Search Results (184)

Squalene, a hydrocarbon with several industrial applications, is obtained from plants, animals, and microorganisms. Oleaginous thraustochytrids are also potential sources of squalene. In eukaryotes, squalene, an intermediary in the sterol/cholesterol pathway, accumulates when the activity of squalene epoxidase or an Alternative SQualene Epoxidase (AltSQE) is inhibited. The objective of this study was to evaluate the polyphenols extracted from barley bagasse for enhancement of the squalene content in Thraustochytrium sp. RT2316-16. In the media supplemented with terbinafine, an antifungal compound known as an inhibitor of squalene epoxidase, or the polyphenols from barley bagasse 72 h after inoculation, the squalene concentration was 308.7 ± 0.8 and 286.5 ± 0.1 mg L⁻¹ after 168 h, respectively, whereas in the control medium, it was 85.6 ± 0.2 mg L⁻¹. The final concentrations of the lipid-free biomass (4.5 ± 0.1 g L⁻¹) and total lipids (2.5 ± 0.3 g L⁻¹) were not affected by the polyphenols from barley bagasse; on the contrary, the concentration of total lipids in the terbinafine treatment was 30% lower than in the control. In RT2316-16, the gene coding for AltSQE, which is not found in all thraustochytrids, was upregulated under the control treatment, whereas its relative expression was not affected by terbinafine. The squalene accumulation in RT2316-16 in response to the treatment with polyphenols and the antifungal agent makes this strain a promising source of the triterpenoid. Full article

Background/Objectives: Bipolar disorder (BD) is increasingly recognized as a multisystem condition in which metabolic abnormalities, particularly insulin resistance (IR), may be linked to illness severity and neuroprogression. Despite growing evidence linking IR to adverse clinical outcomes, the data is heterogeneous and preliminary, and its specific association in hospitalized patients with BD remains underexplored. Methods: This cross-sectional study included 86 inpatients with a primary diagnosis with BD at the IRCCS Ospedale Policlinico San Martino, Genoa, Italy, between July 2023 and January 2024. Sociodemographic, clinical, and metabolic characteristics were systematically investigated. IR was defined as a HOMA-IR index ≥ 2.5. Results: Twenty-eight patients met criteria for IR. Insulin resistant patients showed a significantly longer illness duration, more frequent residual symptoms, and higher rates of ≥5 lifetime psychiatric hospitalizations. They also exhibited greater polypharmacy (≥4 psychotropics at discharge) and daily alcohol use. Furthermore, the IR subgroup was significantly associated with higher body mass index and triglycerides, lower HDL cholesterol and physical activity levels. Conclusions: Our findings indicate that IR is associated with markers of greater illness burden in BD. While these results are consistent with emerging hypotheses on metabolic dysfunction in BD, longitudinal studies are required to clarify temporal and causal relationships. These associations suggest that IR may represent a clinically relevant component of BD rather than a secondary metabolic consequence. Routine metabolic screening and the preferential use of metabolically neutral agents may improve long-term outcomes and align with the emerging paradigm of precision psychiatry. Full article

Background/Objectives: Immature watermelon (WM) rind contains higher levels of citrulline and potassium than mature fruit and may exert diuretic and metabolic benefits. This study aimed to evaluate the anti-obesity and diuretic effects of WM and salt-treated watermelon rind extract (WMS) in high-fat diet (HFD)-induced obese mice, focusing on changes in lipid metabolism, sodium handling, and tissue-level alterations. Methods: Citrulline concentrations in WM and WMS were quantified using high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Four-week-old male C57BL/6 mice were fed an HFD for 6 weeks and subsequently administered WM (380 mg/kg) or WMS (380 mg/kg) orally for an additional 6 weeks. Body weight, food intake, organ and fat-pad weights, serum biochemical markers, and sodium (Na⁺) levels were measured. Histopathological analyses of liver and epididymal adipose tissue were performed to assess non-alcoholic steatohepatitis (NASH) scores and adipocyte morphology. Results: WM and WMS contained citrulline at levels substantially higher than those reported for mature watermelons. Both treatments significantly reduced body weight, liver weight, and epididymal fat mass compared with the HFD control. Serum total cholesterol and triglyceride levels were lowered in the WM- and WMS-treated groups. Serum Na⁺ concentrations increased by 43.2 ± 7.6% in WM-treated mice and 21.5 ± 6.6% in WMS-treated mice, suggesting enhanced sodium handling. Histological assessment revealed reduced NASH scores and smaller adipocyte sizes in both groups. These improvements are consistent with the known diuretic and metabolic actions of citrulline and potassium. Conclusions: WM and WMS exhibit significant anti-obesity and diuretic effects in HFD-induced obese mice. Their combined actions on sodium excretion, lipid metabolism, and adipose tissue remodeling suggest that immature watermelon rind extracts may serve as promising natural agents for preventing obesity and related metabolic dysfunction. Full article

