Search Results (520)

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Hemolin has been identified as a crucial immune gene in insect immune defense. The silkworm is susceptible to infections by pathogenic microorganisms when reared on artificial diets. In this study, through comparative analysis of the expression patterns of BmHemolin in silkworms fed on mulberry leaves and artificial diets, we found that the expression of BmHemolin was significantly upregulated in silkworms reared on artificial diets, and this upregulation was highly likely induced by pathogenic microorganisms. Further interaction analysis revealed that BmHemolin could bind to pathogenic microorganisms and form aggregates. Meanwhile, BmHemolin enhanced the melanization and aggregation of hemocytes. Subsequent in vitro antibacterial experiments showed that BmHemolin had the ability to inhibit the growth of Escherichia coli. In vivo clearance experiments demonstrated that BmHemolin facilitated the clearance of pathogens in the body. Moreover, CRISPR/Cas9-mediated knockout of the BmHemolin gene led to the downregulation of antimicrobial peptides and phagocytosis-related factors, while an excess of BmHemolin could enhance the expression of these genes, thereby improving the silkworm’s immune resistance to Enterococcus mundtii and increasing survival rates. In summary, our research demonstrates that BmHemolin played a pivotal role in both humoral and cellular immunity in the silkworm, thereby defending against pathogen invasion. Full article

Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

Background/Objectives: Obesity, a major risk factor for cardiometabolic traits, is influenced by both genetic and environmental factors. Genetic studies have identified multiple single-nucleotide polymorphisms (SNPs) associated with obesity and related traits. This study aimed to examine the association between genetic risk score (GRS) and obesity-associated traits, while incorporating SNPs with established gene–diet interactions to explore their potential role in precision nutrition (PN) strategies. Methods: A total of 4279 participants were stratified into low- and intermediate-/high-GRS groups based on 18 SNPs linked to obesity and cardiometabolic traits. This study followed a case–control design, where cases included individuals with overweight/obesity, T2DM-positive (+), or CVD-positive (+) individuals and controls, which comprised individuals free of these traits. Logistic regression area under the curve (AUC) models were used to assess the predictive power of the GRS and traditional risk factors on BMI, T2DM and CVD. Results: Individuals in the intermediate-/high-GRS group had higher odds of being overweight or obese (OR = 1.23, CI: 1.03–1.48, p = 0.02), presenting as T2DM+ (OR = 1.56, CI: 1.03–2.49, p = 0.03) and exhibiting CVD-related traits (OR = 1.56, CI: 1.25–1.95, p < 0.0001), compared to the low-GRS group. The GRS was the second most predictive factor after age for BMI (AUC = 0.515; 95% CI: 0.462–0.538). The GRS also demonstrated a predictive power of 0.528 (95% CI: 0.508–0.564) for CVD and 0.548 (95% CI: 0.440–0.605) for T2DM. Conclusions: This study supports the potential utility of the GRS in assessing obesity and cardiometabolic risk, while emphasizing the potential of PN approaches in modulating genetic susceptibility. Incorporating gene–diet interactions provides actionable insights for personalized dietary strategies. Future research should integrate multiple gene–diet and gene–gene interactions to enhance risk prediction and targeted interventions. Full article

Type 2 diabetes (T2D) represents a public health problem globally, with the highest prevalence reported among older adults. While an interplay of various determinants including genetic, epigenetic, environmental factors and unhealthy lifestyle, particularly diet, has been established to contribute to T2D development, emerging evidence supports the role of interactions between nutrients or dietary patterns and genes in the pathogenesis of this metabolic disorder. The amount, and especially the type of carbohydrates, in particular, have been correlated with the risk of non-communicable chronic disease and mortality. This narrative review aims to discuss the updated data on the complex and not fully elucidated relationship between carbohydrate–gene interactions and incidence of T2D, identifying the most susceptible genes able to modulate the dual association between carbohydrate intake and risk of developing T2D. The identification of genetic polymorphisms in response to this macronutrient represents a potentially powerful target to estimate individual risk and prevent the development of T2D in the context of personalized medicine. The postulation around novel foods potentially tailored to minimize the risks of developing T2D will pave the way for a new era into food research in relation to the safeguarding of well-being status in patients affected by, or at risk for, T2D. Full article

