Ablation of Tacr2 in mice leads to gastric emptying disturbance.

Background: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists.

Grape seed proanthocyanidin extract ameliorates inflammation and adiposity by modulating gut microbiota in high-fat diet mice.

Scope: Obesity and associated metabolic complications is a worldwide public health issue. Gut microbiota have been recently linked to obesity and its related inflammation. In this study, we have explored the anti-inflammatory effect of grape seed proanthocyanindin extract (GSPE) in the high-fat diet (HFD)-induced obesity and identified the contribution of the gut microbiota to GSPE effects on metabolism.

P120-Catenin Mediates Intermittent Cyclic Mechanical Tension-Induced Inflammation in Chondrocytes.

To study the role of the nuclear factor (NF)-κB signaling pathway and P120-catenin in the inflammatory effects of intermittent cyclic mechanical tension (ICMT) on endplate chondrocytes. Inflammatory reactions of endplate chondrocyte were measured by real-time reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assays, a dual-luciferase reporter assay system, immunofluorescence, and Western blot analysis. ICMT loading led to inflammatory reactions of endplate chondrocytes in both the rabbit endplate cartilage model and rat endplate chondrocytes in vitro.

Gpr110 deficiency decelerates carcinogen-induced hepatocarcinogenesis via activation of the IL-6/STAT3 pathway.

Hepatocarcinogenesis is a complex process that includes pronounced necroinflammation, unregulated hepatocyte damage, subsequent extensive fibrosis, and carcinogenesis. was an adhesion G protein-coupled receptor. Analysis of the expression pattern of in mice displayed that was expressed highly in liver, implicating the tissue compartments where Gpr110 could execute its functions, the role of Gpr110 in the physiological and pathological state of liver remains unclear.

Fibronectin 1 promotes migration and invasion of papillary thyroid cancer and predicts papillary thyroid cancer lymph node metastasis.

Lymph node metastasis (LNM) is common in papillary thyroid cancer (PTC), and is an indicator of recurrence. The detailed molecular mechanism of LNM in PTC has not been well described. This study aimed to investigate the role of fibronectin 1 in PTC LNM and its clinical relevance.

TNF-α-induced LRG1 promotes angiogenesis and mesenchymal stem cell migration in the subchondral bone during osteoarthritis.

The incomplete understanding of aberrant neovascularization, which contributes to osteoarthritis suggests that additional modulators have yet to be identified. Our objective was to identify the role of Leucine-rich-alpha-2-glycoprotein1 (LRG1), a new regulator of pathogenic angiogenesis, in osteoarthritis progression and to develop effective treatment strategies. In this study, immunohistochemistry showed that LRG1 was increased in the subchondral bone and articular cartilage in anterior cruciate ligament transection (ACLT) mice.

Lacking of palladin leads to multiple cellular events changes which contribute to NTD.

Background: The actin cytoskeleton-associated protein palladin plays an important role in cell motility, morphogenesis and adhesion. In mice, Palladin deficient embryos are lethal before embryonic day (E) 15.5, and exhibit severe cranial neural tube and body wall closure defects.

Adiponectin deficiency contributes to the development and progression of benign prostatic hyperplasia in obesity.

The incidence of benign prostatic hyperplasia (BPH) is increasing among obese individuals, but few studies have fully explained the underlying mechanisms. We aimed to elucidate the relationship between obesity and BPH. Herein, we show that in prostatic epithelial and stromal cells, adiponectin exerts multifunctional effects including anti-proliferation, blocking of G1/S-phase progression and the promotion of apoptosis via inhibiting the MEK-ERK-p90RSK axis.

Genetic interaction of DGAT2 and FAAH in the development of human obesity.

Purpose: DGAT2 is the critical catalyzing enzyme for triglyceride biosynthesis, and excess triglyceride accumulation in fat tissues is a fundamental process for obesity. Mutations in DGAT2 or other genes interacting with DGAT2 associated with adiposity have not been reported in human to date.

Methods: DGAT2 mutation was identified based on our in-home database-exome sequencing 227 young obese subjects (body-mass index (BMI), 35.

Mechanical stimulation promote the osteogenic differentiation of bone marrow stromal cells through epigenetic regulation of Sonic Hedgehog.

Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro.

Cyclic compressive stress-induced scinderin regulates progress of developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs).

A point mutation in Fgf9 impedes joint interzone formation leading to multiple synostoses syndrome.

Human multiple synostoses syndrome (SYNS) is an autosomal dominant disorder characterized by multiple joint fusions. We previously identified a point mutation (S99N) in FGF9 that causes human SYNS3. However, the physiological function of FGF9 during joint development and comprehensive molecular portraits of SYNS3 remain elusive.

Rare Loss-of-Function Variants in Predispose to Human Obesity.

