Search Results (281)

The conservation of poultry biodiversity is a growing global priority, yet it necessarily relies on the scientific valorization of specific local breeds. This study aimed to characterize the lipid composition and cholesterol content of eggs from three native Sicilian chicken breeds (Cornuta, Valplatani, and Siciliana) reared under semi-extensive conditions, in order to evaluate their nutritional potential and support biodiversity preservation strategies. A total of 170 eggs from 11 farms were analyzed. Fatty acid composition and nutritional indices (atherogenic index, thrombogenic index, n-6/n-3 ratio, HH index) were determined according to ISO and AOAC standards. Results showed that Cornuta eggs exhibited the most favorable lipid profile, with the lowest saturated fatty acid (SFA) content (38.55%), the lowest n-6/n-3 ratio (7.35), and the best values for AI (0.52), TI (1.22), and HH (2.02), compared to Valplatani and Siciliana. Conversely, the lowest cholesterol content was found in Siciliana eggs (1463.58 mg/kg), significantly lower than Cornuta (1789 mg/kg; p < 0.05). Although no commercial hybrids were included, the literature data were used for contextual comparison. These findings suggest that native breeds may produce eggs with functional nutritional properties, supporting both healthier food choices and local genetic conservation. Moreover, this study provides a replicable framework for the nutritional valorization of underutilized poultry breeds, reinforcing the role of biodiversity in sustainable food systems. Full article

Transmembrane protein 43 (TMEM43 or LUMA) encodes a highly conserved protein found in the nuclear and endoplasmic reticulum membranes of many cell types and the intercalated discs and adherens junctions of cardiac myocytes. TMEM43 is involved in facilitating intra/extracellular signal transduction to the nucleus via the linker of the nucleoskeleton and cytoskeleton complex. Genetic mutations may result in reduced TMEM43 expression and altered TMEM43 protein cellular localization, resulting in impaired cell polarization, intracellular force transmission, and cell–cell connections. The p.S358L mutation causes arrhythmogenic right ventricular cardiomyopathy type-5 and is associated with increased absorption of lipids, fatty acids, and cholesterol in the mouse small intestine, which may promote fibro-fatty replacement of cardiac myocytes. Mutations (p.E85K and p.I91V) have been identified in patients with Emery–Dreifuss Muscular Dystrophy-related myopathies. Other mutations also lead to auditory neuropathy spectrum disorder-associated hearing loss and have a negative association with cancer progression and tumor cell survival. This review explores the pathogenesis of TMEM43 mutation-associated diseases in humans, highlighting animal and in vitro studies that describe the molecular details of disease processes and clinical, histologic, and molecular manifestations. Additionally, we discuss TMEM43 expression-related conditions and how each disease may progress to severe and life-threatening states. Full article

Obesity and pediatric fatty liver disease are increasingly prevalent, yet the underlying mechanisms linking these conditions to heightened inflammatory and immune responses remain poorly understood. Using a murine model reflecting early-life obesity and hepatic steatosis, we tested the hypothesis that obesity-driven hepatic inflammation intensifies systemic immune responses and exacerbates vascular dysfunction following innate immune activation. Newly weaned C57BL/6 mice were fed either a high-saturated-fat, high-cholesterol diet (HFD) or a control diet (CD) for four weeks, modeling adolescence in humans. HFD-fed mice exhibited hepatic and splenic enlargement, elevated plasma cholesterol levels, increased activity levels of liver enzymes (alanine and aspartate aminotransferases), and higher plasma serum amyloid A (SAA) concentrations. Following a sublethal dose of lipopolysaccharide (LPS), the expression of hepatic inflammatory genes (VCAM-1 and iNOS) was significantly elevated in HFD-fed mice, indicating an exaggerated local immune response. Mice fed an HFD also showed significant impairment in endothelium-dependent vasorelaxation compared to CD mice and saline-treated controls, while endothelium-independent responses remained intact. These vascular changes occurred in the context of hepatic inflammation, suggesting that early-life diet-induced steatosis sensitizes the vasculature to inflammatory insult. These findings suggest that obesity-driven hepatic inflammation primes exaggerated systemic immune responses to innate immune stimuli, potentially contributing to the vascular dysfunction and variable clinical morbidity observed in pediatric inflammatory conditions. Full article

Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the BEST1 gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated the surface behavior and organization of recombinant hBest1 and its interactions with membrane lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol) in models of biological membranes, which affect the hBest1 structure–function relationship. The main aim of our current investigation is to integrate pure hBest1 protein into lipid bilayer nanostructures. We synthesized and characterized various hBest1-containing nanostructures based on 1,2-Dipalmitoylphosphatidylcholine (DPPC), SM, glycerol monooleate (GMO) and Chol in different ratios and determined their cytotoxicity and incorporation into cell membranes and/or cells by immunofluorescence staining. Our results show that these newly designed nanoparticles are not cytotoxic and that their incorporation into MDCK II cell membranes (used as a model system) may provide a mechanism that could be applied to RPE cells expressing mutated hBest1 in order to restore their ion transport functions, affected by mutated and malfunctioning hBest1 molecules. Full article

Forskolin (FSK) induces the browning of white adipose tissue (WAT) through the activation of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) generation. When administered intravenously or orally, FSK undergoes significant metabolism and accumulation in the liver and other tissues, resulting in high side effects and low anti-obesity effects due to trivial amounts reaching WAT. This study examines the potential anti-obesity and metabolic effects of the inguinal WAT (IWAT) delivery of FSK in high-fat diet-induced C57BL/6J obese mice. Mice received one of the following treatments twice weekly for 4 weeks: 1. Control into both IWAT depots (Con^both); 2. FSK 15 mg/kg body weight (BW)/injection into both inguinal WAT (IWAT) depots (FSK15^both); 3. FSK 7.5 mg/kg BW/injection into both IWAT depots (FSK7.5^both); and 4. FSK 7.5 mg/kg BW/injection into the left IWAT depot (FSK7.5^left). Both the FSK15^both and FSK7.5^both treatments improved metabolic parameters by lowering blood glucose, enhancing glucose tolerance, and reducing serum insulin and cholesterol. The FSK15^both treatment had a greater impact on IWAT, resulting in smaller adipocytes and increased expression of Ucp1 and Tmem26 mRNA levels. All FSK treatments also reduced inflammatory and lipogenic markers in the liver, indicating improved hepatic metabolism. These findings suggest that local delivery of FSK into subcutaneous WAT is a potential strategy for combating obesity and improving metabolic health. However, further studies are needed to confirm the statistical and biological significance of these effects. Full article

Background/Objectives: Thymol, one of the main compounds of thyme essential oil, has shown promising effects in treating various skin disorders owing to its anti-inflammatory, antimicrobial and antioxidative activities. Due to its limited solubility in water, thymol is commonly used in higher concentrations to achieve a suitable therapeutic effect, which can consequently lead to skin irritation. To overcome these limitations, we incorporated thymol into a vesicular phospholipid gel (VPG), a novel semisolid dermal vehicle consisting of highly concentrated dispersion of phospholipid vesicles (liposomes). Methods: Thymol was successfully loaded into two VPGs differing in bilayer fluidity, which were characterized for the physicochemical and rheological properties, storage stability, in vitro release, ex vivo skin permeability, in vitro compatibility with epidermal cells, wound healing potential, and antibacterial activity against skin-relevant bacterial strains. Results: High pressure homogenization method enabled preparation of VPG-liposomes of neutral surface charge in the size range 140–150 nm with polydispersity indexes below 0.5. Both types of VPGs exhibited viscoelastic solid-like structures appropriate for skin administration and ensured skin localization of thymol. Although both types of VPGs enabled prolonged release of thymol, the presence of cholesterol in the VPG increased the rigidity of the corresponding liposomes and further slowed down thymol release. Conclusions: Loading of thymol into VPGs significantly reduced its cytotoxicity toward human keratinocytes in vitro even at very high concentrations, compared to free thymol. Moreover, it facilitated in vitro wound healing activity, proving its potential as a vehicle for herbal-based medicines. However, the antibacterial activity of thymol against Staphylococcus aureus and methicillin-resistant S. aureus was hindered by VPGs, which represents a challenge in their development. Full article