Background: Lewisite, a potent chemical warfare agent, induces rapid and progressive cutaneous damage, necessitating treatment strategies that offer both immediate decontamination and prolonged therapeutic action. This study aimed to develop and evaluate a composite topical formulation comprising 4-phenylbutyric acid (4-PBA)-loaded emulsomes embedded within a foam vehicle to address both aspects of vesicant-induced skin injury intervention. Methods: Emulsomes composed of a stearic acid–cholesterol solid lipid core stabilized by a lecithin shell were prepared via thin film hydration and optimized by varying lipid ratios and drug loading parameters. Formulations were characterized for drug loading, particle size, and zeta potential. Physicochemical compatibility was assessed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses. Stability was evaluated under accelerated refrigerated (25 °C/60% RH) and room temperature (40 °C/75% RH) conditions. The optimized formulation was incorporated into a foam base and evaluated for decontamination efficiency, drug release kinetics, in vitro permeation, and in vivo efficacy. Results: The selected formulation (E2) exhibited high drug loading (17.01 ± 0.00%), monodisperse particle size (PDI = 0.3 ± 0.07), and stable zeta potential (−40 ± 1.24 mV). FTIR and DSC confirmed successful encapsulation with amorphous drug dispersion. The emulsome-foam demonstrated dual functionality: enhanced decontamination (66.84 ± 1.27%) and sustained release (~30% over 24 h), fitting a Korsmeyer–Peppas model. In vitro permeation showed significantly lower 4-PBA delivery from E2 versus free drug, confirming sustained release, while in vivo studies demonstrated therapeutic efficacy. Conclusions: This emulsome-foam system offers a promising platform for topical treatment of vesicant-induced skin injury by enabling both immediate detoxification and prolonged anti-inflammatory drug delivery. Full article

Background/objectives: Chronic degenerative complications of diabetes, such as atherosclerotic cardiovascular disease and chronic kidney disease, contribute to an increased morbimortality in patients with type 2 diabetes (T2D), and thus, a multifactorial approach becomes essential. Among the classes of antihyperglycemic agents with beneficial pleiotropic cardiorenal effects, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven to reduce the risk of major adverse cardiovascular (CV) and renal events. This study aims to assess the impact of treatment with GLP-1 RA on CV risk factors, insulin sensitivity, and renal function in Romanian patients with T2D. Methods: In an observational retrospective study, 150 patients with T2D were evaluated at the start of therapy with a GLP-1 RA and then after 6 and 12 months. Results: After 12 months of treatment, 59.3% of patients succeeded in achieving weight loss of over 5% of their initial weight, and 24.7% of patients achieved weight loss of over 10% of their initial weight, with the most significant decrease being measured in the first 6 months. HbA1c has shown a similar profile, with a significant reduction in the first 6 months of treatment, continued at a slower rate in the following 6 months. Additionally, the lipid profile, blood pressure values, and uric acid values, alongside the triglyceride/high-density lipoprotein cholesterol (TG/HDLc) ratio and the triglyceride–glucose (TyG) index have improved in these T2D patients treated with GLP-1 RA, while their eGFR decrease was slower than the one expected for similar populations without such a pharmacologic agent in their regimen. Conclusions: Treatment with GLP-1 RA in patients with T2D is associated with an improved cardiovascular–kidney–metabolic risk profile, ameliorated glycemic control, reduced weight, lower insulin resistance, and slower kidney disease progression. Full article

