Search Results (2,483)

Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance of discerning the role of different cellular proteins involved in VLDL biogenesis, transport, and secretion. Small VCP-Interacting Protein (SVIP) has been identified as a component of VLDL transport vesicles and VLDL secretion. This study evaluates the cellular effects stemming from the CRISPR-Cas9-mediated depletion of SVIP in rat hepatocytes. The SVIP-knockout (KO) cells display an increased VLDL retention with elevated intracellular levels of ApoB100 and neutral lipid staining. RNA sequencing studies reveal an impaired PPARα and Nrf2 signaling in the SVIP KO cells, implying a state of metabolic reprograming, with a shift from fatty acid uptake, synthesis, and oxidation to cells favoring the activation of glucose by impaired glycogen storage and increased glucose release. Additionally, SVIP KO cells exhibit a transcriptional profile indicative of acute phase response (APR) in hepatocytes. Many inflammatory markers and genes associated with APR are upregulated in the SVIP KO hepatocytes. In accordance with an APR-like response, the cells also demonstrate an increase in mRNA expression of genes associated with protein synthesis. Together, our data demonstrate that SVIP is critical in maintaining hepatic lipid homeostasis and metabolic balance by regulating key pathways such as PPARα, Nrf2, and APR. Full article

Childhood obesity increases chronic disease risk, but no comprehensive synthesis has evaluated the impact of school-based combined nutrition education and physical activity interventions on cardiometabolic biomarkers in children aged 3 to 12 years. This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251085194). Five databases were systematically searched through June 2025. Twelve randomized controlled trials involving 18,231 children were included and assessed using the PEDro scale. Ten trials demonstrated significant improvements in at least one cardiometabolic biomarker. Blood pressure (8 studies) outcomes showed systolic reductions of 1.41–6.0 mmHg in six studies. Glucose metabolism (5 studies) improved in two studies with reductions of 0.20–0.22 mmol/L. Lipid profiles (7 studies) improved in three studies, including total cholesterol (−0.32 mmol/L). Insulin levels (5 studies) decreased significantly in two investigations. Anthropometric improvements included BMI and body fat. Physical activity increased by >45 min/week and dietary habits improved significantly. Programs with daily implementation (90-min sessions 4x/week), longer duration (≥12 months), family involvement (parent education), and curriculum integration (classroom lessons) showed superior effectiveness. Interventions targeting children with overweight/obesity demonstrated higher changes compared to the general population. However, methodological limitations included a lack of assessor blinding, absence of subject/therapist blinding, and inadequate retention rates. School-based interventions combining nutrition and physical activity can produce significant improvements in cardiometabolic biomarkers, supporting comprehensive, sustained multicomponent programs for early chronic disease prevention. Full article

Cardiac arrhythmias remain a major source of morbidity and mortality, often stemming from molecular and structural abnormalities that are insufficiently addressed by current pharmacologic and interventional therapies. Gene therapy has emerged as a transformative approach, offering precise and durable interventions that directly target the arrhythmogenic substrate. Across the spectrum of inherited and acquired arrhythmias—including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and post-infarction ventricular tachycardia—gene-based strategies such as allele-specific silencing, gene replacement, CRISPR-mediated editing, and suppression-and-replacement constructs are showing growing translational potential. Advances in delivery platforms, including cardiotropic viral vectors, lipid nanoparticle-encapsulated mRNA, and non-viral reprogramming tools, have further enhanced the specificity and safety of these approaches. Additionally, innovative applications such as biological pacemaker development and mutation-agnostic therapies underscore the versatility of genetic modulation. Nonetheless, significant challenges remain, including vector tropism, immune responses, payload limitations, and the translational gap between preclinical models and human electrophysiology. Integration of patient-derived cardiomyocytes, computational simulations, and large-animal studies is expected to accelerate clinical translation. This review provides a comprehensive synthesis of the mechanistic rationale, therapeutic strategies, delivery platforms, and translational frontiers of gene therapy for cardiac arrhythmias. Full article

