Search Results (5,229)

Cisplatin is an effective chemotherapeutic agent, yet its clinical utility is limited by dose-dependent nephrotoxicity. Alpha-1 antitrypsin (AAT) has cytoprotective, anti-inflammatory, and antiapoptotic properties, but its therapeutic potential in cisplatin-induced acute kidney injury (AKI) remains unclear. A murine cisplatin–AKI model was used to evaluate whether AAT (80 mg/kg) ameliorates renal injury. Renal function, oxidative stress, NADPH oxidase (NOX) isoforms, mitochondrial metabolism, inflammatory mediators, apoptosis, and fibrosis-related markers were assessed using biochemical, histological, immunohistochemical, and Western blot analyses. Cisplatin markedly impaired renal function and induced tubular injury; meanwhile, AAT significantly reversed these changes. Cisplatin also induced severe oxidative stress and disrupted the balance of NOX isoforms; AAT restored redox homeostasis. Cisplatin upregulated CPT1A/PDK4 and suppressed CPT2, UCP3, PGC1α, and DRP1, inducing maladaptive mitochondrial changes, indicating impaired β-oxidation and defective mitochondrial dynamics; AAT reversed these alterations, restoring normal mitochondrial metabolism. IL-1β, IL-6R, OPN, and F4/80 expression, recovery of the Bax/Bcl-2 ratio, and MAPK activation were reduced, indicating decreased inflammation and apoptosis; profibrotic markers were also reduced. AAT confers multifaceted protection against cisplatin-induced AKI by restoring redox balance, mitochondrial homeostasis, and inflammatory and apoptotic signaling. These findings support AAT as a promising therapeutic agent for preventing cisplatin nephrotoxicity. Full article

The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually mature primiparous Hu sheep meeting the mating criteria were randomly assigned to two groups. The control group was fed a basal diet, while the NCG group received the basal diet supplemented with 0.11% NCG, with both feeding regimens maintained for 90 days. By measuring uterine and fetal growth indices, maternal plasma biochemical parameters, and amino acid levels, as well as assessing cotyledon indices and observing cotyledon morphology and histological structure, basic data related to placental function and fetal growth in pregnant ewes was collected. Combined with transcriptomic sequencing of maternal placental tissue, the mechanism by which NCG influences placental function and fetal growth and development in pregnant ewes was further investigated. The supplementation of NCG could increase the number of fetuses, total weight of fetuses, the number of corpus luteum and the ratio of fetuses to corpus luteum, but the difference was not significant (p > 0.05). The levels of plasma NO, inducible Nitric Oxide Synthase (iNOS) and several amino acids were significantly increased (p < 0.05). In ewes’ uteri, the average uterine weight, number of uterine glands, total cotyledon weight, and average weight per cotyledon were significantly increased (p < 0.05), whereas uterine mucosal thickness was markedly decreased. The Quantitative Real-time PCR (q-PCR) results for differentially expressed genes were consistent with those of transcriptomic analysis, showing significant changes in the expression levels of certain differentially expressed genes in maternal placental tissues. These changes regulated pathways such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) signaling pathways and Mitogen-Activated Protein Kinase (MAPK) pathway, which are involved in angiogenesis, energy supply and metabolism, and somatic growth and development. Dietary supplementation with NCG during early pregnancy can significantly improve the reproductive performance of primiparous Hu sheep, optimize the intrauterine environment and nutrient supply, and thereby facilitate pregnancy maintenance and fetal development. The underlying mechanism may involve promoting endogenous arginine synthesis in ewes, increasing plasma levels of NO, arginine, and certain amino acids, which collectively validate the positive effects of NCG on the reproductive performance and growth of Hu sheep during early pregnancy at the molecular level. Full article

