MiR-125a-5p ameliorates monocrotaline-induced pulmonary arterial hypertension by targeting the TGF-β1 and IL-6/STAT3 signaling pathways.

Pulmonary vascular remodeling due to excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is the hallmark feature of pulmonary arterial hypertension (PAH). Recent evidence suggests that miR-125a-5p plays a role in a rat model of monocrotaline-induced PAH (MCT-PAH); however, the underlying mechanism is currently unknown. Here, we examined the expression profile of miR-125a-5p in MCT-PAH rats and investigated the putative therapeutic effect of miR-125a-5p using the miR-125a-5p agomir.

Meta-analysis of urinary C-terminal telopeptide of type II collagen as a biomarker in osteoarthritis diagnosis.

Objective: This study aims to discover that the urinary C-terminal telopeptide of type II collagen (uCTX-II) levels differ between osteoarthritis (OA) patients and healthy individuals (controls). According to this difference, we may conclude that uCTX-II can be a biomarker for OA diagnosis.

Methods: We searched MEDLINE and EMBASE databases updated to 2014 to find literature on OA biomarkers.

Improving Bone Regeneration Using Chordin siRNA Delivered by pH-Responsive and Non-Toxic Polyspermine Imidazole-4,5-Imine.

Background/aims: Bone nonunion remains a challenge for orthopaedists. The technological advancements that have been made in precisely silencing target genes have provided promising methods to address this challenge.

Methods: We detected the expression levels of the bone morphogenetic protein (BMP) inhibitors Chordin, Gremlin and Noggin using realtime PCR in bone mesenchymal stem cells (BMSCs) isolated from patients with normal fracture healing and those with bone nonunion.

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.

Evaluation of the novel TSPO radiotracer 2-(7-butyl-2-(4-(2-([F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide in a preclinical model of neuroinflammation.

Translocator Protein (18 kDa, TSPO) is regarded as a useful biomarker for neuroinflammation imaging. TSPO PET imaging could be used to understand the role of neuroinflammation in brain diseases and as a tool for evaluating novel therapeutic effects. As a promising TSPO probe, [F]DPA-714 is highly specific and offers reliable quantification of TSPO in vivo.

Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth.

Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic.

Uniportal video assisted thoracic surgery with 2 cm skin incision for right middle lobectomy with systematic lymphadenectomy.

Today, video-assisted thoracic surgery (VATS) was very popular and more and more common, which could be carried out at all levels of medical centers, most of which used multiple-ports VATS techniques. However, uniportal VATS was more difficult technique compared with multiple-ports VATS, and was not yet completely universal. Uniportal port VATS with 2 cm incision was more difficult surgery, and asked the surgeon to master more surgical techniques and good collaborations with each other, however, which not only could reduce the postoperative pain and skin numbness but supply cosmetology and psychological comfort for patients.

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).

Lack of adiponectin and adiponectin receptor 1 contributes to benign prostatic hyperplasia.

Purpose: The incidence of benign prostatic hyperplasia increases among obese individuals, but few studies have fully explained the underlying mechanisms. Adiponectin has drawn much attention in recent years due to its protective role in obesity-related diseases. Here we aimed to investigate the possible molecular mechanisms and clinical significance of adiponectin in relation to benign prostatic hyperplasia.

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.

IRX3 Promotes the Browning of White Adipocytes and Its Rare Variants are Associated with Human Obesity Risk.

Background: IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity.

Methods: IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes.

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.

Nhe5 deficiency enhances learning and memory via upregulating Bdnf/TrkB signaling in mice.

Nhe5, a Na /H exchanger, is predominantly expressed in brain tissue and is proposed to act as a negative regulator of dendritic spine growth. Up to now, its physiological function in vivo remains unclear. Here we show that Nhe5-deficient mice exhibit markedly enhanced learning and memory in Morris water maze, novel object recognition, and passive avoidance task.

Biscarbamate Cross-Linked Low-Molecular-Weight Polyethylenimine for Delivering Anti-chordin siRNA into Human Mesenchymal Stem Cells for Improving Bone Regeneration.

Small-interfering RNA (siRNA) provides a rapid solution for drug design and provides new methods to develop customizable medicines. Polyethyleneimine 25 kDa (PEI25kDa) is an effective transfection agent used in siRNA delivery. However, the lack of degradable linkage causes undesirable toxicity, hindering its clinical application.

Suppression of CHRN endocytosis by carbonic anhydrase CAR3 in the pathogenesis of myasthenia gravis.

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis.

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.

Gold nanoparticles promote osteogenic differentiation of human periodontal ligament stem cells via the p38 MAPK signaling pathway.

Gold nanoparticles (AuNPs) are a promising material for use in regenerative medicine due to their biocompatibility and easy functionalization with biomolecules including growth factors, DNA and peptides. In the present study, transmission electron microscopy indicated that the AuNPs were monodisperse and spherical in shape, with an estimated average diameter of 13 nm. And the cellular effects of AuNPs on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and the associated signaling pathways in cell differentiation were investigated based on histochemical analysis of alkaline phosphatase activity and mineralization, quantitative polymerase chain reaction, and western blotting.

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.

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).

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.

Tumor invasiveness defined by IASLC/ATS/ERS classification of ground-glass nodules can be predicted by quantitative CT parameters.

Background: To investigate the potential value of CT parameters to differentiate ground-glass nodules between noninvasive adenocarcinoma and invasive pulmonary adenocarcinoma (IPA) as defined by IASLC/ATS/ERS classification.

Methods: We retrospectively reviewed 211 patients with pathologically proved stage 0-IA lung adenocarcinoma which appeared as subsolid nodules, from January 2012 to January 2013 including 137 pure ground glass nodules (pGGNs) and 74 part-solid nodules (PSNs). Pathological data was classified under the 2011 IASLC/ATS/ERS classification.