Search Results (2,105)

Background and Objectives: Methotrexate (MTX) is widely used in clinical settings but is often associated with hepatotoxic side effects, including oxidative stress, inflammation, and fibrosis. Novel therapeutic strategies are needed to mitigate MTX-induced liver injury. This study aimed to evaluate the hepatoprotective effects of ivermectin in a rat model of MTX-induced hepatotoxicity. Materials and Methods: Thirty male Wistar albino rats were randomly divided into three groups (n = 10 per group): control (saline only), MTX (single intraperitoneal dose of 20 mg/kg MTX), and MTX + ivermectin (20 mg/kg MTX + 0.5 mg/kg/day ivermectin for 10 days). At the end of the experiment, blood and liver tissues were collected for histopathological and biochemical evaluation, including ALT, malondialdehyde (MDA), TGF-β, and syndecan-1 levels. Results: MTX administration significantly increased plasma and hepatic MDA, TGF-β, syndecan-1, and ALT levels, alongside histological evidence of necrosis, fibrosis, and inflammatory infiltration (p < 0.001 vs. control). Ivermectin treatment significantly attenuated these alterations, with reductions in MDA (both plasma and liver), TGF-β, syndecan-1, and ALT levels (p < 0.05–0.001 vs. MTX). Histological scoring also revealed improved liver architecture and decreased necrosis, fibrosis, and leukocyte infiltration. Conclusions: Ivermectin demonstrates a strong hepatoprotective effect against MTX-induced liver injury, likely through antioxidant, anti-inflammatory, antifibrotic, and endothelial-protective mechanisms. These findings support the repurposing potential of ivermectin in mitigating drug-induced hepatic damage. Full article

This study rigorously evaluated the safety profile of dietary fiber extracted from cassava pulp, a promising functional food ingredient, through acute and 28-day sub-acute oral toxicity assessments in Wistar rats. This research hypothesized that cassava pulp fiber would exhibit minimal toxicity across a range of doses. In the acute study, rats received single oral doses of 175, 550, or 2000 mg/kg, while the sub-acute toxicity study involved daily doses of 250, 500, or 1000 mg/kg, with satellite groups included for reversibility assessment. Comprehensive monitoring encompassed clinical signs, mortality, body weight, food intake, hematological and biochemical parameters, relative organ weights, and detailed histopathological examination. Remarkably, no treatment-related mortality or overt clinical signs of toxicity were observed in either study. The LD₅₀ was higher than 2000 mg/kg for the acute study and the no-observed-adverse-effect level (NOAEL) was determined to be 2000 mg/kg for the acute study and 1000 mg/kg for the sub-acute toxicity study, indicating a high margin of safety. While statistically significant alterations were noted in some hematological, biochemical, and relative organ weight parameters, these changes were not considered toxicologically relevant. Notably, histopathological changes in the lungs were observed across all groups, including controls, warranting further investigation. These findings suggest that cassava pulp fiber is well tolerated at high oral doses, supporting its potential for safe application in food and nutraceutical formulations. However, the observed lung alterations necessitate further research to elucidate their etiology and clinical significance. Full article

Cell migration, shape maintenance, and intracellular signaling are closely linked to dynamic changes in cell morphology and the cytoskeleton. These processes involve the reorganization of the cytoskeleton within the cytoplasm, affecting all its key components: intermediate filaments, microtubules, and microfilaments. A promising strategy for remotely controlling cellular functions is the use of magnetic nanoparticles, which can influence cellular physiology. This approach, known as magnetogenetics, has been applied in various areas of cell and molecular biology. Applying a magnetic field allows for the non-invasive modulation of biochemical processes, cell migration, and morphological changes in cells containing magnetic nanoparticles. In our study, magnetic nanoparticles were conjugated with antibodies targeting cytoskeletal components, enabling the magnetically induced manipulation and deformation of the cell cytoskeleton. Our research introduces a novel approach to manipulating specific cytoskeletal components and altering cell polarity with spatial precision in vitro using magnetic nanoparticles associated with the cytoskeleton. Full article