Doxorubicin-induced cardiotoxicity (DIC) significantly constrains the clinical efficacy of anthracycline chemotherapy, primarily through the induction of ferroptosis, an iron-dependent, regulated cell death driven by oxidative stress and lipid peroxidation. However, the upstream regulators of ferroptosis in DIC remain incompletely defined. Cold-inducible RNA-binding protein (CIRBP) exhibits cardioprotective effects in various pathological contexts, but its precise role in ferroptosis-related cardiotoxicity is unknown. This study investigated whether CIRBP mitigates DIC by modulating the ferroptosis pathway via the SLC7A11 (Solute carrier family 7 member 11)/GPX4 (Glutathione peroxidase 4) axis. We observed marked downregulation of CIRBP in cardiac tissues and cardiomyocytes following doxorubicin exposure. CIRBP knockout significantly exacerbated cardiac dysfunction, mitochondrial damage, oxidative stress, and lipid peroxidation, accompanied by increased mortality rates. Conversely, CIRBP overexpression alleviated these pathological changes. Molecular docking and dynamics simulations, supported by transcriptomic analyses, revealed direct binding of CIRBP to the 3′-UTR of Slc7a11 mRNA, enhancing its stability and promoting translation. Correspondingly, CIRBP deficiency markedly suppressed SLC7A11 and GPX4 expression, impairing cystine uptake, glutathione synthesis, and antioxidant defenses, thus amplifying ferroptosis. These ferroptotic alterations were partially reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, this study identifies CIRBP as a critical regulator of ferroptosis in DIC, elucidating a novel post-transcriptional mechanism involving Slc7a11 mRNA stabilization. These findings offer new insights into ferroptosis regulation and highlight CIRBP as a potential therapeutic target for preventing anthracycline-associated cardiac injury. Full article

Cloudy huyou juice is increasingly popular for its unique flavor, but flocculent precipitation after cold storage and thawing affects its sensory quality and increases production costs. This study optimized the clarification of thawed cloudy huyou juice using a composite of carboxymethyl chitosan (CC) and sodium alginate (SA), prepared via ionic and covalent crosslinking. The composite was characterized by SEM, FTIR, and thermal analysis. Transmittance was used to evaluate clarification performance. The effects of dosage, adsorption time, and temperature were first assessed through single-factor experiments, followed by optimization using a Box–Behnken response surface methodology. The composite significantly improved clarity (p < 0.05), reaching 85.38% transmittance under optimal conditions: 22 mg dosage, 80 min time, and 38 °C. The composite dosage and temperature were the most influential factors. Reusability tests showed declining performance, with the transmittance dropping to 57.13% after five cycles, likely due to incomplete desorption of adsorbed compounds. These results suggest that the CC-SA composite is an effective and reusable clarifying agent with potential for industrial applications in turbid fruit juice processing. Full article

The food industry consumes large amounts of water across various processes, and generates wastewater characterized by parameters like biochemical oxygen demand, chemical oxygen demand, pH, suspended solids, and nutrients. To meet environmental standards and enable reuse or valorization, treatment methods such as physicochemical, biological, and membrane-based processes are applied. This review focuses on the valorization of food industry wastewater in the biotechnological production of high-value products, with an emphasis on starch-rich wastewater, wineries and confectionery industry wastewater, and with a focus on new technologies for reduces environmental burden but also supports circular economy principles. Starch-rich wastewaters, particularly those generated by the potato processing industry, offer considerable potential for biotechnological valorization due to their high content of soluble starch, proteins, organic acids, minerals, and lipids. These effluents can be efficiently converted by various fungi (e.g., Aspergillus, Trichoderma) and yeasts (e.g., Rhodotorula, Candida) into value-added products such as lipids for biodiesel, organic acids, microbial proteins, carotenoids, and biofungicides. Similarly, winery wastewaters, characterized by elevated concentrations of sugars and polyphenols, have been successfully utilized as medium for microbial cultivation and product synthesis. Microorganisms belonging to the genera Aspergillus, Trichoderma, Chlorella, Klebsiella, and Xanthomonas have demonstrated the ability to transform these effluents into biofuels, microbial biomass, biopolymers, and proteins, contributing to sustainable bioprocess development. Additionally, wastewater from the confectionery industry, rich in sugars, proteins, and lipids, serves as a favorable fermentation medium for the production of xanthan gum, bioethanol, biopesticides, and bioplastics (e.g., PHA and PHB). Microorganisms of the genera Xanthomonas, Bacillus, Zymomonas, and Cupriavidus are commonly employed in these processes. Although there are still certain regulatory issues, research gaps, and the need for more detailed economic analysis and kinetics of such production, we can conclude that this type of biotechnological production on waste streams has great potential, contributing to environmental sustainability and advancing the principles of the circular economy. Full article

