Search Results (508)

Quercetin is a biologically active flavonoid compound that exerts numerous beneficial effects in humans and animals, including anti-diabetic activity. Its action has been explored in rodent models of type 1 and type 2 diabetes. It was revealed that quercetin mitigated diabetes-related hormonal and metabolic disorders and reduced oxidative and inflammatory stress. Its anti-diabetic effects were associated with advantageous changes in the relevant enzymes and signaling molecules. Quercetin positively affected, among others, superoxide dismutase, catalase, glutathione peroxidase, glucose transporter-2, glucokinase, glucose-6-phosphatase, glycogen phosphorylase, glycogen synthase, glycogen synthase kinase-3β, phosphoenolpyruvate carboxykinase, silent information regulator-1, sterol regulatory element-binding protein-1, insulin receptor substrate 1, phosphoinositide 3-kinase, and protein kinase B. The available data support the conclusion that the action of quercetin was pleiotropic since it alleviates a wide range of diabetes-related disorders. Moreover, no side effects were observed during treatment with quercetin in rodents. Given that human diabetes affects a large part of the population worldwide, the results of animal studies encourage clinical trials to evaluate the potential of quercetin as an adjunct to pharmacological therapies. Full article

Trichomes are specialized epidermal structures that protect plants from environmental stresses, regulated by transcription factors integrating hormonal and environmental cues. This study investigates the roles of two C2H2 zinc finger proteins, GIS2 and ZFP8, in regulating trichome patterning in Arabidopsis thaliana. Using dexamethasone-inducible overexpression lines, transcriptomic profiling, and chromatin immunoprecipitation, we identified 142 GIS2- and 138 ZFP8-associated candidate genes involved in sterol metabolism, senescence, and stress responses. GIS2 positively and directly regulated the expression of SQE5, linked to sterol biosynthesis and drought tolerance, and repressed SEN1, a senescence marker associated with abscisic acid and phosphate signaling. ZFP8 modulated stress-related target genes, including PR-4 and SPL15, with partial functional overlap between GIS family members. Spatially, GIS2 functions in inflorescence trichomes via integrating gibberellin-cytokinin pathways, while ZFP8 influences leaf trichomes through cytokinin and abscisic acid signal. Gibberellin treatment stabilized GIS2 protein and induced SQE5 expression, whereas SEN1 repression was gibberellin-independent. Chromatin immunoprecipitation and DEX-CHX experiment confirmed GIS2 binding to SQE5 and SEN1 promoters at conserved C2H2 motifs. These findings highlight hormone-mediated transcriptional regulation of trichome development by GIS2 and ZFP8, offering mechanistic insight into signal integration. The results provide a foundation for future crop improvement strategies targeting trichome-associated stress resilience. Full article

The Steinernema carpocapsae nematode is known to release several excretory/secretory products (ESPs) in its venom upon contact and during the parasitic infection process of insect hosts. A recurrent family of proteins found in this nematode’s venom is the CAP (cysteine-rich secretory protein/antigen 5/pathogenesis-related 1) protein, but the functional role of these proteins remains unknown. To elucidate the biological function, this study focused on characterising the secreted protein, first identified in the venom of the nematode’s parasitic stage, and the sequence retrieved from transcriptomic analysis. The structural comparisons of the Sc-CAP protein model, as determined by AlphaFold2, revealed related structures from other parasitic nematodes of vertebrates. Some of these closely related proteins are reported to have sterol-binding ability. The Sc-CAP recombinant protein was successfully produced in Escherichia coli in conjunction with a chaperone protein. The results showed that the Sc-CAP protein binds to cholesterol, and docking analyses of sterols on the protein revealed potential molecular interactions. Immunoassays performed in Galleria mellonella larvae revealed that this venom protein has an inhibitory effect against phenoloxidase and the antimicrobial response of insects. This suggests that the venom protein has an immunomodulatory function against insects, emphasising its importance during the parasite–host interaction. Full article