Malaria, typhoid fever, respiratory tract infections, and urinary tract infections significantly impact women, especially in remote, resource-constrained settings, due to limited access to quality healthcare and certain risk factors. Most studies have focused on vector control measures, such as insecticide-treated nets and time series analysis, often neglecting emerging yet critical risk factors vital for effectively preventing febrile diseases. We address this gap by investigating the use of machine learning (ML) models, specifically extreme gradient boost and random forest, in predicting adult females’ susceptibility to these diseases based on biological, environmental, and socioeconomic factors. An explainable AI (XAI) technique, local interpretable model-agnostic explanations (LIME), was applied to enhance the transparency and interpretability of the predictive models. This approach provided insights into the models’ decision-making process and identified key risk factors, enabling healthcare professionals to personalize treatment services. Factors such as high cholesterol levels, poor personal hygiene, and exposure to air pollution emerged as significant contributors to disease susceptibility, revealing critical areas for public health intervention in remote and resource-constrained settings. This study demonstrates the effectiveness of integrating XAI with ML in directing health interventions, providing a clearer understanding of risk factors, and efficiently allocating resources for disease prevention and treatment. Full article

Background: There are known associations between periodontitis and colorectal cancer, but knowledge on the connections existing between the two are not fully understood. The aim of our study was to assess prevalence and clinical severity of periodontitis in patients with localized colorectal cancer. Secondly, the dynamics of metabolic derangements, particularly glucose metabolism, insulin resistance, and diabetes mellitus were studied as well. Methods: Diagnostic procedures included endoscopies with patohistology, laboratory exams, the insulin resistance homeostatic model assessment method (HOMA index), anthropometrics, and radiology imaging. Periodontal status was evaluated by full-mouth periodontal examination. Results: A total of 79 patients with localized colorectal carcinoma, with slight male predominance of 55.7%, and an age of 65.7 ± 12.4 years participated in this study. Three-quarters of patients (73.4%; 95% CI: 63.0–82.2%) were diagnosed with periodontitis. Patients with periodontitis and colorectal cancer had significantly increased glucose levels (fasting and after oral glucose challenge), (both p < 0.05). Also, increased values of the HOMA index were found in patients with periodontitis vs. controls (without periodontitis) and colorectal cancer; 6.38 ± 5.74 vs. 3.58 ± 2.6 (p = 0.012); Spearman’s Rho correlation coefficient = 0.271 (p = 0.039). There were significant differences in high-density cholesterol in patients with periodontitis vs. controls, 1.41 ± 0.28 vs. 1.23 ± 0.35 mmol/L (p = 0.016), but correlations were insignificant; Rho c.c. = 0.045 (p = 0.738). Conclusions: The most consorted connections between periodontitis and colorectal cancer were found among parameters of metabolic domain, especially glucose concentrations and insulin resistance. Further studies, which would include novel and emerging antidiabetic treatments and their effects on the prevention or control of both diseases, would be warranted. Full article

CHROMR is a primate-specific long noncoding RNA with emerging roles in homeostasis and pathophysiology. Elevated blood levels of CHROMR have been observed in patients with cardiovascular disease and several cancers, where it is correlated with poor clinical outcomes. Like many lncRNAs, CHROMR accumulates in both the nucleus and the cytoplasm, and it assumes distinct functions in each of these cellular compartments. In the nucleus, CHROMR sequesters a transcriptional repressor complex to activate interferon-stimulated gene expression and antiviral immunity. In the cytoplasm, CHROMR competitively inhibits microRNAs involved in cholesterol efflux and cell cycle regulation, thereby impacting gene pathways involved in reverse cholesterol transport, HDL biogenesis, and tumor growth. In this review, we detail the multifaceted functions of CHROMR in cholesterol metabolism, innate immunity, and cancer progression. We also explore the potential molecular mechanisms that govern its expression and dynamic subcellular localization, which may be key to its functional versatility. Advancing our understanding of the regulatory networks and cellular environments that shape CHROMR activity will be critical for assessing its promise as a therapeutic target and diagnostic biomarker. Full article

