Search Results (13,793)

Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver–intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases. Full article

Salinity stress adversely affects plant growth, yield, and productivity. It requires an investigation of ameliorative techniques, for example, spraying synthesized nanoparticles such as zinc oxide nanoparticles (ZnOnps). This current research studied the impact of sodium chloride as a stressor (150 mM NaCl) and the application of ZnOnps (2 g L⁻¹) on some biochemical properties of maize (Zea mays) leaves. The experiment involved examining some mineral concentrations (Na, K, Mg, Zn, Cu, Mn), fatty acid profile, and the antimicrobial (antibacterial and antifungal) properties of aqueous and diethyl ether maize leaf extracts, supported by molecular docking studies of the 17 previously determined phenolic compounds against DNA gyrase and alpha-L-fucosidase enzymes. Applying ZnOnps markedly decreased sodium concentrations from 5.8 to 1.9 mg g⁻¹ dry weight (DW) and established ion balance. ZnOnps also reduced γ-linolenic acid levels to 60% under stress, returning them to normal (34%), while increasing palmitic acid to 30%. Determining the antimicrobial activities indicated that extracts from plants sprayed with ZnOnps exhibited enhanced antimicrobial activity, as evidenced by the lowest minimum inhibitory concentrations against bacterial and fungal strains, including Salmonella typhi and Aspergillus flavus. The computational molecular docking confirmed the antimicrobial findings, with the compound apigenin-7-glucoside, which exhibited the highest binding affinity scores for antibacterial (−7.4 kcal/mol), and the compound chlorogenic acid as antifungal (−7.2 kcal/mol) against the enzyme targets. Thus, ZnOnps can be considered an efficient strategy for mitigating salinity stress in maize plants while elevating the antimicrobial activity and stability of variant secondary compounds. Full article

Galaxolide (HHCB), a synthetic polycyclic musk widely used as a fragrance ingredient in numerous personal care and household products, has raised increasing environmental concern due to its persistence, bioaccumulation potential, and widespread occurrence in aquatic environments. In this context, the need to establish a concrete ecotoxicological risk profile, defining both the toxicity levels and the mechanisms of action, is fundamental. For this reason, in the current study, we selected the freshwater leech Hirudo verbana as a suitable in vivo model to assess the HHCB ability in inducing inflammatory response and oxidative stress. By means of morphological, immunofluorescence, and molecular analyses, HHCB was shown not only to affect the leech innate immune response by modulating angiogenesis and macrophage-like cells recruitment, but also to promote the expression of enzymes involved in the antioxidant response, such as superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT). Overall, these findings indicate that HHCB could induce significant physiological alterations, with sub-lethal concentrations able to affect immune homeostasis. Furthermore, this study supports the use of alternative invertebrate models to better understand the possible harmful effects of emerging contaminants. Full article

Chlorine dioxide (ClO₂) is a neutral oxidant molecule with a short lifespan once in contact with electron donors (organic matter). ClO₂ solutions have antiviral, antibacterial, antifungal, anti-protozoan, anti-inflammatory, anticancer, and wound-healing activity and it was used at safe concentrations on patients from different countries during the COVID-19 pandemic. In Mexico, 1067 COVID-19 patients received compassionate treatments with ClO₂ during the 2020/2021 pandemic years. We describe the treatments and clinical reports of these patients, as it concerns the oxygen saturation (SpO₂) recovery, and provide a biochemical explanation. The number of healed patients was 1057, >99% of the total and SpO₂ showed a hyperbolic fast increase. This might happen because ClO₂ attracts one electron from the organic matter and produces a chlorite anion (${\mathrm{ClO}}_2^{-}$). This new molecule is known to exhibit metabolic activity in the blood stream. On the one hand, it will perform the aforementioned antibiotic and healing properties. On the other hand, it will also allow the production of oxygen (O₂) to be transported by the Oxyhemoglobin. This reaction is mediated by an intermediate state of a ferryl molecule (Fe=O) in the allosteric heme site of methemoglobin, which behaves as a reductase enzyme. This reaction can explain the rapid and steady increase in O₂ saturation in healed patients. Full article

Galactooligosaccharides (GOS) are one of the internationally recognized prebiotic products, which have become a hot research focus in the field of biofoods because of their strong prebiotic, sugar substitution and inflammation alleviation functions. β-galactosidase (Bgal) of different microorganisms is utilized industrially in order to achieve the biosynthesis of GOS. Although the biosynthesis of GOS has been supported by certain technologies, there is still room for further improvement of its synthetic yield. This paper mainly introduces the function and biosynthesis of GOS and its research progress in recent years to enhance the yield of biosynthesis. This paper also combines the research progress in related fields in recent years, based on the basic theories of molecular biology and bioinformatics, discusses the research progress of green, innovative approaches including enzyme engineering, enzyme immobilization, surface display, and microbial fermentation on the synthesis of GOS. Full article

