Search Results (30,064)

Peripheral nerve injury is a leading cause of disability, which can result in partial or complete loss of motor, sensory, and autonomic function, and currently, there is no effective treatment for this incapacitating condition. It is important to identify new compounds that enable rapid and complete functional recovery. This study evaluated the effects of isorhamnetin (ISO) on functional rehabilitation in a mouse model of sciatic nerve injury. A total of 30 BALB/c mice, aged 8–10 weeks, were randomly assigned to three groups: sham, control, and treatment (n = 10/group). The mice in the ISO and Ctrl groups were operated on, whilst the animals in the sham group had their sciatic nerves exposed but left intact without crushing. The Ctrl and Sham groups received DMSO and normal saline intraperitoneally in equal volumes. In contrast, the ISO-treated group received ISO (10 mg/kg) dissolved in DMSO intraperitoneally from the day of nerve crush until the end of the study. All groups were fed regular chow and provided with sufficient water throughout the experiment. Behavioural analyses evaluated sensorimotor function recovery. Biochemical and haematological assays quantified oxidative stress markers and total blood count, while morphometric analysis determined structural recovery of muscle fibers. Nerve regeneration was indirectly evaluated by analyzing S100β protein levels and proinflammatory cytokines (IL-6 and TNF-α) expression. In the mouse model, ISO treatment resulted in substantial improvement in sensorimotor function recovery (p < 0.001). A substantial difference (p < 0.001) in blood glucose levels and oxidative stress markers was observed among all groups. The treated group displayed a remarkable improvement in the cross-sectional area of muscle fibers. At the end of the study, it was noted that ISO treatment significantly downregulated the expression of S100β, TNF-α, and IL-6, suggesting a positive impact of ISO on nerve regeneration. These findings indicate that ISO expedites the restoration of sensorimotor function following sciatic nerve injury by modulating S100β and proinflammatory cytokine expression and improving oxidative stress. Full article

Background: Primary biliary cholangitis (PBC) is a rare autoimmune liver disease characterized by marked clinical and serological heterogeneity. Although diagnosis is mainly based on antimitochondrial antibodies (AMAs) and alkaline phosphatase (ALP), non-classical presentations remain a relevant cause of diagnostic delay. In this context, laboratory medicine plays a pivotal role in both diagnosis and long-term disease management. Methods: This manuscript represents a structured clinical review of laboratory biomarkers relevant to the diagnosis, monitoring, and prognostic stratification of PBC, integrated with a representative atypical case with long-term follow-up to illustrate the practical application of laboratory-driven diagnostic. Results: The analysis confirms the central role of immunological and biochemical markers in treatment monitoring and prognostic assessment, while highlighting their limitations in selected clinical scenarios. The reported case, characterized by persistent AMA negativity and consistently normal ALP levels, illustrates how expanded laboratory testing can support the identification of non-standard disease phenotypes. In this setting, parallel testing for AMA- and PBC-specific autoantibodies was essential to achieve a correct diagnosis. Moreover, alternative biomarkers, including gamma-glutamyl transferase (GGT) and selected immunological markers, provided clinically meaningful information when conventional markers were not informative. Conclusions: By integrating current evidence with a long-term clinical case, this work moves beyond a descriptive overview and proposes a practical, laboratory-driven diagnostic and follow-up framework for PBC. It highlights laboratory opportunities to facilitate timely diagnosis, appropriate prognostic stratification, and disease monitoring, including the assessment of associated comorbidities. Full article

Background: Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype–phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study aimed to define the GCDH variant spectrum in GA1 patients with mild hepatopathy and assess genotype–phenotype correlations. Methods: We performed integrated clinical, biochemical, and molecular characterization of 15 unrelated patients with infantile-onset GA1. Whole-exome sequencing (WES) was performed for all participants, and the resulting data were compared with the reference sequence of the GCDH gene. Results: All patients presented within the first 6 months of life with macrocephaly, seizures, dystonia, and feeding difficulties. Neurological impairment and mild hepatopathy were variably observed, and one patient developed an acute encephalopathic crisis. Six homozygous GCDH variants were identified, predominantly missense. A common variant, c.541G>C (p.Glu181Gln), accounted for 73.3% of cases and defined a consistent phenotype of early macrocephaly and movement disorder with frequent mild hepatic involvement, suggesting regional enrichment and raising the possibility of a founder effect that warrants confirmation in future haplotype studies. A truncating variant, c.382C>T (p.Arg128Ter), was associated with severe early encephalopathy. Exon 6 represented a mutational hotspot. Biochemically, all patients showed elevated urinary glutaric and 3-hydroxyglutaric acids, increased glutarylcarnitine, and low-to-normal free carnitine, with higher metabolite levels in clinically more severe cases. All variants were pathogenic or likely pathogenic and extremely rare in population databases. Conclusions: This cohort reveals a striking predominance of the GCDH c.541G>C variant and establishes a clear biochemical signature with genotype-associated clinical patterns in infantile-onset GA1. These findings support a population-specific mutational spectrum, refine genotype–phenotype correlations, and underscore the importance of early molecular diagnosis to guide targeted neurological and hepatic monitoring as well as regional screening strategies. Full article