Background/Objectives: Cardiovascular diseases continue to be the foremost global cause of morbidity and mortality, representing about 40% of all causes of death. Atherosclerotic cardiovascular disease is the most common and clinically important type of these, occurring when cholesterol accumulates over time in the artery intima, which induces an inflammatory process that leads to the production of atherosclerotic plaques. Nowadays, lipid profile alterations and high/very high cardiovascular risk can be observed in more and more patients. Combination therapy, which includes high-intensity statins, ezetimibe, bempedoic acid, and PCSK9-targeted medicines, can lower LDL-C by more than 80%, which is far more than the 50% that statin monotherapy usually achieves. Thus, novel lipid-lowering therapies are needed, as current agents—though effective in reducing cardiovascular events—leave considerable residual risk in many patients. Methods: The aim of our study was to evaluate the cost-effectiveness of Inclisiran and its association with standard of care for the prevention of cardiovascular events across multiple international settings, in articles that reported quality-adjusted life years gained and cost-effectiveness metrics. Results: Our findings suggest that the cost-effectiveness of Inclisiran is highly context-dependent, shaped by local pricing, population risk, and system-level capacity. While Inclisiran demonstrates potential economic value in high-income settings or among high-risk patients, its widespread adoption for primary prevention appears unjustified under current conditions. Conclusions: Policymakers should consider risk-based targeting, price renegotiation, and performance-based reimbursement models to improve the value proposition of such interventions. Full article

Atherosclerotic cardiovascular disease (ASCVD) persists as the foremost cause of global morbidity and mortality. Central to its pathogenesis, atherosclerosis emerges as a chronic inflammatory disorder fueled by the intricate interplay between dysregulated lipid metabolism and immune cell activation. Recent insights reveal that inflammatory cues within atherosclerotic plaques or ischemic tissues orchestrate metabolic reprogramming in immune cells, thereby modulating disease trajectories. While cholesterol-lowering agents such as statins and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors have long been recognized for their lipid-modulating properties, accumulating evidence now underscores their pleiotropic anti-inflammatory effects mediated through immune cell modulation. For instance, recent clinical observations reveal that PCSK9 inhibitors not only substantially reduce low-density lipoprotein cholesterol (LDL-C) and triglycerides but also appear to reduce advanced glycoprotein signals, emerging composite biomarkers of systemic inflammation. This highlights a novel and more nuanced dimension of inflammation modulation by PCSK9 inhibitors, although current evidence remains limited and requires further confirmation. Moreover, this dual immune-metabolic influence reshapes our understanding of therapeutic mechanisms and calls for a reassessment of treatment paradigms in ASCVD management. Here, we present a synthesis of current findings that emphasize how both established and novel therapies transcend lipid-lowering to exert profound immunomodulatory actions, offering promising avenues to attenuate cardiovascular disease progression through integrated metabolic and inflammatory control. Full article

Background: Korean red ginseng marc (KRGM), a by-product of Korean red ginseng (KRG) processing, retains numerous bioactive compounds with potential health benefits. Among them, KRGM-derived gintonin (KRGM-gintonin) is particularly rich in lysophosphatidic acid (LPA) and phospholipids, which have been linked to favorable metabolic effects. This study investigated the anti-obesity potential of KRGM-gintonin in high-fat diet (HFD)–induced obese mice, focusing on its impact on weight regulation, liver health, and energy metabolism. Methods: Obese mice (C57BL/6N, 4 weeks, male) were administered KRGM-gintonin either orally for 25 weeks or through intracerebroventricular (ICV) injection for 14 weeks. Throughout the study, body weight, food intake, metabolic parameters, liver tissue morphology, behavioral performance, and thermogenic gene expression were carefully monitored to evaluate treatment effects. Results: Both oral and ICV administration of KRGM-gintonin significantly reduced body weight gain in HFD-fed obese mice without altering food intake, suggesting enhanced energy expenditure. Treatment through both routes improved physical performance and increased metabolic rate. Oral KRGM-gintonin also alleviated fatty liver, reduced plasma triacylglycerol and cholesterol levels, and promoted the expression of thermogenesis-related genes, including uncoupling protein-1 (UCP1) and hormone-sensitive lipase (HSL), specifically in brown adipose tissue. Additionally, oral administration lowered tumor necrosis factor-α (TNF-α) expression, indicating anti-inflammatory activity and further supporting metabolic health. Conclusions: KRGM-gintonin exerts strong anti-obesity effects, primarily through oral administration, with supportive evidence from central ICV action. These findings highlight its potential as a functional therapeutic agent for obesity prevention and management, offering dual benefits in metabolic regulation and inflammation control. Full article

