (87.6%) being the most frequently expressed VF. The highest resistance rates were observed for ampicillin (62.1%), ampicillin-sulbactam (39.8%), and trimethoprim-sulfamethoxazole (25.2%). Interestingly, 3.8% of isolates exhibited colistin resistance, despite the absence of the mcr-1 gene. Conclusions: This study highlights the detection of MDR-UPEC isolates that showed strong resistance to fluoroquinolones and were ESBL producers with high virulence in Argentina, justifying future research encompassing genomic and epidemiological monitoring of local UPEC, which is essential for managing infections and developing new therapeutic and preventive measures. Full article
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22 pages, 1565 KB  
Article
Protective Effects of Vitamin D Against Doxorubicin Chemotherapy–Induced Hepatotoxicity in Wistar Albino Rats: Evidence from 99mTc-Pyrophosphate Scintigraphy and Oxidative–Inflammatory Pathways
by Murat Kalın, Haluk Kerim Karakullukcu, Mina Karakullukcu, Aylin Arslan, Serdar Savaş Gül, Reyhan Toyran, Ömer Faruk Özkan, Gülçin Ercan and Hatice Aygun
Nutrients 2026, 18(7), 1097; https://doi.org/10.3390/nu18071097 (registering DOI) - 29 Mar 2026
Abstract
Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and [...] Read more.
Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D3 (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic 99mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, 99mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article
(This article belongs to the Section Micronutrients and Human Health)
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20 pages, 17893 KB  
Article
Integrative Multiomics Analysis Reveals the Ameliorative Effects of Astragalus membranaceus Extract on Metabolic Dysfunction-Associated Steatotic Liver Disease
by Jiayi An, Yi Li, Zunhan Zhang, Yaru Chang and Guanxiu Xiao
Molecules 2026, 31(7), 1120; https://doi.org/10.3390/molecules31071120 (registering DOI) - 28 Mar 2026
Abstract
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, [...] Read more.
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
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11 pages, 320 KB  
Article
Effects of Outdoor Rearing System on the Growth Performance and Blood Parameters of Duroc Pigs
by Kaliyah Hayes, Andrea Gentry-Apple, Lin Yang, Julisa Cruz, Joseline Mora-Obrajero, Daisha Peele-Kendrick, Shilei Zhang, Derrick Coble and Yongjie Wang
Animals 2026, 16(7), 1040; https://doi.org/10.3390/ani16071040 (registering DOI) - 28 Mar 2026
Abstract
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 [...] Read more.
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
16 pages, 789 KB  
Article
Performance of Serum-Based Non-Invasive Fibrosis Scores Compared with Liver Biopsy in Patients with Chronic Hepatitis B
by Umut Devrim Binay, Faruk Karakeçili, Orçun Barkay and Betül Kuru
Medicina 2026, 62(4), 646; https://doi.org/10.3390/medicina62040646 (registering DOI) - 28 Mar 2026
Abstract
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 [...] Read more.
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
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17 pages, 1890 KB  
Article
Paired In-Hospital Dynamics in Hepatitis E: Rapid Transaminase Decline and Persistent Hyperbilirubinemia in a Romanian Cohort
by Florentina Dumitrescu, Eugenia-Andreea Marcu, Vlad Pădureanu, Virginia Maria Rădulescu and Ion Rogoveanu
Diagnostics 2026, 16(7), 1012; https://doi.org/10.3390/diagnostics16071012 - 27 Mar 2026
Abstract
Background/Objectives: Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute hepatitis in Europe, but short-term in-hospital laboratory dynamics remain insufficiently described in hospitalized cohorts. We aimed to characterize admission biochemical abnormalities and paired admission-to-discharge laboratory changes in hospitalized patients [...] Read more.