Candida auris is an emerging multidrug-resistant fungal pathogen with a high affinity for skin colonization and significant potential for nosocomial transmission. This study aimed to develop and evaluate chitosan-based hydrogels loaded with nystatin and propolis as a topical antifungal strategy for skin decolonization of C. auris. The formulations were selected based on our previous results and optimized for cutaneous application. The internal structure of the hydrogels was investigated by polarized light microscopy, confirming the amorphous nature of propolis and the partial dispersion of nystatin. The antifungal activity was assessed against ten fluconazole-resistant C. auris strains. The CS-NYS-PRO1 formulation demonstrated the highest antifungal performance in the agar test, also reducing viable cell counts to undetectable levels within 6 h. Time–kill assays and SEM imaging confirmed the rapid fungicidal effect and revealed severe membrane disruption and cytoplasmic leakage. Molecular docking analyses indicated the strong binding of nystatin to both sterol 14α-demethylase (CYP51) and dihydrofolate reductase (DHFR) from C. auris, suggesting complementary membrane and intracellular mechanisms of action. These findings support the use of such hydrogels as a local, non-invasive, and biocompatible strategy for managing C. auris colonization, with promising implications for clinical use in infection control and the prevention of skin-mediated transmission in healthcare settings. Full article

Phytopythium vexans is a plant pathogen responsible for a variety of destructive diseases in crops worldwide. This includes patch canker, damping-off, root, and crown rots in economically important crops, such as apple, pear, grapevine, citrus, avocado, and kiwi. The pathogen has a global distribution, and a recent report confirmed its presence in southern Ontario, Canada. This study presents the first genome sequencing, assembly, and annotation of the Canadian P. vexans strain SS21. To explore how variation in secreted protein repertoires may relate to infection strategies and host adaptation, we compared the predicted secretome of SS21 with reference strains from Iran (CBS 119.80) and China (HF1). The analysis revealed that HF1 harbors a larger set of CAZymes, sterol-binding proteins, and predicted effectors, which may suggest broader adaptive potential. In contrast, strain SS21 appears to have adapted to a niche-specific strategy, with fewer necrosis-inducing proteins, glucanase inhibitors, and effectors, possibly indicating adaptation to specific hosts or ecological conditions. Comparative genome data highlight distinct evolutionary trajectories that may have shaped each strain’s infection strategy, with SS21 potentially serving as a robust additional reference for future studies on P. vexans biology and host interactions. While this analysis identifies key candidate effectors, gene expression studies are required to validate their functional roles in infection and host manipulation. Full article

Humans are continuously exposed to blue light from sunlight, computers, and smartphones. While blue light has been reported to affect living organisms, its role in fat synthesis and weight changes remains unclear. In this study, we investigated the effects of prolonged blue light exposure on weight changes in mice and the protective role of tranexamic acid (TA). Mice were exposed daily to blue light from a light-emitting diode for five months. Blue light exposure led to increased fat mass and body weight. The expression of the clock genes arnt-like 1 (Bmal1) and Clock was reduced in the brain and muscle of exposed mice. In addition, reduced Sirt1 and increased mammalian target of rapamycin complex 1 (mTORC1)/sterol regulatory element-binding protein 1 (SREBP1) were observed. The levels of liver X receptor a and liver kinase B1/5′AMP-activated protein kinase a1, both involved in SREBP1-mediated lipogenesis, were also elevated. TA treatment prevented the blue light-induced suppression of Bmal1/Clock and modulated the subsequent series of signal transduction. These findings suggest that prolonged blue light exposure suppresses the clock gene Bmal1/Clock, reduces Sirt1, and activates lipogenic pathways, contributing to weight gain. TA appears to regulate clock gene expression and mitigate blue light-induced weight gain. Full article

Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide–alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases. Full article

