Search Results (39,638)

Background/Objectives: This exploratory study (n = 6 per group) investigated the associations between supplementation with α-lipoic acid (AL), betaine (BT), and L-carnitine (LC) and gut microbiota composition in a high-fat diet (HFD)-induced obesity mouse model. Methods: Four-week-old male C57BL/6J mice were fed a control diet (10% fat), HFD (60% fat), or HFD supplemented with AL, BT, or LC (300 mg/kg BW/day) for nine weeks. Results: All three compounds were associated with shifts in microbial composition compared to the HFD-only group. While AL and BT supplementation moderately modulated specific Firmicutes and Bacteroidetes taxa, LC supplementation was linked to a more pronounced reduction in the Firmicutes/Bacteroidetes ratio and a decreased abundance of genera such as Christensenellaceae, Lachnospiraceae, and Coprococcus 3. These microbial changes were correlated with obesity-related metabolic and adiposity markers, including leptin and lipid parameters. Furthermore, functional profiling via PICRUSt suggested potential alterations in amino acid metabolism; however, these findings represent inferred metabolic potential rather than direct metagenomic measurements. Conclusions: Collectively, these results indicate differential associations between dietary supplementation and gut microbiota composition in HFD-fed mice. Although this study was conducted within an exploratory framework and utilized a modest sample size, the observed microbial shifts consistently paralleled metabolic alterations, supporting biologically plausible associations that warrant further mechanistic investigation. Full article

Ferroptosis is a recently discovered form of cell death, driven by membrane lipid peroxidation with the contribution of intracellular iron. In recent years, many researchers have discovered the involvement of ferroptotic mechanisms in the etiology of various diseases, including several forms of cancer. Different points in the ferroptotic pathway can be crucial for arising or sustained pathologies, given the contribution of numerous molecular mechanisms concerning membrane channels, several proteins, enzymes, and also kinases. The latter, in particular, seems to be very important in the control of ferroptosis in different manners depending on the pathology. Therefore, many articles in recent years have described how the pathways that involve kinases can determine, control, or alter the physiological ferroptotic contribution. Interestingly, in a tumoral context, oncogenes and tumor suppressor activity affect the correct ferroptotic process directly or indirectly promoted by abnormal kinase activity. Expanding the understanding of how kinases contribute to tumorigenesis by altering ferroptosis mechanisms may provide important insights to improve current anticancer therapies. Furthermore, new data have indicated how kinase-dependent ferroptotic activity may influence the efficacy of immunotherapy. Since one of the major obstacles to this promising anticancer therapy concerns the resistance induced by cancer cells, finding new targets, such as kinases, to improve ferroptosis in tumor cells could open an intriguing door to enhancing immunotherapy and overcoming the current obstacle. Full article

This study evaluated Apis mellifera brood fat extracts as a sustainable alternative to beeswax for anti-inflammatory topical delivery, including their formulation into nanostructured lipid carriers (NLCs). Brood fat was extracted using acetone, ethyl acetate (EA), and hexane, and the resulting extracts were characterized for fatty acid composition and physicochemical properties. Safety was assessed using the hen’s egg chorioallantoic membrane test and cytotoxicity testing in RAW 264.7 macrophages. Anti-inflammatory activity was assessed by inhibition of lipopolysaccharide-induced interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) production. The most suitable extract was formulated into NLCs using sugar squalane as liquid lipid, and the effects of lipid ratio and preparation method were investigated. The results showed that the ethyl acetate extract had the highest yield. Compared with beeswax, all fat extracts exhibited a favorable oleic acid–rich fatty acid profile with comparable crystallinity and thermal behavior, while showing significantly enhanced anti-inflammatory activity (p < 0.05). All extracts and their NLCs were non-irritating and non-cytotoxic. Ethyl acetate extract-based NLCs exhibited favorable particle sizes (72.1 ± 0.3 nm) and narrow polydispersity (0.14 ± 0.00), with high-pressure homogenization producing smaller particles compared to probe sonication without affecting IL-6 or TNF-α inhibition. Therefore, A. mellifera brood fat extract is a sustainable anti-inflammatory lipid source with strong potential as an alternative to beeswax in topical nano-formulations. Full article