Background/Objectives: Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute hepatitis in Europe, but short-term in-hospital laboratory dynamics remain insufficiently described in hospitalized cohorts. We aimed to characterize admission biochemical abnormalities and paired admission-to-discharge laboratory changes in hospitalized patients with acute hepatitis E from Craiova, Romania, with exploratory sex- and age-stratified analyses. Methods: We conducted a single-center retrospective observational study including 40 consecutive hospitalized patients with acute hepatitis E during 2024–2025. Admission and discharge laboratory values were compared at the within-patient level, and exploratory subgroup analyses by sex and age class were performed. Given the limited sample size, multivariable analyses were restricted to parsimonious age-adjusted models for selected endpoints. Results: The cohort comprised 22 females (55%) and 18 males (45%), with a mean age of 53.05 ± 21.44 years; two in-hospital deaths occurred. At admission, marked transaminase elevation and frequent hyperbilirubinemia were observed, with 70% of patients having total bilirubin ≥ 2 mg/dL and 40% ≥ 10 mg/dL. During hospitalization, ALT and AST declined markedly, whereas total and direct bilirubin improved more modestly, indicating slower resolution of jaundice/cholestatic abnormalities. Platelets increased, while prothrombin index changes were heterogeneous. Male patients had higher bilirubin values at admission and discharge and more frequent clinically relevant hyperbilirubinemia thresholds; however, these findings should be interpreted cautiously given the small sample size, the retrospective design, and the absence of standardized clinical confounders and mechanistic data. Exploratory age-stratified analyses did not identify robust differences after multiplicity control. Conclusions: In hospitalized hepatitis E, hepatocellular injury markers improved rapidly during hospitalization, whereas cholestatic abnormalities resolved more slowly and often remained clinically relevant at discharge. The observed sex-related cholestatic pattern should be considered exploratory and requires confirmation in larger studies with standardized clinical covariates and longer follow-up. These findings support closer monitoring of bilirubin trajectories at discharge, particularly in male patients, and highlight the need for integrating laboratory dynamics into short-term clinical assessment of hospitalized HEV cases. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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14 pages, 710 KB  
Article
Low-Fishmeal Dietary Supplementation with Crayfish By-Product Protein Hydrolysate Affects Growth Performance, Appetite-Related Metabolic Signaling and Intestinal Microbiota of Pacific White Shrimp (Litopenaeus vannamei)
by Lina Ren, Wanshan Gu, Huangbing Sun, Guoqiang Fan and Xiaojing Yang
Metabolites 2026, 16(4), 221; https://doi.org/10.3390/metabo16040221 - 27 Mar 2026
Abstract
Background/Objectives: Low-fishmeal diets are widely adopted to improve sustainability in shrimp aquaculture, yet reduced palatability and metabolic stress frequently suppress feed intake and growth. We evaluated whether a crayfish (Procambarus clarkii) by-product protein hydrolysate (CBPH) could mitigate low-fishmeal-induced performance losses by [...] Read more.
Background/Objectives: Low-fishmeal diets are widely adopted to improve sustainability in shrimp aquaculture, yet reduced palatability and metabolic stress frequently suppress feed intake and growth. We evaluated whether a crayfish (Procambarus clarkii) by-product protein hydrolysate (CBPH) could mitigate low-fishmeal-induced performance losses by modulating feeding-related metabolic signaling and gut microbiota features in Pacific white shrimp (Litopenaeus vannamei). Methods: In an 8-week feeding trial, 360 juveniles (initial body weight 0.46 g) were assigned to three diets (four replicates per diet): a commercial control (CON), a low-fishmeal diet (LFM), and LFM supplemented with 2% CBPH (CBPH). Growth, feed utilization, whole-body composition, hemolymph biochemical indices (TP, TG, GLU, AST, ALT), intestinal appetite-related gene expression (5-HTR, CART, CCK1R, D2-like, NPY), and intestinal microbiota profiles (full-length 16S rRNA sequencing, V1–V9, PacBio) were assessed. Results: Compared with the LFM group, CBPH supplementation increased feed intake and improved feed conversion, restoring final body weight and growth rates to levels comparable to CON. CBPH also alleviated low-fishmeal-associated metabolic stress, including reduced AST and ALT activities and lower glucose levels. The LFM diet induced upregulation of anorexigenic genes (5-HTR, CART, D2-like) and downregulation of NPY in the shrimp intestine, whereas CBPH supplementation reversed these transcriptional changes. In addition, microbiota richness indices (ACE and Chao1) were elevated by CBPH relative to LFM, accompanied by compositional shifts at the phylum and genus levels. Conclusions: CBPH effectively alleviated low-fishmeal-induced reductions in feeding and growth, accompanied by coordinated changes in feeding-related gene expression, systemic biochemical markers, and gut microbiota composition, supporting its potential as a functional ingredient to stabilize metabolic responses in low-fishmeal shrimp feeds. Full article
(This article belongs to the Special Issue Metabolism and Nutrition in Fish)
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7 pages, 25033 KB  
Case Report
Left Atrial Myxoma Surgery in Cryoglobulinemic Vasculitis Associated with Hepatitis B: A Clinical Case Report
by Iustina Maria Andrieș, Radu Sebastian Gavril, Cristina Andreea Adam, Grigore Tinica and Florin Mitu
Reports 2026, 9(2), 101; https://doi.org/10.3390/reports9020101 - 27 Mar 2026
Viewed by 68
Abstract
Background and Clinical Significance: Left atrial myxoma is the most common benign primary cardiac tumor and is associated with embolic and hemodynamic complications. Complete surgical excision is the treatment of choice, while postoperative cardiovascular rehabilitation is essential for functional recovery. Case Presentation [...] Read more.