Parkinson’s disease (PD) is a heterogeneous neurodegenerative disorder in which oxidative stress represents a final common pathway linking diverse genetic and environmental insults to dopaminergic neuron loss. This review synthesizes evidence on how the commonly observed pathological changes in PD converge on excessive reactive oxygen species generation and redox imbalance. We present an overview on these pathways and key PD-linked genes that perturb mitochondrial quality control, lysosomal function, and inflammatory signaling, reinforcing oxidative stress. The major classes of redox-targeted therapeutic strategies under preclinical and clinical evaluation are outlined. Although many candidates show robust target engagement and neuroprotection in models, clinical trials have frequently yielded neutral or modest results, highlighting challenges related to brain delivery, off-target effects, optimal treatment window, and the fact that oxidative stress alone may be necessary but not sufficient to drive human disease progression. In the current paper, beyond cataloguing oxidative pathways, we explain the role of etiologic heterogeneity on biochemical target engagement and clinical outcomes. We outline subtype-enriched trial strategies and rational combination approaches. Targeting oxidative stress–related pathways thus remains a promising avenue for disease modification in PD, provided that future interventions are mechanistically informed and adapted to patient-specific redox vulnerabilities. Full article

Carotenoids accumulate in both the skin and the macula, but their biochemical specificity, anatomical localization, optical environments, and temporal kinetics differ fundamentally. Despite superficial similarities, these distinctions raise questions about whether non-invasive skin carotenoid measurements, which are obtained using reflection spectroscopy or resonance Raman spectroscopy, can meaningfully reflect macular pigment optical density (MPOD), a retina-specific biomarker associated with visual performance and neuroprotective function. This review synthesizes evidence across biochemistry, tissue distribution, optical pathways, kinetic behavior, and statistical correlations to evaluate this proposed relationship. Skin carotenoid measurements capture a broad mixture of dietary carotenoids, which are dominated by β-carotene and lycopene, that accumulate superficially within the epidermis and dermis and respond rapidly to short-term dietary and environmental changes. In contrast, MPOD reflects only lutein, zeaxanthin, and meso-zeaxanthin, which are selectively transported into the foveal neurosensory retina and change slowly through regulated retinal uptake and deposition. Across human studies, correlations between skin carotenoids and MPOD are weak, inconsistent, and biologically implausible, with large cohort analyses demonstrating near-zero associations. Collectively, evidence across biochemical, anatomical, optical, physiological, and statistical domains shows that skin carotenoid values encode general systemic antioxidant exposure, whereas MPOD reflects a highly localized, retina-specific carotenoid reservoir. Therefore, skin carotenoid measurements cannot be used to estimate, substitute for, or infer macular pigment levels. Accurate assessment of MPOD requires direct retinal imaging technologies. Full article

Feeding systems are key factors shaping the biochemical and bioactive composition of camel milk, yet their impact on the milk fat globule membrane (MFGM) remains insufficiently understood. This study employed 2D-DIGE MALDI mass spectrometry-based proteomics to compare the MFGM protein profiles of milk obtained from desert-fed camels (DFCs) (n = 5) and farm-fed camels (FFCs) (n = 5), of the Waddah breed. The proteomic analysis revealed statistically significant changes in abundance (ANOVA p ≤ 0.05; fold change ≥ 1.5) in 40 proteins between the two groups. Nine proteins were upregulated and thirty-one proteins were downregulated in the DFCs compared to the FFCs. The DFC group showed a statistically significant increase in proteins including erythropoietin, keratin isoforms, COX16, and αS2-casein, while levels of Lactotransferrin, Lactadherin, Toll-like receptor 2, and superoxide dismutase among others were decreased. Increased abundance of proteins seen in the MFGM component of the DFC group is probably associated with stress adaptation related to desert feeding. Our findings from this pilot study provide proof-of-concept that the composition of proteins in the MFGM fraction varies according to feeding environment and practices. Farm feeding improved the bioactive protein content, whereas DFC milk contained higher levels of proteins related to stress adaptation. These insights have important implications and should be further evaluated in larger cohorts. Full article