Lipid metabolism disorders represent a significant risk factor for the pathogenesis of Alzheimer’s disease (AD). Apolipoprotein E (APOE) has been regarded as a pivotal regulator of lipid homeostasis in the central nervous system (CNS), with polymorphic alleles identified as genetic risk factors for late-onset AD. Despite advances in APOE research and the development of numerous pharmaceutical approaches targeting distinct APOE isoforms, there remain limited treatment approaches for AD that focus on lipid metabolic homeostasis. Consequently, it is necessary to reevaluate the lipid metabolic process in the CNS. Apolipoprotein A1 (APOA-I), a major component of high-density lipoprotein (HDL), plays a crucial role in reverse cholesterol transport from tissues to the liver to maintain lipid homeostasis. Over the past few decades, numerous studies have suggested a connection between reduced APOA-I levels and a higher risk of AD. APOA-I is synthesized exclusively in the liver and intestines, and there is a lack of conclusive evidence supporting its functional significance within the central nervous system, in contrast to APOE, which is produced locally by glial cells and neurons within the CNS. Moreover, APOA-I’s ability to penetrate the blood-brain barrier (BBB) is still poorly understood, which causes its significance in central lipid metabolism and AD pathophysiology to be mainly disregarded. Recent advancements in tracing methodologies have underscored the essential role of APOA-I in regulating lipid metabolism in the CNS. This review aims to elucidate the physiological functions and metabolic pathways of APOA-I, integrating its associations with AD-related pathologies, risk factors, and potential therapeutic targets. Through this discourse, we aim to provide novel insights into the intricate relationship between AD and APOA-I, paving the way for future research in this field. Full article

Background/Objectives: Dental implant success is influenced by a range of systemic and local factors. Emerging evidence suggests that metabolic markers such as lipid profiles and vitamin D levels may play a role in osseointegration and implant survival. The aim of this study was to evaluate the influence of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and vitamin D levels on the short-term survival rate of dental implants. Materials and Methods: A prospective observational study was conducted on patients receiving dental implants. Preoperative serum levels of LDL, HDL, triglycerides, and vitamin D were recorded. A total of 556 conical, platform-switching implants were placed in 166 patients, smokers and no smokers with mean age 48 years ± 4.7. Implant survival was evaluated from 14 to 21 days after placement, at 6- and at a 12-month follow-up. Spearman’s rank correlation was performed to assess potential correlations between the abovementioned systemic factors and implant loss. Results: Out of 556 implants, 13 (2.34%) were lost from 14 to 21 days after placement, a further two (0.35%) were lost after 6 months after surgery and a further eight (1.44%) were lost 12 months after placement. No significant correlation was found between HDL levels, cholesterol levels, triglyceride levels and implant loss. Spearman’s correlation analysis revealed a strong negative correlation between vitamin D levels and implant loss with no statistical significance. Conclusions: Within the limitations of this study, no statistically significant associations were found between lipid profile markers or vitamin D levels and early dental implant loss. Further large-scale and long-term studies are warranted to validate these findings and better understand the interplay between systemic biochemical markers and implant survival rate. Full article

The identification of causal genomic regions for liver fat accumulation in the context of metabolic dysfunction remains a challenging goal. This study aimed to identify potential endophenotypes for liver fat content and employ them in bivariate linkage searches for pleiotropic genetic regions where targeted association analysis is more likely to reveal significant variants. Multiple metabolic risk and adiposity distribution traits were assessed using the endophenotype ranking value. The top-ranked endophenotypes were then used in a bivariate linkage analysis, paired with liver fat content. Quantitative trait loci (QTLs) identified as significant or suggestive were targeted for measured genotype association analyses. The highest-ranked endophenotypes for liver fat accumulation were insulin resistance (IR), visceral adipose tissue (VAT), and high-density lipoprotein cholesterol (HDL-C). The univariate linkage analysis for liver fat content identified one significant QTL at chromosome 17p13.2 (Logarithm of odds score (LOD) = 2.90, p = 1.29 × 10⁻⁴). The bivariate linkage analysis pairing liver fat with IR and VAT improved the localization of two suggestive QTLs at 13q21.31 (LOD = 2.11, p = 9.03 × 10⁻⁴), and 6q21 (LOD = 2.35, p = 5.07 × 10⁻⁴), respectively. Targeted association analyses within the -1-LOD score regions of these QTLs revealed 17 marginally significant single nucleotide polymorphisms (SNPs) associated with liver fat content or its combination with the selected endophenotypes. The endophenotype-informed linkage analysis successfully identified regions suitable for the targeted association analysis of liver fat content, either alone or in combination with IR or VAT, leading to the discovery of marginally significant variants with potential for future functional studies. Full article

