Search Results (1,671)

Background: Familial hypercholesterolemia (FH) is a monogenic disorder causing markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in antioxidant defense via NADPH production. G6PD deficiency, an X-linked disorder impairing redox homeostasis, may contribute to cardiovascular disease (CVD) risk. This study examined whether G6PD deficiency increases CVD risk in FH patients. Methods: We retrospectively analyzed 217 FH patients. Clinical data included demographics, lipid profiles, G6PD status, and atherosclerotic CVD outcomes (coronary, cerebrovascular, or peripheral arterial disease). In a subset, FH was confirmed by LDLR gene sequencing, and G6PD Mediterranean and Seattle variants were genotyped. Cumulative CVD prevalence was compared between G6PD-deficient and G6PD-normal FH patients. Multivariable logistic regression was adjusted for age, sex, body mass index, high blood pressure, and smoking. Results: Participants (mean age 47 years, 60% female) had markedly elevated LDL-C (mean 292 mg/dL at diagnosis). Atherosclerotic CVD was present in 119 (55%) patients. G6PD-deficient FH patients had a significantly higher CVD prevalence than those with normal G6PD activity (77.4% vs. 39.8%, p < 0.0001). LDL-C levels were higher in the G6PD-deficient group than in the non-deficient group, and this difference reached statistical significance in the univariate analysis. In the multivariable analysis, G6PD deficiency remained an independent CVD predictor (adjusted OR 3.57, 95% CI 1.30–9.83) after controlling for conventional risk factors. Conclusions: In FH, hereditary G6PD deficiency is associated with a markedly increased risk of atherosclerotic CVD. A pro-oxidative state in G6PD-deficient FH patients may play a role in premature atherogenesis. G6PD status may represent a cardiovascular risk modifier in FH, warranting further research into underlying mechanisms and targeted management. Full article

Nitric oxide (NO), a reactive nitrogen species (RNS), plays a role in multiple biological functions and signal transduction. However, the mechanisms by which NO counteracts stress tolerance in microbes have been poorly explored. In addition, the decomposition of salty food waste poses a significant challenge for food-degrading microbes. Therefore, we investigated how S-nitrosocysteine (CysNO) affects the cellular salt stress response of Burkholderia vietnamiensis TVV75, a strain isolated from a commercial food waste composite. Under the additional 2% NaCl treatment, increased reactive oxygen species (ROS) inhibited bacterial cell growth and viability. In contrast, CysNO treatment alleviated the cellular ROS levels and growth inhibition by augmenting the superoxide dismutase (SOD) and catalase (CAT) activities. CysNO supplementation also promotes the nitrate reduction pathway in B. vietnamiensis TVV75 under salt stress, suggesting NO-mediated nitrogen metabolism for microbial adaptation to salt stress. Furthermore, CysNO restored the intracellular lipid-degrading lipase enzyme activities, which were compromised by salt stress alone. This restoration was accompanied by a concentration-dependent increase in the relative expression of the lipA (lipase A) and ELFPP (esterase lipase family protein) genes. These results suggest that external NO supplementation can regulate redox balance, nitrate reduction, and lipase activity to maintain microbial cell growth in high-salt environments, pinpointing a NO-dependent salt stress adaptation strategy for salt-sensitive microbes involved in food waste decomposition. Full article

Cisplatin (CIS) is a widely used chemotherapeutic agent known for its efficacy; however, it induces several adverse effects, most notably cachexia, which is characterized by progressive loss of skeletal muscle mass, weakness, and reduced body weight. N-acetylcysteine (NAC) a compound with antioxidants properties, has been shown to mitigate CIS-induced neurotoxicity in experimental models. This study aimed to investigate the myoprotective effects of NAC during CIS treatment and explore the redox and molecular mechanisms involved in this response. For this, female Wistar rats were divided into four experimental groups: Control, NAC (300 mg/day/8 days), CIS (3 mg/kg i.p for 5 days), and NAC + CIS (NAC for 8 days, with CIS administered from day 4 onward). After treatment, muscle strength, redox status, mitochondrial biogenesis, expression of myogenic microRNAs and morphological changes were evaluated. CIS treatment caused muscle atrophy, decreased GSH/GSSG ratio, impaired cellular function, increased lipid peroxidation and altered antioxidant enzymes activity. These effects were mitigated by NAC coadministration. CIS also reduced the mtDNA/nDNA ratio; however, NAC treatment tended to increase TFAM and PGC-1α expression levels. Furthermore, CIS suppressed the expression of muscular miR-1-3p, miR-133a-3p and miR-206-3p, while NAC restored their levels when co-administered with CIS. These findings suggest that NAC may serve as a promising adjuvant therapeutic strategy to counteract CIS-induced myotoxicity through redox regulation and modulation of molecular pathways related to muscle integrity and regeneration. Full article