Nephrocalcinosis, defined as the deposition of calcium salts within the renal parenchyma, represents a radiologic and pathologic endpoint shared by a broad spectrum of metabolic and monogenic disorders. Advances in genomic medicine have identified more than 30 genes involved in tubular transport, mineral and acid–base homeostasis, oxalate metabolism, mitochondrial function, ciliary signaling, and nephron development, reframing nephrocalcinosis as a heterogeneous manifestation of discrete molecular defects rather than a single disease entity. Despite this diversity, these conditions converge on common physicochemical pathways of tubular supersaturation, crystal nucleation, growth, and intrarenal retention. These processes are amplified by the intrinsic vulnerability of the renal medulla—characterized by hyperosmolality, hypoxia, and slow tubular flow—and by epithelial injury, loss of crystallization inhibitors, and impaired ciliary signaling. Distinct genotype–phenotype signatures, including age at onset, biochemical profiles, and extrarenal manifestations, provide important diagnostic clues and help differentiate major monogenic entities. The increasing availability of targeted gene panels, whole-exome sequencing, and whole-genome sequencing has substantially improved diagnostic yield, particularly in pediatric populations. Molecular diagnosis now directly informs therapeutic decision-making and long-term management, enabling a shift toward precision nephrology. This narrative review integrates genetic, mechanistic, and clinical perspectives to illustrate how molecular diagnosis reshapes the evaluation, prognosis, and treatment of nephrocalcinosis. Full article

Background/Objectives: Developing novel strategies to combat respiratory infections caused by multidrug-resistant “priority pathogens” like the ESKAPEE Pseudomonas aeruginosa and Staphylococcus aureus is an urgent priority. Methods: We investigated two shortened variants of the proline-rich antimicrobial peptide (PrAMP) B7-005, B7-006 (15-mer) and B7-007 (13-mer). Evaluation included MIC assays against laboratory and clinical multidrug-resistant isolates, mechanistic studies of membrane permeabilization, cytotoxicity testing on BEAS-2B bronchial epithelial cells, and proteolytic stability assays in human elastase and sputum. Results: Despite their reduced size, lower positive charge, and decreased proline content, both variants retained full antimicrobial activity against clinical pathogens with consistent MIC values ≤ 25 µM. These variants exhibit membrane permeabilization in P. aeruginosa but may also relay on a hybrid mode of action involving also intracellular targets. Notably, B7-006 and B7-007 displayed low cytotoxicity compared to the lytic peptide BMAP-18. While B7-007 showed greater susceptibility to proteolytic degradation than its parent B7-005, it preserved partial integrity during the initial hours of exposure. Conclusions: Overall, these findings demonstrate that the B7 scaffold tolerates substantial truncation while preserving potency and selectivity, identifying a minimal 13-amino-acid active core. This work provides critical insights into structure–activity relationships and supports the development of compact, mechanistically versatile antimicrobial peptides to address the growing threat of multidrug-resistant respiratory pathogens. Full article

Kynurenic acid (KYNA), a metabolite of the L-kynurenine pathway of L-tryptophan degradation, is an endogenous blocker of glutamate ionotropic excitatory amino acid (EAA) receptors and nicotinic acetylcholine receptors (nAChRs). KYNA plays a significant role in various neuropsychiatric disorders and the aging process. Some researchers have suggested that KYNA may contribute to memory impairment. In this study, we examined the impact of L-kynurenine (a KYNA substrate) and the anti-dementia drugs D-cycloserine and Cerebrolysin on kynurenine aminotransferase (KAT) activity, an enzyme forming KYNA, in liver homogenates of Helix pomatia snails. Furthermore, a memory model was established using these snails, wherein tentacle shortening served as an indicator of learning activity. In vitro experiments on Helix pomatia demonstrated the significant impact of L-kynurenine and anti-dementia drugs on KYNA synthesis. KYNA levels increased significantly in the presence of L-kynurenine in liver homogenate. However, KYNA formation decreased when anti-dementia drugs, including Cerebrolysin or D-cycloserine, were administered to the snails’ liver homogenate. L-kynurenine has been shown to impair the learning process in vivo in snails, but an anti-dementia drug has been demonstrated to reverse this effect. Significant inhibition of tentacle lowering was observed in response to L-kynurenine treatment, which corresponded with elevated KYNA levels in the central nervous system. Administering D-cycloserine or Cerebrolysin alongside L-kynurenine reversed its effects. The Helix pomatia memory model is a valuable tool for studying learning and memory formation in various conditions and in the presence of different pharmacological agents. A drug or natural extract that blocks KYNA synthesis has the ability to increase tentacle lowering and could be considered an anti-dementia agent. Furthermore, this metabolite may also protect against aging and delay damage to the central nervous system related to memory. Full article