Background and Clinical Significance: Left atrial myxoma is the most common benign primary cardiac tumor and is associated with embolic and hemodynamic complications. Complete surgical excision is the treatment of choice, while postoperative cardiovascular rehabilitation is essential for functional recovery. Case Presentation: We report the case of a 75-year-old woman with arterial hypertension, dyslipidemia, and chronic venous insufficiency (Clinical–Etiological–Anatomical–Pathophysiological (CEAP) class 2), and chronic hepatitis B virus (HBV) infection who underwent surgical excision of a left atrial myxoma and was subsequently admitted three weeks postoperatively for phase II cardiovascular rehabilitation. The postoperative course was complicated by transient atrial fibrillation, peripheral edema, pleural effusion, and progressive purpuric lesions of the lower limbs. Laboratory and immunological evaluation revealed positive cryoglobulins, markedly elevated rheumatoid factor (1058 UI/mL) and IgM levels (715 mg/dL), reduced complement levels (C3, C4), normocytic normochromic anemia, microscopic hematuria, and elevated ALT (156 U/L), AST (142 U/L), total bilirubin (1.4 mg/dL), and INR (1.6), suggestive of hepatic inflammatory activity. HBV status was scheduled for evaluation through Gastroenterology referral (HBV DNA viral load, serological markers: HBsAg, HBeAg, anti-HBe), as our Cardiology Rehabilitation Clinic lacks the possibility of evaluation. After systematic exclusion of alternative etiologies, secondary cryoglobulinemic vasculitis in the context of chronic HBV infection with biochemical evidence of hepatic activity was considered the most plausible diagnosis. Conclusions: This case highlights the complexity of managing elderly patients after cardiac tumor surgery, particularly in the presence of systemic comorbidities. Early recognition of extracardiac complications and an individualized, multidisciplinary strategy are essential to optimize outcomes. Full article
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18 pages, 6274 KB  
Article
Resveratrol Attenuates Liver Inflammation in Non-Alcoholic Fatty Liver Disease by Activating PINK1-Mediated Mitophagy
by Shujing Tan, Ran Yu, Longwei Sun, Manman Shen, Juan Framirez Pedroso, Osmani Chacón Chacón, Chengmin Li and Weiguo Zhao
Animals 2026, 16(7), 1022; https://doi.org/10.3390/ani16071022 - 27 Mar 2026
Viewed by 63
Abstract
Resveratrol (RES) has been shown to exhibit therapeutic efficacy against fatty liver disease. Yet, the molecular mechanisms by which RES ameliorates liver injury remain unclear. The aim of this study was to investigate the therapeutic effect and mechanism of resveratrol in fatty liver [...] Read more.