Tellurite (TeO₃²⁻) is a highly soluble and toxic oxyanion that inhibits the growth of Escherichia coli at concentrations as low as ~1 µg/mL. This toxicity has been primarily attributed to the generation of reactive oxygen species (ROS) during its intracellular reduction by thiol-containing molecules and NAD(P)H-dependent enzymes. However, under anaerobic conditions, E. coli exhibits significantly increased tellurite tolerance—up to 100-fold in minimal media—suggesting the involvement of additional, ROS-independent mechanisms. In this study, we combined chemical-genomic screening, untargeted metabolomics, and targeted biochemical assays to investigate the effects of tellurite under both aerobic and anaerobic conditions. Our findings reveal that tellurite perturbs amino acid and nucleotide metabolism, leading to intracellular imbalances that impair protein synthesis. Additionally, tellurite induces notable changes in membrane lipid composition, particularly in phosphatidylethanolamine derivatives, which may influence biophysical properties of the membrane, such as fluidity or curvature. This membrane remodeling could contribute to the increased resistance observed under anaerobic conditions, although direct evidence of altered membrane fluidity remains to be established. Overall, these results demonstrate that tellurite toxicity extends beyond oxidative stress, impacting central metabolic pathways and membrane-associated functions regardless of oxygen availability. Full article

In this study, the design and synthesis of a novel series of cinnamic acid and 1,2,4-triazole hybrids were reported, aiming to enhance antioxidant and lipoxygenase inhibitory activities through pharmacophore combination. Cinnamic acid derivatives and 1,2,4-triazoles exhibit a broad spectrum of biological activities; therefore, by synthesizing hybrid molecules, we would like to exploit the beneficial characteristics of each scaffold. The general synthetic procedure comprises three synthetic steps, starting from the reaction of appropriate substituted cinnamic acid with hydrazine monohydrate in acetonitrile with cyclohexane and resulting in the formation of hydrazides. Consequently, the hydrazides reacted with phenylisothiocyanate under microwave irradiation conditions. Then, cyclization proceeded to the 1,2,4-triazole after the addition of NaOH solution and microwave irradiation. All the synthesized derivatives have been studied for their ability (a) to interact with the free radical DPPH, (b) inhibit lipid peroxidation induced by AAPH, and (c) inhibit soybean lipoxygenase. The synthesized derivatives have shown significant antioxidant activity and have been proved to be very good lipoxygenase inhibitors. Compounds 4b and 4g (IC₅₀ = 4.5 μM) are the most potent within the series followed by compound 6a (IC₅₀ = 5.0 μM). All the synthesized derivatives have been subjected to docking studies related to soybean lipoxygenase. Compound 4g exhibited a docking score of −9.2 kcal/mol and formed hydrophobic interactions with Val126, Tyr525, Lys526, Arg533, and Trp772, as well as a π−cation interaction with Lys526. Full article

The objective of this experiment was to investigate the effects of tartary buckwheat flavonoids (TBF) and 25-hydroxyvitamin D₃ (25-OHD) on fatty liver syndrome (FLS) in laying hens. A total of 450 35-wk-old Lohmann laying hens were selected and randomly divided into five groups, with six replicates per treatment and 15 laying hens in each replicate. The control group was fed a corn-soybean meal basal diet. The FLS group was fed a high- energy–low-protein (HELP) diet, and the other three experimental groups were fed HELP diets supplemented with 60 mg/kg TBF, 69 μg/kg 25-OHD, and 60 mg/kg TBF plus 69 μg/kg 25-OHD, respectively. The experiment lasted 8 weeks. The results demonstrated that feeding laying hens with a HELP diet led to a significant accumulation of fat in their livers, liver enlargement and yellowing, as well as a decline in liver antioxidant capacity and an aggravation of inflammation. TBF alone, 25-OHD alone, and their combination had no effect on the laying performance of laying hens fed with a HELP diet. However, 25-OHD significantly enhanced the albumin content, eggshell strength, and eggshell thickness of eggs (p < 0.05). Compared with the HELP group, TBF, 25-OHD, or their combination reduced serum LDL-C and TG (p < 0.05). The combined treatment further lowered serum NEFA and MDA, enhanced liver SOD activity (p < 0.05), and unlike TBF alone (which reduced hepatic TG) or 25-OHD alone (which decreased liver index), reduced both liver index and hepatic TG (p < 0.05). Liver gene expression analysis showed that combined TBF and 25-OHD significantly inhibited the expression of fat synthesis-related genes (ACC, FAS, GPAT1, ChREBP1, LXRα, SREBP-1C, SREBP-2, FABP) as well as inflammation-related genes (IL-6, TNF-α, NF-κB, TLR4) (p < 0.05). At the phylum level of the cecal microbiota, TBF increased the abundance of Bacteroidota (p < 0.05), and combined TBF and 25-OHD tended to increase the abundance of Firmicutes_D. At the genus level, TBF increased the abundance of Phocaeicola_A (p < 0.05). Furthermore, TBF, 25-OHD, or their combination reduced the abundance of Faecalibacterium (p < 0.05). These findings suggest that combined TBF and 25-OHD mitigates FLS in laying hens potentially through remodeling gut microbiota and maintaining lipid metabolic homeostasis. Full article