Photoacoustic imaging (PAI) is an emerging hybrid biomedical imaging modality that combines the high molecular contrast of optical excitation with the deep tissue penetration of ultrasound detection. This review presents recent advances in PAI-based techniques for the detection and characterization of gynecological diseases in women, with particular focus on endometriosis and uterine-related disorders. We summarize the application of PAI across preclinical and translational studies, highlighting progress in photoacoustic microscopy, spectroscopic photoacoustic imaging, and endoscopic and probe-based implementations for non-invasive, high-resolution tissue evaluation. The role of functional and contrast-enhanced PAI approaches is discussed, emphasizing their ability to enhance diagnostic sensitivity, enable longitudinal monitoring, and provide detailed information on vascular, biochemical, and structural tissue characteristics. Furthermore, the expanding applications of PAI in assessing uterine, cervical, and ovarian pathologies, including tumor detection and tissue remodeling, are reviewed. Finally, current challenges, limitations, and future directions toward clinical translation are addressed. Collectively, this review underscores the potential of photoacoustic imaging as a powerful, non-invasive platform for early diagnosis, disease monitoring, and improved management of women’s health conditions. Full article

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, complex neurochemical, and metabolic disturbances. Parishin B, a major bioactive component of Gastrodia elata, has shown neuroprotective potential, but its systemic mechanisms remain unclear. Methods: A pentylenetetrazol (PTZ)-induced seizure model in zebrafish larvae was developed and used to evaluate the anti-seizure effects of Parishin B. Behavioral analysis, ELISA-based biochemical assays, integrated untargeted metabolomics with DIA-based proteomics, and qPCR were performed to decipher underlying molecular mechanisms. Results: Parishin B (0.0625–0.25 mg/mL) significantly alleviated PTZ-induced hyperactivity without developmental toxicity. Parishin B restored neurotransmitter balance by increasing GABA, dopamine, and norepinephrine levels while reducing 5-HT. In addition, it suppressed neuroinflammation and enhanced antioxidant capacity. Integrated multi-omics analysis revealed that Parishin B modulated key metabolic pathways, particularly the TCA cycle and lipid metabolism, and reversed the downregulation of ATP-citrate lyase (ACLY). Parishin B was also associated with the regulation of ferroptosis-related pathways, supported by changes in acsl4a and fth1a expression. qPCR results further confirmed the regulation of aclya, unc13c, and GABAergic signaling genes. Conclusions: Parishin B exerts anti-seizure effects through coordinated regulation of neurotransmitter homeostasis, neuroinflammation, and ACLY-associated energy–lipid metabolism, with potential involvement in ferroptosis-related processes. These findings provide molecular insights supporting Parishin B as a promising candidate for epilepsy therapy. Full article

As a representative form of extreme weather, typhoons inflict widespread and systemic damage, posing a severe threat to the livestock industry. The stress they induce, typhoon stress (TS), is an unavoidable and complex environmental challenge that severely disrupts the ovarian function of Wenchang chickens. In this preliminary study, we employed a two-group comparison design (n = 6 per group) integrating behavioral observations, serum biochemical assays, histopathological examinations, and molecular analyses (qPCR, 16S rDNA sequencing, and transcriptome sequencing) to explore the role of the microbiota–gut–brain–ovarian axis (MGBOA) in this process. The findings revealed that TS markedly reduced water intake and locomotor activity, while it elevated serum corticosterone (CORT) and oxidative stress markers. It also induced shifts in gut microbiota composition, including a decrease in Bacteroides and an increase in Escherichia–Shigella. Furthermore, TS compromises duodenal intestinal barrier integrity, as evidenced by downregulation of the tight junction proteins TJP1 and CLDN1, structural damage to intestinal villi, and a reduced villus-to-crypt ratio. In the hypothalamus, VIP mRNA expression was upregulated, while GHSR expression was downregulated; the expression of the tight junction protein CLDN5 was also reduced. In the ovary, reproductive potential was suppressed, manifested by a reduction in follicle number and downregulation of STAR expression. Ovarian transcriptome analysis highlighted enrichments in pathways associated with inflammation (e.g., Toll-like receptor signaling) and lipid metabolism (e.g., PPAR signaling). These results support the hypothesis that TS impairs egg production via the MGBOA, providing preliminary mechanistic insights into how environmental stressors might disrupt animal productivity through MGBOA-mediated pathways. Full article