Gammaherpesviruses are oncogenic viruses that reprogram host cell metabolism to support viral production. Among these, murine herpesvirus 68 (MHV-68) serves as a model system for studying lytic gammaherpesvirus infection and associated host cell changes. To characterize host transcriptional alterations induced throughout lytic gammaherpesvirus infection and identify novel host pathways that may be therapeutically targeted, we performed temporal bulk RNA-sequencing of mock- and MHV-68-infected NIH 3T3 cells at various timepoints throughout the lytic cycle. Our analysis revealed widespread and progressive host gene expression changes, including robust innate immune pathways and extensive remodeling of metabolic gene expression. We further identified a strong activation of the pentose phosphate pathway (PPP) genes, accompanied by increased abundance in PPP metabolic intermediates. Pharmacological inhibition of the PPP with 6-aminonicotinamide (6-AN) reduced infectious virus production. Moreover, at the intersection of metabolic and transcriptional reprogramming, we identified infection-associated gene expression changes in chromatin-modulating enzymes, including Tet2, and their metabolite co-factors, such as α-KG. Pharmacological inhibition of Ten-Eleven Translocation (TET) enzymatic activity led to a marked decrease in infectious MHV-68 production. Collectively, these findings define a novel metabolic–epigenetic crosstalk that supports productive gammaherpesvirus replication and identifies host pathways that can be targeted to treat lytic gammaherpesvirus infections. Full article

In the context of the circular economy, the valorization of natural biomolecules from by-products has recently represented a major goal in health promotion. From this perspective, this study examined the antioxidant potential of Sicilian white grape pomace from the Pinot Gris variety, using subcritical water extraction as an eco-friendly and innovative method to recover bioactive compounds. Different extraction parameters allowed for comparing the potential of various fractions. Among these, the Subcritical Water Extract obtained after 5 min at 160 °C (SWE^160.1) was rich in gallic acid and protocatechuic acid, as evidenced by characterization with UHPLC-Q Exactive Orbitrap-HRMS system. SWE^160.1 showed efficacious antioxidant activity, as confirmed by DPPH assay and total polyphenol and flavonoid content. Interestingly, SWE^160.1 displayed cytotoxic activity in tumor cell lines, while preserving the viability of non-tumor bronchial epithelial cells. Specifically, SWE^160.1 protected these cells from exogenous oxidative stress, reducing the ROS levels and activating Nrf2-mediated antioxidant response. Surprisingly, upregulation of antioxidant enzymes (HO-1 and SOD-2) induced by SWE^160.1 was maintained in the presence of lipopolysaccharide, indicating a specific involvement of SWE^160.1 in the anti-inflammatory response. Finally, SWE^160.1 was also able to limit the formation of stress granules following acute stress, thereby supporting its potential to maintain cellular homeostasis. Overall, this study highlights the potential of grape pomace as a source of active molecules to prevent oxidative stress and inflammation. Full article

The genus Cymbopogon comprises neocosmopolitan grasses widely used as medicinal plants and in the perfume, pharmaceutical and herbal product industries. Despite their economic relevance, these species are still considered orphan crops, with limited phytotechnical, genomic and evolutionary studies within the Poaceae family. In this study, we investigated the evolutionary relationships of Cymbopogon flexuosus and Cymbopogon winterianus, with a focus on differences in gene expression associated with the biosynthesis of secondary metabolites. De novo transcriptome assembly yielded 25,576 transcripts in C. flexuosus and 42,250 in C. winterianus. A total of 5318 and 8631 more informative differentially expressed transcripts (DETs) were identified in each mapping, among which 76 and 94 were associated with secondary metabolism pathways. When mapping the libraries against related species, the highest percentages of mapped reads per transcriptome and per gene (depth) were observed in Andropogon gerardi, Sorghum bicolor, Saccharum officinarum, Miscanthus sinensis, Miscanthus lutarioriparius and Zea mays. These results indicate A. gerardi, S. bicolor and Z. mays as the most promising genomic models for future studies within the genus Cymbopogon. Comparison of the expression of transcripts that are homologous to the precursor enzymes of terpenoids, phenylpropanoids, flavonoids and other secondary metabolites revealed a complex and non-linear interaction between the metabolic pathways in each species and it was not possible to predict the predominance of greater expression of a class of metabolites on a given species. Full article

