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Search Results (2,418)

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34 pages, 3051 KiB  
Article
Harnessing the Hepatoprotective and Nephroprotective Potential of Nigella sativa Fractions via per os Administration in CCl4-Intoxicated Wistar Rats: A Mixed Approach
by Mohammed Dalli, Nour Elhouda Daoudi, Salah-eddine Azizi, Mohammed Roubi, Ilyass Alami Merrouni, Faiza Souna, Mohammed Choukri, Bonglee Kim and Nadia Gseyra
Pharmaceuticals 2025, 18(8), 1147; https://doi.org/10.3390/ph18081147 (registering DOI) - 1 Aug 2025
Abstract
Background: Nigella sativa, known as black cumin, is traditionally used to treat various illnesses. Objective: The current study aims to investigate the potential hepatoprotective and nephroprotective effect of black cumin fractions via per os route in CCl4-intoxicated Wistar rats. This [...] Read more.
Background: Nigella sativa, known as black cumin, is traditionally used to treat various illnesses. Objective: The current study aims to investigate the potential hepatoprotective and nephroprotective effect of black cumin fractions via per os route in CCl4-intoxicated Wistar rats. This study used a computational approach to assess the interaction of bioactive compounds with key proteins (CYP P450 3E1, TNF-α, and Cox-2). Methods: Wistar rats were treated with CCl4 to induce liver injury and with different Nigella sativa fractions (250 mg/Kg) or Sylimarin (50 mg/Kg). Liver and kidney functions were assessed through biochemical markers, hepatic glycogen, malondialdehyde levels, molecular docking, and ADMET analysis to evaluate drug-likeliness. Results: The results revealed that intoxication with CCl4 induced an elevation in different liver and kidney biochemical parameters such as (ALT, AST, creatinine, urea...) indicating kidney and hepatic toxicity. However, treatment with different Nigella sativa fractions showed a significant improvement in animal body weight and significant amelioration of biochemical markers indicating a protective potential of these fractions against CCl4-induced intoxication. Furthermore, the molecular docking approach demonstrated high binding affinity with the target proteins. Conclusions: These current findings shed light on the therapeutic potential of Nigella sativa fractions as a promising protective agent of the liver and kidney against CCl4 intoxication. Full article
(This article belongs to the Section Natural Products)
21 pages, 1148 KiB  
Article
Polymorphic Variants of Selected Genes Regulating Bile Acid Homeostasis in Women with Intrahepatic Cholestasis of Pregnancy
by Krzysztof Piątek, Grażyna Kurzawińska, Marcin Ożarowski, Piotr Józef Olbromski, Adam Kamiński, Maciej Brązert, Tomasz M. Karpiński, Wiesław Markwitz and Agnieszka Seremak-Mrozikiewicz
Int. J. Mol. Sci. 2025, 26(15), 7456; https://doi.org/10.3390/ijms26157456 (registering DOI) - 1 Aug 2025
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is [...] Read more.
Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is to evaluate the association between CYP7A1, NR1H1, RXRA, and PPARA gene variants and risk of ICP. Five single nucleotide variants (SNVs), rs3808607 (CYP7A1), rs56163822 (NR1H4), rs1800206 (PPARA), rs749759, and rs11381416 (NR2B1), were genotyped in a group of 96 ICP and 211 controls. The T allele of the CYP7A1 (rs3808607) variant may be a protective factor against ICP risk (OR = 0.697, 95% CI: 0.495–0.981, p = 0.038). Genetic model analysis showed that rs3808607 was associated with decreased risk of ICP under dominant (OR = 0.55, 95% CI: 0.32–3.16, p = 0.032, AIC = 380.9) and log-additive models (OR = 0.71, 95% CI: 0.51–1.00, p = 0.046, AIC = 381.4). The A insertion in the rs11381416 NR2B1 variant was associated with the degree of elevation in the liver function tests TBA (34.3 vs. 18.8 μmol/L, p = 0.002), ALT (397.0 vs. 213.0 IU/L, p = 0.017), and AST (186.0 vs. 114.4 IU/L, p = 0.032) in ICP women. Results indicate an association between the CYP7A1 rs3808607 and the risk of ICP and the association of the rs11381416 of the NR2B1 receptor with higher values of liver function tests in women with ICP. A better understanding of the cooperation of proteins involved in BA metabolism may have important therapeutic implications in ICP and other hepatobiliary diseases. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
21 pages, 3146 KiB  
Article
TnP as a Multifaceted Therapeutic Peptide with System-Wide Regulatory Capacity
by Geonildo Rodrigo Disner, Emma Wincent, Carla Lima and Monica Lopes-Ferreira
Pharmaceuticals 2025, 18(8), 1146; https://doi.org/10.3390/ph18081146 (registering DOI) - 1 Aug 2025
Abstract
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling [...] Read more.
Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article
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12 pages, 257 KiB  
Article
Evaluating the Diagnostic Potential of the FIB-4 Index for Cystic Fibrosis-Associated Liver Disease in Adults: A Comparison with Transient Elastography
by Stephen Armstrong, Kingston Rajiah, Aaron Courtenay, Nermeen Ali and Ahmed Abuelhana
J. Clin. Med. 2025, 14(15), 5404; https://doi.org/10.3390/jcm14155404 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive [...] Read more.
Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive and invasive. Non-invasive biomarkers like the Fibrosis-4 (FIB-4) index have shown promise in diagnosing liver fibrosis in various chronic liver diseases. This study explores the potential of the FIB-4 index to predict CFLD in an adult CF population and assesses its correlation with transient elastography (TE) as a potential diagnostic tool. The aim of this study is to evaluate the diagnostic performance of the FIB-4 index for CFLD in adults with CF and investigate its relationship with TE-based liver stiffness measurements (LSM). Methods: The study was conducted in a regional cystic fibrosis unit, including 261 adult CF patients. FIB-4 scores were calculated using an online tool (mdcalc.com) based on patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. In parallel, 29 patients underwent liver stiffness measurement using TE (Fibroscan®). Statistical analyses included non-parametric tests for group comparisons and Pearson’s correlation to assess the relationship between FIB-4 scores and TE results. Results: The mean FIB-4 score in patients diagnosed with CFLD was higher (0.99 ± 0.83) compared to those without CFLD (0.64 ± 0.38), although the difference was not statistically significant (p > 0.05). TE results for CFLD patients (5.9 kPa) also did not show a significant difference compared to non-CFLD patients (4.2 ± 1.6 kPa, p > 0.05). However, a positive correlation (r = 0.401, p = 0.031) was found between FIB-4 scores and TE-based LSM, suggesting a potential complementary diagnostic role. Conclusions: The FIB-4 index, while not sufficient as a standalone diagnostic tool for CFLD in adults with CF, demonstrates potential when used in conjunction with other diagnostic methods like TE. This study introduces a novel approach for integrating non-invasive diagnostic markers in CF care, offering a pathway for future clinical practice. The combination of FIB-4 and TE could serve as an accessible, cost-effective alternative to invasive diagnostic techniques, improving early diagnosis and management of CFLD in the CF population. Additionally, future research should explore the integration of these tools with emerging biomarkers and clinical features to refine diagnostic algorithms for CFLD, potentially reducing reliance on liver biopsies and improving patient outcomes. Full article
(This article belongs to the Section Intensive Care)
19 pages, 4753 KiB  
Article
Biosynthesized Gold Nanoparticles from Eruca sativa Mill. Leaf Extract Exhibit In Vivo Biocompatibility, Antimicrobial, and Antioxidant Activities
by Abdullah Muhsin Hazbar, Abdulkadir Mohammed Noori Jassim, Mustafa Taha Mohammed and Younis Baqi
Antibiotics 2025, 14(8), 776; https://doi.org/10.3390/antibiotics14080776 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Antimicrobial resistance (AMR) is a health related threat world-wide. Biosynthesized gold nanoparticles (AuNPs) using plant extracts have been reported to exhibit certain biological activity. This study aimed to biosynthesize AuNPs using an aqueous extract of Eruca sativa leaves and to evaluate their [...] Read more.