Betalains are nitrogen-containing pigments found only in Caryophyllales plants and a few Basidiomycetes; no Ascomycota species have been found to contain them. Here, global untargeted metabolomics analysis revealed that the violet pigment generated by the ascomycete Aspergillus sydowii H-1 under standard conditions of cultivation contains six distinct betalains compounds. Genetic analysis revealed tyrosinase (AsTYRs) and DOPA 4,5-dioxygenase (AsDODA1) as key enzymes essential for the synthesis of both the violet pigment and betalains. In addition, AsTYRs and AsDODA1 were found to regulate hyphal development and branching, mycelial pellet compactness, redox homeostasis, and stress responses, all of which had a significant impact on A. sydowii H-1 secondary metabolism. Crucially, two MYB transcription factors, AsMYB1 and AsMYB3, were identified to be negative regulators of violet pigment synthesis. Deletion of AsMYB1 or AsMYB3 boosted pigment yield by 6.7 and 7.3 times, respectively, and increased betalain accumulation, whereas overexpressing them completely eliminated pigment production. Yeast one-hybrid assays and luciferase reporter assays revealed AsMYB1 and AsMYB3 directly bind to the promoters of AsTYR1 and AsTYR2 to suppress the synthesis of betalains and the violet pigment. Our study reported the first betalain-producing ascomycete species and elucidated the molecular basis of its pigment regulation, providing valuable insights for the microbial synthesis of natural colorants. Full article

Background: Sepsis is a leading cause of mortality in intensive care units, with liver dysfunction representing a critical determinant of poor outcome, mainly associated with excessive inflammation and oxidative stress. Lycopene, a carotenoid with potent antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study investigated whether lycopene supplementation mitigates lipopolysaccharide-induced oxidative and inflammatory liver injury in rats. Methods: Male Wistar rats, divided into four groups, were exposed to either lipopolysaccharide or a combination of lipopolysaccharide (10 mg/kg) and lycopene (6 mg/kg). In order to assess liver damage induced by lipopolysaccharide, hepatocellular injury markers, oxidative stress indices, nitric oxide metabolism, glutathione redox status, apoptotic enzyme activity, and inflammatory mediators were assessed in serum and liver tissue. Results: Lipopolysaccharide induced marked hepatocellular damage, characterized by elevated serum liver-cell damage parameters, and liver tissue xanthine oxidase, myeloperoxidase, thiobrabituric reactive substances, protein carbonyl content, deoxyribonuclease I/II activity, nuclear factor kappa B, tumor necrosis factor-α, and interleukin-6, alongside depletion of reduced glutathione and reduced glutathione reductase and glutathione peroxidase activities. Lyc pretreatment significantly attenuated liver enzyme leakage, oxidative damage, and cytokine release while restoring reduced glutathione and glutathione reductase activity. In contrast, lycopene had limited effects on glutathione peroxidase activity, nitric oxide/inducible nitric oxide synthase signaling, and nuclear factor erythroid 2-related factor 2 expression. Conclusions: These findings demonstrate that lycopene confers partial hepatoprotection in endotoxemic rats, primarily through suppression of oxidative damage and nuclear factor kappa B-mediated inflammation. Further studies are needed to clarify tissue-specific mechanisms and optimize dosing strategies in order to increase the efficacy of this carotenoid. Full article

Biocatalysis is fundamental to biological processes and sustainable chemical productions. Over time, the biocatalysis strategy has been widely researched. Initially, biomanufacturing and catalysis of high-value chemicals were carried out through direct immobilization and application of biocatalysts, including natural enzymes and living cells. With the evolution of green chemistry and environmental concern, hybrid photoelectro-biocatalysis (HPEB) platforms are seen as a new approach to enhance biocatalysis. This strategy greatly expands the domain of natural biocatalysis, especially for bio-based components. The selective valorization of renewable furan derivatives, such as 5-hydroxymethylfurfural (HMF) and furfural, is central to advancing biomass-based chemical production. Biocatalysis offers high chemo-, regio-, and stereo-selectivity under mild conditions compared with traditional chemical catalysis, yet it is often constrained by the costly and inefficient regeneration of redox cofactors like NAD(P)H. Photoelectrocatalysis provides a sustainable means to supply reducing equivalents using solar or electrical energy. In recent years, hybrid systems that integrate biocatalysis with photoelectrocatalysis have emerged as a promising strategy to overcome this limitation. This review focuses on recent advances in such systems, where photoelectrochemical platforms enable in situ cofactor regeneration to drive enzymatic transformations of furan-based substrates. We critically analyze representative coupling strategies, materials and device configurations, and reaction engineering approaches. Finally, we outline future directions for developing efficient, robust, and industrially viable hybrid catalytic platforms for green biomass valorization. Full article