The study of the gas-phase behavior of proteins has recently gained momentum due to numerous prospective applications in, e.g., the construction of molecular sensors or nano-machines. The study of proteins outside their standard water environment, necessary to arrive at their successful applied use, is, however, limited by the loss of the structure and function of the macromolecules in the gas phase. We selected two enzymatic proteins with great potential for applied use, the digestive enzyme trypsin and the cytochrome sterol demethylase, for which to develop gas-phase structural models. The employed levels of theory were semiempirical, density functional tight binding, and polarizable force-field techniques. The convergence of the self-consistent field equations was very slow and in most cases led to oscillatory behavior, encouraging careful tuning of the convergence parameters. The structural optimization and molecular dynamics simulations indicated the parts of the proteins most prone to structural distortion under gas-phase conditions with unscreened electrostatics. This problem was more pronounced for cationic trypsin, for which the stability of the simulation was lower. The fate of the hydrogen bonding network of the catalytic triad in the gas phase was also investigated. Full article

Background/Objectives: Obesity is a major health concern that can lead to various chronic diseases. Little is known about the anti-obesity effect of a standardized hot water extract from the stems of Ipomoea batatas (WIB). This study aimed to evaluate the therapeutic potential of WIB as a natural alternative to conventional anti-obesity treatments by assessing its effects on body weight, fat accumulation, and key metabolic biomarkers in a high-fat diet-induced obesity model. Methods: A high-fat diet (HFD) induced obesity in C57BL/6 mice. The mice were then treated orally with either orlistat (positive control) or WIB. Changes in body weight, food intake, and fat weight were measured, along with blood lipid profiles and adipokines. Western blot analyses were conducted to determine protein levels in each tissue. H&E staining in white adipose tissue and liver, and the gut microbiota composition were analyzed. Results: WIB treatment significantly reduced body weight and fat mass compared to the HFD group and demonstrated comparable effects to orlistat. WIB improved blood lipid profiles and adipokine levels. H&E staining revealed reduced fat accumulation in the white adipose tissue and liver. Also in those tissues, WIB restored expression levels of sterol regulatory element-binding protein-1 (SREBP-1) and CCAAT/enhancer-binding protein α (C/EBPα) and increased AMP-activated protein kinase (AMPK) phosphorylation. In brown adipose tissue, WIB enhanced AMPK phosphorylation and upregulated thermogenic-related proteins, including peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), sirtuin 1 (SIRT1), uncoupling protein-1 (UCP-1), and cytochrome C oxidase subunit 4 (COX-IV). Analysis of gut microbiota revealed that WIB normalized β-diversity and reversed HFD-induced phyla imbalances (notably in Bacteroidetes, Firmicutes, and Proteobacteria). Conclusions: By reducing adiposity under the conditions tested in a murine model, improving metabolic markers, and favorably modulating gut microbiota, WIB demonstrates potential in mitigating obesity-related risks. These findings suggest that WIB may serve as a promising natural substance for the management of obesity. Further studies are warranted to confirm its efficacy and explore the potential underlying mechanisms in overweight or obese humans as a health supplement to help manage or prevent obesity. Full article

The difference in chicken egg production is closely related to the efficiency of follicle selection, which is marked by granulosa cell differentiation and progesterone production with cholesterol as the substrate. The conversion of 7-dehydrocholesterol to cholesterol catalyzed by 7-Dehydrocholesterol reductase (DHCR7) is the rate-limiting step in cholesterol synthesis. Our previous study revealed that estrogen enhanced the mRNA expression of three DHCR7 transcript variants (T1, T3, and T4) in a dose-dependent manner in the granulosa cells of chicken pre-hierarchical follicles (Pre-GCs). This study investigates the molecular mechanisms through which estrogen regulates DHCR7 in chicken Pre-GCs. At the transcriptional level, through CUT&RUN-qPCR, we found that under basal conditions, sterol-regulatory element binding protein 2 (SREBP2) bound to the promoters of three DHCR7 transcript variants to promote cholesterol synthesis in Pre-GCs to maintain low cholesterol levels; meanwhile upon estrogen treatment, estrogen receptors α and β bound to the regulatory regions of three chicken DHCR7 transcript variants, leading to a reduction in the interaction between SREBP2 and DHCR7. At the translational level, the upstream open reading frames (uORFs) and N6-methyladenosine (m⁶A) modification in the 5′UTR of different DHCR7 transcripts differentially regulate the expression of T3 and T4, as detected by dual-luciferase reporter assays, but this regulation is not affected by estrogen. This study systematically explores the molecular mechanisms through which estrogen upregulates DHCR7 expression in chicken Pre-GCs and provides a clue for understanding the molecular mechanisms underlying cholesterol synthesis in chicken ovarian follicles. Full article