Resveratrol (RES) has been shown to exhibit therapeutic efficacy against fatty liver disease. Yet, the molecular mechanisms by which RES ameliorates liver injury remain unclear. The aim of this study was to investigate the therapeutic effect and mechanism of resveratrol in fatty liver disease. It was found that dairy cows with fatty liver exhibit characteristic hepatic pathologies, including ballooning degeneration, lipid accumulation and elevated serum AST and ALT levels. Parallel to these changes, we observed significant upregulation of the NLRP3 inflammasome alongside suppression of mitophagy in the liver. Additionally, it was demonstrated in vitro that resveratrol pretreatment effectively alleviated PA-triggered NLRP3 inflammasome activation and mitochondrial dysfunction. Furthermore, RES’s mitigating effects against NLRP3 inflammation and mitochondrial injury were reversed by suppressing PINK1-medicated mitophagy. In vivo experiments further demonstrated that resveratrol administration attenuated HFD-induced liver injury and lipid accumulation in a mouse model, concurrent with suppressed NLRP3 activation and an increase in mitophagy, further confirming the mechanism identified in vitro. Our findings reveal that RES ameliorates fatty liver injury primarily by inhibiting the NLRP3 inflammasome through PINK1-mediated mitophagy, which provides a potential novel therapeutic strategy for mitigating fatty liver disease. Full article
(This article belongs to the Section Animal Physiology)
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13 pages, 3495 KB  
Article
End-to-End Timeliness of Blood Culture Diagnostics: A One-Month Observational Study of 5121 Bottles
by Carlotta Magrì, Damiano Squitieri, Barbara Fiori, Tiziana D’Inzeo, Maurizio Sanguinetti, Brunella Posteraro and Giulia Menchinelli
Antibiotics 2026, 15(4), 335; https://doi.org/10.3390/antibiotics15040335 - 26 Mar 2026
Viewed by 168
Abstract
Background/Objectives: To quantify end-to-end timeliness of the blood culture (BC) diagnostic workflow over one month using operational key performance indicators (KPIs)—transportation time (TT), time to detection (TTD), time to preliminary report (TTPR), and time to antimicrobial susceptibility testing (AST; TTAST)—and to identify [...] Read more.
Background/Objectives: To quantify end-to-end timeliness of the blood culture (BC) diagnostic workflow over one month using operational key performance indicators (KPIs)—transportation time (TT), time to detection (TTD), time to preliminary report (TTPR), and time to antimicrobial susceptibility testing (AST; TTAST)—and to identify actionable bottlenecks. Methods: This retrospective observational analysis included BC bottles processed between 29 September and 29 October 2023 at a large tertiary-care hospital in Italy. KPIs were computed from laboratory information system (LIS) timestamps and structured observations and were summarized as medians (interquartile range [IQR]). Results: 44.7% (2290/5121) of bottles reached the laboratory within 2 h (median 2.2 h, IQR 1.3–3.7), suggesting pre-analytical delays. Among adult bottles (n = 4995), 68.9% were underfilled (<8 mL), 12.9% met the 8–10 mL target, and 18.2% were overfilled (>10 mL). There were 932 positive bottles (18.2%), with a nocturnal peak in instrument flags despite reduced staffing. Median TTD was 12.6 h (IQR 8.9–18.4), with earlier detection for Gram-negatives than Gram-positives and yeasts (11.9, 14.5, and 30.9 h). In bacterial-positive bottles with complete timestamps (n = 294), median TTPR was 3.8 h (IQR 1.7–8.8); median TTAST was 19.2 h (IQR 14.3–27.8). From collection, median times were 17.9 h (IQR 14.2–23.1) to the preliminary report and 36.0 h (IQR 28.8–48.7) to the AST result. Conclusions: Within-laboratory steps were generally rapid, whereas transport planning and collection volumes emerged as major bottlenecks. Targeted interventions—enforcing ≤2 h TT and training to achieve an 8–10 mL fill—should further improve BC turnaround time. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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13 pages, 1304 KB  
Article
Characterizing Biomarkers of Muscle Damage in Collegiate Football Players: A Prospective, Repeated Measures Study
by Grace Brandhurst, Erik Piedy, Stephen Etheredge, Matthew Martone, Heather D. Quiriarte, Paul Phillips, Derek Calvert, Nathan P. Lemoine, Jack Marucci, Brian A. Irving, Robert Zura, Guillaume Spielmann, Neil M. Johannsen and Rachel Matthews
J. Clin. Med. 2026, 15(7), 2502; https://doi.org/10.3390/jcm15072502 - 25 Mar 2026
Viewed by 199
Abstract
Background/Objectives: Exertional rhabdomyolysis (ER) is a possibly fatal condition resulting from extreme or novel exercise that causes substantial muscle breakdown. ER has been observed during preseason football; however, prospective research has yet to characterize normal versus ER responses using a repeated measures design. [...] Read more.