Shale gas extraction releases significant quantities of organic iodides of “unknown origin”, which generally pose high ecological and health risks, yet their toxic mechanisms remain unclear. In this study, the human hepatocellular carcinoma (HepG2) cell line was employed as an in vitro cell model to assess the cytotoxic effects of three typical organic iodides (1,2-diiodoethane, 1,3-diiodopropane, and 1,4-diiodobutane) identified in shale gas extraction wastewater from Chongqing, China. The results demonstrated that all three diiodoalkanes exhibited significant toxic effects on HepG2 cells at a concentration of 25 µM, and this effect demonstrated a dose-dependent pattern. As the concentration of diiodoalkanes increased, the viability of HepG2 cells decreased significantly, while cell mortality increased markedly. The transcriptomic analysis indicated that exposure to these three diiodoalkanes induced abnormal expression of genes associated with the extracellular space, extracellular matrix (ECM), and endoplasmic reticulum (ER) in HepG2 cells, which was presumed to be linked to the disruption of the intracellular redox-antioxidant system homeostasis by the diiodoalkanes. Furthermore, assays of intracellular reactive oxygen species (ROS) and antioxidant enzyme/molecule levels suggested that diiodoalkane exposure triggered excessive intracellular ROS production, induced oxidative stress, and ultimately resulted in cell death. Full article

Both primary and secondary hemostasis consist of finely regulated pathways, forming a blood clot to stop bleeding. These orchestrated mechanisms involve multiple plasma- and platelet/endothelial-derived receptors, factors, enzymes, and proteins, such as the von Willebrand factor (vWF), fibrinogen, and thrombin. Over-activation or improper resolution of the coagulation cascade leads to severe pathological disorders, arterial and venous. Despite the fact that the genetic etiology of thrombophilia has gained the main research interest, there is growing evidence that the disturbed redox network of key hemostatic pathways signals thrombus formation. Oxidized LDL in dyslipidemias and many endogenous and exogenous compounds act as pro-oxidant stimuli that lead to post-translational modifications of proteins, such as sulfenylation, nitrosation, disulfide formation, glutathionylation, etc. Oxidation of cysteine and methionine residues of vWF, fibrinogen, and thrombomodulin has been detected at thrombotic episodes. Increased homocysteine levels due to, but not restricted to, methylenetetrahydrofolate reductase gene (MTHFR) mutations have been incriminated as a causative factor for oxidative stress, leading to a pro-thrombotic phenotype. Alterations in the vascular architecture, impaired vascular relaxation through decreased bioavailability of NO, accumulation of Nε-homocysteinylated proteins, ER stress, and endothelial cells’ apoptosis are among the pro-oxidant mechanisms of homocysteine. This review article focuses on describing key concepts on the oxidant-based molecular pathways that contribute to thrombotic episodes, with emphasis on the endogenous compound, homocysteine, aiming to promote further molecular, clinical, and pharmacological research in this field. Full article

This study aimed to assess the biocompatibility and bioactivity of three different silver nanoparticles (AgNPs) and calcium hydroxide [Ca(OH)₂] mixtures against human dental pulp stem cells (hDPSCs). hDPSCs were treated with one of the following medicaments: 2 nm mixture, 5 nm mixture, 10 nm mixture, Ca(OH)₂ alone, and triple antibiotic paste (TAP). Cell viability was evaluated using the Cell Counting Kit-8 and LIVE/DEAD Viability/Cytotoxicity Kit. Reactive oxygen species (ROS) were quantified using the 2′,7′-dichlorofluorescein diacetate redox probe. Transforming growth factor (TGF)-β1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α>, and alkaline phosphatase (ALP) were quantified using enzyme-linked immunosorbent assays. Mineralization was assessed using Alizarin Red S staining. Data were compared across groups using the Kruskal–Wallis test and within groups using the Wilcoxon signed-rank test (p < 0.05). Ca(OH)₂ alone and the 10 nm mixture demonstrated the highest cell viability and lowest ROS release (p < 0.05), while the 2 nm and 5 nm mixtures resulted in decreased viability and significant morphological distortion of the cells. Ca(OH)₂ alone and the 10 nm mixture comparably demonstrated the highest production of anti-inflammatory cytokine TGF-β1 (p < 0.05), the lowest production of proinflammatory cytokines IL-1β and TNF-α (p < 0.05), and the highest ALP release and mineralization (p < 0.05). Within the limitations of this in vitro study, Ca(OH)₂ alone and the 10 nm mixture improved hDPSCs’ viability, proliferation, differentiation, and mineralization. Both illustrated a significantly higher anti-inflammatory response by the residing stem cell population. Full article

