Single-Cell RNA Sequencing (scRNA-seq) Identifies L1CAM as a Key Mediator between Epithelial Tuft Cell and Innate Lymphoid Cell in the Colon of Knockout Mice.

(1) Background: Knockout (KO) of heterogeneous nuclear ribonucleoprotein I () in mouse intestinal epithelial cells (IECs) induced a severe inflammatory response in the colon, followed by hyperproliferation. This study aimed to investigate the epithelial lineage dynamics and cell-cell communications that underlie inflammation and colitis. (2) Methods: Single cells were isolated from the colons of wildtype (WT) and KO mice and used in scRNA-seq.

Increasing dietary nutrient levels modulates colon immune adaptation and alleviates inflammation in the epithelial heterogeneous nuclear ribonucleoprotein I (Hnrnp I) knockout mice.

Heterogeneous nuclear ribonucleoprotein I (HNRNP I) is an RNA-binding protein essential for neonatal immune adaptation by downregulating interleukin-1 receptor-associated kinase (IRAK1) in toll-like receptor (TLR)-mediated NF-κB signaling pathways. TLR-mediated NF-κB is associated with chronic inflammation, including the development of inflammatory bowel diseases. Meanwhile, dietary protein intake is one of the major concerns for individuals with inflammatory bowel diseases.

One-carbon metabolism and related pathways in ruminal and small intestinal epithelium of lactating dairy cows.

Physiological and environmental stresses such as the transition into lactation and heat load contribute to gastrointestinal tract (GIT) dysfunction. The nonruminant gastrointestinal tract has mechanisms to cope with pro-oxidant and pro-inflammatory stressors arising from the gut lumen or within intestinal cells. One-carbon metabolism (OCM) contributes to anti-oxidant capacity via the production of glutathione (GSH) and taurine, and the synthesis of phospholipid, creatine, and the osmolyte glycinebetaine among others.

Genome-wide cross-cancer analysis illustrates the critical role of bimodal miRNA in patient survival and drug responses to PI3K inhibitors.

Heterogeneity of cancer means many tumorigenic genes are only aberrantly expressed in a subset of patients and thus follow a bimodal distribution, having two modes of expression within a single population. Traditional statistical techniques that compare sample means between cancer patients and healthy controls fail to detect bimodally expressed genes. We utilize a mixture modeling approach to identify bimodal microRNA (miRNA) across cancers, find consistent sources of heterogeneity, and identify potential oncogenic miRNA that may be used to guide personalized therapies.

A maternal low-protein diet during gestation induces hepatic autophagy-related gene expression in a sex-specific manner in Sprague-Dawley rats.

This study investigates the mechanism by which maternal protein restriction induces hepatic autophagy-related gene expression in the offspring of rats. Pregnant Sprague-Dawley rats were fed either a control diet (C, 18 % energy from protein) or a low-protein diet (LP, 8·5 % energy from protein) during gestation, followed by the control diet during lactation and post-weaning. Liver tissue was collected from the offspring at postnatal day 38 and divided into four groups according to sex and maternal diet (F-C, F-LP, M-C and M-LP) for further analysis.

Weight loss with exercise improves muscle architecture and progenitor cell populations compared with weight loss alone in mice with preneoplastic colorectal lesions.

Weight loss and exercise reduce colorectal cancer (CRC) risk in persons with obesity. Whether weight loss and exercise effect myofiber characteristics and muscle stem/progenitor cell populations in mice with preneoplastic colorectal lesions, a model of CRC risk, is unknown. To address this gap, male C57Bl/6J mice were fed a high-fat diet (HFD) to induce obesity or a control (CON) diet prior to azoxymethane injection to induce preneoplastic colorectal lesions.

Caloric restriction following early-life high fat-diet feeding represses skeletal muscle TNF in male rats.

Chronic metabolic diseases are on the rise worldwide and their etiology is multifactorial. Among them, inflammatory components like Tumor Necrosis Factor (TNF), contribute to whole-body metabolic impairment. Caloric Restriction (CR) combats metabolic diseases, but how it reduces inflammation remains understudied.

Maternal high-fat diet activates hepatic interleukin-4 in rat male offspring accompanied by increased eosinophil infiltration.

Interleukin-4 (IL-4) is activated as an immune response during infection or tissue injury. Epigenetic programming of maternal high-fat (HF) diet has long-term effects in the offspring. In the present study, we investigated the epigenetic regulation of IL-4 in a maternal HF diet model in the liver of adult offspring.