Zearalenone (ZEA), a mycotoxin primarily generated by the Fusarium species, constitutes a prevalent contaminant in both human and animal feedstuffs. Chronic exposure to this mycotoxin induces hepatic inflammatory responses in livestock species including rabbits, ultimately leading to organ damage. Selenomethionine (SeMet), an organic selenium source recognized for its antioxidant properties and anti-inflammatory bioactivity, demonstrates protective benefits in animals through its detoxification mechanism and growth promotion. The present study investigated the protective effect of SeMet against ZEA-induced hepatic inflammation and elucidated its underlying mechanisms. Fifty healthy 90-day-old rabbits were randomly divided into five groups: control, ZEA-exposed and three SeMet-supplemented groups receiving 0.2, 0.35 or 0.5 mg/kg via dietary inclusion. After two weeks of SeMet pretreatment, ZEA administration (1.2 mg/kg B.W.) was imitated via oral gavage daily for one week in both the ZEA group and three SeMet-treated groups. As a result, ZEA exposure induced the significant structural disruption of the hepatic lobules, accompanied by increased collagen deposition, elevated pro-inflammatory cytokine profiles (IL-6, IL-1β, TNF-α) and reduced anti-inflammatory mediator levels (IL-10, TGF-β). SeMet supplementation alleviated ZEA-induced histological alterations, including inflammatory cell infiltration and collagen accumulation. Biochemical analysis indicated the restoration of inflammatory markers to near-normal levels when treated with SeMet. Notably, immunohistochemical results showed that SeMet significantly reduced the protein levels of IL-6 and its downstream target STAT3 under ZEA exposure. These findings indicated that SeMet attenuated ZEA-induced hepatic inflammation by modulating the IL-6/STAT3 signaling axis, with dietary supplementation of 0.35 mg/kg SeMet exhibiting the most significant effect on alleviating ZEA-induced hepatic inflammatory injury. Full article

Exercise suppresses appetite in individuals with obesity irrespective of the type, duration, or intensity of the exercise. This effect is mediated through various physiological and biochemical mechanisms. Exercise influences appetite-regulatory hormones such as ghrelin and leptin, reducing hunger signals. Additionally, exercise generates metabolites and myokines, along with hepatokines, which modulate appetite suppression. Brain-derived neurotrophic factor (BDNF) is also implicated in modulating appetite. Changes in eating behaviors, gastric motility, and gastric emptying further contribute to a reduced appetite. Mental stress and body temperature alterations during exercise can also impact hunger levels. This review synthesizes current evidence and provides specific biochemical, metabolic and molecular mechanisms of how exercise and obesity affect appetite regulation. More specifically, it is extensively discussed the effect of exercise and obesity on: (1) endocrine mediators (hepatokines, metabolites, myokines, and neurotrophins); (2) physiological modulators (gastric emptying and body temperature); and (3) behavioral influences (eating patterns and visual food cues) in association with appetite regulation. Collectively, these factors highlight the complex interplay between physical activity and appetite regulation, offering insights into potential therapeutic strategies for managing obesity through exercise. Full article

The Nuclear factor erythroid 2-related factor 2 (NRF2) Neurogenic locus NOTCH homolog protein (NOTCH) crosstalk has emerged as a critical regulatory axis in the progression of solid cancers, especially lung, affecting tumor growth and resistance to therapy. NRF2 is a master transcription factor that orchestrates the cellular antioxidant response, while NOTCH signaling is involved in the cell–cell communication processes by influencing the patterns of gene expression and differentiation. Although frequently altered independently, genetic and epigenetic dysregulation of both NRF2 and NOTCH pathways often converge to deregulate oxidative stress responses and promote tumor cell survival. Recent findings reveal that the NRF2/NOTCH interplay extends beyond canonical signaling, contributing to metabolic reprogramming and reshaping the tumor microenvironment (TME) to promote cancer malignancy. Emerging scientific evidences highlight the key role of biochemical and metabolomic changes within NRF2–NOTCH crosstalk, in contributing to cancer progression and metabolic reprogramming, beyond facilitating the adaptation of cancer cells to the TME. Actually, the effects of the NRF2–NOTCH bidirectional interaction in either supporting or suppressing lung tumor phenotypes are still unclear. This review explores the molecular mechanisms underlying NRF2–NOTCH crosstalk in lung cancer, highlighting the impact of genetic and epigenetic deregulation mechanisms on neoplastic processes, modulating the TME and driving the metabolic reprogramming. Furthermore, we discuss therapeutic opportunities for targeting this regulatory network, which may open new avenues for overcoming drug resistance and improving clinical outcomes in lung cancer. Full article