Zinc excess (Zn stress) could lead to deleterious effects in plants such as enhanced ROS production, inhibition of photosynthetic machinery, and impairment of nutrient uptake. Hence, we aimed to investigate the complexity of metabolic responses to Zn stress in Amaranthus caudatus young and mature leaves, as well as in roots by means of proteomics. Our previous metabolomics research has indicated potential involvement of gluconate and salicylate in Zn tolerance mechanisms. However, proteomics study of metabolic adjustments underlying Zn stress tolerance can give additional insight to the issue, as a lot of enzymes are known to be affected by the excess of transitional metals. The results obtained through bottom-up proteomics were complementary to our earlier metabolomics data and, furthermore, enlightened other important details in the metabolic response of A. caudatus plants to the applied Zn stress. In particular, the significant involvement of redox-related enzymes was shown, especially for the roots, and their possible interactions with salicylate and jasmonate signaling could be proposed. Furthermore, Zn²⁺-induced changes in roots and young leaves strongly affected sugar metabolism, enhanced protein quality control system, while mature leaves were characterized by remarkable decrease in subunits of photosynthetic electron transport complexes. Thus, this work emphasizes massive metabolic reprogramming aimed to reinforce root defense responses while supporting young leaves with sugar metabolites. Mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD069557. Full article

Metal–organic frameworks (MOFs) have been increasingly recognized as promising platforms for enzyme modulation, owing to their tunable porosity, high surface area, and versatile chemical functionality. In this review, the potential of MOFs for the inhibition and modulation of protein kinases and phosphatases—key regulators of cellular signaling and disease progression—is examined. The structural fundamentals of MOFs are outlined, followed by a discussion of common synthesis strategies, including solvothermal, microwave-assisted, sonochemical, and mechanochemical methods. Emphasis is placed on how synthesis conditions influence critical features such as particle size, crystallinity, surface chemistry, and functional group accessibility, all of which impact biological performance. Four primary mechanisms of MOF–enzyme interaction are discussed: surface adsorption, active site coordination, catalytic mimicry, and allosteric modulation. Each mechanism is linked to distinct physicochemical parameters, including pore size, surface charge, and metal node identity. Special focus is given to biologically relevant metal centers such as Zr⁴⁺, Ce⁴⁺, Cu²⁺, Fe³⁺, and Ti⁴⁺, which have been shown to contribute to both MOF stability and enzymatic inhibition through Lewis acid or redox-mediated mechanisms. Recent in vitro studies are reviewed, in which MOFs demonstrated selective inhibition of disease-relevant enzymes with minimal cytotoxicity. Despite these advancements, several limitations have been identified, including scalability challenges, limited physiological stability, and potential off-target effects. Strategies such as post-synthetic modification, green synthesis, and biomimetic surface functionalization are being explored to overcome these barriers. Through an integration of materials science, coordination chemistry, and molecular biology, this review aims to provide a comprehensive perspective on the rational design of MOFs for targeted enzyme inhibition in therapeutic contexts. Full article

Cinnamomum burmanni (Nees & T. Nees) Blume, a member of the Lauraceae family, exhibits adaptability to diverse environmental conditions by synthesizing a diverse array of specialized secondary metabolites, including terpenoids and cinnamaldehyde. Nevertheless, the molecular mechanisms underlying the chemical diversity in the leaves of C. burmanni and their remarkable adaptation to subtropical and tropical forests in South China have not been thoroughly investigated. This research integrates transcriptomic and proteomic analyses across five chemotypes of C. burmanni, namely, the borneol-type (BORCB), cinnamaldehyde-type (PROCB), eucalyptol-type (EUCCB), phytol-type (PHYCB), and chlorophyllinol-type (CARCB), by means of the Nanopore and Nano UPLC-MS/MS sequencing data. The findings indicate that PROCB demonstrates an up-regulation of the phenylpropanoid pathway (such as PAL, C4H, PR proteins), which is associated with biotic stress defense. In contrast, the terpenoid-dominated chemotypes (BORCB, EUCCB, PHYCB) prioritize the biosynthesis of monoterpenes and diterpenes as well as redox homeostasis. Protein–protein interaction networks highlight functional specialization; BORCB up-regulates the expression of enzymes GGPPS and TPS2, which are involved in monoterpene production; PHYCB enhances the activity of diterpene synthases (CPS, KSL) and chloroplast retrograde signaling; EUCCB activates SOD/GST to mitigate oxidative stress. PROCB induced defense hubs (NPR1, WRKY33) mediated by salicylic acid and pathogenesis-related proteins. The study establishes a comprehensive multi-omics resource for a gene–protein–metabolite framework, elucidating the mechanisms of stress resilience of C. burmanni in South China. Full article