Considerations for feature selection using gene pairs and applications in large-scale dataset integration, novel oncogene discovery, and interpretable cancer screening.

Background: Advancements in transcriptomic profiling have led to the emergence of new challenges regarding data integration and interpretability. Variability between measurement platforms makes it difficult to compare between cohorts, and large numbers of gene features have encouraged the use black box methods that are not easily translated into biologically and clinically meaningful findings. We propose that gene rankings and algorithms that rely on relative expression within gene pairs can address such obstacles.

Epigenetic stratification of head and neck cancer survivors reveals differences in lycopene levels, alcohol consumption, and methylation of immune regulatory genes.

Background: Inflammation has been associated with higher rates of recurrence and mortality in head and neck cancer (HNC). While the biological mechanisms predisposing patients to heightened inflammatory states remain largely unknown, DNA methylation has been proposed to reflect systemic inflammation. In this analysis, we attempt to identify meaningful epigenetic patterns in HNC survivors by stratifying individuals based on DNA methylation profiles in leukocytes.

Early-life Programming of Type 2 Diabetes Mellitus: Understanding the Association between Epigenetics/Genetics and Environmental Factors.

Type 2 Diabetes Mellitus is an increasing public health problem that poses a severe social and economic burden affecting both developed and developing countries. Defects in insulin signaling itself are among the earliest indications that an individual is predisposed to the development of insulin resistance and subsequently Type 2 Diabetes Mellitus. To date, however, the underlying molecular mechanisms which result in resistance to the actions of insulin are poorly understood.

Hepatic Cystathionine β-Synthase Activity Is Increased by Greater Postruminal Supply of Met during the Periparturient Period in Dairy Cows.

Background: Postruminal supply of Met during the periparturient period enhances production efficiency (feed conversion to milk) in dairy cows partly through alleviation of oxidant and inflammatory status. Whether alterations in hepatic 1-carbon metabolism (major contributor of antioxidants) and/or energy metabolism contribute to these beneficial effects is unknown.

Objectives: To investigate alterations in hepatic 1-carbon and energy metabolism and associations with plasma amino acids (AAs) and production efficiency in response to enhanced postruminal supply of Met.

Role of glucocorticoid signaling in exercise-associated changes in high-fat diet preference in rats.

The simultaneous introduction of wheel running (WR) and diet choice (high-carbohydrate chow vs. high-fat diet) results in sex-specific diet choice patterns in rats. WR induces a high-fat (HF) diet avoidance, and such avoidance persists in the majority of males, but not females, throughout a 2-wk period.

A Low Protein Diet during Gestation and Lactation Increases Hepatic Lipid Accumulation through Autophagy and Histone Deacetylase.

The present study examined the mechanism of a low protein (LP) diet on hepatic lipid metabolism during gestation and lactation. Timed-pregnant Sprague-Dawley rats were fed a control or an LP diet during gestation and lactation. LP dams had increased hepatic triglyceride accumulation and significantly higher aspartate/alanine transaminase ratio, accompanied by a decrease in circulating very low-density/low-density lipoprotein ratio.

Maternal Low-Fat Diet Programs the Hepatic Epigenome despite Exposure to an Obesogenic Postnatal Diet.

Obesity and metabolic disease present a danger to long-term health outcomes. It has been hypothesized that epigenetic marks established during early life might program individuals and have either beneficial or harmful consequences later in life. In the present study, we examined whether maternal diet alters DNA methylation and whether such modifications persist after an obesogenic postnatal dietary challenge.

The Efficacy of miR-20a as a Diagnostic and Prognostic Biomarker for Colorectal Cancer: A Systematic Review and Meta-Analysis.

: MicroRNAs have altered expression levels in various diseases and may play an important role in the diagnosis and prognosis of colorectal cancer (CRC). : We systemically reviewed and quantitatively synthesized the scientific evidence pertaining to microRNA-20a (miR-20a) as a CRC biomarker. A keyword and reference search in PubMed yielded 32 studies, in which miR-20a was measured in feces, serum, or tumor tissue.

Hepatic betaine-homocysteine methyltransferase and methionine synthase activity and intermediates of the methionine cycle are altered by choline supply during negative energy balance in Holstein cows.