Background: High-energy diets enriched in simple sugars and saturated fatty acids alter metabolic homeostasis, yet how distinct nutrients are integrated at the transcriptional level remains incompletely understood. Methods: Here, we profiled the larval midgut transcriptome of Drosophila melanogaster following 24 h exposure to diets enriched with 5% fructose (FD), 1% palmitic acid (PD), or their combination (MD). RNA sequencing (Illumina NovaSeq) was performed on pooled third-instar larval midguts, and differential expression analyses were conducted to identify diet-associated transcriptional changes. Results: The results revealed extensive transcriptional remodeling, with most responses being diet-specific, alongside a conserved core of genes regulated across all treatments. Shared transcriptional signatures were associated with proteostasis and amino acid transport pathways. Comparative and pattern-based analyses further uncovered discordant gene sets and pathway enrichments that were unique to individual diets or to the combined exposure. Notably, the mixed diet induced distinct expression patterns with specific functional signatures that were not predictable from either nutrient alone. Conclusions: Together, these findings indicate that the larval midgut integrates carbohydrate and lipid inputs through coordinated and context-dependent transcriptional responses, highlighting the importance of nutrient combinations in shaping epithelial metabolic programs. Full article

Sclerodermus guani Xiao et Wu, 1983 plays a significant role in the biological control of agricultural and forestry pests. To investigate whether different sugar types significantly affect the longevity, fecundity, and nutrient reserves of female S. guani adults, this study provided 1 mol/L solutions of sucrose, fructose, glucose, mannose, or trehalose under laboratory conditions, with a distilled water group serving as the control. The longevity and nutrient content of parasitoids were measured after varying feeding durations, while fecundity was assessed in preliminary experiments. The results demonstrated that prolonged sugar feeding significantly extended parasitoid longevity, with fructose, glucose, and sucrose exhibiting the most pronounced effects and no significant differences among them. Nutrient analysis revealed that sugar consumption significantly increased total carbohydrate content, slowed lipid depletion, and promoted protein accumulation. Sucrose, fructose, and glucose outperformed other sugars and the control in these aspects. Fecundity assays indicated that glucose and trehalose significantly shortened the pre-oviposition period and enhanced egg production. In conclusion, nutritional supplementation markedly improves the longevity and reproductive performance of S. guani, with 1 mol/L glucose identified as the optimal dietary source. Full article

The rising cost of conventional protein sources such as soybean meal has prompted the search for sustainable and economical alternatives in aquafeeds. Sugar beet pulp (SBP), an abundant by-product of the sugar industry, possesses nutritional potential but is limited by its high fiber and anti-nutritional factors. Solid-state fermentation (SSF) offers a promising approach to enhance its nutritive value and functional properties. This study evaluated the effects of dietary inclusion of mixed microbial solid-state fermented beet pulp (FBP) on the growth, systemic health and intestinal function of juvenile yellow catfish (Pelteobagrus fulvidraco). First, orthogonal optimization determined Lactiplantibacillus plantarum:Saccharomycopsis fibuligera:Bacillus subtilis = 1:3:3 as the optimal ratio, significantly improving the nutritional profile of FBP. Based on this optimized FBP, an 8-week feeding trial, five isonitrogenous and isolipidic diets were formulated by replacing 0–12% soybean meal with FBP. The results demonstrated that 9% FBP inclusion yielded optimal growth performance and significantly improved muscle texture. At the systemic level, FBP supplementation reduced serum lipid markers and liver enzyme activities while enhancing antioxidant capacity. At the intestinal level, FBP promoted intestinal health by increasing key digestive enzyme (lipase, trypsin, amylase) activities, stimulating villus development, and improving intestinal antioxidant status. Furthermore, gut microbiota analysis revealed that dietary FBP supplementation significantly modulated intestinal microbial composition, with notable enrichment of genera such as Leucobacter. In conclusion, FBP is a multi-functional ingredient that enhances growth, product quality, systemic physiology, and intestinal health in yellow catfish aquaculture. These findings provide a viable strategy for the sustainable utilization of agricultural by-products in aquafeeds. Full article

Monoacylglycerol lipase (MAGL) is a key regulator of lipid signaling networks implicated in tumor progression and represents an attractive anticancer target. To combine MAGL inhibition with potentially enhanced uptake by highly glycolytic cancer cells, we designed glycoconjugated analogs of a N-benzoylpiperidine MAGL inhibitor scaffold bearing a glucopyranose unit. An alkyne-functionalized benzoylpiperidine intermediate was prepared and coupled to azido sugars through a CuAAC “click” reaction to afford two triazole-linked glycoconjugates. In a colorimetric assay on human MAGL, the new compounds 17 and 18 inhibited the enzyme with IC₅₀ values of 43.3 and 68.8 μM, respectively, confirming compatibility with MAGL inhibition albeit with reduced potency versus reference triazole-substituted benzoylpiperidine 13 (IC₅₀ = 4.1 μM). In PANC-1 pancreatic cancer cells, both glycoconjugates were inactive in high-glucose medium, but displayed antiproliferative activity under low-glucose conditions (GI₅₀ 17 = 129 μM; GI₅₀ 18 = 12 μM), consistent with glucose-dependent uptake/competition. Overall, these first-in-class MAGL-targeting glycoconjugates provide a starting point for optimizing dual MAGL inhibition and metabolically driven cellular selectivity. Full article