Triacylglycerols (TAGs) are essential energy reservoirs and industrial raw materials, while structured TAGs (STAGs) with tailored fatty acid distributions possess unique nutritional and functional values but low natural abundance. Enzymatic synthesis is strictly limited by feedstock and cost, making microbial de novo synthesis via metabolic engineering a promising alternative. This review summarizes advances in the fatty acid biosynthesis pathway and its regulation, key enzymes in TAG synthesis (GPAT, LPAAT, and DGAT), and microbial production of major STAGs (OPO, MLM, CBEs, and PUFA-rich STAGs). Current challenges and future perspectives are also discussed, promoting the shift toward rational design of functional STAGs. Full article

Skin aging is characterized by decreased collagen synthesis and increased extracellular matrix degradation, leading to wrinkle formation and reduced skin elasticity. This study evaluated the anti-aging potential of hydrolyzed fish skin (HFS) extract through complementary in vitro and clinical investigations. In human dermal fibroblasts, treatment with HFS extract enhanced type I procollagen production and suppressed UVB-induced matrix-degrading enzymes, including matrix metalloproteinase-1 (MMP-1) and elastase, suggesting a mechanism that supports dermal matrix homeostasis. A randomized, double-blind, split-face clinical trial was conducted in 20 female participants over 12 weeks. A formulation containing 0.5% HFS extract was applied to one side of the face, while an identical vehicle control formulation without HFS extract was applied to the contralateral side. Wrinkle parameters were assessed using a three-dimensional imaging system. After 12 weeks, the test group showed significant improvements compared to baseline, with reductions of 12.75% in arithmetic mean roughness (Ra), 12.46% in root mean square roughness (Rq), and 11.32% in maximum wrinkle height (Rmax) (p < 0.05). No adverse events were observed. These findings demonstrate that HFS extract improves wrinkle-related skin parameters, potentially through promoting collagen synthesis while inhibiting matrix degradation. The combined molecular and clinical evidence supports its application as a functional cosmetic ingredient in anti-aging formulations. Full article

Grape pomace, the main solid by-product of winemaking, is a promising feedstock for the recovery of trans-resveratrol, a high-value stilbene of increasing interest for food, nutraceutical, and pharmaceutical applications. However, its efficient isolation remains challenging because of matrix complexity, the co-occurrence of structurally related stilbenes and polyphenols, and the chemical instability of trans-resveratrol. This review critically examines recent advances in the recovery of trans-resveratrol from grape pomace, while also incorporating relevant findings from other grapevine-derived matrices to distinguish matrix-specific recovery potential and to place grape pomace within the broader context of grapevine by-product valorization from extraction intensification and selective purification to analytical determination. Various extraction technologies, including ultrasound-, microwave-, and enzyme-assisted extraction, natural deep eutectic solvents, and subcritical water extraction, are assessed alongside conventional solvent extraction with emphasis on yield, selectivity, solvent compatibility, and process feasibility. Downstream separation methods such as liquid–liquid partitioning, solid-phase isolation, adsorbent resins, counter-current chromatography, molecularly imprinted polymers, and foam fractionation are compared in terms of selectivity, enrichment efficiency, solvent demand, and scale-up potential. Although significant progress has been achieved, major challenges remain regarding process integration, solvent sustainability, product stability, and industrial feasibility. Combining mild extraction with selective downstream purification is essential for producing stable, high-purity trans-resveratrol fractions suitable for future use in functional ingredients, natural preservation strategies, and other value-added applications within sustainable food systems. Full article

The physiological performance of the Pacific oyster Magallana gigas in subtropical lagoon systems is shaped by the interaction between environmental variability, reproductive dynamics, and oxidative stress. This study quantified monthly changes in the growth and proximate composition of oysters cultivated in Estero La Cruz, Sonora, and evaluated their relationship with temperature and chlorophyll-a as proxies for thermal stress and trophic availability. Shell growth was continuous, while somatic biomass increased markedly during winter, indicating high thermal tolerance and metabolic flexibility. Proximate composition showed pronounced seasonal oscillations, with energy reserves accumulating during periods of high primary productivity and declining sharply in December, coinciding with peak gametogenic activity. Antioxidant enzyme activities (SOD, CAT, GPx) increased toward winter, reflecting elevated oxidative stress. Correlation and regression analyses revealed consistent relationships among environmental variables and biological responses, identifying temperature as the main factor associated with growth variability. Overall, these results demonstrate a strong coupling between environmental forcing, energy allocation, and oxidative stress, providing an integrative framework for understanding oyster performance and supporting aquaculture management in subtropical coastal systems. Full article