Dyslipidemia is a well-known risk factor in the development and progression of atherosclerosis. VLDL plays a crucial role in maintaining lipid homeostasis; however, even minor fluctuations in its production, intracellular trafficking, and secretion can contribute to the progression of atherosclerosis. Fenofibrate is an FDA-approved drug that effectively lowers plasma triglycerides and VLDL-associated cholesterol while simultaneously increasing HDL levels. Although fenofibrate is a known PPARα agonist with several proposed mechanisms for its lipid-altering effects, its impact on the intracellular trafficking of VLDL has not yet been investigated. We observed that treatment of HepG2 cells with 50 µM of fenofibrate resulted in a significant reduction in VLDL secretion, as evidenced by a significant decrease in the secretion of ³H-labeled TAG, fluorescent TAG, and ApoB100 protein into the media. Using confocal microscopy to monitor VLDL intracellular trafficking, we observed a distinct change in VLDL triglyceride localization, suggesting delayed transport through the endoplasmic reticulum and Golgi. An immunoblot analysis revealed a decrease in Sar1B protein expression, a key regulator of COPII protein recruitment, which is essential for VTV formation and intracellular VLDL trafficking, the rate-limiting step in VLDL secretion. Our data reveal a novel mechanism by which fenofibrate alters the lipid profile by interfering with intracellular VLDL trafficking in hepatocytes. Full article

Lipid metabolism and oxidative stress are major contributors to ocular diseases, including drusen formation and photoreceptor damage. Aster-B, encoded by GRAMD1B, mediates the non-vesicular transport of cholesterol and carotenoids and is highly expressed in the human eye, though its specific ocular functions remain unknown. We investigated Aster-B’s role in ARPE-19 cells, a model of the retinal pigment epithelium (RPE), using CRISPR/dCas9 to generate an Aster-B-expressing cell line. Aster-B expression significantly improved cell survival under oxidative stress induced by hydrogen peroxide (H₂O₂) and was associated with the activation of the p53 and TGFβ signaling pathways, indicating a role in modulating stress responses. To confirm its lipid transport activity, we treated cholesterol-depleted cells with carotenoids and tracked their localization. In Aster-B-expressing cells, carotenoids accumulated in mitochondria, while in control cells, they remained in other cellular compartments. Under oxidative stress, mitochondrial carotenoid levels declined in Aster-B-expressing cells but not in control cells. Interestingly, carotenoids enhanced survival in control cells exposed to H₂O₂ but had a detrimental effect in Aster-B-expressing cells, suggesting that carotenoid function is context and location dependent. These findings highlight Aster-B’s role in coordinating lipid transport and stress responses in the RPE, with implications for oxidative stress-related eye diseases. Full article

Diosgenin, a crucial precursor for steroidal drug production, has poorly understood regulatory pathways. Diosgenin is the primary active component of Dioscorea zingiberensis. Notably, D. zingiberensis also possesses the highest diosgenin content among Dioscorea species, reaching up to 16.15% of dry weight. This study identified DZHDZ32 as a potential regulator of diosgenin biosynthesis in D. zingiberensis through transient overexpression. To validate its function, we developed an optimized genetic transformation method for D. zingiberensis and generated two DZHDZ32-overexpressing lines. The DZHDZ32 transcription factor belongs to the HD-ZIP I subfamily and is localized to the nucleus. Notably, overexpression of DZHDZ32 resulted in a significant increase in its transcript levels in leaves (264.59- and 666.93-fold), leading to elevated levels of diosgenin and its biosynthetic intermediates, including cholesterol and β-sitosterol. Specifically, diosgenin content increased by 41.68% and 68.07%, cholesterol by 10.29% and 16.03%, and β-sitosterol by 12.33% and 19.49% in leaves compared to wild-type plants. Yeast one-hybrid and dual-luciferase assays demonstrated that DZHDZ32 directly binds to the promoters of ACAT and GPPS1, consistent with the significant upregulation of ACAT and GPPS1 expression (3.69- and 4.87-fold and 4.75- and 6.53-fold, respectively) in the overexpressing lines. This study established an optimized genetic transformation method for D. zingiberensis and identified DZHDZ32 as a key regulator of diosgenin biosynthesis. The discovery of DZHDZ32 has significant implications for enhancing diosgenin production and advancing steroidal drug development. Full article