Vascular Regulation by Super Enhancer-Derived LINC00607.

Vascular endothelial cells (ECs) play a pivotal role in whole body homeostasis. Recent advances have revealed enhancer-associated long non-coding RNAs (lncRNAs) as essential regulators in EC function. We investigated LINC00607, a super enhancer-derived lncRNA (SE-lncRNA) in human arteries with an emphasis on ECs.

Epigenetic modifications in metabolic memory: What are the memories, and can we erase them?

Inherent and acquired abnormalities in gene regulation due to the influence of genetics and epigenetics (traits related to environment rather than genetic factors) underlie many diseases including diabetes. Diabetes could lead to multiple complications including retinopathy, nephropathy, and cardiovascular disease that greatly increase morbidity and mortality. Epigenetic changes have also been linked to diabetes-related complications.

Reversal of obesity development in Ceacam1 male mice by bone marrow transplantation or introduction of the human CEACAM1 gene.

Objective: Although Ceacam1 male mice become obese on normal chow, the effect of bone marrow transplantation or introduction of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) gene has not been studied, to the knowledge of the authors.

Methods: This study analyzed Ceacam1 mice on normal diet or high-fat diet (HFD), including effects of bone marrow transplantation or introduction of the CEACAM1 gene.

Results: Male Ceacam1 mice on normal diet versus HFD for 24 weeks gained significantly more weight than controls, and Ceacam1 mice aged up to 2 years had a high frequency of liver cancer.

LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.

Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4/GPR48), a member of the GPCR (G protein-coupled receptors) superfamily, subfamily B, is a common intestinal crypt stem cell marker. It binds R-spondins/Norrin as classical ligands and plays a crucial role in Wnt signaling potentiation. Interaction between LGR4 and R-spondins initiates many Wnt-driven developmental processes, e.

Steroid nuclear receptor coactivator 2 controls immune tolerance by promoting induced T differentiation via up-regulating Nr4a2.

Steroid nuclear receptor coactivator 2 (SRC2) is a member of a family of transcription coactivators. While SRC1 inhibits the differentiation of regulatory T cells (T) critical for establishing immune tolerance, we show here that SRC2 stimulates T differentiation. SRC2 is dispensable for the development of thymic T, whereas naive CD4 T cells from mice deficient of SRC2 specific in T () display defective T differentiation.

Polycomb Repressive Complexes: Shaping Pancreatic Beta-Cell Destiny in Development and Metabolic Disease.

Pancreatic beta-cells secrete the hormone insulin, which is essential for the regulation of systemic glucose homeostasis. Insufficiency of insulin due to loss of functional beta-cells results in diabetes. Epigenetic mechanisms orchestrate the stage-specific transcriptional programs that guide the differentiation, functional maturation, growth, and adaptation of beta-cells in response to growth and metabolic signals throughout life.

Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance.

The skeletal muscle is the largest organ in the body and secretes circulating factors, including myokines, which are involved in various cellular signaling processes. Skeletal muscle is vital for metabolism and physiology and plays a crucial role in insulin-mediated glucose disposal. Myokines have autocrine, paracrine, and endocrine functions, serving as critical regulators of myogenic differentiation, fiber-type switching, and maintaining muscle mass.

Generation of human islet cell type-specific identity genesets.

Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells.

The Cellular and Molecular Interaction Between Erythrocytes and Merozoites.

is the most lethal human malaria parasite, partly due to its genetic variability and ability to use multiple invasion routes via its binding to host cell surface receptors. The parasite extensively modifies infected red blood cell architecture to promote its survival which leads to increased cell membrane rigidity, adhesiveness and permeability. Merozoites are initially released from infected hepatocytes and efficiently enter red blood cells in a well-orchestrated process that involves specific interactions between parasite ligands and erythrocyte receptors; symptoms of the disease occur during the life-cycle's blood stage due to capillary blockage and massive erythrocyte lysis.

Promoting antibody-dependent cellular phagocytosis for effective macrophage-based cancer immunotherapy.

Macrophages are essential in eliciting antibody-dependent cellular phagocytosis (ADCP) of cancer cells. However, a satisfactory anticancer efficacy of ADCP is contingent on early antibody administration, and resistance develops along with cancer progression. Here, we investigate the mechanisms underlying ADCP and demonstrate an effective combinatorial strategy to potentiate its efficacy.

Lubabegron fumarate acts as a β-adrenergic receptor antagonist in cultured bovine intramuscular and subcutaneous adipocytes.

We hypothesized that lubabegron fumarate (LUB) (Experior, Elanco Animal Health, Greenfield, IN) would act as an antagonist to β-adrenergic receptor (β-AR) subtypes in primary bovine subcutaneous (s.c.) and intramuscular (i.