Although choline requirements are unknown, enhanced postruminal supply may decrease liver triacylglycerol (TAG) storage and increase flux through the methionine cycle, helping cows during a negative energy balance (NEB). The objective was to investigate effects of postruminal choline supply during NEB on hepatic activity of betaine-homocysteine methyltransferase (BHMT), methionine synthase (MTR), methionine adenosyltransferase, transcription of enzymes, and metabolite concentrations in the methionine cycle. Ten primiparous rumen-cannulated Holstein cows (158 ± 24 d postpartum) were used in a replicated 5 × 5 Latin square design with 4-d treatment periods and 10 d of recovery (14 d/period).

Maternal and Post-weaning High-Fat Diets Produce Distinct DNA Methylation Patterns in Hepatic Metabolic Pathways within Specific Genomic Contexts.

Calorie-dense high-fat diets (HF) are associated with detrimental health outcomes, including obesity, cardiovascular disease, and diabetes. Both pre- and post-natal HF diets have been hypothesized to negatively impact long-term metabolic health via epigenetic mechanisms. To understand how the timing of HF diet intake impacts DNA methylation and metabolism, male Sprague-Dawley rats were exposed to either maternal HF (MHF) or post-weaning HF diet (PHF).

Tissue-specific changes in and expression and DNA methylation with perinatal phthalate exposure.

Perinatal exposure to endocrine disrupting chemicals negatively impacts health, but the mechanism by which such toxicants damage long-term reproductive and metabolic function is unknown. Lipid metabolism plays a pivotal role in steroid hormone synthesis as well as energy utilization and storage; thus, aberrant lipid regulation may contribute to phthalate-driven health impairments. In order to test this hypothesis, we specifically examined epigenetic disruptions in lipid metabolism pathways after perinatal phthalate exposure.

Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction.

Chronic caloric restriction (CR) without malnutrition is known to affect different cellular processes such as stem cell function, cell senescence, inflammation, and metabolism. Despite the differences in the implementation of CR, the reduction of calories produces a widespread beneficial effect in noncommunicable chronic diseases, which can be explained by improvements in immuno-metabolic adaptation. Cellular adaptation that occurs in response to dietary patterns can be explained by alterations in epigenetic mechanisms such as DNA methylation, histone modifications, and microRNA.

Methionine Supply During Late-Gestation Triggers Offspring Sex-Specific Divergent Changes in Metabolic and Epigenetic Signatures in Bovine Placenta.

Background: Nonruminant male and female offspring respond differently to gestational nutrition, with placenta contributing to the underlying mechanisms. However, similar data are lacking in large ruminants.

Objectives: The aim of this study was to investigate the impact of methionine supply during late-gestation on metabolism and DNA methylation in placenta from cows carrying male or female calves.

Epigenetic regulation of carnitine palmitoyltransferase 1 (Cpt1a) by high fat diet.

Carnitine palmitoyltransferase 1 (Cpt1a) is a rate-limiting enzyme that mediates the transport of fatty acids into the mitochondria for subsequent beta-oxidation. The objective of this study was to uncover how diet mediates the transcriptional regulation of Cpt1a. Pregnant Sprague Dawley rats were exposed to either a high-fat (HF) or low-fat control diet during gestation and lactation.

Perinatal phthalate and high-fat diet exposure induce sex-specific changes in adipocyte size and DNA methylation.

Environmental factors such as diet and endocrine-disrupting chemicals have individually been shown to mediate metabolic function. However, the underlying mechanism by which the combination disrupts adipocyte morphology and fat storage remains unknown. The current study evaluated early-life programming by diet and phthalate exposure.

Computational methods to identify bimodal gene expression and facilitate personalized treatment in cancer patients.

Standard methods for detecting cancer-associated genes rely on comparison of sample means between cancer patients and healthy controls. While such methods have successfully identified several oncogenes and tumor suppressor genes, they neglect to account for heterogeneity within the cancer population. Genetic mutations, translocations, and amplifications are often inconsistent across tumors, and instead they often affect smaller subsets of patients.

Perinatal High-Fat Diet and Bisphenol A: Effects on Behavior and Gene Expression in the Medial Prefrontal Cortex.

Both high-fat diets (HFD) and bisphenol A (BPA), an environmental endocrine disruptor, are prevalent in industrialized societies. Previous studies have detected separate effects of BPA and HFD; however, none have assessed possible interactive effects. Here, pregnant dams consumed 0, 40, or 400 µg BPA/kg/day and were fed either a control (CON; 15.