Pollution with heavy metals, such as cadmium (Cd), can significantly affect insect growth, development, and behavior. The midgut is an essential organ for stress response. Chitin synthase-2 (CHS-2) is closely associated with forming the peritrophic membrane (PM). The fourth-instar larvae of Aedes albopictus were exposed to varying concentrations of Cd. The results showed that Cd inhibited chitin synthesis and metabolism-related genes, but thickened the midgut PM, indicating that the larvae could respond to Cd stress through the midgut PM. Silencing CHS-2 by RNA interference resulted more severe vacuolization and malformation of midgut epithelial cells without midgut PM protection. Additionally, there was an intensified redox reaction, upregulated expression of metallothionein (MT) and heat shock proteins 70 (HSP70), and increased activity of antioxidant enzymes at some scattered time points. This study confirms that CHS-2 is involved in oxidative stress induced by Cd exposure by regulating PM formation. This study also contributes to further understanding the resistance mechanism of Ae. albopictus under Cd stress, thereby establishing a theoretical foundation for the future studies of them, which is concerned with the possibility of Ae. albopictus as a water environment detection and the control of Ae. albopictus based on resistance mechanism. Full article

Chondroitin sulfate (CS) chains on the cell surface are sulfated in various patterns, and this structure is the basis of CS function. We aimed to investigate the role of chondroitin 4-O-sulfotransferase-1 (C4ST-1), the enzyme responsible for the 4-sulfation of CS, in redox homeostasis and protein aggregation in mouse neuroblastoma Neuro2a and neural progenitor C17.2 cells. Results showed that C4ST-1 deficiency significantly reduced 4-sulfated CS, which led to markedly decreased intracellular glutathione levels and increased reactive oxygen species production. Mechanistically, C4ST-1 loss reduced the CS modification of neurocan, decreased the stability of the cystine transporter xCT, and decreased intracellular glutathione levels. This redox imbalance promoted protein aggregation and caused lysosomal membrane damage, indicating a failure of protein quality control. Although C4ST-1 deficiency alone did not cause tau protein aggregation, it significantly accelerated the aggregation of a familial tauopathy mutant following the introduction of seeds. These findings suggest that C4ST-1-mediated CS sulfation regulates the intracellular redox state and tau pathology. Thus, C4ST-1 may serve as a therapeutic target for neurodegenerative diseases. Full article

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide which act as signaling molecules. Monitoring NADPH levels, NADPH/NADP⁺ ratio, and especially distinguishing from NADH, provides vital information about cellular redox status, energy generation, survival, lineage specification, and death pathway selection. NADPH detection is key to understanding metabolic reprogramming in cancer, aging, and cardiovascular, hormonal, neurodegenerative, and autoimmune diseases. Liquid chromatography combined with mass spectrometry (LC-MS) is crucial for NADPH detection in redox signaling because it offers the high sensitivity, specificity, and comprehensive profiling needed to quantify this vital but labile redox cofactor in complex biological samples. Using hepatoma cell lines, liver tissues, and primary hepatocytes from mice lacking transaldolase or nicotinamide nucleotide transhydrogenase, or having lupus, this study demonstrates that accurate measurement of NADPH depends on its preservation in reduced form which can be optimally achieved by extraction of metabolites in alkaline solution, such as 0.1 M potassium hydroxide (KOH) in comparison to 80% methanol (MeOH) alone or 40:40:20 methanol/acetonitrile/formic acid solution. While KOH extraction coupled with hydrophilic interaction liquid chromatography (HILIC) and mass spectrometry most reliably detects NADPH, NADP, NADH, NAD, polyamines, and polyols, MeOH extraction is best suited for detection of glutathione and overall discrimination between complex metabolite extracts. This study therefore supports performing parallel KOH and MeOH extractions to enable comprehensive metabolomic analysis of redox signaling. Full article