Clinical and Physiological Characterization of Elevated Plasma Glucagon-Like Peptide-1 Levels (Hyperglipemia) in a Dipeptidyl Peptidase IV Mutation Carrier.

The clinical application of dipeptidyl peptidase IV inhibitors (DPP4i) increasing active glucagon-like peptide-1 (AGLP-1) levels has been linked to pancreatitis, pancreatic tumors, and cardiovascular events. However, mutations in humans or the long-term outcomes of high glucagon-like peptide-1 (GLP-1) level exposure have not been reported. A trio family with a proband showing an extremely high AGLP-1 level [defined here as hyperglipemia (hyper-glucagon-like peptide-1-emia)] were conducted whole-exome sequencing for potential pathogenic genetic defects.

Cholesterol Homeostasis and Liver X Receptor (LXR) in Atherosclerosis.

Cholesterol is an important lipid for maintaining cell membrane fluidity and generation of various hormones and bile acids. Thus, it is critical to maintain cholesterol homeostasis including absorption, trafficking, biosynthesis, and efflux; dysregulation of cholesterol homeostasis may lead to human disorders such as atherosclerosis. As a cholesterol sensor, nuclear receptor liver X receptor (LXR) is an important factor regulating cholesterol homeostasis.

Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.

Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker.

TiO nanoparticles cause mitochondrial dysfunction, activate inflammatory responses, and attenuate phagocytosis in macrophages: A proteomic and metabolomic insight.

Titanium dioxide nanoparticles (TiO NPs) are widely used in food and cosmetics but the health impact of human exposure remains poorly defined. Emerging evidence suggests that TiO NPs may elicit immune responses by acting on macrophages. Our proteomic study showed that treatment of macrophages with TiO NPs led to significant re-organization of cell membrane and activation of inflammation.

Involvement of microRNA-23b in TNF-α-reduced BMSC osteogenic differentiation via targeting runx2.

Elucidation of the molecular mechanism governing bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation is of great importance for improving the treatment of osteoporosis. TNF-α is a well-known inhibitory factor during osteogenic differentiation of BMSCs. In our experiment, we consistently observed that TNF-α significantly inhibited BMSC osteogenic differentiation, which was partially rescued by BAY 11-7082 (NF-κB inhibitor).

Osteon Myospalacem Baileyi attenuates osteoclast differentiation through RANKL induced NFAT pathways.

Ethnopharmacological Relevance: Osteon Myospalacem Baileyi, known as Sai long gu (Tibetan language, means "blind rat bone"), is the whole skeleton of Tibet plateau rodentia animal Myospalacem Baileyi. Osteon Myospalacem Baileyi had been widely used in the Tibet region as an anti-osteoporosis drug and since 1991 Osteon Myospalacem Baileyi has been listed in the Pharmacopoeia of People's Republic of China as the first-class animal new medical material. However, the mechanism of its anti-osteoporosis activities is still unclear.

MicroRNA-145 attenuates TNF-α-driven cartilage matrix degradation in osteoarthritis via direct suppression of MKK4.

Cartilage dyshomeostasis contributes to osteoarthritis (OA) pathogenesis, and tumor necrosis factor (TNF)-α has critical role in this process by driving inflammatory cascades and cartilage degradation. However, the negative regulation of TNF-α-mediated signaling remains undefined. Here we demonstrate the crucial role of miR-145 in the modulation of TNF-α-mediated signaling and cartilage matrix degradation.

Sophoridine from Sophora Flower Attenuates Ovariectomy Induced Osteoporosis through the RANKL-ERK-NFAT Pathway.

An imbalance in osteogenesis and osteoclastogenesis is a crucial pathological factor in the development of osteoporosis. Osteoclasts (OCs) play a pivotal role in osteoporosis, whose new therapy exploration has been focused on the suppression of OC formation. Sophoridine is found from the Chinese traditional food sophora flower to exhibit anti-osteoporosis capacity by screening.

Furan fatty acids - Beneficial or harmful to health?

Furan fatty acids are found in plants, algae, and fish, and reported to have some positive health benefits, including anti-oxidant and anti-inflammatory activities, and inhibition of non-enzymatic lipid peroxidation. A major metabolite of furan fatty acids, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), has been reported to be increased in patients who progress from prediabetes to type 2 diabetes, although CMPF is not necessarily associated with impaired glucose metabolism. Other studies report that CMPF levels are lower in subjects with diabetes than control subjects.