Background/Objectives: Exertional rhabdomyolysis (ER) is a possibly fatal condition resulting from extreme or novel exercise that causes substantial muscle breakdown. ER has been observed during preseason football; however, prospective research has yet to characterize normal versus ER responses using a repeated measures design. This study characterized ER biomarker responses related to muscle damage, and renal and hepatic stress, after two NCAA Division I preseason football scrimmages. Methods: Following a prospective, repeated measures design, blood and urine samples from 17 players were collected immediately (IPS) and 24 h post-scrimmage (24hPS). A subset (n = 13) provided samples after 48 h of rest as a non-exertion (NE) comparator group. A Comprehensive Metabolic Panel was run on serum samples, and urine samples were analyzed for myoglobin and creatinine. Values were compared with reference ranges, mixed models evaluated time effects, and linear regressions examined associations between CPK and renal and hepatic biomarkers. Results: No participants were diagnosed with ER. A time effect was observed for CPK (p < 0.01), with CPK greater IPS (991.6 ± 560.8 IU/L) compared to NE (267.7 ± 205.3 IU/L), and remaining elevated above reference ranges at 24hPS (739.2 ± 442.6 IU/L). Similar time effects were observed with LDH, AST, and ALT (p < 0.01). Serum creatinine increased above reference values and NE concentrations (p < 0.01). CPK correlated (p < 0.01 for all) with LDH (r = 0.69), serum myoglobin (r = 0.57), creatinine (r = 0.42), AST (r = 0.77), and ALT (r = 0.38). Conclusions: Biomarkers of muscle damage, renal stress, and liver function were higher IPS, with only partial recovery by 24hPS. These findings provide preliminary reference patterns for biomarker fluctuations and support individualized, serial monitoring to identify abnormal responses and promote early detection of ER. Full article
(This article belongs to the Special Issue Clinical Advances in Musculoskeletal Disorders: 2nd Edition)
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20 pages, 13290 KB  
Article
NGR1 Ameliorates Hepatocyte Steatosis and Mitochondrial Dysfunction Associated with the Restoration of NDUFS2
by Min Liu, Dongsheng Liu, Qian Zhang, Rui Zhang, Jiye Aa, Guangji Wang and Yuan Xie
Pharmaceuticals 2026, 19(4), 524; https://doi.org/10.3390/ph19040524 - 24 Mar 2026
Viewed by 166
Abstract
Background: Metabolic disorder-associated fatty liver disease (MASLD) is closely related to obesity and type 2 diabetes. Its pathogenesis involves many factors, including mitochondrial dysfunction, endoplasmic reticulum stress and intestinal flora disorders. Notoginsenoside R1 (NGR1) is a key bioactive component of Panax notoginseng. [...] Read more.