Some Shanghai Clinical Center f a role of Niemann-Pick type C1 () for obesity traits. However, whether the loss-of-function mutations in cause adiposity in humans remains unknown. We recruited 25 probands with rare autosomal-recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous mutations on adiposity.

Salidroside reduces tau hyperphosphorylation via up-regulating GSK-3β phosphorylation in a tau transgenic model of Alzheimer's disease.

Background: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe treatment against AD. Salidroside (Sal) is the main effective component of , which has several pharmacological activities.

Whole exome sequencing of thymic neuroendocrine tumor with ectopic ACTH syndrome.

Objective: Thymic neuroendocrine tumor is the second-most prevalent cause of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), which is a rare disease characterized by ectopic ACTH oversecretion from nonpituitary tumors. However, the genetic abnormalities of thymic neuroendocrine tumors with EAS remain largely unknown. We aim to elucidate the genetic abnormalities and identify the somatic mutations of potential tumor-related genes of thymic neuroendocrine tumors with EAS by whole exome sequencing.

Bcl-3 regulates TGFβ signaling by stabilizing Smad3 during breast cancer pulmonary metastasis.

Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis.

Electrical Stimulation Enhances Cardiac Differentiation of Human Induced Pluripotent Stem Cells for Myocardial Infarction Therapy.

Aims: Electrical stimulation (EleS) can promote cardiac differentiation, but the underlying mechanism is not well known. This study investigated the effect of EleS on cardiomyocyte (CM) differentiation of human induced pluripotent stem cells (hiPSCs) and evaluated the therapeutic effects for the treatment of myocardial infarction (MI).

Results: Cardiac differentiation of hiPSCs was induced with EleS after embryoid body formation.

Palladin is involved in platelet activation and arterial thrombosis.

The dynamics of actin cytoskeleton have been shown to play a critical role during platelet activation. Palladin is an actin-associated protein, serving as a cytoskeleton scaffold to bundle actin fibers and actin cross linker. The functional role of palladin on platelet activation has not been investigated.

Retinol dehydrogenase 13 deficiency diminishes carbon tetrachloride-induced liver fibrosis in mice.

Retinol dehydrogenase 13 (RDH13) is a mitochondrion-localized member of the short-chain dehydrogenases/reductases (SDRs) superfamily that participates in metabolism of some compounds. Rdh13 mRNA is most highly expressed in mouse liver. Rdh13 deficiency reduces the extent of liver injury and fibrosis, reduces hepatic stellate cell (HSC) activation, attenuates collagen I (II), tissue inhibitor of metalloproteinase 1 (TIMP-1) and transforming growth factor beta 1 (Tgf-β1) expression.

A Central Role for Phosphorylated p38α in Linking Proteasome Inhibition-Induced Apoptosis and Autophagy.

Autophagy and the ubiquitin proteasome system (UPS), as two major protein degradation pathways, coordinate with each other in regulating programmed cell death. Autophagy can compensate for the UPS impairment-induced cell dysfunction and apoptosis. However, it is not clear how cells maintain the delicate balance between UPS-related apoptosis and autophagy.

Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice.

Abnormal shifts in the composition of gut microbiota contribute to the pathogenesis of metabolic diseases, including obesity and type 2 diabetes (T2DM). The crosstalk between gut microbes and the host affects the inflammatory status and glucose tolerance of the individuals, but the underlying mechanisms have not been elucidated completely. In this study, we treated the lean chow diet-fed mice with Akkermansia muciniphila, which is thought to be inversely correlated with inflammation status and body weight in rodents and humans, and we found that A.

Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells.

A large number of genetic variants have been associated with human diseases. However, the lack of a genetic diversification approach has impeded our ability to interrogate functions of genetic variants in mammalian cells. Current screening methods can only be used to disrupt a gene or alter its expression.

Low levels of PRSS37 protein in sperm are associated with many cases of unexplained male infertility.

PRSS37, a putative trypsin-like serine protease, is highly conserved during mammalian evolution as revealed by multiple sequence alignment. Mice deficient for Prss37 gene exhibit male infertility, but their mating behavior, spermatogenesis, sperm morphology, and motility remain unaffected, similar to a situation called unexplained male infertility (UMI) in men (human being). Here, we demonstrated that PRSS37 is restrictively expressed in human testis, where it is mainly located in the elongating and elongated spermatids during spermiogenesis as shown by immunohistochemical analysis of normal human testicular sections.

Spermidine alleviates experimental autoimmune encephalomyelitis through inducing inhibitory macrophages.

Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease, characterized by chronic inflammatory demyelination in the nervous tissue and subsequent neurological dysfunction. Spermidine, a natural polyamine, has been shown to affect inflammation in some experimental models. We show here that spermidine could alleviate experimental autoimmune encephalomyelitis (EAE), a model for MS, through regulating the infiltration of CD4 T cells and macrophages in central nervous system.