Search Results (7,688)

Introduction: The metabolic complications and poor biocompatibility of conventional glucose-based (GLU) peritoneal dialysis fluid (PDF) have driven the need for improved alternatives. To address this, we developed and evaluated a novel PDF utilizing succinylated gelatin (GEL) as osmotic agent and citrate as buffer, designed to provide effective solute clearance while offering enhanced biocompatibility. Methods: Physicochemical parameters (pH and osmolality) of the novel GEL-PDF were measured. Its performance was assessed in rats with chronic kidney disease. A total of 20 rats were randomized into short-term experiments to evaluate 4 h creatinine clearance and ultrafiltration (UF). A 12-week long-term experiment (n = 35) compared the GEL-PDF against normal saline (NS), GLU, and icodextrin-based (ICO) PDFs, monitoring survival, biochemical parameters, peritoneal membrane histology, and kidney histology. Results: The GEL-PDF demonstrated a neutral pH (7.30) and lower osmolality (317 mOsm/L) compared to GLU-PDF. In the short-term experiment, GEL-PDF achieved effective creatinine clearance by 4 h and provided higher 4 h UF than NS and GLU, comparable to ICO. However, during prolonged dwells (6–16 h), its UF was inferior to ICO. In the long-term experiment, GEL-PDF preserved peritoneal membrane structure, showing the least thickness and collagen deposition. Furthermore, the GEL-PDF demonstrated superior preservation of serum albumin compared to the GLU-PDF. It also exhibited a more favorable lipid profile, as evidenced by significantly lower total cholesterol levels than the ICO group at 12 weeks (p = 0.035), with no adverse effects on electrolytes, liver function, or glucose metabolism. Conclusions: The novel GEL and citrate-based PDF provide effective short-dwell UF and solute removal while exhibiting superior biocompatibility, as evidenced by significant protection against peritoneal membrane injury and favorable metabolic profiles. Although its long-duration UF was lower than that of ICO, it substantially outperformed GLU-PDF. These properties position the GEL-PDF as a promising candidate for short- to medium-dwell exchanges, particularly for daytime use, where it could fill an important clinical gap by providing enhanced UF without the high GLU exposure associated with conventional PDF. Full article

Background: Parkinson’s disease (PD) is increasingly recognized as a multisystem disorder in which metabolic dysfunction may contribute to disease susceptibility and progression. Peripheral insulin resistance (IR) has been implicated in PD, but data in levodopa-naïve patients are currently limited. Objective: To investigate the prevalence of IR and metabolic dysfunction in early-stage, levodopa-naïve PD patients and their association with clinical features. Methods: We conducted an exploratory case–control study including 20 levodopa-naïve PD patients and 40 age-, sex-, and BMI-matched healthy controls. Participants underwent comprehensive clinical and metabolic assessments, including fasting glucose, insulin, lipid profiles, and HOMA-IR calculation. Peripheral IR was defined using HOMA-IR cut-offs of ≥2.0 (primary analysis) and ≥2.5 (sensitivity analysis). ANCOVA adjusted for age, sex, and BMI was used for between-group comparisons. Results: PD patients exhibited higher fasting insulin (10.7 ± 5.2 vs. 8.0 ± 4.4 µIU/mL; p = 0.020) and HOMA-IR (2.63 ± 1.40 vs. 1.89 ± 1.21; p = 0.014) compared to controls. Using a HOMA-IR ≥ 2.0, IR prevalence was 70% in PD vs. 32.5% in controls (OR = 4.85, 95% CI 1.52–15.50, p = 0.012). ANCOVA analysis confirmed group differences after adjusting for covariates (respectively, p = 0.032 for insulin and p = 0.023 for HOMA-IR). A sensitivity analysis excluding six patients receiving dopaminergic therapy further supported the robustness of the results. No significant correlations were observed between IR and disease severity scores. Conclusions: Early-stage, levodopa-naïve PD patients exhibit a higher prevalence of peripheral insulin resistance compared with matched controls. These findings support the hypothesis that metabolic dysfunction is an intrinsic component of PD pathophysiology and may represent a target for early intervention. Full article