T-betCD11c B cells are critical for antichromatin immunoglobulin G production in the development of lupus.

Background: A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, a novel CD11c B-cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c B cells in the development of lupus is unclear.

The role of long non-coding RNAs in rheumatic diseases.

Long non-coding RNAs (lncRNAs) have emerged as key epigenetic regulators that govern gene expression and influence multiple biological processes. Accumulating evidence demonstrates that lncRNAs have critical roles in immune cell development and function. In this Review, the molecular mechanisms of gene expression regulation by lncRNAs are described and current knowledge of the role of lncRNAs in immune regulation and inflammation are presented, highlighting strategies for defining the roles of lncRNAs in the pathogenesis of multiple rheumatic diseases.

Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P.

We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8-20.

Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration.

Unlabelled: Silicate bioceramics have been considered to possess a wide prospect of clinical application for orthopedic tissue regeneration due to their excellent osteogenesis and angiogenesis. However, the mechanism for silicate bioceramics stimulating bone formation is not fully understood. The host immune defense to implants is proved to greatly influence the osteogenesis and new bone formation, but up to now, few studies are focused on the silicate bioceramics modulated host immune responses.

Prominent topologically associated domains differentiate global chromatin packing in rice from Arabidopsis.

The non-random three-dimensional organization of genomes is critical for many cellular processes. Recently, analyses of genome-wide chromatin packing in the model dicot plant Arabidopsis thaliana have been reported . At a kilobase scale, the A.

DNMT1-maintained hypermethylation of Krüppel-like factor 5 involves in the progression of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the major subtype of renal cell carcinoma (RCC) that is resistant to conventional radiation and chemotherapy. It is a challenge to explore effective therapeutic targets and drugs for this kind of cancer. Transcription factor Krüppel-like factor 5 (KLF5) exerts diverse functions in various tumor types.

Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK.

The major energy source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease.

Sitagliptin, An Anti-diabetic Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis and Inhibits RANKL-Induced Osteoclast Formation and Bone Resorption .

Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms.

Lineage conversion of mouse fibroblasts to pancreatic α-cells.

α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells.

miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells.

MicroRNAs (miRNAs) play important roles in cell fate decisions. However, the miRNAs and their targets involved in the regulation of cardiac lineage specification are largely unexplored. Here, we report novel functions of miR-142-3p in the regulation of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs).

Comprehensive investigation of temporal and autism-associated cell type composition-dependent and independent gene expression changes in human brains.

The functions of human brains highly depend on the precise temporal regulation of gene expression, and the temporal brain transcriptome profile across lifespan has been observed. The substantial transcriptome alteration in neural disorders like autism has also been observed and is thought to be important for the pathology. While the cell type composition is known to be variable in brains, it remains unclear how it contributes to the temporal and pathological transcriptome changes in brains.

Anti-inflammatory and anti-osteoarthritis effects of tectorigenin.

Osteoarthritis (OA) is a common and dynamic disease of the joints, including the articular cartilage, underlying bones and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec) is known to affect many biological processes; however, its effects on articular chondrocytes remain unclear.

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention.

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites.

Novel insights of microRNAs in the development of systemic lupus erythematosus.

Purpose Of Review: To provide a brief overview of recent progress in microRNA biogenesis and homeostasis, its function in immune system and systemic lupus erythematosus (SLE), as well as successful microRNA-based therapy in vivo.

Recent Findings: Stepwise microRNA biogenesis is elaborately regulated at multiple levels, ranging from transcription to ultimate function. Mature microRNAs have inhibitory effects on various biological molecules, which are crucial for stabilizing and normalizing differentiation and function of immune cells.

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells.

The processing of most eukaryotic RNAs is mediated by RNA Binding Proteins (RBPs) with modular configurations, including an RNA recognition module, which specifically binds the pre-mRNA target and an effector domain. Previously, we have taken advantage of the unique RNA binding mode of the PUF domain in human Pumilio 1 to generate a programmable RNA binding scaffold, which was used to engineer various artificial RBPs to manipulate RNA metabolism. Here, a detailed protocol is described to construct Engineered Splicing Factors (ESFs) that are specifically designed to modulate the alternative splicing of target genes.