Background/Objectives: Antimicrobial resistance (AMR) is a health related threat world-wide. Biosynthesized gold nanoparticles (AuNPs) using plant extracts have been reported to exhibit certain biological activity. This study aimed to biosynthesize AuNPs using an aqueous extract of Eruca sativa leaves and to evaluate their biocompatibility, antimicrobial activity, and antioxidant properties. Methods: AuNPs were biosynthesized using an aqueous extract of Eruca sativa leaves. Their biocompatibility was evaluated through hemolytic activity and assessments of hepatic and renal functions in rats. AuNPs were biologically evaluated as antimicrobial and antioxidant agents. Results: The AuNPs exhibited particle sizes of 27.78 nm (XRD) and 69.41 nm (AFM). Hemolysis assays on red blood cells revealed negligible hemolytic activity (<1%). Hepatic enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were studied. ALT, AST, and ALP levels showed no significant changes compared to the negative control. However, LDH levels were elevated at higher concentration (52.8 µg/mL), while the lower concentration (26.4 µg/mL) appeared to be safer. Renal biomarkers, urea and creatinine, showed no significant changes at either concentration, indicating minimal nephrotoxicity. The antimicrobial activity of AuNPs, plant extract, and gold salt was tested against five microorganisms: two Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae), two Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), and a fungal strain (Candida albicans). The AuNPs exhibited minimum inhibition concentrations (MICs) of 13.2 µg/mL against S. aureus and S. pneumoniae, 26.4 µg/mL against E. coli and C. albicans, and 39.6 µg/mL against P. aeruginosa, suggesting selectivity towards Gram-positive bacteria. Furthermore, the AuNPs demonstrated strong antioxidant activity, surpassing that of vitamin C. Conclusions: The biosynthesized AuNPs exhibited promising biocompatibility, selective antimicrobial properties, and potent antioxidant activity, supporting their potential application in combating the AMR. Full article
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20 pages, 576 KiB  
Article
Effectiveness of a Physiotherapy Stress-Management Protocol on Cardiorespiratory, Metabolic and Psychological Indicators of Children and Adolescents with Morbid Obesity
by Pelagia Tsakona, Alexandra Hristara-Papadopoulou, Thomas Apostolou, Ourania Papadopoulou, Ioannis Kitsatis, Eleni G. Paschalidou, Christos Tzimos, Maria G. Grammatikopoulou and Kyriaki Tsiroukidou
Children 2025, 12(8), 1010; https://doi.org/10.3390/children12081010 - 31 Jul 2025
Abstract
Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate [...] Read more.
Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO2 were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO2, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article
(This article belongs to the Special Issue Childhood Obesity: Prevention, Intervention and Treatment)
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14 pages, 267 KiB  
Article
Impact of Short-Term Liraglutide Therapy on Non-Invasive Markers of Liver Fibrosis in Patients with MASLD
by Aleksandra Bołdys, Maciej Borówka, Łukasz Bułdak and Bogusław Okopień
Metabolites 2025, 15(8), 510; https://doi.org/10.3390/metabo15080510 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and [...] Read more.
Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and its progression increases the risk of liver-related and overall mortality. This exploratory research evaluated the potential impact of a 3-month intervention involving dietary counseling and liraglutide therapy on liver fibrosis and related metabolic markers in patients with MASLD and obesity without diabetes. Methods: In this prospective, single-arm exploratory intervention, 28 adult patients with MASLD and obesity received structured dietary counseling and daily subcutaneous liraglutide for 12 weeks. Liver fibrosis was assessed using non-invasive indices (FIB-4, APRI, BARD, ELF) and transient elastography performed with the FibroScan® device (Echosens, Paris, France). Results: After 3 months, a significant reduction in liver stiffness (−7.14%, p < 0.05) and ELF score (from 6.71 to 6.63; −1.2%, p < 0.05) was observed. APRI (p = 0.06) and FIB-4 (p = 0.09) showed trends toward improvement, while the BARD score and AST/ALT ratio remained unchanged. Conclusions: Short-term liraglutide therapy combined with lifestyle modification may improve early-stage liver fibrosis in patients with MASLD and obesity, as indicated by reductions in liver stiffness and ELF score. These preliminary findings highlight the potential of advanced non-invasive fibrosis markers in monitoring treatment response. However, as an exploratory study, results should be interpreted with caution, and larger, long-term trials are needed to confirm these observations and evaluate efficacy in patients with more advanced fibrosis stages. Full article
17 pages, 2131 KiB  
Article
Investigating Neuroprotective Effects of Berberine on Mitochondrial Dysfunction and Autophagy Impairment in Parkinson’s Disease
by Hae-Rim Cha, Jin-Seok Kim, Jin-Hyeob Ryu and Hyun-Jeong Cho
Int. J. Mol. Sci. 2025, 26(15), 7342; https://doi.org/10.3390/ijms26157342 (registering DOI) - 29 Jul 2025
Viewed by 131
Abstract
Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. [...] Read more.
Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases. Full article
(This article belongs to the Section Molecular Neurobiology)
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16 pages, 1591 KiB  
Article
Molecular and Drug Resistance Characteristics of Haemophilus influenzae Carried by Pediatric Patients with Adenoid Hypertrophy
by Nan Xiao, Jia-Hao Qin, Xiu-Ying Zhao and Lin Liu
Microorganisms 2025, 13(8), 1764; https://doi.org/10.3390/microorganisms13081764 - 29 Jul 2025
Viewed by 132
Abstract
Purpose: The adenoid microbiota plays a key role in adenoid hypertrophy (AH). This study explored the molecular epidemiology and antimicrobial resistance of Haemophilus. Influenzae (H. influenzae) strains in pediatric AH patients. Methods: Retrospective analysis of pediatric AH patients undergoing endoscopic adenoidectomy. [...] Read more.
Purpose: The adenoid microbiota plays a key role in adenoid hypertrophy (AH). This study explored the molecular epidemiology and antimicrobial resistance of Haemophilus. Influenzae (H. influenzae) strains in pediatric AH patients. Methods: Retrospective analysis of pediatric AH patients undergoing endoscopic adenoidectomy. Adenoid tissue samples were cultured to screen for pathogens. H. influenzae strains were identified by 16S rRNA sequencing and serotyped via q-PCR. Multilocus sequence typing (MLST) and ftsI gene analysis were conducted using PubMLST. β-lactamase genes (blaTEM-1, blaROB-1) were detected by PCR, and antibiotic susceptibility testing (AST) was performed using the Etest method. For imipenem-resistant strains, the acrRAB efflux pump gene cluster and ompP2 porin gene were sequenced and compared with those of the wild-type strain Rd KW20. Results: Over 8 months, 56 non-duplicate H. influenzae strains were isolated from 386 patients. The detection rate was highest in children under 5 years (30.5%) compared to those aged 5–10 years (13.4%) and 10–15 years (8.7%). Of 49 sub-cultured strains, all were non-typeable H. influenzae (NTHi). MLST identified 22 sequence types (STs) and 13 clonal complexes (CCs), with CC11 (26.5%), CC3 (14.3%), and CC107 (14.3%) being predominant. Common STs included ST103 (22.4%), ST57 (10.2%), and ST107 (10.2%). Most strains belonged to the ftsI group III-like+ (57.1%). β-lactamase positivity was 98.0% (48/49), with blaTEM-1 (95.9%) and blaROB-1 (18.4%) detected. AST showed low susceptibility to ampicillin (10.2%), amoxicillin–clavulanate (34.7%), azithromycin (12.2%), and trimethoprim–sulfamethoxazole (14.3%). Among the β-lactamase-positive strains, 44/48 were β-lactamase-positive ampicillin-resistant (BLPAR); none were β-lactamase-negative ampicillin-resistant (BLNAR). Imipenem susceptibility was 91.8% (45/49). No carbapenemases were found in the imipenem-resistant strains, but mutations in acrRAB (88.12–94.94% identity) and ompP2 (77.10–82.94% identity) were observed. Conclusions: BLPAR NTHi strains of CC11 are major epidemic strains in pediatric AH. Imipenem resistance in H. influenzae likely results from porin mutations rather than carbapenemase activity. Enhanced surveillance of H. influenzae’s role in AH and its resistance patterns is warranted. Full article
(This article belongs to the Section Medical Microbiology)
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23 pages, 1310 KiB  
Review
Evaluating Antimicrobial Susceptibility Testing Methods for Cefiderocol: A Review and Expert Opinion on Current Practices and Future Directions
by Stefania Stefani, Fabio Arena, Luigi Principe, Stefano Stracquadanio, Chiara Vismara and Gian Maria Rossolini
Antibiotics 2025, 14(8), 760; https://doi.org/10.3390/antibiotics14080760 - 28 Jul 2025
Viewed by 573
Abstract
Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial [...] Read more.
Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial systems. Variability in interpretive criteria and areas of technical uncertainty (ATUs) further complicate assessments. Methods: This review and expert opinion presents: (1) an overview of non-susceptibility to FDC and then delves into the performance of current FDC AST methods for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex; (2) a practical decision framework to guide clinical microbiologists in making informed choices. Results and Conclusions: For Enterobacterales, including carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa, we propose disk diffusion (DD) as a preliminary screening tool to classify isolates as susceptible (S) or resistant (R). Confirmatory testing using the UMIC® FDC system or the ID-CAMHB BMD method is recommended for R isolates. In cases of discrepancy, repeating the test with ID-CAMHB BMD is advised. Additionally, isolates falling within the ATU during DD testing should be retested using the UMIC® system or ID-CAMHB BMD. For A. baumannii complex, since EUCAST breakpoints have not been defined yet, we propose a stepwise framework based on the first DD result: isolates with inhibition zones < 17 mm are considered non-susceptible and should be confirmed with standard BMD. Those between 17 and 22 mm require retesting with a commercial BMD method, with further confirmation recommended if S isolates with zones ≥ 23 mm may be considered S without additional testing. Full article
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21 pages, 2139 KiB  
Article
Blue Light Effect on Metabolic Changes in Induced Precocious Puberty in Rats
by Luciana-Mădălina Gherman, Elena-Mihaela Jianu, Ștefan Horia Roșian, Mădălin Mihai Onofrei, Lavinia Patricia Mocan, Veronica Sanda Chedea, Ioana Corina Bocsan, Dragoş Apostu, Andreea Roxana Todea, Eva Henrietta Dulf, Emilia Laura Mogoșan, Carmen Mihaela Mihu, Cătălina Angela Crişan, Ștefan Cristian Vesa, Anca Dana Buzoianu and Raluca Maria Pop
Biology 2025, 14(8), 951; https://doi.org/10.3390/biology14080951 (registering DOI) - 28 Jul 2025
Viewed by 236
Abstract
Modern life, characterized by constant exposure to artificial light from electronic devices, such as light-emitting diodes (LEDs), disrupts the natural circadian rhythm and induces important metabolic changes. The impact of blue light exposure on male and female rat’s onset of puberty, hormonal and [...] Read more.
Modern life, characterized by constant exposure to artificial light from electronic devices, such as light-emitting diodes (LEDs), disrupts the natural circadian rhythm and induces important metabolic changes. The impact of blue light exposure on male and female rat’s onset of puberty, hormonal and biochemical parameters was assessed by comparison between the four study groups: the control group (CTRL) maintained under normal light conditions, the group exposed to blue light from a mobile phone (MP), the group subjected to blue light from a computer screen (PC), and the group exposed to blue light from an LED lamp (LED). Both female and male rats exposed to PC and LED failed to thrive, with a significantly lower body weight intake than the CTRL group. All three distinct sources of blue light interfered with the cyclicity of the estrous cycle in female rats. A marked decrease in the number of complete estrous cycles and the highest incidence of incomplete cycles were noticed in the LED group. Elevated ALT, AST, glucose, and insulin levels were influenced in a gender-specific manner, and depending on the source of emitted light. Prolonged blue light exposure induces significant metabolic disruptions and possesses important future research potential in identifying explicit pathways regarding this environmental stressor. Full article
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25 pages, 3545 KiB  
Article
Combined Effects of PFAS, Social, and Behavioral Factors on Liver Health
by Akua Marfo and Emmanuel Obeng-Gyasi
Med. Sci. 2025, 13(3), 99; https://doi.org/10.3390/medsci13030099 - 28 Jul 2025
Viewed by 184
Abstract
Background: Environmental exposures, such as per- and polyfluoroalkyl substances (PFAS), in conjunction with social and behavioral factors, can significantly impact liver health. This research investigates the combined effects of PFAS (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), alcohol consumption, smoking, income, and education [...] Read more.