Background: Childhood obesity is becoming an increasingly prevalent global health issue. Pesticides, which pose significant threats to human health and the environment are major risk factors for various diseases, including cancer, obesity, diabetes, autoimmune disorders, and food allergies. Paraoxonase 1 (PON1) is an enzyme found on high-density lipoproteins (HDL) in serum, which hydrolyzes toxic oxon metabolites of organophosphate pesticides, certain carbamates, aromatic and aliphatic lactones, aromatic esters, and oxidized lipids through its calcium-dependent glycoprotein structure. This study aimed to evaluate the relationship between environmental pesticide exposure, childhood obesity, and PON1 levels. Methods: The study included 58 obese children with a body mass index above the 95th percentile and 43 healthy children of the same age group. Serum PON1 levels were measured using the ELISA method. Levels of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and organophosphorus pesticides (OPPs) in the blood were determined through LC/MS/MS and GC analysis methods. Results: According to ELISA analysis, the PON1 level was significantly lower in the obesity group (102.8 ± 12.49 ng/mL) compared to the control group (134.8 ± 14.29 ng/mL) (p < 0.001). LC/MS/MS and GC analyses showed significantly higher levels of Σ₄OPPs and Σ₄PCBs in obese children compared to the control group (p < 0.001). However, no significant difference was observed between the two groups in terms of Σ₄OCP levels (p > 0.05). Conclusions: Our findings highlight the presence of OPPs and PCBs in the blood of obese children. Although these factors are associated with PON1, further research is needed to evaluate their potential role as risk indicators for obesity. Full article

Background/Objectives: An intensive lipid-lowering therapy is needed in familial hypercholesterolemia (FH) subjects; however, the adherence to the Mediterranean diet (MD) and its effects have not been fully evaluated in FH subjects. This study aimed to evaluate the impact of the MD on metabolic and vascular profiles in FH subjects. Methods: In this cross-sectional study 253 genetically confirmed FH subjects were included. Adherence to MD was assessed by the validated Pyramid-based MD Score (PyrMDS) and FH subjects were stratified according to the tertiles of PyrMDSs (low, intermediate, and high), with a higher score indicating higher adherence to MD. The lipid profile as well as the subendocardial viability ratio (SEVR), an indirect measure of myocardial perfusion, were assessed in all FH subjects. Results: Compared to the low-PyrMDS group, FH subjects with a high MD adherence showed lower levels of low-density lipoprotein cholesterol (LDL-C) (149.7 ± 71.4 vs. 176.7 ± 77.4 mg/dL, p = 0.006). After accounting for lipid-lowering therapies, smoking habit, and arterial hypertension, individuals in the high-PyrMDS group showed higher SEVR than those in the intermediate- and low-PyrMDS groups (167 ± 3.51 [standard error—SE] vs. 150 ± 5.03 [SE] vs. 148 ± 3.75 [SE], all p < 0.01). After adjusting for age, sex, and lipid-lowering therapies, PyrMDS was independently associated with LDL-C (β = −0.11, p = 0.03). Conclusions: Greater adherence to the MD was associated with more favorable metabolic and vascular profiles in FH subjects independent of lipid-lowering therapies. This suggests that MD adherence should be actively promoted in clinical practice alongside pharmacological interventions. Full article