Fucoxanthin, a marine carotenoid abundantly derived from brown algae, has been increasingly recognized for its broad-spectrum antitumor activities; however, its role in regulating ferroptosis remains insufficiently defined. Hypopharyngeal carcinoma is a highly aggressive head and neck malignancy with limited therapeutic options, highlighting the need for novel marine-derived anticancer agents. In this study, we investigated whether fucoxanthin induces ferroptosis in human hypopharyngeal carcinoma cells (Fadu) and elucidated the underlying molecular mechanisms. Transcriptome profiling combined with in vitro validation revealed that fucoxanthin markedly upregulated heme oxygenase−1 (HO−1), leading to increased intracellular Fe²⁺ levels, excessive reactive oxygen species (ROS) generation, and pronounced lipid peroxide accumulation. Fucoxanthin simultaneously reduced cysteine and glutathione (GSH) levels, disrupted mitochondrial membrane potential, and triggered ferroptotic cell death, which was significantly reversed by the ferroptosis inhibitor ferrostatin−1. Mechanistically, fucoxanthin activated the p53 pathway while suppressing SLC7A11 and GPX4, thereby impairing antioxidant defenses. Pharmacological inhibition of p53 with Pifithrin−α markedly attenuated fucoxanthin-induced cytotoxicity and ferroptosis. Together, these findings identify fucoxanthin as a promising marine-derived compound capable of inducing ferroptosis via modulation of the p53/SLC7A11/GPX4 axis, providing new insights into its potential application in hypopharyngeal carcinoma therapy. Full article

Obesity is associated with profound metabolic, inflammatory, and neurobehavioral dysfunctions. Dietary interventions leading to weight loss are commonly employed, yet it remains unclear whether all obesity-related alterations are fully reversed upon reaching normal body weight. Poor adherence to dietary regimens often results in weight cycling, or yo-yo dieting, characterized by repeated episodes of weight gain and loss, a phenomenon linked to adverse health outcomes. Here, we investigated the consequences of weight cycling in C57BL/6J mice. The Control Group was maintained on a standard chow diet throughout the protocol, whereas the experimental group underwent two alternating cycles of high-fat diet feeding (weight gain) and standard diet reversion (weight loss), until the end of the protocol where both groups reached 80 weeks of age. Despite achieving a final body weight and glucose and lipid metabolic profile comparable to lean controls, weight-cycled mice exhibited impaired sensorimotor function, increased anxiety-like behavior (evaluated through behavioral tests), and persistent inflammation, including a peritoneal macrophage pro-inflammatory profile and adipose tissue infiltration. We define this phenomenon as “obesogenic inflammatory memory”, highlighting that obesity leaves an immunological imprint that sustains inflammation even after normalization of weight and metabolic parameters. These findings demonstrate that weight cycling is associated with chronic macrophage-mediated inflammatory states, linked to long-term behavioral and neurological manifestations, and opening new avenues for future investigation and therapeutic approaches. Full article

Breast cancer remains one of the most prevalent and lethal malignancies affecting women worldwide, underscoring the need for safer and more effective therapeutic strategies. This study investigated the phytochemical composition, antioxidant activity, and antiproliferative potential of POW9™, a proprietary botanical blend formulated from nine medicinal plant extracts. Comprehensive phytochemical profiling was performed using ultrahigh-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) in both positive and negative ionization modes. A total of 34 compounds were identified in negative mode and 27 compounds in positive mode, comprising flavonoids, terpenoids, steroids, organic acids, peptides, glycosides, and lipids. POW9™ exhibited high total phenolic content (190.3 ± 3.5 mg gallic acid equivalents/g) and total flavonoid content (115.2 ± 1.5 mg quercetin equivalents/g), along with strong antioxidant activity, demonstrated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging with a half-maximal inhibitory concentration (IC₅₀) of 1.66 mg/mL (33.73 mg Trolox equivalents/g). Cytotoxicity assessment revealed minimal toxicity toward normal Vero cells. In contrast, POW9™ significantly inhibited the proliferation of human breast cancer cell lines in a concentration- and time-dependent manner. The IC₅₀ values were 6.75 mg/mL for MCF-7 cells and 18.08 mg/mL for MDA-MB-231 cells after 72 h of treatment, while prolonged exposure (96 h) further enhanced antiproliferative efficacy, reducing the IC₅₀ to 2.34 mg/mL. These findings demonstrate that POW9™ is a chemically diverse herbal formulation with potent antioxidant and selective anti-breast cancer activities, supporting its potential development as a complementary therapeutic or nutraceutical agent for breast cancer management. Full article