Background: Environmental exposures, such as per- and polyfluoroalkyl substances (PFAS), in conjunction with social and behavioral factors, can significantly impact liver health. This research investigates the combined effects of PFAS (perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), alcohol consumption, smoking, income, and education on liver function among the U.S. population, utilizing data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). Methods: PFAS concentrations in blood samples were analyzed using online solid-phase extraction combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS), a highly sensitive and specific method for detecting levels of PFAS. Liver function was evaluated using biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin, and the fatty liver index (FLI). Descriptive statistics and multivariable linear regression analyses were employed to assess the associations between exposures and liver outcomes. Bayesian Kernel Machine Regression (BKMR) was utilized to explore the nonlinear and interactive effects of these exposures. To determine the relative influence of each factor on liver health, Posterior Inclusion Probabilities (PIPs) were calculated. Results: Linear regression analyses indicated that income and education were inversely associated with several liver injury biomarkers, while alcohol use and smoking demonstrated stronger and more consistent associations. Bayesian Kernel Machine Regression (BKMR) further highlighted alcohol and smoking as the most influential predictors, particularly for GGT and total bilirubin, with posterior inclusion probabilities (PIPs) close to 1.0. In contrast, PFAS showed weaker associations. Regression coefficients were small and largely non-significant, and PIPs were comparatively lower across most liver outcomes. Notably, education had a higher PIP for ALT and GGT than PFAS, suggesting a more protective role in liver health. People with higher education levels tend to live healthier lifestyles, have better access to healthcare, and are generally more aware of health risks. These factors can all help reduce the risk of liver problems. Overall mixture effects demonstrated nonlinear trends, including U-shaped relationships for ALT and GGT, and inverse associations for AST, FLI, and ALP. Conclusion: These findings underscore the importance of considering both environmental and social–behavioral determinants in liver health. While PFAS exposures remain a long-term concern, modifiable lifestyle and structural factors, particularly alcohol, smoking, income, and education, exert more immediate and pronounced effects on hepatic biomarkers in the general population. Full article
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12 pages, 1159 KiB  
Article
The Protective Effect of Thiamine and Thiamine Pyrophosphate Against Linezolid-Induced Oxidative Liver Damage and Lactic Acidosis in Rats
by Bahar Isik, Irem Ates, Nurinisa Yucel, Bahadir Suleyman, Ali Sefa Mendil, Esra Tuba Sezgin and Halis Suleyman
Antioxidants 2025, 14(8), 920; https://doi.org/10.3390/antiox14080920 - 27 Jul 2025
Viewed by 365
Abstract
Linezolid, an antimicrobial agent, has been linked to lactic acidosis, oxidative stress, and liver damage. Oxidative stress is considered to play a key role in this damage. Thiamine pyrophosphate (TPP), the active form of thiamine, may prevent lactate accumulation and enhance aerobic capacity. [...] Read more.
Linezolid, an antimicrobial agent, has been linked to lactic acidosis, oxidative stress, and liver damage. Oxidative stress is considered to play a key role in this damage. Thiamine pyrophosphate (TPP), the active form of thiamine, may prevent lactate accumulation and enhance aerobic capacity. Therefore, this study aimed to evaluate the protective effect of TPP against possible linezolid-induced liver damage and lactic acidosis in rats. Twenty-four male Wistar albino rats were randomly assigned to four groups (n = 6): healthy control (HG), linezolid (LZD), thiamine plus linezolid (TLZD), and TPP plus linezolid (TPLZD). Thiamine and TPP (20 mg/kg, intraperitoneal (i.p.)) were administered once daily, while linezolid (125 mg/kg, per os (p.o.)) was given twice daily (250 mg/kg/day) for 28 days. Animals were euthanized under high-dose anesthesia (with 50 mg/kg, i.p. thiopental sodium). Liver tissues were analyzed for MDA, tGSH, SOD, and CAT, and examined histopathologically. Blood samples were collected prior to euthanasia to assess lactate, LDH, ALT, AST, and TPP levels. In the LZD group, MDA, lactate, ALT, AST, and LDH levels significantly increased, while tGSH, SOD, CAT, and TPP decreased (p < 0.001). Histopathology showed hydropic degeneration, necrosis, and mononuclear cell infiltration (p < 0.05). Thiamine did not prevent these alterations (p > 0.05), whereas TPP significantly prevented both biochemical and histopathological changes (p < 0.05), indicating its protective efficacy. TPP may offer significant protection against linezolid-induced hepatotoxicity and lactic acidosis. Full article
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14 pages, 4594 KiB  
Article
Short-Term Exposure to Tebuconazole Triggers Haematological, Histological and Biochemical Disturbances in Rainbow Trout (Oncorhynchus mykiss)
by Akif Er
Toxics 2025, 13(8), 630; https://doi.org/10.3390/toxics13080630 - 27 Jul 2025
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Abstract
Tebuconazole (TBZ), a triazole-class fungicide widely used in agriculture, is frequently detected in aquatic environments due to runoff and leaching, where it poses a threat to non-target aquatic organisms. This study investigates the acute toxicity of TBZ on juvenile rainbow trout (Oncorhynchus [...] Read more.