Oxidative stress occurs when there is an excess of reactive oxygen species (ROS) in the cell, primarily produced by mitochondria. Excess ROS trigger membrane lipid peroxidation (LPO), cause mitochondrial swelling, and release proapoptotic proteins into the cytoplasm, which can lead to apoptosis. It is assumed that antioxidants that reduce excessive ROS formation by mitochondria can increase the body’s resistance to stress factors. We investigated the effects of hypoxia and the antioxidant Ambiol (2-methyl-4-dimethylaminomethylbenzimidazole-5-ol dihydrochloride) on the functional characteristics of mitochondria, which were assessed by measuring lipid peroxidation intensity using spectrofluorimetry, mitochondrial membranes fatty acid composition using chromatography, mitochondrial morphology using atomic force microscopy, and respiration rate using polarography. Injecting mice with Ambiol at a dose of 10⁻⁶ mol/kg for 5 days prevented the stress-induced activation of lipid peroxidation, a decrease in the unsaturation index of C₁₈ and C₂₀ fatty acids in mitochondrial membranes, and swelling of these organelles. The drug also increased the efficiency of oxidative phosphorylation during the oxidation of NAD-dependent substrates. Furthermore, Ambiol increased the lifespan of mice by 3.0–4.0 times under various types of hypoxia. Ambiol’s ability to maintain initial (control) levels of C₁₈ and C₂₀ unsaturated fatty acids appears to protect against stress-induced mitochondrial dysfunction. Full article

Coastal ecosystems are increasingly threatened by climate change, especially the rising frequency of marine heatwaves (MHWs), which often co-occur with emerging nanomaterials such as graphene oxide (GO), whose ecological risks are still being evaluated. While the effects of GO have been studied in isolation, little is known about its interaction with thermal stress events. This research studied the combined effects of temperature (18 °C and 23 °C, simulating control and MHW conditions) and GO nanosheets exposure (0.01 mg/L) on two key estuarine bivalves: the clam Scrobicularia plana and the mussel Mytilus galloprovincialis. After 7 days of exposure (duration of many MHWs), energy metabolism, antioxidant defenses, oxidative damage, and neurotransmission were assessed. The results revealed that clams exhibited lower ETS and SOD activity when exposed to MHWs and lower SOD and AChE activities at MHW + GO, compared to the control treatment. Mussels relied primarily on SOD activity across treatments but showed increased susceptibility to GO nanosheets, with higher LPO levels and a significant reduction in AChE activity when exposed to GO at both temperatures. Overall, our findings suggest that S. plana shows a stronger response to the environmental alterations tested than M. galloprovincialis. Combined exposure to GO + MHW triggers species-specific biochemical responses in estuarine bivalves, highlighting how physiological traits shape the assessment of ecological risks posed by nanomaterial pollution under climate change. Full article

This study evaluates the impact of recirculating aquaponic cultivation on the biochemical, mineral, and antioxidant profiles of Swiss chard (Beta vulgaris var. cicla) integrated with Nile tilapia (Oreochromis niloticus), which serves as a source of nutrients through metabolic waste transformation within the system. Water quality parameters and microbiological testing confirmed efficient nitrification and system safety, with no Escherichia coli detected. Results showed that aquaponic cultivation yields a high nutritional value of Swiss chard, yielding high crude protein (31.4% DW) and mineral-rich biomass (ash 22.8% DW). Substantial concentrations of essential elements were recorded, including Ca, Mg, Fe (253.7 mg/kg DW), Zn, and Cu, suggesting high ionic bioavailability in the recirculating system. Physiological stability was reflected by a chlorophyll a content of 4.74 mg/g DW. Furthermore, the plants exhibited a robust phytochemical profile, with total phenolics (4.13 mg GAE/g DW) and flavonoids (5.18 mg QE/g DW) driving strong antioxidant activity (93.1% ABTS inhibition). These findings demonstrate that integrated aquaponic systems function as effective nutrient bioreactors, supporting high plant functional quality while supporting sustainable food production. The results validate aquaponics as a viable, climate-smart strategy for high-quality leafy vegetable cultivation within a circular bioeconomy framework. Full article