Background: Hemodialysis (HD) patients frequently develop muscle wasting and chronic inflammation, conditions associated with functional decline and reduced quality of life (QoL). Nutritional strategies that provide targeted anabolic support without increasing nitrogen load may offer clinical benefits. The aim of this study was to evaluate the possible impact of a food for special medical purposes (FFSMP), composed of free-form branched-chain amino acids, β-hydroxy-β-methylbutyrate, and zinc, on muscle mass and strength, laboratory parameters, physical performance (PP), and QoL in HD patients. Methods: in this randomized double-blind crossover study, 24 adult HD patients received the FFSMP (10 g/day; two sachets) supplementation or placebo for 12 weeks, separated by an 8-week wash-out (protocol code RS 29.23). Measured outcomes included quadriceps rectus femoris thickness (QRFT) muscle, body composition analysis, inflammatory markers, oxidative stress indices, other routine biochemical parameters, PP, and QoL (SF-36 questionnaire). Results: FFSMP supplementation resulted in significant increases in QRFT and in fat-free mass percentage. Reductions in oxidative stress and inflammatory biomarkers were observed. Routine biochemical parameters remained stable, with the exception of a decrease in pre-dialysis urea. Functional performance measures did not differ between treatment periods. Improvements were noted in selected SF-36 domains, specifically energy/fatigue and general health. No major adverse events occurred during the study. Conclusions: In HD patients, this FFSMP produced favorable changes in markers of muscle mass and systemic inflammation without affecting short-term physical performance. These findings support the potential clinical utility of targeted amino acid supplementation in this patient population, highlighting the need for larger, longer-term trials. Full article

Drought is the primary stress factor in semiarid environments. Consequently, selecting plant genetic resources capable of tolerating temporary periods of water scarcity, such as Physalis angulata, becomes essential. This study aimed to identify P. angulata accessions with potential for use under water deficit conditions by evaluating plant water status and physiological and biochemical responses. Five accessions, including two from Bahia (BA1 and BA2), Pará-PA, Rio de Janeiro-RJ, and Piauí-PI, were grown under well-watered and water deficit conditions. Relative water content, gas exchange parameters, and organic solute accumulation were assessed. All accessions exhibited changes in plant water status and reductions in CO₂ assimilation, stomatal conductance, and leaf transpiration under water deficit. The accumulation of compatible solutes varied among accessions, with notable contrasts between Bahia accession 2 and Pará accession, particularly for total soluble sugars and reducing sugars. These findings highlight the complexity of the species and the distinct mechanisms underlying its response to limited water availability. Overall, gas exchange was the trait most sensitive to water restriction, followed by alterations in biochemical attributes. Therefore, the Physalis angulata accessions from Bahia accession 2 and Pará accession show potential for use under water-deficit conditions and could provide valuable insights, particularly through transcriptome analysis. Full article

Advancements in phenotyping technologies, including object imaging, high-throughput monitoring, and soft computing, are pivotal for understanding plant responses to environmental stresses. These technologies enable detailed analyses of morphological, physiological, and structural adaptations under abiotic and biotic stresses, such as drought. Current work using multimodal and multi-perspective image processing methods can capture the essential processes that enhance plant resilience and counteract stress by identifying morphological and biochemical indicators. However, the dynamic and complex nature of plant responses poses multiple challenges for generating precise analytics and descriptors of evolving phenotypes. This work introduces analytics for concurrent imaging, adopting the underlying principle of cosegmentation to create taxonomies for new phenotypes. Here, unidimensional refers to the concurrent analysis of multiple images within a single phenotyping dimension: temporal, modal, or perspective, rather than combining information across dimensions. The proposed unidimensional phenotypes integrate concurrent images within individual temporal, modal, or perspective dimensions to capture dynamic morphological and physiological responses that are not observable with conventional single-image or cumulative metrics. Within a high-throughput imagery production system, these phenotypes enable more nuanced quantification of phenotypic changes, leveraging the strengths of simultaneous image analysis to enhance insight into plant adaptations. This workflow aligns with the investigation of plants’ adaptive strategies under abiotic stress and provides quantitative indicators of plant health under adverse environmental conditions. Full article

Neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) share key molecular features, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and progressive neuronal loss. Increasing evidence indicates that gut dysbiosis and alterations in microbiota-derived metabolites are involved in these processes through multiple pathways along the gut–brain axis. However, while broad compositional changes are well-documented, a critical knowledge gap remains regarding the specific biochemical signal transduction pathways translating dysbiosis into pathology. This narrative review addresses this gap by synthesizing current human and experimental studies addressing gut microbiota alterations in AD, PD, and ALS, with particular emphasis on the biochemical and molecular mechanisms mediated by gut-derived metabolites. Dysbiosis in neurodegenerative diseases is frequently associated with reduced abundance of short-chain fatty acid (SCFA)-producing bacteria and altered metabolism of SCFAs, bile acids, tryptophan-derived indoles, trimethylamine-N-oxide (TMAO), and lipopolysaccharides (LPS). These microbial metabolites have been shown to modulate intestinal and blood–brain barrier integrity, influence Toll-like receptor- and G protein-coupled receptor-dependent signaling, regulate microglial activation, and affect molecular pathways related to protein aggregation in experimental models. In addition, emerging evidence highlights the involvement of oxidative and nitrosative stress, immune–metabolic crosstalk, and altered xenobiotic metabolism in microbiota–host interactions during neurodegeneration. By integrating microbiological, metabolic, and molecular perspectives, this review underscores the important and emerging role of microbiota-derived molecules in neurodegenerative disorders and outlines key chemical and metabolic pathways that may represent targets for future mechanistic studies and therapeutic strategies. Full article

This study adopts a biochemical approach to sequester CO₂ while producing biomass rich in protein and lipids, using an adapted strain of Chlorella vulgaris (ALE-Cv), which had previously evolved to tolerate a gas mixture containing 10% CO₂ and 90% air. The research studied the operating parameters of the batch photobioreactor for ALE-Cv to evaluate the effects of inoculum size, photoperiod, light intensity, pH of culture, and CO₂ supply rate on biomass productivity and CO₂ bio-fixation rate. The optimal conditions were identified as 16:8 h light–dark cycles, 5000 lux, pH 7, 20 mL of 10 g/L inoculum, and 0.6 VVM; the system achieved a maximum total biomass production of 7.03 ± 0.21 g/L with a specific growth rate of 0.712 day⁻¹, corresponding to a CO₂ bio-fixation of 13.4 ± 0.45 g/L in batch cultivation. While the pre-adapted strain of Chlorella vulgaris under the same operating conditions, except for the gas supply, which was air, achieved a maximum total biomass production of 0.52 ± 0.008 g/L, and the total CO₂ bio-fixation was 1.036 ± 0.021 g/L during 7-day cultivation. A novel semi-continuous harvesting process, with and without nutrient addition, was also investigated to maximise biomass yield and enable water recycling for culture media. The maximum biomass production in semi-continuous harvesting process with and without nutrition added was 5.29 ± 0.09 and 9.91 ± 0.11 g/L, while the total corresponding CO₂ bio-fixation was 9.70 ± 0.13 and 18.16 ± 0.11 g/L, respectively, during 15-day cultivation. The findings provide critical insights into enhancing CO₂ bio-fixation through adaptive evolution of ALE-Cv and offer optimal operational parameters for future large-scale microalgae cultivation. This research also links microalgae-based CO₂ sequestration to green technologies and the bioeconomy, highlighting its potential contribution to climate change mitigation while supporting environmental sustainability, food security, and ecosystem resilience. Full article