The composition of the lipophilic components of Centaurea scabiosa L. has been studied. The raw material was subjected to extraction with hexane and methyl tert-butyl ether (MTBE) using both exhaustive and sequential schemes for a detailed characterization. The resulting extracts were fractionated into acidic and neutral components via treatment with alkali solutions. The acidic compounds were converted into methyl esters for subsequent gas chromatography–mass spectrometry (GC-MS) analysis, while the neutral unsaponifiable fractions were separated into groups of different polarities using column chromatography on silica gel. This approach enabled the identification of a complex profile of lipophilic substances. In the acidic fractions, aliphatic acids with chain lengths from C₁₀ to C₃₂, including unsaturated variants, were characterized. The neutral fractions revealed over compounds, encompassing n-alkanes, substantial levels of the unsaturated branched hydrocarbon squalene, and a diverse array of oxygenated terpenoids. The latter were mainly represented by highly active triterpene alcohols and ketones belonging to the ursane, oleanane, lupane, and cycloartane types. The sterol composition was dominated by β-sitosterol and accompanied by cholesterol, campesterol, stigmasterol, stigmast-7-en-3-β-ol, fucosterol, and stigmastan-3-β-ol. Bioactivity screening demonstrated that several of the obtained lipophilic extracts, particularly those of lower polarity, exhibited high inhibitory activity against the main protease of SARS-CoV-2, underscoring the potential of C. scabiosa as a valuable source of anti-coronavirus agents. Full article

Even when people with diabetes mellitus (DM) meet their cholesterol goals, they still face a higher risk of heart and blood vessel problems. One major reason is a particle called lipoprotein(a), or Lp(a), which is similar to LDL cholesterol. Raised levels of Lp(a) are inherited rather than caused by lifestyle. Lp(a) can build up in the body and make it easier for blood clots to form because it closely resembles a protein called plasminogen, reducing its ability to form plasmin that dissolves blood clots. At the same time, chemical changes like oxidation and glycation can make blood vessels more inflamed, adding to the risk. Elevated concentrations of Lp(a) (>30 mg/dL; 75 nmol/L), and particularly >50 mg/dL (125 nmol/L), are independently associated with coronary artery disease, ischemic stroke, diabetic nephropathy, retinopathy, and neuropathy. Conventional lipid-lowering therapies exert neutral or modest effects on Lp(a), in contrast to RNA-based targeted agents (antisense oligonucleotides and siRNA [Small Interfering RNA]), which achieve reductions of 70–95% and show consistent results in Phase 2 clinical trials. In this review, we bring together findings from laboratory research and clinical studies, and highlight why it is important to measure Lp(a) levels—at least once in a person’s life, and especially in those with diabetes—to help doctors better assess risk and plan more effective treatments. In diabetic populations, the adaptation of Lp(a)-targeted therapies could redefine the management of residual risk and improve both cardiovascular and microvascular outcomes. Full article