Objective: This study aimed to investigate the structural, vascular, and biochemical alterations in patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PXG) and to evaluate the associations between serum biomarkers, the retinal nerve fiber layer (RNFL), choroidal thickness (CT), and vessel density (VD) in these groups. Methods: All subjects underwent spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) to assess RNFL thickness, CT, and VD. Serum levels of inflammatory and oxidative stress biomarkers—including malondialdehyde (MDA), glutathione (GSH), interleukin-6 (IL-6), nitric oxide (NO), inducible NO synthase (iNOS), galectin-3, and SCUBE-1—were analyzed, and regression and ROC curve analyses were performed to evaluate predictive value and diagnostic performance. Results: A total of 80 patients were included and are listed as follows: 25 controls, 30 with PES, and 25 with PXG. There were no significant differences among groups in terms of age or gender. RNFL thickness, CT, and VD were significantly reduced in the PXG group compared to the PES and control groups (p < 0.001). PXG patients showed the most pronounced reductions in both peripapillary and macular CT, as well as superficial and deep VD. Serum iNOS, SCUBE-1, galectin-3, and MDA levels were significantly elevated in PXG, while GSH levels were lower (p < 0.001); NO levels showed no significant differences. In the PES and PXG groups, several ocular parameters correlated significantly with serum biomarkers, particularly iNOS, MDA, and GSH. Regression analysis in PXG patients identified iNOS and MDA as significant predictors of RNFL thickness and VD. ROC analysis demonstrated that MDA and GSH exhibited the highest diagnostic accuracy among the tested biomarkers for distinguishing PXG patients from controls. Conclusions: PXG is associated with significant structural, vascular, and biochemical alterations, including reduced RNFL thickness, choroidal thinning, and decreased VD. Altered serum levels of MDA and GSH were significantly associated with these ocular changes and demonstrated the highest diagnostic accuracy among the biomarkers evaluated. These findings support their potential utility as non-invasive biomarkers for distinguishing PXG from PES and healthy controls and for monitoring disease progression. Full article

Background/Objectives: Serum diagnostic tests for alopecia areata may be used to monitor response to treatment, aiding in the objective assessment of disease activity and helping to change treatment at an earlier point. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy offers a nondestructive and user-friendly approach for analyzing a wide range of samples. In this study, we evaluated whether ATR-FTIR spectroscopy combined with machine learning can detect alopecia areata and quantify disease activity. We also established whether patient-specific spectral differences correlate with response to therapy, offering molecular insight into treatment response. Methods: Serum samples from 42 patients with alopecia areata and 41 healthy donors were compared. Logistic regression models were developed to separate alopecia areata patients from controls and to monitor treatment response based on clinical scoring. Results: Significant spectral variations were found in the 3000–2800 cm⁻¹ and 1800–1000 cm⁻¹ regions corresponding to the principal biochemical constituents such as proteins, lipids, carbohydrates, and nucleic acids. The AUC of the logistic regression model for distinguishing alopecia areata patients from healthy controls was 0.85 (95% CI: 0.75–0.94) with a sensitivity of 0.89 and a specificity of 0.71. In terms of prediction of treatment response, the model showed discriminative potential (AUC = 0.86, 95% CI: 0.71–0.98), with distinct alterations in the spectrum, particularly in the Amide I band, associated with improvement in the patient’s condition. Conclusions: ATR-FTIR spectroscopy assisted by machine learning offers a serum-based solution for treatment monitoring in alopecia areata patients with clinical applicability. This technique has highly promising potential for the development of rapid, non-invasive, and objective biomarkers in autoimmune dermatology. Additional multi-center trials are required to validate and incorporate these spectral biomarkers into individual treatment regimens. Full article

Background/Objectives: Wheat gluten intolerance increases intestinal permeability, triggering inflammation that may directly affect liver function and compromise metabolic health. Methods: Male Wistar rats (n = 50) aged 21 days were divided into five groups (n = 10) based on dietary gluten levels over 100 days: G0 (0%), G14 (14%), G42 (42%), G70 (70%), and G70/0 (70% for the first 70 days, then 0% until euthanasia). At 121 days, the animals were weighed and euthanized, and blood samples were collected for biochemical analyses. Adipose tissue deposits and the liver were excised and weighed. Liver lobes were isolated and fixed for morphological and morphometric analysis of hepatocytes, tissue glycogen percentage, and intracellular lipid assessment. Results: The hepatic oxidative status was evaluated. The ingestion of diets with excess gluten (70%) increased final body mass and reduced liver mass, though it did not alter the adiposity index. Cholesterol, triglycerides, and myeloperoxidase enzyme activity exhibited distinct patterns across all groups. Conclusions: Elevated gluten levels increased oxidative stress and altered tissue hepatic morphology and morphometry. Full article