Objectives: The study explores the comparative effects of atorvastatin (ATV), policosanol (PCO), and their combination (ATV+PCO) on metabolic stress and associated organ damage in hyperlipidemic–hyperglycemic zebrafish. Methodology: Hyperlipidemic–hyperglycemic zebrafish (n = 112) were segregated into four groups (n = 28/group) and fed either with a high-cholesterol (HC, 4% w/w) and a high-galactose (HG, 30% w/w) diet, HCHG diet with policosanol (PCO, 0.1% w/w), atorvastatin (ATV, 0.1% w/w), or ATV+PCO (0.1% w/w each). After 12 weeks of supplementation, survivability and embryo production were assessed, along with biochemical and histological examinations of various organs across the groups. Results: Following a 12-week dietary regime, compromised zebrafish survival probability (0.75) was observed in the ATV group, compared to the PCO group (0.89), which increased to 0.82 with combined intake of ATV+PCO. A significantly greater effect of ATV than PCO was observed in reducing the HCHG elevated TC, TG, and LDL-C levels. However, compared to the ATV, a significantly higher HDL-C/TC (%) ratio was spotted in the PCO. Unlike individual supplementation (ATV or PCO), a combined intake (ATV+PCO) proved highly effective in counteracting dyslipidemia, especially by augmenting the HDL-C/TC (%) ratio. Interestingly, no protective effect of ATV was observed against elevated blood glucose levels, oxidative stress, or diminished antioxidant markers. Whereas ATV, in combination with PCO, significantly reduced blood glucose and MDA levels and elevated sulfhydryl content and antioxidant variables (ferric iron reduction ability and paraoxonase activity). ATV+PCO supplementation effectively mitigated HCHG-induced fatty liver, inflammation, ROS generation in the kidney, and brain senescence. Likewise, ATV+PCO improved reproductive health, elevating spermatozoa counts and embryo production ability of zebrafish. Notably, ATV+PCO supplementation significantly inhibited the HCHG-induced eye damage and demyelination in the retina, while ATV alone failed to establish any such changes. Conclusions: The study indicates the combinational therapy of ATV+PCO may offer a possible treatment to counter the metabolic stress and associated events in hyperlipidemic–hyperglycemic zebrafish. Full article

Soil-borne oomycetes, such as Phytophthora and Pythium species, are highly destructive pathogens responsible for severe diseases in crops, ornamentals, and natural ecosystems. These pathogens can persist in soil for many years, making them particularly difficult to control. To establish infection, they deploy a diverse arsenal of effector proteins that manipulate host immune responses, disrupt vital cellular functions, and may influence the rhizosphere microbiome to facilitate successful colonization. Phytophthora relies heavily on RxLR effectors to disrupt intracellular immunity, while Pythium species predominantly deploy necrosis-inducing NLPs and cell wall-degrading enzymes, with no confirmed canonical RxLR effectors, suggesting distinct evolutionary strategies. This review aims to explore the detailed mechanisms of plant-pathogen interaction. In recent years, significant progress has been made in understanding the molecular dialogue between pathogens and their hosts, particularly how pathogenic species such as Phytophthora and Pythium manipulate plant immunity through effector secretion, and how plants counteract by activating defense mechanisms at molecular, cellular, and biochemical levels, including changes in hormone signaling, reactive oxygen species (ROS) dynamics, and defense gene expression. The review also outlines emerging disease management strategies and integrative approaches guided by effector biology and microbiome insights. Full article

Background: Trail running (TR) is an endurance discipline characterized by prolonged exercise, irregular terrain, and marked elevation changes, which increase eccentric muscular load and may induce muscular, neuromuscular, and cardiac damage. Objective: This study aimed to systematically review the evidence on muscular, neuromuscular, and cardiac damage associated with TR participation. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251135043). Five databases (PubMed, Web of Science, Scopus, SportDiscus, and ScienceDirect) were searched up to 31 August 2025. Observational, longitudinal, prospective, and case studies involving healthy adolescent or adult trail runners were included. Outcomes comprised muscle damage biomarkers (e.g., creatine kinase, alanine aminotransferase), neuromuscular function (e.g., squat jump performance, maximal voluntary isometric contraction), and cardiac biomarkers (e.g., CK-MB, cardiac troponins, NT-proBNP). Methodological quality was assessed using the National Heart, Lung, and Blood Institute Study Quality Assessment Tool. Results were synthesized qualitatively. Results: Fifteen studies met the inclusion criteria, including a total of 247 participants. Post-race analyses consistently showed marked increases in muscle damage biomarkers and significant reductions in neuromuscular performance. Transient elevations in cardiac biomarkers were also observed, suggesting acute but reversible cardiac stress following TR events. Limitations: Evidence was limited by methodological heterogeneity, small sample sizes, and underrepresentation of female athletes. Conclusions: It was found that trail running induces substantial acute muscular, neuromuscular, and cardiac stress, particularly in events with high eccentric loading. Monitoring biochemical and neuromuscular markers may support training load optimization, recovery strategies, and injury prevention. Full article