Biebersteinia heterostemon is a traditional Tibetan medicine known for its antioxidant, hypoglycemic, and anti-atherosclerotic properties. However, its therapeutic effects and mechanisms in the treatment of hyperlipidemia remain unclear. In this study, the ethyl acetate extract of B. heterostemon (BHEE) was first identified as the most effective lipid-lowering fraction through its inhibitory activity on pancreatic lipase and cholesterol esterase. Chemical characterization of BHEE by UHPLC-MS/MS revealed 108 compounds. Network pharmacology and molecular docking analyses were then employed to predict key active components and signaling pathways involved in BHEE’s lipid-lowering effects. A total of 50 active components and 623 targets were selected from the PubChem, SwissADME, and Swiss Target Prediction databases. These targets were intersected with 1606 hyperlipidemia-related targets from GeneCards, OMIM, and DrugBank, resulting in 144 common targets. The “drug-active component-intersecting target-pathway-HLP” and protein–protein interaction (PPI) networks suggested key active components such as 6-methoxytricin, vulgarin, flazin, ganhuangenin, and eupatorin, and core targets including TNF, IL6, AKT1, PPARG, and EGFR. GO and KEGG pathway enrichment analysis highlighted potential signaling pathways, such as AGE-RAGE, PPAR, insulin resistance, TNF, and lipid and atherosclerosis pathways. Molecular docking further predicted the strong binding affinity between key active components and core targets. At the cellular level, BHEE dose-dependently reduced lipid accumulation in FFA-induced HepG2 cells and improved oxidative stress (CAT, GSH, SOD, MDA) and inflammation (TNF-α, IL-6) markers. In conclusion, BHEE may exert its anti-hyperlipidemic effects through modulation of key targets like TNF, IL6, AKT1, PPARG, and EGFR. These findings suggest a multi-target mechanism, though further experimental validation is necessary to confirm these effects. This study provides valuable insights into the potential application of B. heterostemon as a natural therapeutic agent for hyperlipidemia. Full article

Background and Objectives: Non-pharmaceutical interventions such as cognitive training, transcranial electrical stimulation (tES), and repetitive transcranial magnetic stimulation (rTMS) have shown promise in improving cognitive outcomes in Alzheimer’s disease (AD) and dementia. However, the long-term effects of repeated non-invasive interventions remain unknown. This study investigated whether repeated non-invasive interventions administered over a span of 1 to 3 years were associated with slower cognitive decline compared to typical AD progression, and whether longer no-treatment intervals between treatments predicted greater post-treatment decline. Materials and Methods: Seventy-three participants living with dementia or AD received 2 to 9 blocks of non-invasive treatments (including tES, rTMS, cognitive training). Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores were collected longitudinally up to 3 years (36 months), across multiple intervention and assessment sessions. A mixed-effects model was used to estimate the rate of cognitive decline, adjusting for baseline age, sex, and baseline cognition (MoCA) with participants being the random effect. The observed rate of change was compared to a meta-analysis estimate of AD progression. Additionally, a linear mixed-effects model using robust sandwich estimation of standard errors was employed to assess whether the no-treatment interval was associated with changes in ADAS-Cog scores. Results: Participants showed a significantly slower rate of cognitive decline than expected from the AD reference rate (p < 0.001), with many demonstrating stabilized ADAS-Cog scores during their respective treatment periods, ranging from 1 to 3 years. Medication analyses revealed no significant effect of AD medications, antidepressants, antihypertensives, or cholesterol-lowering agents on cognitive outcomes. Furthermore, longer no-treatment intervals were significantly associated with greater post-treatment decline (p < 0.001). Conclusions: Repeated non-invasive treatments seem to slow the rate of cognitive decline in individuals living with dementia when administered over a prolonged period. This study provides evidence supporting the feasibility and effects of personalized long-term non-invasive treatment strategies for dementia. Full article