Early-stage fungal contamination in maize kernels is difficult to identify visually and it can cause severe quality and safety risks during storage and transportation. Short-wave infrared (SWIR) hyperspectral imaging offers a rapid, non-destructive approach by capturing chemical information related to water, proteins, and lipids. This study investigates the early detection and classification of Gibberella zeae contamination in maize kernels using SWIR hyperspectral imaging combined with machine learning. Two maize varieties were artificially inoculated and cultured under controlled conditions, followed by hyperspectral data collection over six contamination stages. Various preprocessing techniques including standard normal variate (SNV), second derivative (SD), multiplicative scatter correction (MSC), and derivatives were evaluated to enhance data quality. Feature wavelength selection was performed using successive projections algorithm (SPA), competitive adaptive reweighted sampling (CARS), and uninformative variable elimination (UVE), significantly reducing redundancy and improving classification performance. Multiple models, including linear discriminant analysis (LDA), multilayer perceptron (MLP), support vector machine (SVM), a convolutional neural network (CNN), long short-term memory (LSTM) network, and a hybrid architecture Transformer that integrated a CNN, a LSTM network, and a Transformer (abbreviated as CLT), were constructed for both binary (healthy vs. contaminated) and multiclass classification tasks. Specifically, the multiclass task consisted of six contamination stages corresponding to contamination time from Day 0 to Day 5. The best binary classification task accuracy of 100% was achieved using SNV-preprocessed data with the MLP model. For multiclass classification task, the SD-preprocessed LDA model reached a test accuracy of 92.56%. Combined with appropriate preprocessing, feature selection and modeling, these results demonstrate that hyperspectral imaging is a powerful tool for the non-destructive, early-stage identification of fungal contamination in maize kernels, offering strong support for food safety and quality monitoring. Full article

The present study investigated the impact of dietary papaya leaf meal (PLM) at three inclusion levels (0%, 6%, and 12%) with or without multi-enzyme supplementation (0.5 g/kg diet) on growth performance, nutrient digestibility, carcass characteristics, serum biochemistry, lipid profile, and antioxidant status in Arbor Acres broiler chickens. A total of 240 one-day-old chicks were allocated to six treatments in a 3 × 2 factorial arrangement for 42 days. Enzyme supplementation significantly improved body weight gain, feed conversion ratio, and nutrient efficiency (p < 0.001), while moderate PLM inclusion (6%) supported optimal performance. Digestibility of crude fiber and ether extract was enhanced by enzymes (p < 0.05), with a notable PLM × enzyme interaction for fiber digestibility. Carcass yield was unaffected, but enzyme supplementation increased dressing percentage and reduced abdominal fat. Serum biochemistry remained largely unchanged, except for elevated AST at 12% PLM (p < 0.01). Lipid profile improved with enzyme supplementation, reducing total cholesterol, triglycerides, and LDL while increasing HDL (p < 0.05). Enzyme supplementation significantly increased SOD and CAT activities (p < 0.001), whereas TAC responses were inconsistent across treatments. Lipid peroxidation (MDA) increased at 12% PLM, indicating a potential oxidative imbalance at higher inclusion levels. In conclusion, multi-enzyme supplementation was the primary driver of growth performance and nutrient utilization improvements, while moderate PLM inclusion (6%) exerted supportive and synergistic effects without compromising carcass traits. Full article

Objective: This study aimed to investigate the association between the neutrophil-to-albumin ratio (NAR) and coronary atherosclerotic burden, assessed using the Gensini score, in patients referred for coronary angiography (CAG). Methods: A total of 987 patients who underwent CAG at Sanliurfa Mehmet Akif Inan Training and Research Hospital between January 2020 and June 2023 were retrospectively analyzed. Demographic, clinical, and laboratory data, including complete blood count, albumin, lipid profile, and creatinine, were collected prior to angiography. The NAR was calculated as the ratio of absolute neutrophil count to serum albumin. Coronary atherosclerotic burden was assessed using the Gensini scoring system and analyzed across predefined score categories representing increasing anatomical disease extent: normal (score 0), mild (1–24), and severe (≥25). Statistical analyses included group comparisons and multivariable regression analyses appropriate to the study design. Results: Higher NAR values were associated with increased angiographic coronary atherosclerosis severity at the group level across Gensini score categories. This association remained statistically significant after prespecified multivariable adjustment for established cardiovascular risk factors. Conclusions: Higher NAR values were associated with greater angiographic coronary atherosclerotic burden, as quantified by the Gensini score, in an angiography-referred population. Full article