The aging population and increasing prevalence of oxidative stress-related diseases underscore the need for functional food and pharmaceutical formulations enriched with bioactive compounds. This study aimed to design sustainable emulsion systems incorporating enzymatically modified fats with enhanced functional and bioactive properties. Enzymatic interesterification was employed as an environmentally friendly alternative to chemical catalysis, enabling the transformation of natural lipids without generating undesirable trans isomers. The lipid phase was formulated from blends of hemp oil, a plant-derived source rich in polyunsaturated fatty acids with documented antioxidant potential, and mutton tallow, in an effort to valorize meat industry by-products. Systematic evaluation of emulsion stability, viscosity, and textural properties was conducted using Turbiscan analysis and texture profile analysis. The results demonstrated that xanthan gum concentration was the primary determinant of structural stability, physicochemical stability, and structural integrity of the emulsion systems. Formulation no. 38 (0.8% w/w xanthan gum) was identified as the statistically most stable system based on Turbiscan Stability Index values (TSI = 1.4). Although emulsions containing 1.0% w/w xanthan gum exhibited similarly low TSI values and slightly smaller final droplet diameters, formulation E38 showed the smallest increase in droplet size during storage (<1 µm), indicating superior resistance to structural changes over time. Fat composition showed minimal influence on emulsion behavior, suggesting that lipid selection should prioritize nutritional and bioactive value. These findings indicate that emulsions based on enzymatically modified fats and stabilized with natural polysaccharides can serve as physically stable systems with potential applicability in food, cosmeceutical, and pharmaceutical formulations intended for bioactive compound delivery. Full article

Lower respiratory tract infections caused by Pseudomonas aeruginosa are a global concern. Patients with chronic lung diseases such as cystic fibrosis and non-cystic fibrosis bronchiectasis often do not receive adequate antibiotic delivery through conventional routes. P. aeruginosa employs several mechanisms, including biofilm formation and efflux pumps to limit the accumulation of bactericidal drug concentrations. Direct drug delivery to the lung epithelial lining fluid can increase antibiotic concentration and reduce treatment failure rates. This review discusses current research and developments in inhaled antibiotic formulations for treating P. aeruginosa infections. Recent studies on particle engineering for the dry powder inhalers of antibiotics emphasized three fundamental principles of development: micro, nano, and nano-in-microparticles. Carrier-free microparticles showed potential for high-dose delivery but suffered from poor aerosolization, which could be improved through a drug–drug combination. Amino acids in a co-spray-dried system improved powders’ aerodynamics and reduced moisture sensitivity while incorporating the chitosan/poly(lactic-co-glycolic acid) (PLGA)-modified release of the drug. Nano-in-microsystems, embedding lipid carriers, showed improved antibiofilm activity and controlled release. We also highlight emerging biologics, including antibacterial proteins/peptides, vaccines, bacteriophages, and probiotics. Research on antibiotics and biologics for inhalation suggests excellent safety profiles and encouraging efficacy for some formulations, including antimicrobial peptides and bacteriophage formulations. Further research on novel molecules and synergistic biologic combinations, supported by comprehensive animal lung safety investigations, will be required in future developments. Full article