Background: Metabolic disorder-associated fatty liver disease (MASLD) is closely related to obesity and type 2 diabetes. Its pathogenesis involves many factors, including mitochondrial dysfunction, endoplasmic reticulum stress and intestinal flora disorders. Notoginsenoside R1 (NGR1) is a key bioactive component of Panax notoginseng. The purpose of this study was to investigate the therapeutic effect of notoginsenoside R1 (NGR1) on metabolic disorder-associated steatohepatitis (MASH) and its potential mechanism. Methods: Mice were fed a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD) for 6 weeks and received NGR1 (50/100 mg/kg/day) in the last 3 weeks. The role of NGR1 was evaluated by developing metabolomics, proteomics and functional analysis. In addition, the effects of NGR1 on lipid droplet content, mitochondrial function and fatty acid oxidation in hepatocytes were also verified. Results: NGR1 improved MASH progression in CDAHFD-fed mice, significantly reduced liver triglyceride content from 31.2 ± 5.1 mmol/g to 20.5 ± 4.8 mg/g (p < 0.001), free fatty acid from 0.12 ± 0.03 mmol/g prot to 0.06 ± 0.028 mg/g (p < 0.001), TNF-α (p < 0.01), IL-1β (p < 0.001), α-SMA (p < 0.05) and Collagen1A1 levels (p < 0.01), as well as serum ALT and AST concentrations (p < 0.001), and alleviated hepatomegaly and lipid droplet accumulation. Metabolomics and proteomics analysis showed that NGR1 normalized liver metabolism in MASH mice and upregulated mitochondrial OXPHOS components, including NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2), and effectively reversed CDAHFD-induced mitochondrial dysfunction. Mitochondrial membrane potential and ATP production were restored. Conclusions: This study confirmed that NGR1 has significant therapeutic potential for MASH and improves mitochondrial function by upregulating NDUFS2. This study provides new insights for the future clinical treatment of MASH. Full article
(This article belongs to the Section Pharmacology)
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24 pages, 9043 KB  
Article
Lingguizhugan Decoction Ameliorates MASLD by Modulating the Gut Microbiota and Enriching Non-12-OH Bile Acids to Activate TGR5-Mediated Thermogenesis
by Yun-Hong Sun, Pei-Lun Ding, Xue Wang, Yi-Rong Wang, Ming-Zhe Zhu, Kai Wang, Liang Dai, Yan-Qi Dang, Guang Ji, Meng Li and Wen-Jun Zhou
Pharmaceuticals 2026, 19(4), 523; https://doi.org/10.3390/ph19040523 - 24 Mar 2026
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Abstract
Objective: Based on previous findings on the Lingguizhugan (LGZG)-mediated gut–liver axis, this study clarifies the therapeutic mechanisms of LGZG in metabolic dysfunction-associated steatotic liver disease (MASLD), with a focus on the gut microbiota–bile acid–TGR5 (GPBAR1) axis. Methods: C57BL/6J mice were fed [...] Read more.
Objective: Based on previous findings on the Lingguizhugan (LGZG)-mediated gut–liver axis, this study clarifies the therapeutic mechanisms of LGZG in metabolic dysfunction-associated steatotic liver disease (MASLD), with a focus on the gut microbiota–bile acid–TGR5 (GPBAR1) axis. Methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce MASLD, followed by 4-week LGZG intervention (21.57 g/kg/day, oral gavage). Metabolic phenotypes, gut microbiota (16S rRNA sequencing), serum/hepatic bile acids (targeted metabolomics), and molecular targets (qPCR/Western blot) were analyzed. Results: LGZG significantly alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis, while enhancing whole-body energy expenditure (increased oxygen consumption (VO2), and heat production (p < 0.05). It also reduced serum ALT (p < 0.001) and AST levels (p < 0.01). Mechanistically, LGZG remodeled the gut microbiota, specifically increasing Akkermansia, Bifidobacterium and Lachnospiraceae_NK4A236_group while decreasing Lactobacillus. This shift inhibited the intestinal FXR-Fgf15 axis, concurrently activating the hepatic alternative bile acid synthesis pathway (upregulating CYP27A1 and CYP7B1 protein expression; p < 0.001 and p < 0.01, respectively). Consequently, systemic accumulation of non-12α-hydroxylated bile acids (non-12-OH BAs) such as hyocholic acid (HCA) and 7-ketolithocholic acid (7-ketoLCA) occurred—known TGR5 agonists and intestinal FXR antagonists. These changes elevated serum GLP-1 levels (p < 0.05) and activated adipose TGR5-cAMP/PKA/CREB signaling. The metabolic benefits primarily originated from non-12-OH BAs enrichment and TGR5-mediated adipose browning, not hepatic FXR activation. Conclusions: Our findings show that LGZG ameliorates MASLD by remodeling bile acid profiles via intestinal FXR-Fgf15 axis inhibition and hepatic alternative synthesis pathway activation. This study highlights the TGR5-targeting properties of LGZG, providing a mechanistic basis for its therapeutic use in metabolic disorders. Full article
(This article belongs to the Section Pharmacology)
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14 pages, 2116 KB  
Article
The Biological Activities of Mango Seed Fractions and Its Hepatoprotective Effects on Alcoholic Liver Disease and Modulation of Intestinal Flora
by Zaixiang Lou, Xu Cheng, Zejun Pei, Caihua Liu, Zhengjie Zhu, Yuemei Liao, Huili Huang, Rui Huang and Yaqin Li
Foods 2026, 15(7), 1116; https://doi.org/10.3390/foods15071116 - 24 Mar 2026
Viewed by 151
Abstract
In this study, the active components in the seed of Mangifera indica L. were isolated, the main chemical components were identified, and then their antioxidant activities and their effects on liver injury and intestinal microbiota were evaluated. The results showed that all the [...] Read more.