Background/objectives: The interplay between genetic factors and nutritional patterns is critical in understanding metabolic health. This analysis evaluated the potential reciprocal relationships between the TNF-α -308 G/A gene polymorphism, the Composite Dietary Antioxidant Index (CDAI), and insulin-related variables in Spanish adults with obesity. Methods: A cross-sectional analysis was conducted in 292 adults with obesity. Anthropometric, biochemical, and dietary variables were assessed. TNF-α -308 G/A genotyping was performed. Associations and potential interactions between CDAI and genotype on insulin and homeostatic model assessment for insulin resistance (HOMA-IR) were examined using multivariate regression and two-way ANOVA. Results: Higher CDAI scores were significantly associated with lower insulin levels (p < 0.001) and HOMA-IR (p < 0.001), regardless of genotype. Carriers of the A allele (GA/AA) showed a non-significant trend toward higher insulin levels (p = 0.087) and a steeper decrease in insulin levels with increasing CDAI, with a significant interaction observed between TNF-α genotype and CDAI (interaction p = 0.003). Multivariate analyses confirmed that CDAI and TNF-α genotype were independently associated with insulin and HOMA-IR levels. However, interaction terms were not consistently significant across all models. Conclusions: These findings emphasize the potential of antioxidant-rich diets to help modulate the influence of pro-inflammatory genotypes on insulin resistance, highlighting the relevance of integrating genetic and dietary factors in managing obesity-related metabolic risks. Further studies are warranted to confirm these preliminary findings and to better understand the mechanisms underlying gene–diet interactions in metabolic regulation. Full article

A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and impaired cellular function. Mutations in the OPA1 (OPtic Atrophy 1) gene, crucial for mitochondrial dynamics and functions, are responsible for dominant optic atrophy (DOA), a mitochondrial neurodegenerative disease associated with increased reactive oxygen species (ROS). The expressivity of DOA is highly variable, even within the same family. This suggests that both modifying genetics and environmental factors could influence the penetrance of the disease. We previously demonstrated that genetic background modulates DOA expressivity and now ask if this is also the case for external cues. We thus explore how OPA1 deficiency interacts with HFD-induced metabolic disturbances, hypothesizing that long-term HFD consumption impairs brain mitochondrial function and disrupts oxidative metabolism. OPA1^+/− mice were thus subjected to a HFD for a period of 12 weeks, and ROS levels and the expression of antioxidant genes were evaluated by Western blot and spectrophotometry. Cortices from high-fat diet-fed OPA1^+/− mice showed lower aconitase activity than those of their wild-type (WT) litter mates, indicative of an unbalanced increase in mitochondrial ROS. Accordingly, OPA1^+/− mice present lower levels of the antioxidant enzyme superoxide dismutase 2 compared to WT mice. Therefore, this study (i) reveals the onset of oxidative stress in brain cortices from OPA1^+/− mice challenged with a HFD, (ii) shows that diet is a modifying factor for DOA, and (iii) suggests that food control could be used to moderate the severity of the disease. Full article

IMF (intramuscular fat, IMF), as a key index for evaluating meat quality traits (shear force and cooking loss, etc.), and its deposition process are jointly regulated by nutritional and genetic factors. In this study, we analyzed the molecular regulation mechanism of IMF deposition in the LD (longissimus dorsal muscle, LD) by dietary energy level in Pamir yaks. Meat quality assessment showed that the meat quality of the High-energy diet group (1.53 MJ/Kg, G) and the Medium-energy diet group (1.38 MJ/Kg, Z) were significantly improved compared with that of the Low-energy diet group (0.75 MJ/Kg, C), in which IMF content in the LD of yaks in G group was significantly higher (p < 0.05) compared with Z and C groups. Further analysis by combined transcriptomics and lipid metabolomics revealed that the differences in IMF deposition mainly originated from the metabolism of lipids, such as TG (triglycerides, TG), PS (phosphatidylserine, PS), and LPC (lysophosphatidylcholine, LPC), and were influenced by SFRP4, FABP4, GADD45A, PDGFRA, RBP4, and DGAT2 genes, further confirming the importance of lipid–gene interactions in IMF deposition. This study reveals the energy-dependent epigenetic regulatory mechanism of IMF deposition in plateau ruminants, which provides molecular targets for optimizing yak nutritional strategies and quality meat production, while having important theoretical and practical value for the sustainable development of livestock husbandry on the Tibetan Plateau. Full article

Animal feed made from fermented agricultural residues using Lactobacillus sp. and Bacillus sp. has received significant attention. However, interactions between differentially expressed genes (DEGs) in adipose, liver, and muscle tissues and bacteria or fungi in the rumen remain largely unknown. This study determined effects of normal diet feed (NF) and alternative diet feed made by Lactobacillus sp. and Bacillus sp. (AF) on gene expression in major metabolic organs and on microbial populations in the rumen of Bos-Taurus using high-throughput sequencing methods. Rumen bacteria/fungi interaction with DEGs in key metabolic organs was also investigated. According to our findings, 34, 36, and 28 genes were differentially expressed in adipose, liver, and muscle tissues, respectively. Most DEGs were associated with osteoclast differentiation and immune functions. Microbial dynamics analysis showed that the AF diet significantly (p < 0.05) increased Firmicutes but reduced Bacterioidetes abundances. At the genus level, Faecalicatena, Intestinimonas, Lachnoclostridium, Faecalicatena, and Intestinimonas were significantly higher (p < 0.05) in animals fed with the AF diet. Regarding fungal populations, Neocallimastigomycota accounted for 98.2% in the NF diet and 86.88% in the AF diet. AF feeding increased Orpinomyces and Piromyces but decreased Neocallimastix abundances. These findings highlight the potential of fermented feeds to improve metabolic responses and rumen microbial balance, contributing to enhanced animal performance. Full article