Background: Overweight and metabolic disorders are strongly associated with gut microbiota dysbiosis. Probiotics represent a safe dietary strategy to improve metabolic health, although strain-specific effects remain unclear. This study evaluated the metabolic and gut microbiota-modulating effects of Lactobacillus helveticus (UA881) in overweight adults. Methods: In a randomized, double-blind, placebo-controlled trial, 50 overweight adults (Body mass index, BMI 25–27 kg/m²) were assigned to receive UA881 (5 × 10⁹ CFU/day) or placebo for 28 days. Anthropometric parameters, body composition, serum biochemical markers, inflammatory cytokines, fecal short-chain fatty acids (SCFAs), and gut microbiota composition (16S rRNA sequencing) were assessed at baseline and after 28 days. Statistical analyses included paired t-tests and ANCOVA adjusted for baseline values. Results: After 28 days of supplementation, UA881 significantly reduced body weight, BMI, and body fat mass. The primary endpoint, serum triglycerides, was significantly decreased, and the increases in uric acid, total cholesterol, and Low density lipoprotein-cholesterol (LDL-C) observed in the placebo group were attenuated. No significant changes were observed in interleukin-6 (IL-6) or tumor necrosis factor-α (TNF-α) levels. Fecal butanoic acid showed an increasing trend, and gut microbiota alpha diversity was significantly improved. At the genus level, Anaerostipes and Blautia were enriched, while Collinsella was reduced. Conclusions: A 28-day supplementation with L. helveticus UA881 (5 × 10⁹ CFU/day) improved body composition and lipid-related metabolic parameters and favorably modulated gut microbiota composition in overweight adults, supporting its potential as a probiotic candidate for metabolic health. Full article

Background/Objectives: This study evaluated whether yoghurt containing Apilactobacillus kunkeei DSM 12361 protects rats against non-alcoholic fatty liver disease (NAFLD). We hypothesized that this fructophilic probiotic, with anti-inflammatory properties, may affect NAFLD progression by improving the gut microbiome, lowering intestinal ethanol production, and modulating inflammatory and metabolic pathways linked to hepatic fat accumulation. Methods: Wister rats were randomized into three groups; rats in the control group (HFrD) were fed a high-fructose (70%) diet while rats in experimental groups were fed the same diet mixed with 10% of yoghurt containing YC-180 starter culture (HFrD-Y) or yoghurt containing YC-180 and Apilactobacillus kunkeei DSM 12361 (HFrD-Y-A). Results: After six weeks of intervention, levels of plasma triglycerides, cholesterol, glucose, liver enzymes (ALT and AST), interleukin (IL)-6, fecal ethanol, Enterobacteriaceae, and hepatic index were significantly increased (p < 0.05) in the HFrD group as compared to rats in both experimental groups. Moreover, plasma levels of liver enzymes, lipid profile, glucose, and IL-6 were significantly lower (p < 0.05) in rats of the HFrD-Y-A group than those in the HFrD-Y group. Furthermore, plasma levels of IL-10 and fecal Lactobacilli and Bifidobacteria were significantly increased (p < 0.05) in the experimental groups when compared to rats in the control group. Conclusions: In sum, the obtained results indicated that yoghurt containing Apilactobacillus kunkeei could decrease the risk of non-alcoholic fatty liver disease (NAFLD) through (a) blocking the inflammation process associated with NAFLD, (b) enhancing the lipid profile, (c) lowering fecal ethanol, and (III) decreasing the levels of fecal Enterobacteriaceae in comparison with levels of fecal Lactobacilli and Bifidobacteria in rats. More research on molecular mechanisms of the potential effects of the Apilactobacillus kunkeei strain against NAFLD is still required. Full article

Aging alters cardiac resilience to anesthetic and surgical stress, yet the molecular basis for these effects remain poorly understood. To define age-dependent transcriptional responses, we profiled cardiac gene expression across young adult (3 m), late middle-aged (17 m), and old mice (27 m) following 2 h isoflurane and operative (Iso/Op) exposure. Across all age groups, 24 h after cessation, Iso/Op induced distinct transcriptional signatures relative to the sham, with conserved perturbations in oxidative stress responses, Ca²⁺ handling, hypertrophy-associated signaling, and energy metabolism. In 3 m hearts, transcriptional alterations were characterized by dysregulation of small-molecule catabolism, fatty acid metabolism, endoplasmic reticulum processing, and cytoskeletal organization. In 17 m hearts, lipid metabolic disruption was amplified and accompanied by suppression of muscle system and calcium signaling pathways. In 27 m hearts, Iso/Op robustly activated PPAR and AMPK signaling and fatty acid catabolic programs while downregulating pathways governing contractility, actin organization, and morphogenesis, consistent with age-associated maladaptive metabolic reprogramming. To assess persistence, we analyzed a longitudinal cohort of 20 m mice five weeks after exposure and observed sustained transcriptomic remodeling driven predominantly by isoflurane, including mitochondrial dysfunction and altered expression of genes linked to diabetic cardiomyopathy, extracellular matrix integrity, and neurodegeneration-associated pathways. Together, these data suggest that isoflurane-based perioperative stress can produce age-amplified and durable metabolic and structural cardiac remodeling, implicating impaired lipid utilization and mitochondrial homeostasis as potential mechanisms of long-term cardiovascular vulnerability.  Full article