Cardiometabolic diseases (CVDs) are the leading cause of premature mortality and disability worldwide, arising from of cardiovascular and metabolic dysregulation. This review focuses on six critical therapeutic targets established in cardiometabolic regulation: GLP-1R, GIPR, FGFR1/β-Klotho, PCSK9, NF-κB, and the NLRP3 inflammasome. Drawing on curated structural datasets, we analyze the mechanisms of action and map key binding domain features that govern ligand efficacy and specificity. Dual GLP-1R/GIPR agonists, such as tirzepatide, demonstrate superior outcomes in glycemic control and weight reduction. Concurrently, inhibiting PCSK9, NF-κB, and NLRP3 helps to lower cholesterol and reduce harmful inflammation, offering cardioprotection. Structural analysis across these targets reveals complementary motifs (aromatic, hydrophobic, and polar residues). These insights guide the rational design of next-generation multi-target ligands (molecules capable of modulating two or more biological targets involved in related disease pathways, producing integrated therapeutic effects). Such integrated agents are promising for providing combined cardiovascular and metabolic benefits, thus reducing the risks associated with complex therapeutic drug combinations. Full article

Statins are widely used lipid-lowering agents that significantly reduce cardiovascular morbidity and mortality by lowering LDL-cholesterol. Vitamin D, traditionally known for its skeletal role, is increasingly recognized for its cardiovascular relevance. This study aims to focus on the complex relationship between statins, vitamin D, and their impact on cardiovascular outcomes. Both molecules intersect metabolically at 7-dehydrocholesterol, raising interest in their potential interactions. While theoretical concerns exist about statins impairing vitamin D synthesis, clinical studies suggest a neutral or modestly positive effect on circulating 25(OH)D levels. Statins may increase vitamin D levels by inhibiting its catabolism (via CYP3A4) and enhancing absorption. Observational data also suggest synergy between statins and vitamin D in reducing inflammation, oxidative stress, endothelial dysfunction, and atherogenesis. Though large trials showed no benefit of vitamin D supplementation in cardiovascular event reduction among vitamin D–replete individuals, select subgroups (those deficient or with statin-induced myalgia) may benefit from targeted supplementation. Optimizing vitamin D status could improve statin tolerability and adherence, especially in high-risk populations such as the elderly or those with metabolic syndrome. This review highlights the complex interplay between statins and vitamin D and supports a personalized approach to supplementation in statin-treated patients, aiming to enhance cardiovascular protection without overtreatment. Full article

Background/Objectives: Atorvastatin, a lipophilic HMG-CoA reductase inhibitor used for lipid lowering, also exhibits considerable anti-neoplastic activity. Although previous studies have shown that glucose starvation can potentiate several anticancer chemotherapies, atorvastatin has not been rigorously investigated for its impact on metabolic vulnerabilities and the effects on cholesterol-rich lipid rafts in aggressive tumors. This work aims to evaluate the combined anticancer activity of atorvastatin with metabolic interventions, specifically glucose starvation, on U-87 (glioblastoma) and MDA-MB-231 (triple-negative breast cancer) cell lines. Methods: U-87 and MDA-MB-231 cancer cells were cultured in either normal or glucose-free media and treated with different concentrations of atorvastatin. The impact of atorvastatin on these cancer cells was analyzed by examining cell viability, apoptosis, cell cycle, and changes in membrane order within lipid rafts. Results: This study found that glucose starvation increased the sensitivity of U-87 cells to atorvastatin by lowering IC₅₀ values and eliciting arrest in the G1 phase of the cell cycle. MDA-MB-231 cells were less dependent on glucose for viability; however, atorvastatin consistently induced S-phase arrest across both metabolic states. Additionally, atorvastatin induced apoptosis in both U-87 and MDA-MB-231 cells, with the effect being more pronounced and dose-dependent in the fasting state with glucose. Interestingly, both Caspase-3 and Caspase-9 were consistently downregulated by atorvastatin in U-87 cells, regardless of the fasting state, corresponding to the induction of cell cycle arrest. Membrane lipid rafts exhibited decreased membrane order under glucose starvation, which was further decreased in response to atorvastatin in both cell lines, indicating a reduction in cholesterol. Conclusions: These results demonstrate that atorvastatin exhibits anticancer activity, characterized by both contextual and metabolic targeted effects, including a reduction in cancer proliferation, the triggering of cell cycle arrest via the downregulation of caspase pathways, and a decrease in membrane order. Notably, the combined activity of combining antilipemic agents with glucose-fasting provides potential metabolic strategies that could help create more effective and personalized approaches to cancer treatment. Full article