Background/Objectives: Colitis is a chronic condition affecting millions worldwide. Purple muscadine wine polyphenols have a unique composition and possible disease-preventive properties. This study aims to determine how dealcoholized muscadine wine (DMW) affects the development of colitis and gut microbiome in IL-10^−/− mice, compared to wild types (WT). Methods: Six-week-old male IL-10^−/− and WT C57BL/6 mice were fed either a DMW-supplemented diet (4.8% v/w) or a control diet based on AIN-93M for 154 days. Colitis severity was evaluated by disease activity, intestinal permeability, gene expression of cytokines and tight junction proteins in the colon, and inflammatory cytokines in the serum. Fecal samples were collected for gut microbiome profiling via 16S rRNA gene sequencing. Results: DMW contained predominantly anthocyanins and a significant amount of ellagic acid. IL-10^−/− mice developed mild colitis as indicated by the disease activity index. DMW × gene interactions decreased intestinal permeability, colonic mRNA levels of IL-1β, and serum TNF-α in the IL-10^−/− mice. DMW suppressed the colonic mRNA levels of IL-6, enhanced the gene expression of ZO-1, but did not influence the mRNA level of TNF-α or occludin. While DMW did not alter α-diversity of the gut microbiome, it significantly influenced β-diversity in the WT mice. DMW significantly reduced the relative abundances of Akkermansia in the IL-10^−/− and WT mice. DMW and DMW×gene interaction decreased the relative abundance of Parasutterella only in IL-10^−/− mice. Conclusions: These results suggested that polyphenols from DMW interacted with genes to moderately alleviate the development of colitis in IL-10^−/− mice and could be a useful dietary strategy for IBD prevention. Full article

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted social communication and repetitive behaviors. Prenatal stress is critical in neurodevelopment and increases risk for ASD, particularly in those with greater genetic susceptibility to stress. Docosahexaenoic acid (DHA) is one of the most abundant ω-3 fatty acids in the membrane phospholipids of the mammalian brain, and dietary DHA plays an important role in brain development and maintenance of brain structure. In this study, we investigated whether peri-natal supplementation of DHA can alleviate autistic-like behaviors in a genetic risk/stress mouse model and how it alters lipid peroxidation activity and GABAergic system gene expression in the forebrain. Pregnant heterozygous serotonin transporter knockout (SERT-KO) and wild-type (WT) dams were placed in either non-stressed control conditions or chronic variable stress (CVS) conditions and fed either a control diet or a DHA-rich (1% by weight) diet. Offspring of each group were assessed for anxiety and autism-associated behavior at post-natal day 60 using an open field test, elevated plus maze test, repetitive behavior, and the 3-chamber social approach test. A liquid chromatography-mass spectrometry (LC-MS)-based method was used to follow changes in levels of lipid peroxidation products in the cerebral cortex. Male offspring of prenatally stressed SERT-het KO dams exhibited decreased social preference behaviors and increased repetitive grooming behaviors compared to WT control offspring. Moreover, DHA supplementation in male SERT-het mice decreased frequency of grooming behaviors albeit showing no associated effects on social behaviors. Regardless of stress conditions, supplementation of DHA to the WT mice did not result in alterations in grooming nor social interaction in the offspring. Furthermore, no apparent changes were observed in the lipid peroxidation products comparing the stressed and non-stressed brains. Gad2 was downregulated in the cortex of female offspring of prenatally stressed SERT-KO dams, and this change appeared to be rescued by DHA supplementation in offspring. Gad2 was upregulated in the striatum of male offspring of prenatally stressed SERT-KO dams, but DHA did not significantly alter the expression compared to the control diet condition. Full article