Background: Blackberry seed oil (BSO), obtained from Rubus spp. Xavante cultivar via supercritical CO₂ extraction, contains bioactive lipids and antioxidants, but its cosmetic application is limited by poor solubility and stability. Nanoencapsulation with poly(ε-caprolactone) (PCL) can overcome these limitations. Methods: BSO was characterized by Ultra-High-Performance Liquid Chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and incorporated into PCL nanocapsules (NCBSO) using the preformed polymer deposition method. Physicochemical properties, stability (at 4 °C, room temperature, and 37 °C for 90 days), cytotoxicity, and collagen production were assessed in human fibroblasts. Additionally, a predictive in silico analysis using PASS Online, Molinspiration, and SEA platforms was performed to identify the bioactivities of major BSO compounds related to collagen synthesis, antioxidant potential, and anti-aging effects. Results: NCBSO showed a nanometric size of ~267 nm, low polydispersity (PDI < 0.2), negative zeta potential (−28 mV), and spherical morphology confirmed by FE-SEM. The dispersion remained stable across all tested temperatures, preserving pH and colloidal properties. In particular, BSO and NCBSO at 100 µg.mL⁻¹ significantly enhanced in vitro collagen production by 170% and 200%, respectively, compared to untreated cells (p < 0.01). Superior bioactivity was observed for NCBSO. The in silico results support the role of key compounds in promoting collagen biosynthesis and protecting skin structure. No cytotoxic effects were achieved. Conclusions: The nanoencapsulation of BSO into PCL nanocapsules ensured formulation stability and potentiated collagen production. These findings support the potential of NCBSO as a promising candidate for future development as a collagen-boosting cosmeceutical. Full article

Cirrhosis remains a significant global health burden, responsible for nearly 4% of annual deaths worldwide. Despite progress in antiviral therapies and public health measures, its prevalence has plateaued, particularly in regions affected by viral hepatitis, alcohol misuse, and metabolic syndrome. This review presents a comprehensive synthesis of the multifactorial drivers of cirrhosis, including hepatocyte injury, liver stellate cell activation, and immune-mediated inflammation. The emphasis is on the central role of metabolic dysfunction, characterized by mitochondrial impairment, altered lipid and glucose metabolism, hormonal imbalance, and systemic inflammation, in exacerbating disease progression. While current therapies may slow the progression of early-stage disease, they are very often ineffective in reversing established fibrosis. Emerging molecular strategies offer promising alternatives by targeting key pathogenic pathways. These include AMPK activators (e.g., metformin, AICAR), FGF21 analogs, and mitochondria-targeted agents (e.g., MitoQ, urolithin A, NAD+ precursors) to restore bioenergetic balance and reduce oxidative stress. Other approaches, such as mesenchymal stem cell therapy, inflammasome inhibition, and hormonal modulation, aim to suppress fibrogenesis and restore liver homeostasis. The integration of systems biology and multi-omics profiling supports patient stratification and precision medicine. This review highlights a shift toward mechanism-based interventions that have the potential to alter cirrhosis outcomes and improve patient survival. Full article

Hypercholesterolemia is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), affecting a significant proportion of the adult population worldwide. This narrative review provides a comprehensive and up-to-date overview of hyperlipidemia management, spanning from epidemiological trends and underlying pathophysiological mechanisms to the limitations of conventional therapies such as statins and ezetimibe. Particular emphasis is placed on cardiovascular risk assessment, current stratification tools, and international guideline-based interventions. The present paper, focusing primarily on the biological mechanisms of dyslipidemia and the clinical use of traditional lipid-lowering agents, serves as the first part of a two-part series, preceding a forthcoming review of novel pharmacological approaches. Our data synthesis is based on a structured literature search conducted across Google Scholar, PubMed, and Scopus, including studies published up to June 2025. The review also includes aspects related to non-pharmacological strategies, pharmacoeconomic considerations, and pharmacogenetic influences on treatment response. Ultimately, this work aims to equip clinicians with evidence-based, nuanced insights essential for optimizing lipid management and reducing cardiovascular risk, while setting the foundation for understanding how emerging therapies may overcome current therapeutic limitations. Full article