Background: Childhood obesity is a growing global health concern. Metabolomics, the comprehensive study of metabolites within biological systems, offers a powerful approach to better define the phenotype and understand the complex biochemical alterations associated with obesity. The aim of this systematic review was to summarize current knowledge in the field of metabolomics in childhood obesity and to identify metabolic signatures or biomarkers associated with overweight/obesity (Ov/Ob) and Metabolically Unhealthy Obesity (MUO) in children and adolescents. Methods: We performed a systematic search of Medline and Scopus databases according to PRISMA guidelines. We included only longitudinal prospective studies or randomized controlled trials with ≥12 months of follow-up, as well as meta-analyses of the above that assessed the relation between metabolic signatures related to obesity and Body Mass Index (BMI) or other measures of adiposity in children and adolescents aged 2–19 years with overweight or obesity. Initially, 595 records were identified from PubMed and 1565 from Scopus. After removing duplicates and screening for relevance, 157 reports were assessed for eligibility. From the additional search, 75 new records were retrieved, of which none were eligible for our study. Finally, 7 reports were included in the present systematic review (4 reporting on Ov/Ob and 4 on MUO). Results: The presented studies suggest that the metabolism of amino acids and lipids is primarily affected by childhood obesity. Metabolites like glycoprotein acetyls, the Apolipoprotein B/Apolipoprotein A-1 ratio, and lactate have emerged as potential biomarkers for insulin resistance and metabolic syndrome, highlighting their potential value in clinical applications. Conclusions: There is a need for future longitudinal studies to assess metabolic changes over time, interventional studies to evaluate the efficacy of therapeutic strategies, and large-scale population studies to explore metabolic diversity across different demographics. Our findings reveal specific biomarkers in the amino acid and lipid pathway that may serve as early indicators of childhood obesity and its associated cardiometabolic complications. Full article

This trial aimed to investigate the effects of compound essential oils (EO) on the fattening performance, blood physiological–biochemical indices, and intestinal microbiota in late-fattening Simmental crossbred bulls. Twenty healthy Simmental crossbred bulls (Simmental × Charolais × Angus) with similar initial body weights of 442 (±72.49) kg were randomly divided into two groups: a control group (basal diet, CON group) and a compound essential oil group (basal diet + 16 g/head/day, EO group). The trial included a 14-day pre-feeding period and a 42-day experimental period, totaling 56 days. The results showed the following: (1) The EO group exhibited a significantly higher average daily gain (ADG), immunoglobulin A (IgA), immunoglobulin G (IgG), total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX), glucose (GLU), dopamine (DA), basophil count (Baso), mean corpuscular hemoglobin (MCH), and platelet distribution width (PDW) compared to the CON group (p < 0.05), while the mean corpuscular volume (MCV) was significantly lower (p < 0.05). (2) Although the compound essential oil supplementation did not alter the relative abundance of major intestinal microbial taxa, it significantly improved the intestinal microbiota structure (p < 0.05), increased fiberdegrading microbiota, and promoted short-chain fatty acid production. (3) The relative abundance of the intestinal microbiota norank_f__UCG-010 showed significant positive correlations with ADG, GSH-PX, IgG, DA, T-SOD, GLU, IgA, and Baso (p < 0.05), while Christensenellaceae_R-7_group abundance was positively correlated with ADG, IgA, and Baso (p < 0.05). In conclusion, the compound essential oil enhances healthy and efficient fattening in beef cattle by improving the intestinal microbial structure, increasing beneficial bacteria, regulating the nutrient metabolism through key bacterial genera, and enhancing the immune function, antioxidant capacity, and energy metabolism levels. Full article

Radiotherapy (RT) is a treatment method commonly used in oncology. A vast majority of patients undergoing RT suffer from radiation-induced skin injury (RISI), which results from complex biochemical reactions in the irradiated skin. Current strategies for preventing and managing RISI are insufficient for achieving full skin regeneration. Multiple studies have shown that alterations in the skin microbiome correlate with the development and severity of RISI. These studies suggest that dysbiosis is a crucial factor in promoting radiation-associated dermatitis. Targeting the skin microbiota presents a potential therapeutic approach that could significantly improve the quality of life for patients undergoing RT. This review aims to present current findings on the interplay between the skin microbiome and radiation-induced skin damage as well as to discuss potential therapeutic strategies for preventing and mitigating this condition. Full article