In this study, the active components in the seed of Mangifera indica L. were isolated, the main chemical components were identified, and then their antioxidant activities and their effects on liver injury and intestinal microbiota were evaluated. The results showed that all the components of mango column chromatography exhibited antioxidant activity. F2 had the lowest IC50 value of 93.61 μg/mL and exhibited the strongest DPPH radical scavenging activity. Given its superior overall antioxidant activity, F2 was selected for further compositional analysis and activity evaluation. UPLC-MS/MS analysis showed that the isolated components of mango F2 contained 11 active ingredients, including mangiferin, gallic acid and quercetin. The results showed that specific mango fractions significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and showed a protective effect on liver injury induced by alcohol. rRNA sequencing analysis showed that high alcohol intake could reduce the species diversity of intestinal microbiota in mice, and mango fractions could effectively alleviate this phenomenon. High alcohol intake decreases the relative abundance of Bacteroidota and increases the abundance of Bacillota and Thermodesulfobacteriota phyla. The high-dose mango group alleviated the above changes, which was manifested by an increase in the relative abundance of Bacteroidota and Thermodesulfobacteriota bacteria. The relative abundance of families such as Muribaculaceae in the high-dose mango group decreased compared to the model group. This study provides a scientific basis for the analysis and high-value utilization of mango components, and provides a new alternative for protecting against alcoholic liver injury and regulating intestinal microbiota. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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26 pages, 3881 KB  
Article
Characterization and Biological Activity of Rutin Extracted from Filipendula ulmaria (L.) Maxim
by Anna Vesnina, Violeta Le, Svetlana Ivanova, Anna Frolova, Irina Milentyeva, Victor Atuchin and Alexander Prosekov
BioTech 2026, 15(1), 25; https://doi.org/10.3390/biotech15010025 - 23 Mar 2026
Viewed by 153
Abstract
In this work, Filipendula ulmaria (L.) Maxim, a perennial herbaceous plant from the Rosaceae family, was considered a novel source of obtaining rutin for pharmaceutical purposes. Rutin was extracted from the plant parts collected in the flowering summer period and dried at 40 [...] Read more.
In this work, Filipendula ulmaria (L.) Maxim, a perennial herbaceous plant from the Rosaceae family, was considered a novel source of obtaining rutin for pharmaceutical purposes. Rutin was extracted from the plant parts collected in the flowering summer period and dried at 40 ± 3 °C. The process was carried out using the ethanol extraction and fractionation of extracted compounds, and it yields the 95 wt% purity crystalline product. The phase composition of the extracted rutin was verified by the XRD analysis and NMR measurements. It was found that 2.85% of rutin could be extracted from Filipendula ulmaria, which is 1.2 times higher than the results of similar studies. The biological activity of the isolated rutin was tested on rats. It was established in vivo that the extracted rutin normalizes blood glucose levels (glucose and glycosylated hemoglobin), insulin resistance (HOMA-IR index) and reduces the severity of dystrophic changes in the liver caused by high-fat and high-carbohydrate diets. The introduction of rutin corrects lipid profile indicators (triglycerides, cholesterol, cholesterol fractions in lipoproteins and atherogenic indices), cytolysis indicators of hepatocytes, and liver steatosis (ALT, AST/ALT, triglycerides). Thus, the novel source of rutin opens the possibility for a wide use of this flavonoid in the food technology and pharmaceutical industry. Full article
(This article belongs to the Section Medical Biotechnology)
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