Intestinal AMPK modulation of microbiota mediates crosstalk with brown fat to control thermogenesis.

The energy-dissipating capacity of brown adipose tissue through thermogenesis can be targeted to improve energy balance. Mammalian 5'-AMP-activated protein kinase, a key nutrient sensor for maintaining cellular energy status, is a known therapeutic target in Type II diabetes. Despite its well-established roles in regulating glucose metabolism in various tissues, the functions of AMPK in the intestine remain largely unexplored.

Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis.

Skeletal muscle accounts for ~80% of insulin-stimulated glucose uptake. The Group I p21-activated kinase 1 (PAK1) is required for the non-canonical insulin-stimulated GLUT4 vesicle translocation in skeletal muscle cells. We found that the abundances of PAK1 protein and its downstream effector in muscle, ARPC1B, are significantly reduced in the skeletal muscle of humans with type 2 diabetes, compared to the non-diabetic controls, making skeletal muscle PAK1 a candidate regulator of glucose homeostasis.

Enrichment of the exocytosis protein STX4 in skeletal muscle remediates peripheral insulin resistance and alters mitochondrial dynamics via Drp1.

Mitochondrial dysfunction is implicated in skeletal muscle insulin resistance. Syntaxin 4 (STX4) levels are reduced in human diabetic skeletal muscle, and global transgenic enrichment of STX4 expression improves insulin sensitivity in mice. Here, we show that transgenic skeletal muscle-specific STX4 enrichment (skmSTX4tg) in mice reverses established insulin resistance and improves mitochondrial function in the context of diabetogenic stress.

Pleiotropic roles of FXR in liver and colorectal cancers.

Nuclear receptor farnesoid X receptor (FXR) is generally considered a cell protector of enterohepatic tissues and a suppressor of liver cancer and colorectal carcinoma (CRC). Loss or reduction of FXR expression occurs during carcinogenesis, and the FXR level is inversely associated with the aggressive behaviors of the malignancy. Global deletion of FXR and tissue-specific deletion of FXR display distinct effects on tumorigenesis.

Angiotensin II-Induced Long Non-Coding RNA Regulates Chondrogenesis in Vascular Smooth Muscle Cells.

Long non-coding RNAs (lncRNAs) play key roles in Angiotensin II (AngII) signaling but their role in chondrogenic transformation of vascular smooth muscle cells (VSMCs) is unknown. We describe a novel AngII-induced lncRNA (Angiotensin II-induced lncRNA in VSMCs eliciting chondrogenic phenotype) implicated in VSMC chondrogenesis. In rat VSMCs, and the nearby gene , a chondrogenic marker, were induced by growth factors AngII and PDGF and the inflammatory cytokine TNF-α.

Syntaxin 4 Enrichment in β-Cells Prevents Conversion to Autoimmune Diabetes in Non-Obese Diabetic (NOD) Mice.

Syntaxin 4 (STX4), a plasma membrane-localized SNARE protein, regulates human islet β-cell insulin secretion and preservation of β-cell mass. We found that human type 1 diabetes (T1D) and NOD mouse islets show reduced β-cell STX4 expression, consistent with decreased STX4 expression, as a potential driver of T1D phenotypes. To test this hypothesis, we generated inducible β-cell-specific STX4-expressing NOD mice (NOD-iβSTX4).

ImmunoPET: harnessing antibodies for imaging immune cells.

Dramatic, but uneven, progress in the development of immunotherapies for cancer has created a need for better diagnostic technologies including innovative non-invasive imaging approaches. This review discusses challenges and opportunities for molecular imaging in immuno-oncology and focuses on the unique role that antibodies can fill. ImmunoPET has been implemented for detection of immune cell subsets, activation and inhibitory biomarkers, tracking adoptively transferred cellular therapeutics, and many additional applications in preclinical models.

Proteolytic Processing, Maturation, and Unique Synteny of the Hemagglutinin SHA.

SHA is an l-rhamnose- and d-galactose-binding lectin that agglutinates human group B erythrocytes and was first purified almost 50 years ago. Although the original SHA-producing strain was lost, the primary structure of SHA was more recently solved by mass spectrometry of the archived protein, which matched it to a similar sequence in the Streptomyces lavendulae genome. Using genomic and protein biochemical analyses, this study aimed to identify SHA-secreting strains to further investigate the expression and binding activities of these putative proteins.

Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications.

Chronic metabolic disorders such as obesity and diabetes are associated with accelerated rates of macrovascular and microvascular complications, which are leading causes of morbidity and mortality worldwide. Further understanding of the underlying molecular mechanisms can aid in the development of novel drug targets and therapies to manage these disorders more effectively. Long non-coding RNAs (lncRNAs) that do not have protein-coding potential are expressed in a tissue- and species-specific manner and regulate diverse biological processes.