Osteoarthritis (OA) is a chronic joint disorder characterized by progressive degeneration of articular cartilage, pain, synovial inflammation, and bone remodeling. Post-transcriptional RNA modifications, known as epitranscriptome, are a group of biochemical alterations in the primary RNA transcript that might influence RNA structure, stability, and function. Different kinds of RNA modifications have been recognized, such as methylation, acetylation, pseudouridylation, and phosphorylation. N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), 2′-O-ribose methylation (2′-O-Me), and pseudouridylation (Ψ) are the most prevalent RNA modifications. Recent studies have shown that disruption in these modifications can interfere with gene expression and protein function. Here, we will review all types of RNA modifications and how they contribute to the onset and progression of OA. To the best of our knowledge, this is the first review comprehensively addressing all epitranscriptomic modifications in OA. Full article

The widespread use of plastics has led to a substantial increase in plastic waste, resulting in the dissemination of plastic debris throughout ecosystems and posing significant threats to biota. Bis(2-ethylhexyl) phthalate (DEHP), a commonly used plasticizer, enhances plastic flexibility but may also exert subtle toxic effects. This study aimed to investigate the potential toxicological impacts and underlying mechanisms of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP), and their combined exposure (MPs + DEHP) on oxidative stress, apoptotic damage, transcriptomic alterations, and metabolic disturbances in mice. The results demonstrated that exposure to MPs, DEHP, and MPs + DEHP impaired the antioxidant defense system and reduced overall antioxidant capacity. Concurrently, all three exposure conditions significantly increased biochemical markers, particularly those associated with liver dysfunction, prompting further analysis of hepatic tissues. Histopathological examination revealed apoptotic damage in hepatocytes. Integrated transcriptomic and metabolomic analyses indicated that exposure to MPs, DEHP, and MPs + DEHP disrupted carbohydrate, amino acid, and lipid metabolism, induced the expression of genes related to hepatocarcinogenesis, and impaired purine metabolism. Moreover, MP and DEHP exposure aggravated hepatic apoptosis and inflammatory responses via activation of the PI3K/AKT signaling pathway, thereby eliciting notable biotoxic effects. These findings provide new scientific evidence regarding the individual and combined toxicological effects of MPs and the plastic additive DEHP on living organisms. Full article

Nanoplastics (NPs) pose a significant environmental threat due to their small sizes, widespread distribution, and bioavailability, enabling interactions with marine organisms from pelagic to benthic species. In this study, the effects of 10 days of exposure to waterborne poly(methyl)methacrylate (PMMA) NPs were evaluated in the crab Carcinus maenas by assessing behavioral and biochemical endpoints (in gills, hepatopancreas, muscle, and hemolymph). Behavioral assessments using an open field test revealed that exposure to PMMA NPs resulted in an increase in distance walked (from 73.662 ± 17.137 cm in control to 248.560 ± 25.462 cm in the highest PMMA NPs concentration) and in random movement patterns. Muscle acetylcholinesterase (AChE) activity decreased from 10.83 ± 0.73 to 6.75 ± 0.45 nmol/min/mg of protein with PMMA NPs concentration increase, which, combined with behavioral responses, suggests neurological incapacities. In the gills and hepatopancreas, defense and detoxification mechanisms were activated, with a significant increase in superoxide dismutase (SOD) activity (at 20 µg/L in gills and 80 µg/L in hepatopancreas) and glutathione S-transferases (GSTs) activity (all PMMA NPs concentrations in gills and 20 and 320 µg/L in hepatopancreas). Despite these activations, oxidative damage was observed, with a significant increase in protein carbonylation (PC) levels (20, 80, and 320 µg/L in gills and 5, 20, and 80 µg/L in hepatopancreas) and lipid peroxidation (LPO) (80 and 320 µg/L in gills and 80 µg/L in hepatopancreas). Effects on hemolymph followed a pattern similar to those reported for gills and hepatopancreas. An increase in SOD hemolymph activity was observed in organisms exposed to 5 and 80 µg/L, and GSTs activity increased in crabs exposed to 80 µg/L. Oxidative damage in hemolymph was only detected through LPO at 5 and 320 µg/L. Overall, this study showed that PMMA NPs induce biochemical alterations and damage in different tissues of C. maenas and affect its behavior with potential impacts at a population level. Full article