Background/Objectives:α-Mangostin, a natural product from Garcinia mangostana L, presents very strong antibacterial activity in plant flavonoids against Staphylococcus aureus. Recently, it was reported that the quinone pool is a key target of α-mangostin against Gram-positive bacteria. Here, the detail centering this action mechanism of α-mangostin killing S. aureus was further explored. Methods: The interactions between α-mangostin and type II NADH:quinone oxidoreductase (NDH-2), a key enzyme in the respiratory chain, were explored through the enzyme kinetic experiments, fluorescence analyses, and molecular simulation. Simultaneously, the effect of α-mangostin on membrane potential was also investigated as a possible non-enzymatic mechanism. Results: it was found that α-mangostin mainly competes the menaquinone-binding sites of NDH-2 with menaquinone, and the half-maximal inhibitory concentration (IC₅₀) of α-mangostin on NDH-2 is 4.95 μM. Fluorescence analyses indicated that α-mangostin can spontaneously bind to NDH-2 to form an α-mangostin–NDH-2 complex. Subsequently, molecular simulation further showed that α-mangostin can dock to the menaquinone-binding sites of NDH-2. In addition, non-enzymatic mechanism showed that α-mangostin can cause membrane potential depolarization and disrupt the proton motive force balance, thereby promoting the cell-membrane destruction of S. aureus. Conclusions: α-Mangostin can mainly interact with the amino acid residues at the menaquinone-binding pocket of NDH-2 to block the electron transfer at the quinone pool in the respiratory chain of S. aureus, which will hinder the energy supply and act synergistically with cell membrane damage, ultimately leading to the death of S. aureus. Simultaneously, it once again proves that the quinone pool is a key target of plant flavonoids against Gram-positive bacteria. Full article

Background/Objectives: Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder caused by deficiencies in enzymes required for heparan sulfate degradation. While primarily recognized for its devastating neurodegenerative course, the systemic extent of glycosaminoglycan (GAG) accumulation remains under-characterized. This study aims to provide a detailed multisystemic pathological mapping of MPS III to challenge the traditional “brain-only” disease paradigm and highlight the clinical relevance of extracerebral involvement. Methods: We present a comprehensive clinicopathological analysis of a 15-year-old female patient with a history of profound neuropsychomotor delay, refractory epilepsy, and spastic tetraplegia. Following her death due to terminal bronchopneumonia during palliative care, a complete forensic and pathological autopsy was conducted. Tissue samples from all major organ systems were processed using routine Hematoxylin–Eosin (HE) staining, immunohistochemical staining for CD68, and specialized histochemical stains to identify intracellular storage products. Results: Macroscopic evaluation revealed significant diffuse cerebral atrophy, meningoencephalic edema, cardiac valvulopathy with compensatory myocardial remodeling, and hepatosplenomegaly. Furthermore, erosive gastrointestinal lesions and degenerative renal changes were identified. Histopathological examination confirmed widespread cytoplasmic vacuolization across diverse cell populations, including neurons, hepatocytes, renal tubular cells, and the reticuloendothelial system. These findings demonstrate that GAG deposition is a generalized process affecting nearly every parenchymal structure. Conclusions: Although neurological decline dominates the clinical phenotype, our findings underscore that MPS III is a true systemic storage disorder. Significant involvement of the cardiovascular and visceral systems contributes to the disease’s complexity and mortality. This case reinforces the critical diagnostic value of a comprehensive autopsy in delineating the full morphological spectrum of Sanfilippo syndrome, providing essential insights for multidisciplinary management. Full article

The gut microbiota produces molecules that trigger responses at the local and distant levels. It affects the brain through several metabolic products, including serotonin (5-HT). Tryptophan hydroxylase type 1 (Tph1) is the rate-limiting enzyme during 5-HT biosynthesis in the gut. Efavirenz (EFV), an antiretroviral agent against HIV, is associated with depression disorders and Tryptophan hydroxylase type 2 (Tph2) deregulation in mice. The possible association between the depressive effects of EFV secondary to dysbiosis and the expression of Tph1 in the intestine is yet to be studied. Therefore, we aimed to elucidate the role of the gut microbiota in depression mechanisms. We reviewed the gut microbiota, their metabolites (short-chain fatty acids [SCFA]), Tph1 expression in the gut, and systemic 5-HT and tryptophan levels in CD1 mice after 36 days of oral EFV (10 mg/kg) treatment. The proportions of Bacteroidota and Bacillota_A_368345 decreased and increased, respectively, following EFV treatment. Additionally, the abundance of Lactobacillus spp. and Faecalbaculum decreased, whereas that of Dubosiella spp., Blautia_A_141780, and Anaerostipes increased. These bacteria contribute to SCFA production and may have counteracted the lack of protective effects provided by Lactobacillus. Tph1 expression was dysregulated in the gut, whereas serum 5-HT levels decreased following EFV treatment. Lactobacillus species promote 5-HT production in the gut, and the deregulation of Tph1 affects 5-HT synthesis. This disruption in the gut–brain axis decreased peripheral 5-HT levels. This affects the serotonergic system in the brain, which could contribute to depression. Full article