Background:Taraxacum officinale(commonly known as dandelion) is a medicinal and edible plant, with the entire plant being used for therapeutic purposes. Studies have demonstrated that dandelion exhibits inhibitory effects against various types of cancer. However, research on its potential for lung cancer (LC) treatment is limited, and the specific compounds responsible for its anticancer effects, as well as the underlying mechanisms, remain unclear. Methods: This study aimed to elucidate the underlying pharmacological mechanisms by which dandelion exerts therapeutic effects against LC. Initially, active compounds of dandelion and their corresponding targets were retrieved from public databases. Subsequently, network pharmacology approaches were applied to identify LC-associated disease targets. By integrating drug-specific targets and disease-related targets, a comprehensive dandelion–lung cancer interaction network was established. Protein–protein interaction (PPI) analyses and functional enrichment studies were further performed to uncover potential molecular mechanisms. Additionally, molecular docking and molecular dynamics (MD) simulations were conducted to evaluate binding interactions between critical active constituents and core targets. To experimentally validate these findings, in vitro cellular assays combined with scanning electron microscopy (SEM) were employed to investigate the anticancer effects of taraxasterol, a key bioactive sterol compound isolated from dandelion, on LC cells. Results: Our analyses identified 58 active compounds in dandelion linked to 614 potential targets, of which 228 targets were associated with LC. The PPI network highlighted 16 core targets, notably TP53, CASP3 and EGFR. Functional enrichment analysis suggested that dandelion might exert its anticancer effects by modulating the tumor microenvironment through the regulation of these critical targets. Molecular docking results demonstrated stable binding interactions between major active compounds and the identified core targets. Furthermore, the anticancer activity of taraxasterol was experimentally validated through in vitro assays and SEM-based morphological assessments, confirming its inhibitory effects on A549 lung cancer cells. Conclusions: Collectively, our findings reveal a multi-targeted therapeutic mechanism of dandelion against LC and support its potential development as a novel natural candidate for lung cancer treatment. Full article

Hypercapnia, the elevation of CO₂ in blood and tissue, is a risk factor for mortality in patients with severe lung disease and pulmonary infections. We previously showed that hypercapnia increases viral replication and mortality in mice infected with influenza A virus (IAV). Elevated CO₂ also augmented cholesterol content and pseudo-SARS-CoV-2 entry in bronchial epithelial cells. Interestingly, cellular cholesterol facilitates IAV uptake, replication, assembly, and egress from cells. Here, we report that hypercapnia increases viral protein expression in airway epithelium of mice infected with IAV. Elevated CO₂ also enhanced IAV adhesion and internalization, viral protein expression, and viral replication in bronchial epithelial cells. Hypercapnia increased the expression and activation of the transcription factor sterol-regulatory element binding protein 2 (SREBP2), resulting in elevated expression of cholesterol synthesis enzymes, decreased expression of a cholesterol efflux transporter, and augmented cellular cholesterol. Moreover, reducing cellular cholesterol with an SREBP2 inhibitor or statins blocked hypercapnia-induced increases in viral adhesion and internalization, viral protein expression, and IAV replication. Inhibitors of mTOR and Akt also blocked the effect of hypercapnia on viral growth. Our findings suggest that targeting cholesterol synthesis and/or mTOR/Akt signaling may hold promise for reducing susceptibility to influenza infection in patients with advanced lung disease and hypercapnia. Full article