Background/Objectives: Inter-individual metabolic responses to caffeine are shaped by CYP1A2 clearance rate and by concurrent lipid- or glucose-lowering drugs. We investigated how habitual caffeine intake relates to serum cholesterol and fasting glucose under different CYP1A2 rs762551 genotypes and statin or oral antidiabetic (OAD) use. Methods: A prospective cross-sectional analysis was performed on 358 adults (AA = 65, AC = 163, CC = 130) with recorded genotype, daily caffeine intake, total cholesterol, fasting glucose, and medication status. Multivariable linear regression tested the main and interaction effects of caffeine (mg day⁻¹), genotype, and therapy. Results: Caffeine intake was positively associated with cholesterol levels (β = 0.30; p < 0.001). A significant genotype × caffeine interaction (β = 0.27; p < 0.001) revealed the steepest rise in fast metabolisers (AA) not on statins, an effect largely blunted by statin therapy. For glucose, the genotype × caffeine term was also significant (β = 0.30; p < 0.001). Among slow metabolisers (CC) without OADs, caffeine correlated positively with glycaemia (r = 0.34; p = 0.028), whereas in fast metabolisers on OADs the association reversed (r = −0.36; p = 0.015). No meaningful associations occurred in AC carriers. Conclusions: Caffeine’s metabolic impact depends jointly on CYP1A2 genotype and medication. It raises cholesterol in fast metabolisers lacking statins and elevates glucose in slow metabolisers without OADs, yet may lower glucose when rapid metabolisation coincides with antidiabetic therapy. Accounting for this gene–diet–drug interplay could refine caffeine guidance within precision nutrition frameworks. Full article

Serious enteric disease caused by seven species of Eimeira continues to cause significant economic damage to the poultry industry. E. acervulina is one of the most widespread strains in farms and has a significant impact on chicken weight loss. Currently, the use of anticoccidial agents to suppress the occurrence of coccidiosis in farms is considerably restricted due to public health and environmental pollution issues. It is important to understand the protective immunity of the host against Eimeria infections with regard to natural products that could be used as alternatives to anticoccidial agents. Berberine chloride is known for its various biological functions, including its anti-parasite activity. However, its impact on intestinal morphology and immune-related activity in broilers infected with Eimeria still remains unclear. The aim of this study is to evaluate the anticoccidial effects of a berberine-based diet in broilers infected with E. acervulina and to monitor the host immune phenomenon using transcriptomic analysis. Administration of berberine to chickens infected with E. acervulina significantly reduced fecal oocyst production and intestinal lesion scores, and increased duodenal villus height, indicating anticoccidial activity and positive effects on intestinal morphology. Transcriptomic analysis of chickens infected with E. acervulina generally observed the down-regulation of metabolism-related genes and the up-regulation of cell integrity-related genes at day 4 post-infection. At day 6 post-infection, an increase in immune-related genes and cellular-homeostasis-related genes was generally observed. Berberine-treated and E. acervulina-infected chickens showed cytokine-cytokine receptor interaction in the second term in a Kyoto Encyclopedia of Genes and Genomes pathway analysis at day 4 post-infection, but not in chickens infected with E. acervulina alone, suggesting host immune changes induced by berberine. These results suggest that berberine, which exhibits anticoccidial effects, may have therapeutic and/or prophylactic potential in protecting the host from infectious and economic-loss-causing diseases, such as Eimeria infection. Full article

Background/Objectives: Lactobacillus delbrueckii subsp. lactis CKDB001 (LL) has demonstrated anti-inflammatory, antioxidant, and lipid-regulatory effects in vitro and in vivo, including attenuation of hepatic steatosis and modulation of lipid metabolism. Given the known interactions between host metabolism and gut microbiota, these findings suggest a potential role for LL in modulating microbial composition under conditions of diet-induced obesity. This study aimed to investigate the microbiome-related effects of LL using an established murine model. To evaluate the effect of LL supplementation on gut microbial composition and predict microbial metabolic functions in mice with high-fat diet-induced obesity. Methods: Male C57BL/6J mice were fed a high-fat diet and administered LL orally for 12 weeks. Fecal samples were collected and analyzed using 16S rRNA gene sequencing. Microbial taxonomic profiles were assessed using linear discriminant analysis effect size, and functional predictions were performed using PICRUSt2. Results: LL supplementation significantly altered the gut microbiota by increasing the relative abundance of Lactobacillus and other commensal taxa while reducing the prevalence of pro-inflammatory genera such as Alistipes and Bilophila. Functional prediction analysis revealed a downregulation of lipopolysaccharide and ADP-L-glycero-β-D-manno-heptose biosynthesis pathways. Microbial functions associated with carbohydrate metabolism and short-chain fatty acid production were enriched in the LL-treated group. Conclusions: LL modulated gut microbial composition and suppressed pro-inflammatory microbial pathways while enhancing beneficial metabolic functions in high-fat diet-fed mice. These findings support the potential of LL as a safe and effective microbiota-targeted probiotic for managing obesity-related metabolic disorders. Full article