Sensitization to non-specific lipid transfer proteins (nsLTPs) is highly prevalent in Mediterranean countries. Pru p 3 from peach is a major allergen responsible for IgE-mediated food allergies. As a panallergen, Pru p 3 shows high sequence homology with nsLTPs from other Rosaceae fruits but also from botanically unrelated sources, including nuts and pollens, leading to extensive cross-reactivity complicating diagnosis and management. Given the worldwide prevalence of peanut and tree nut allergies, this study aimed to investigate sensitization patterns in Pru p 3-sensitized patients with tree nut allergy, using artificial intelligence (AI) to identify predictors of clinical reactivity and severity. Data from Pru p 3–sensitized patients with symptoms to peach and/or nuts were analyzed. Sensitization profiles were modeled using an XGBoost algorithm to explore associations with symptoms and severity. Patients sensitized to Pru p 3 and symptomatic for peach and nuts showed predominant sensitization to peanut and hazelnut, but AI revealed stronger associations between clinical reactivity and sensitization to hazelnut, walnut, and almond. Among patients with nut allergy and peach-asymptomatic, peanut and hazelnut sensitization were most frequent, while peach-symptomatic ones, walnut and almond sensitization predominated. Overall, walnut sensitization emerged as the main predictor of clinical severity and increasing number of sensitizations correlated with higher severity. The XGBoost algorithm identified specific allergen combinations associated with symptoms and severity, highlighting walnut sensitization as the strongest severity predictor. Machine learning approaches represent a promising tool for refining risk stratification and personalizing management in nsLTP-related food allergy. Full article

China has implemented a series of clean air policies, resulting in improved air quality since 2013. However, there remains a paucity of national prospective evidence regarding the relationship between fine particulate matter (PM_2.5) and kidney disease (KD) incidence in China, as well as the potential mediating effects of lipid profiles in this association. This study aimed to assess the association of decreased PM_2.5 concentration and KD incidence in China from 2013 to 2020. Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS), we included 15,368 participants who were free of KD in 2013 and followed up until 2020. For each participant, we calculated the 3-year and 2-year average PM_2.5 concentrations. The Cox proportional hazards model was employed to estimate the association between PM_2.5 exposure and KD incidence. Mediation analyses were conducted using eight lipid indices, and subgroup analyses were performed. The annual average PM_2.5 concentration for CHARLS participants reduced from 61.72 μg/m³ in 2013 to 32.75 μg/m³ in 2020. A reduction of 5 μg/m³ in 3-year and 2-year average PM_2.5 concentrations was associated with 14.3% (hazard ratio [HR]: 0.857, 95% confidence interval [CI]: 0.841, 0.873) and 14.4% (HR: 0.856, 95% CI: 0.840, 0.873) reductions in KD incidence in the fully adjusted models. The TyG-BMI and TyG-WHtR indices exhibited small mediating effects of 7.36% (95% CI: 2.35%, 12.38%) and 4.48% (95% CI: 0.51%, 8.45%) on the relationship of PM_2.5–KD, while other indicators did not demonstrate significant mediation. The findings of this study suggest that reductions in PM_2.5 concentration were associated with a decreased incidence of KD during the period from 2013 to 2020. The implementation of clean air policies since 2013 may have contributed to the decrease in chronic diseases like KD. Full article