Powdery scab, caused by Spongospora subterranea, is a major disease of potato in which host resistance remains poorly understood at the biochemical level. While previous transcriptomic and proteomic studies have implicated glutathione S-transferases (GSTs) in cultivar-specific defence responses, orthogonal evidence at the metabolite level remains limited. In this study, untargeted metabolomics was applied to investigate root metabolic responses of two potato cultivars with contrasting resistance to S. subterranea. The relatively resistant cultivar ‘Gladiator’ and the susceptible cultivar ‘Iwa’ were inoculated with S. subterranea, and roots were collected at the stage of visible gall formation for analysis by high-resolution liquid chromatography–mass spectrometry (LC-MS/MS). Principal component analysis revealed a distinct metabolic profile in infected ‘Gladiator’ roots compared with both non-inoculated controls and infected ‘Iwa’ roots, indicating a stronger host metabolic response in the resistant cultivar. Among the annotated metabolites, cysteinyl-glycine (Cys-Gly), a central intermediate of glutathione turnover, was significantly more abundant in infected ‘Gladiator’ roots. The accumulation of Cys-Gly provides direct biochemical evidence linking enhanced glutathione cycling and GST activity to effective host defence. These findings highlight glutathione metabolism as a key component of potato resistance and demonstrate the value of metabolomics for additional validation of biochemical mechanisms underlying plant cultivar responses to biotic stress. Full article

To evaluate the potential biological effects of electromagnetic fields from offshore wind farms on Sebastes schlegelii, a laboratory-controlled chronic exposure experiment was conducted using a magnet-based static magnetic field system. Each group contained 60 fish distributed across four replicate tanks, with 15 fish per tank, and the fish were continuously exposed for 20 d under controlled water-quality conditions. Daily video monitoring of collective shoaling behavior was combined with multi-tissue physiological and biochemical analyses. Electromagnetic field exposure increased the swimming speed, burst frequency, activity ratio, spatial coverage, occupancy entropy, and polarization, while reducing the nearest neighbor distance, group radius, and group area. At the physiological level, cortisol increased mainly in the liver and brain, ACTH showed tissue-dependent modulation, SOD remained relatively stable, and glutathione increased in multiple tissues, especially in the liver, gut, and brain. Correlation analysis indicated a close coupling between behavioral reorganization and endocrine–redox regulation, suggesting that chronic EMF exposure shifted Sebastes schlegelii into a stress-associated but functionally coordinated collective state. Full article

Cardiovascular disease (CVD) risk assessment in older adults requires models that are accurate, clinically interpretable, and able to retain performance in independent populations. This study developed an interpretable machine-learning framework for CVD risk stratification in individuals aged 65 years and older using routinely available clinical factors and a selected biochemical extension and then evaluated its performance in a substantially larger independent external cohort. Model development used a development cohort of 100 patients (Almaty, age ≥ 65) with leakage-free nested cross-validation and out-of-fold (OOF) probabilities. Three internally evaluated configurations were compared: a clinical logistic regression baseline (LR clinical), a biomarker-augmented logistic regression (LR selected), and a nonlinear random forest on the selected feature set (RF selected). Discrimination was assessed using ROC-AUC and PR-AUC; probabilistic accuracy using Brier score and log loss. Calibration was examined using OOF calibration curves with sigmoid calibration for selected models. Decision-analytic utility and exploratory operational thresholds were assessed using Decision Curve Analysis (DCA), yielding a three-tier scale with thresholds t__low = 0.23 and t__high = 0.40. In nested cross-validation, LR clinical achieved ROC-AUC 0.9425 ± 0.0188 and PR-AUC 0.9574 ± 0.0092 with Brier 0.1004 ± 0.0215 and log loss 0.3634 ± 0.0652; LR selected performed worse, while RF selected showed competitive discrimination. External validation on an independent cohort (n = 695) showed retained discrimination (ROC-AUC 0.8355; PR-AUC 0.9376) with acceptable probabilistic accuracy (Brier 0.1131; log loss 0.3760), and recalibration (intercept + slope) slightly improved probability metrics. Explainability analyses (odds ratios, permutation importance, SHAP) consistently identified heredity, BMI, physical activity, and diabetes as influential model-associated factors, with clinically plausible directionality. The results suggest that an interpretable model trained on a small geriatric cohort can retain meaningful predictive performance on a substantially larger external cohort, supporting the potential value of transparent risk stratification in older adults, while broader prospective and multi-center validation remains necessary before routine clinical implementation. Full article