High-fat diets (HFDs) have been found to compromise male fertility, with cholesterol dysregulation being a key factor. Sterol regulatory element-binding protein 2 (SREBP2) is a crucial transcription factor that regulates cholesterol biosynthesis and uptake, playing an essential role in maintaining cholesterol homeostasis in the testes. This study investigated the dynamics of SREBP2 and cholesterol levels during rabbit spermatogenesis under HFD conditions. Our findings reveal that SREBP2 expression fluctuates throughout the seminiferous epithelium cycle. However, HFDs induce stage-specific disruptions in cholesterol balance, leading to sperm with increased membrane cholesterol, a reduced sperm count in semen analysis, impaired motility, abnormal morphology, and decreased functionality. In the control group, SREBP2 expression patterns underscored its critical role in normal spermatogenesis. Interestingly, supplementation with extra virgin olive oil (EVOO) reversed the negative effects of HFD, normalizing SREBP2 expression and cholesterol content, which improved sperm quality. These findings emphasize the importance of stage-specific analysis in understanding how dietary fat impacts male fertility and suggest that EVOO may serve as a potential nutritional intervention to protect reproductive health. Full article

Obesity is a significant global health issue, profoundly affecting metabolic and cardiovascular health and other related chronic conditions. In Chile, the prevalence of obesity is among the highest within the Organisation for Economic Cooperation and Development (OECD) countries, highlighting a critical public health challenge. This narrative review examines current evidence on the independent and potential synergistic roles of omega-3 fatty acids and exercise in managing obesity-related metabolic dysfunction. Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), have been shown to lower triglyceride levels, enhance lipid metabolism, and modulate inflammation via pathways involving peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). Exercise interventions, such as moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT), provide distinct yet complementary metabolic benefits. Specifically, MICT improves body fat distribution and mitochondrial efficiency, whereas HIIT has notable effects on metabolic adaptability and insulin signaling. Additionally, emerging evidence points toward a potential role of the kinin-kallikrein system, particularly kallikrein 7 (KLK7), in obesity-associated insulin resistance. Despite these promising findings, several knowledge gaps persist regarding optimal dosing, intervention timing, population-specific effects, and the exact mechanisms behind the potential synergistic interactions between omega-3 supplementation and structured exercise. This review emphasizes the importance of conducting further research, particularly controlled clinical trials, to clarify these combined interventions’ effectiveness and establish targeted therapeutic strategies tailored to individual metabolic profiles. Full article

The rising prevalence of non-alcoholic fatty liver disease among patients with type 2 diabetes mellitus has emerged as a global health challenge. Gossypetin (GTIN) is a natural flavonoid which has recently demonstrated antihyperglycaemic, antioxidant, and anti-inflammatory effects. Despite these findings, no studies have investigated its effects on liver health in the pre-diabetic state. Hence, this study aimed to investigate the effects of GTIN on liver health in diet-induced pre-diabetic male rats in the presence and absence of dietary intervention and to compare these effects with those of metformin (MET). Following 20 weeks of pre-diabetes induction, the animals were divided into six groups (n = 6) as follows: non-pre-diabetic (NPD) control, pre-diabetic (PD) control, and PD groups treated with GTIN (15 mg/kg body weight (bw)) or metformin (500 mg/kg bw) on either a normal diet or a high-fat, high-carbohydrate diet for 12 weeks. The results showed that the PD group had significantly higher liver triglycerides (TAG), liver weights, sterol regulatory binding element regulatory protein-1c (SREBP-1c), malondialdehyde (MDA) levels, and liver injury enzyme levels, along with decreased liver superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and plasma bilirubin levels in comparison to NPD. Histologically, there was an increased lipid droplet accumulation and structural disarray in the PD group. GTIN treatment significantly reduced liver TAGs, liver weights, and plasma SREBP-1c levels, as well as improved liver SOD and GPx activity while decreasing liver MDA levels and liver injury enzymes in comparison to the PD control. Notably, GTIN treatment increased plasma bilirubin levels. Liver histology in the GTIN-treated groups revealed decreased lipid droplet accumulation and improved tissue integrity. Similar results were observed for the liver parameters in the MET-treated groups. The findings of this study may suggest that GTIN and MET exhibit therapeutic effects on liver health in diet-induced pre-diabetes in both the presence and absence of diet intervention. Dietary intervention may confer beneficial effects on liver health, with the most favorable therapeutic outcomes observed through a combination of treatment with dietary intervention. Additionally, GTIN may exhibit greater hepatoprotective effects than MET in rats without dietary intervention. Full article