Tebuconazole (TBZ), a triazole-class fungicide widely used in agriculture, is frequently detected in aquatic environments due to runoff and leaching, where it poses a threat to non-target aquatic organisms. This study investigates the acute toxicity of TBZ on juvenile rainbow trout (Oncorhynchus mykiss), a commercially important cold-water fish species. The 96 h LC50 value was determined to be 9.05 mg/L using probit analysis. In addition to mortality, the physiological responses of fish exposed to both LC50 and maximum tolerance concentration (MTC; 6 mg/L) were evaluated through haematological and histological assessments. TBZ exposure significantly suppressed key haematological parameters, particularly WBC, RBC, HGB, HCT, and LYM, indicating immunosuppression and potential hypoxia. Histological examination revealed progressive and regressive damage in gill tissues, including epithelial lifting, hyperplasia, and hypertrophy, which were more severe in the LC50 group. These alterations were quantified using a semi-quantitative scoring system. Additionally, significant changes in biochemical parameters such as ALT, AST, creatinine, total protein, and glucose levels were observed, further indicating hepatic and renal dysfunctions induced by TBZ exposure. The findings demonstrate that TBZ exposure induces substantial physiological and structural impairments in rainbow trout, highlighting the importance of assessing the ecological risks of fungicide contamination in aquatic environments. The study also provides a dose–response model that can be used to estimate mortality risk in aquaculture operations exposed to TBZ. Full article
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20 pages, 3154 KiB  
Article
The Effect of Astaxanthin on Ochratoxin A-Induced Intestinal Injury in Chickens Through RIPK1/RIPK3/MLKL Pathway
by Ruiwen Fan, Wenqi Tian, Bo Jin, Yuhang Sun, Miao Long, Shuhua Yang and Peng Li
Antioxidants 2025, 14(8), 915; https://doi.org/10.3390/antiox14080915 - 25 Jul 2025
Viewed by 302
Abstract
Ochratoxin A (OTA), as a mycotoxin, can contaminate a variety of feeds and foods. Existing studies have shown that the main toxicity of OTA to organisms is nephrotoxicity, but the toxic mechanism to other organs is still worthy of further study. Whether OTA [...] Read more.
Ochratoxin A (OTA), as a mycotoxin, can contaminate a variety of feeds and foods. Existing studies have shown that the main toxicity of OTA to organisms is nephrotoxicity, but the toxic mechanism to other organs is still worthy of further study. Whether OTA causes intestinal damage through the necroptosis pathway mediated by RIPK1/RIPK3/MLKL remains to be elucidated. Astaxanthin (AST), a feed additive with strong antioxidant properties, was used as an antidote to evaluate the alleviation effect on OTA-induced intestinal injury and the underlying mechanism in this research. Chickens are the most sensitive animals to OTA except pigs. Therefore, 70 white-feathered chickens (n = 15) and Chicken Small Intestinal Epithelial Cells (CSIECs) were used as experimental subjects. Experimental models were established by single or combined exposure of OTA (1.0 mg/kg on chickens for 21 d; 2 μM on CSIEC for 24 h) and AST (100 mg/kg on chickens for 21 d; 40 μM on CSIEC for 24 h). In this study, AST significantly ameliorated OTA-induced intestinal damage by restoring the expression of tight junction proteins (Occludin-1, Claudin-1, and ZO-1), attenuating severe histopathological alterations, mitigating the inflammatory response (elevated pro-inflammatory cytokines and reduced anti-inflammatory mediators), and suppressing necroptosis through downregulation of RIPK1, RIPK3 and MLKL expression. Combined evidence from animal experiments and cell culture experiments demonstrated that AST alleviated the necroptosis and inflammation caused by OTA in CSIECs and the intestine of chickens through the RIPK1/RIPK3/MLKL signaling pathway, thereby reducing the damage caused by OTA. Full article
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