Salicyluric acid (SUA), the main metabolite of aspirin and a natural product, is known for its ability to chelate iron and other metal ions. In particular, the chelation and increased excretion of iron by SUA may contribute to the aspirin-induced iron deficiency anemia observed in long-term aspirin users. The redox activity of iron and copper complexes of drugs and also drug metabolites, such as SUA, is an important parameter of their overall toxicity profile, including the induction of ferroptosis, which has been associated with many diseases. In this context, the effect of SUA on iron- and copper-induced lipid peroxidation and also its localization within a model lipid membrane have been investigated. A combination of physicochemical methods, including Nuclear Magnetic Resonance (¹H NMR), molecular dynamics (MD), and Nuclear Overhauser Effect Spectroscopy (¹H NOESY), has been used to demonstrate that SUA does not promote the peroxidation of linoleic acid micelles in the presence of Fe(II) or Cu(II) ions. NMR experiments revealed that SUA incorporates into the lipid bilayer, which stabilizes the ligands and inhibits its metal chelation ability in comparison to the control. NOESY experiments and MD simulations further showed that SUA localizes shallowly within the membrane, interacting primarily with the head group and upper acyl chain regions of lipids. These findings provide crucial insights into the membrane redox reactivity and other behavior of SUA, explaining its lack of pro-oxidant activity and also highlighting its complex role in the pharmacological and toxicological effects on iron metabolism in long-term aspirin users. Full article

The aim of the study was to characterize the prevalence of comorbidities and molecular genetic status in patients with familial hypercholesterolemia (FH) and non-familial hypercholesterolemia (non-FH). This cross-sectional observational study included 323 patients. Assessments comprised personal and family histories, physical examination, fasting lipid profiling, and molecular genetic testing. Patients with FH were not characterized by an increased prevalence of type 2 diabetes mellitus. In contrast, the non-FH group demonstrated a pronounced cardiometabolic comorbidity profile with a high prevalence of recurrent chronic pancreatitis. Patients with probable or definite FH had a higher prevalence of coronary heart disease and peripheral atherosclerosis, whereas myocardial infarction (MI) was common across all studied groups. Among patients with definite and probable FH, pathogenetic variants were identified in 78.2% and 71.4%, respectively, predominantly in the LDLR gene, with one variant in the APOB gene. In the possible FH group, pathogenic variants were identified in 46.7% of cases (LDLR gene in 64.3% and APOB gene in 28.6%). Patients with FH were characterized by a lower prevalence of concomitant cardiometabolic diseases. The high diagnostic yield of genetic testing in the possible FH category (figured Clinic Network score 3–5) suggests that expanding indications for molecular genetic testing to include this patient group should be considered. Full article

The present study evaluates the impact of cavitation on the performance of the chemical refining of rapeseed oils and the enzymatic interesterification of fat blends using a powerful UP400S ultrasonicator (400 W, 20 kHz). Ultrasound-assisted alkali neutralization achieved efficiency comparable to that of the conventional 60 min process in only 7 min, with similar refining losses (5.04–6.80 wt.%), although slightly higher lipid peroxidation was observed. Performing the ultrasound cavitation under a protective nitrogen atmosphere minimized the formation of lipid peroxides and their breakdown products (i.e., hexanal, nonanal), partially protected tocopherols, and improved oxidative stability (IP at 120 °C = 3.9–4.4 h). Ultrasound-assisted enzymatic interesterification (EIE) of palm kernel fat and a palm stearin blend catalyzed by immobilized lipases (Lipozyme TL IM, Lipozyme RM IM, Novozyme 435) was carried out for the first time. Cavitation accelerated triacylglycerol rearrangement, reduced reaction time from 6 h (9.0·10⁻³ to 1.6·10⁻² min⁻¹) to only 1 h (5.5·10⁻² to 1.2·10⁻¹ min⁻¹), and significantly affected melting point stabilization and solid fat content profile. In summary, ultrasound cavitation substantially enhanced mass transfer and reaction kinetics, demonstrating strong potential for process intensification in the edible oil industry. Further optimization of reaction conditions is required before large-scale industrial implementation. Full article