Prostate cancer (PCa) progression is critically driven by androgen receptor (AR) signaling, which integrates hormonal cues with metabolic programs supporting tumor growth, survival, and therapy resistance. Emerging evidence suggests that intermittent fasting (IF) and related dietary interventions—such as time-restricted eating (TRE), alternate-day fasting (ADF), and fasting-mimicking diet (FMD)—modulate systemic metabolism, including reductions in insulin and insulin-like growth factor 1 (IGF-1), and induce intracellular nutrient stress that can influence AR activity, splice variant expression (e.g., AR-V7), and downstream metabolic pathways. This systematic literature review (Scopus, PubMed, Web of Science; publications up to December 2025; search terms: “prostate cancer,” “androgen receptor,” “AR splice variants,” “intermittent fasting,” “fasting mimicking diet”, “metabolism,” “therapy resistance”) summarizes preclinical and clinical studies addressing the impact of IF on AR signaling, lipogenesis, mitochondrial function, redox homeostasis, and therapy response. Preclinical studies indicate that IF can reduce AR expression, impair nuclear translocation, modulate AR splice variants such as AR-V7 via nutrient-sensitive splicing mechanisms, and enhance sensitivity to androgen deprivation therapy and AR-targeted agents. Mechanistically, IF-induced metabolic stress engages AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and sirtuin pathways, alters lipid and mitochondrial metabolism, and transiently increases reactive oxygen species (ROS), creating vulnerabilities in prostate tumor cells. Translational evidence suggests potential benefits of integrating IF with standard therapy, but effects may depend on fasting regimen, caloric intake, macronutrient composition, and patient metabolic context, including risk of lean mass loss. This review highlights the metabolic crosstalk between IF and AR signaling and emphasizes the need for future clinical studies incorporating biomarker-guided approaches and body composition monitoring to fully exploit this intersection for improved therapeutic outcomes in prostate cancer. Full article

Wound healing is a dynamic and multifaceted biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Topical therapy is widely preferred for wound management due to its localized action and reduced systemic adverse effects. However, the effective delivery of therapeutic agents is often limited by the skin’s barrier properties, the complex wound microenvironment, and the physicochemical characteristics of drugs. This review highlights the key physicochemical parameters governing topical drug delivery in wound therapy, including drug solubility, molecular size, lipophilicity, vesicle size distribution, surface charge, encapsulation efficiency, lipid composition, ethanol concentration, and vesicle deformability, which collectively influence drug permeation and retention at the wound site. Nanovesicular delivery systems have emerged as promising strategies to overcome these limitations. In particular, ultradeformable vesicles such as ethosomes, transferosomes, and transethosomes have demonstrated enhanced skin permeation and improved drug deposition in periwound tissue due to their flexible membrane structure and optimized physicochemical properties. This review systematically discusses the composition, preparation techniques, and critical formulation parameters of these vesicular systems that determine their stability, elasticity, and permeation performance. Furthermore, their applications in delivering anti-inflammatory drugs, antimicrobial agents, bioactive phytochemicals, and regenerative therapeutics for different wound types are examined. Widely used in vitro, ex vivo, and in vivo evaluation methods, including permeation studies and wound healing models such as excision, burn, infected, and diabetic wounds, are also summarized. Finally, the review outlines current challenges related to formulation standardization, physicochemical characterization, safety assessment, and large-scale production, while highlighting the future potential of ultradeformable vesicles as next-generation nanocarriers for advanced wound healing therapies. Full article

High-fat diets (HFDs) containing dietary fats with different fatty acid (FA) compositions alter gut microbiota composition in a fat-source-dependent manner. Immunoglobulin A (IgA) and unabsorbed lipids in the distal gut are potential regulators of the gut microbiota. However, their roles in mediating gut microbiota alterations induced by dietary fats with different FA compositions remain unclear. This study aims to examine the associations of these two factors with fat-source-dependent gut microbiota alterations. BALB/c mice were fed a normal diet, a high-lard diet, a high-olive oil diet, or a high-soybean oil diet for 27 weeks. Fecal samples were collected to assess microbiota composition, the IgA coating index (ICI)—which quantifies the extent of IgA coating on gut microbiota—and fecal fatty acid concentrations. At the phylum level, the concentration of fecal total long-chain fatty acids (LCFAs) was positively correlated with the relative abundance (RA) of Bacillota and negatively correlated with that of Bacteroidota. In addition, a trend toward a positive association between the RA and the ICI was observed for Bacillota but not for Bacteroidota. At the genus level, the RAs of 12 taxa were positively correlated with fecal LCFA concentrations, whereas those of 6 taxa were negatively correlated. Although the RAs of most taxa appeared to be influenced by unabsorbed lipids and additional factors, only four Bacillota genera exhibited a positive correlation between the RA and the ICI. Our observations suggest that IgA coating of the gut microbiota may have a minimal association with fat-source-specific alterations in gut microbiota composition during HFD intake. Full article