Climate change affects surface water quality parameters, including river quality. This study analyses changes in climate parameters, specifically air temperature and solar radiation, and their impact on river water temperature. It also examines how changes in river water temperature and organic matter load affect oxygen saturation levels, a key indicator of river water quality. Using water quality data, the status as well as temporal and spatial trends of the analysed parameters were assessed for the period between 2007 and 2024 on the three largest Slovenian rivers: the Drava, Mura, and Sava. Relative importance analysis of temperature and biochemical oxygen demand (BOD) using the Random Forest machine learning method showed that water temperature in the analysed rivers has an impact ranging from 51% to 66% on predicting oxygen saturation. The selected approach to analysing watercourse quality parameters enables the assessment of the impact of these parameters on river water quality. Based on these results, it will be possible to implement appropriate measures promptly to achieve sustainable river management by establishing a strategy that, under climate change conditions, safeguards water quality and maintains ecosystem protection, ensuring long-term ecological and socio-economic benefits. Full article

Objective: This double-blind, parallel-group randomized controlled trial is the first to investigate the synergistic effects of interval resistance plus progressive aerobic training with fisetin supplementation on adipokines in obesity. Methods: Sixty sedentary men with obesity (BMI < 30 kg/m²) completed 12 weeks of thrice-weekly interval resistance training (eight exercises, 3 × 13 reps at 60% 1RM with 20% 1RM active rest), immediately followed by staged aerobic bouts (50–70% HRmax). Participants were randomized into the control-placebo (P), fisetin (F; 200 mg/day), training-placebo (TP), or training + fisetin (TF) groups. The primary outcomes were asprosin, MCP-1, and adiponectin; secondary outcomes included leptin and lipid profile. Data were analyzed via ANCOVA with Bonferroni post hoc tests. Results: Statistical analyses were conducted following the intention-to-treat (ITT) principle using an analysis of covariance (ANCOVA) model, which revealed extensive effects of the interventions on the participants’ anthropometric and biochemical indices. Regarding body composition, after adjusting for baseline values, a significant difference in mean body weight was observed between groups (F (3, 55) = 9.444, p < 0.001, ηp² = 0.340); Bonferroni post hoc tests confirmed that the training plus fisetin (TF), training-placebo (TP), and fisetin (F) groups all achieved significant weight loss compared to the placebo (P) group. Furthermore, body mass index (BMI) showed a significant inter-group difference (p = 0.021), with post hoc analysis revealing that only the TF group reached a statistically significant reduction compared to the placebo (p = 0.024; 95% CI [−3.760, −0.172]). In the assessment of biochemical and inflammatory variables, the interventions exerted a highly significant effect on asprosin (F (3, 55) = 36.047, p < 0.001; ηp² = 0.663) and MCP-1 (F (3, 55) = 29.570, p < 0.001; ηp² = 0.617). The findings indicated that the TF group experienced the most substantial reductions in both asprosin (−60.71%) and MCP-1 (−46.50%) levels. Regarding adipokines, significant increases in adiponectin levels were observed in the TP (29.38%) and TF (27.67%) groups (p < 0.05), whereas changes in leptin were statistically significant only in the TF group relative to the placebo (p = 0.049). The lipid profile results indicated a statistically significant difference in the TF group in improving all markers; this group achieved greater reduction compared to other groups, including reductions in LDL-C, triglycerides (TG), and total cholesterol (TC) (p < 0.001), while simultaneously showing a significant elevation in HDL-C. Post hoc analyses confirmed robust statistical differences in all lipid parameters for both the TF and TP groups compared to the placebo group (p < 0.05), whereas the placebo group experienced a deterioration in status characterized by a significant increase in LDL-C (p = 0.027) and a significant decline in HDL-C concentrations (p = 0.006). Conclusions: In conclusion, 12 weeks of combined interval resistance–aerobic training and fisetin supplementation significantly reduced pro-inflammatory adipokines and improved lipid profiles in obese men. These findings suggest that asprosin serves as a potential modulator in metabolic risk reduction; however, since direct mechanistic assays were not conducted, these implications remain hypothetical. Future research employing molecular readouts is warranted to confirm the underlying pathways involved. Full article