Hyperlipidemia (HLP) is a disorder of human lipid metabolism or transport, primarily characterized by abnormally elevated levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) in the blood. It is a key factor contributing to the development of non-alcoholic fatty liver disease, obesity, diabetes, atherosclerosis, and cardiovascular and cerebrovascular diseases. Statistics show that the prevalence of dyslipidemia among Chinese adults is as high as 35.6%, and it has shown a trend of younger onset in recent years, posing a serious threat to public health. Therefore, the prevention and treatment of dyslipidemia carry significant social significance. The pathogenesis of hyperlipidemia is complex and diverse, and currently used medications are often accompanied by side effects during treatment, making the research and development of new therapeutic approaches a current focus. Numerous studies have shown that flavonoids, which are abundant in most medicinal plants, fruits, and vegetables, exert effects on regulating lipid homeostasis and treating hyperlipidemia through a multi-target mechanism. These compounds have demonstrated significant effects in inhibiting lipid synthesis, blocking lipid absorption, promoting cholesterol uptake, enhancing reverse cholesterol transport, and suppressing oxidative stress, inflammation, and intestinal microbiota disorders. This article reviews the latest progress in the mechanisms of flavonoids in the treatment of hyperlipidemia, providing a theoretical basis for future research on drugs for hyperlipidemia. Full article

Dietary administration of fermented goat milk (FGM) with the starter strain Lactobacillus delbrueckii subsp. indicus CRL1447 and supplemented with different functional cultures (FCs) of lactobacilli strains (FC1: Limosilactobacillus fermentum CRL1446 + Lactiplantibacillus paraplantarum CRL1449 + Lactiplantibacillus paraplantarum CRL1472; FC2: CRL1446 + CRL1449; FC3: CRL1446 + CRL1472; and FC4: CRL1449 + CRL1472) was investigated in mice fed a high-fat diet (HFD). FGM supplemented with different FCs, referred to as Probiotic Goat Milk (PGM), demonstrated significant anti-obesity activity by reducing body weight and improving blood lipid profiles in obese mice. The animals that received the PGM showed less fat infiltration in the hepatocytes compared to the obese mice fed FGM. Hepatic proteomics data show that HFD generally upregulates proteins involved in fatty acid oxidation and downregulates proteins implicated in lipid synthesis, whereas the administration of FGM supplemented with FC3 (PGM3) improves the proteomic profile. These results suggest that PGM exerts systemic metabolic effects through modulation of the gut–liver axis, highlighting its potential as a dietary strategy against obesity-related disorders. Full article

Ancient grains, including wild rice, millet, fonio, teff, quinoa, amaranth, and sorghum, are re-emerging as vital components of modern diets due to their dense nutritional profiles and diverse health-promoting bioactive compounds. Rich in high-quality proteins, dietary fiber, essential micronutrients, and a broad spectrum of bioactive compounds such as phenolic acids, flavonoids, carotenoids, phytosterols, and betalains, these grains exhibit antioxidant, anti-inflammatory, antidiabetic, cardioprotective, and immunomodulatory properties. Their health-promoting effects are underpinned by multiple interconnected mechanisms, including the reduction in oxidative stress, modulation of inflammatory pathways, regulation of glucose and lipid metabolism, support for mitochondrial function, and enhancement of gut microbiota composition. This review provides a comprehensive synthesis of the essential nutrients, phytochemicals, and functional properties of ancient grains, with particular emphasis on the nutritional and molecular mechanisms through which they contribute to the prevention and management of chronic diseases such as cardiovascular disease, type 2 diabetes, obesity, and metabolic syndrome. Additionally, it highlights the growing application of ancient grains in functional foods and nutrition-sensitive dietary strategies, alongside the technological, agronomic, and consumer-related challenges limiting their broader adoption. Future research priorities include well-designed human clinical trials, standardization of compositional data, innovations in processing for nutrient retention, and sustainable cultivation to fully harness the health, environmental, and cultural benefits of ancient grains within global food systems. Full article