Fibroblast growth factor 21 (FGF21) has emerged as an important metabolic regulator of glucose and lipid metabolism. The aims of the current study are to evaluate the role of FGF21 in energy metabolism and to provide mechanistic insights into its glucose and lipid-lowering effects in a high-fat diet-induced obesity (DIO) model.

Aortic stenosis (AS) affects 3 percent of persons older than 65 years and leads to greater morbidity and mortality than other cardiac valve diseases. Surgery with aortic valve replacement (AVR) for severe symptomatic AS is currently the only treatment option. Unfortunately, in patients with poor ventricular function, the mortality and long-term outcome is unsatisfied, and only a minority of these patients could bear surgery. Our previous studies demonstrated that vascular endothelial growth factor (VEGF) protects cardiac function in myocardial infarction model through classic VEGF-PI3k-Akt and unclear mitochondrial anti-apoptosis pathways; promoting cardiomyocyte (CM) proliferation as well. The present study was designed to test whether pre-operative treatment with VEGF improves AS-induced cardiac dysfunction, to be better suitable for AVR, and its potential mechanism.

Hepatocyte nuclear factor 1beta (HNF1beta) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1beta were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1beta in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1beta gene in a Chinese population.

MiR-200c has been shown to be related to cancer formation and progression. However, the prognostic and clinicopathologic significance of miR-200c expression in cancer remain inconclusive. We carried out this systematic review and meta-analysis to investigate the prognostic value of miR-200c expression in cancer. Pooled hazard ratios (HRs) of miR-200c for overall survival (OS) and progression-free survival (PFS) were calculated to measure the effective value of miR-200c expression on prognosis. The association between miR-200c expression and clinical significance was measured by odds ratios (ORs). Twenty-three studies were included in our meta-analysis. We found that miR-200c was not significantly correlated with OS (HR = 1.41, 95%Cl: 0.95-2.10; P = 0.09) and PFS (HR = 1.12, 95%Cl: 0.68-1.84; P = 0.67) in cancer. In our subgroup analysis, higher expression of miR-200c was significantly associated with poor OS in blood (HR = 2.10, 95%CI: 1.52-2.90, P<0.00001). Moreover, in clinicopathology analysis, miR-200c expression in blood was significantly associated with TNM stage, lymph node metastasis and distant metastasis. MiR-200c may have the potential to become a new blood biomarker to monitor cancer prognosis and progression.

Inflammation and complement activation initiated by mannose-binding lectin (MBL) may be implicated in the pathogenesis of diabetic vascular complications. We investigated serum MBL levels in type 2 diabetes with diabetic nephropathy (DN) and with persistent normoalbuminuria.

Identification of pathway effects responsible for specific diseases has been one of the essential tasks in systems epidemiology. Despite some advance in procedures for distinguishing specific pathway (or network) topology between different disease status, statistical inference at a population level remains unsolved and further development is still needed. To identify the specific pathways contributing to diseases, we attempt to develop powerful statistics which can capture the complex relationship among risk factors.

MicroRNA-19b (miR‑19b) is part of the miR‑17‑92 cluster which is associated with cardiac development. It has previously been reported that the overexpression of miR‑19b increases proliferation, inhibits apoptosis and promotes differentiation of embryonic carcinoma cells (P19 cells). The aim of the current study was to investigate the effects of miR‑19b knockdown on the proliferation, apoptosis, differentiation and regulation of the Wnt/β‑catenin signaling pathway in P19 cells. P19 cells were transfected with an miR‑19b knockdown plasmid or an empty vector. MiR‑19b knockdown or vector control stable cell lines were selected using puromycin. Cell Counting kit‑8 and flow cytometry were used to analyze the levels of cellular proliferation, cell cycle progression and the levels of apoptosis, respectively. Caspase‑3 activity and mitochondrial function assays were also used to analyze apoptosis. An inverted microscope was used to observe the morphological changes of P19 cells during differentiation. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were used to detect P19 cell differentiation markers and Wnt/β‑catenin signaling pathway‑related genes and their corresponding proteins. The results demonstrated that miR‑19b knockdown inhibited the proliferation and apoptosis of P19 cells. However, the levels of expression of Wnt and β‑catenin increased. MiR‑19b knockdown activated the Wnt/β‑catenin signaling pathway, which may regulate cardiomyocyte differentiation. The results of this study indicate that miR‑19b is a novel therapeutic target for cardiovascular diseases and provide insight into the mechanisms underlying congenital heart diseases.

Wedelolactone (WEL), a major coumestan ingredient in Wedelia chinensis, has been used to treat septic shock, hepatitis and venom poisoning in traditional Chinese medicines. The objective of the study was to elucidate the anti-inflammatory effects and mechanism of WEL with a cellular model of lipopolysaccharide (LPS)-induced RAW 264.7 cells.

As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed extract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that l-3-n-butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cerebral repetitive ischemia/reperfusion, and intragastrically administered l-3-n-butylphthalide daily for 28 consecutive days after ischemia/reperfusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of l-3-n-butylphthalide, especially pretreatment with l-3-n-butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of l-3-n-butylphthalide can reduce loss of pyramidal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular dementia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after l-3-n- butylphthalide treatment. Experimental findings demonstrate that l-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.

From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12(th) day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neonatal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cells in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cell apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cell line-derived neurotrophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cell apoptosis through the glial cell line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

S100A12 is involved in the inflammatory response and is considered an important marker for many inflammatory diseases in humans. Our previous studies indicated that the S100A12 gene was abundant in the immune tissues of pigs and was significantly upregulated during infection with Haemophilus parasuis (HPS) or porcine circovirus type 2 (PCV2). In this study, the mechanism of transcriptional regulation of S100A12 was investigated in pigs. Our results showed that S100A12, CCAAT/enhancer-binding protein beta (C/EBPβ) and activator protein-1 (AP-1) genes were up-regulated in PK-15 (ATCC, CCL-33) cells when treated with LPS or Poly I: C. Additionally, the promoter activity and expression level of the S100A12 gene were significantly upregulated when C/EBPβ or AP-1 were overexpressed. We utilized electromobility shift assays (EMSA) to confirm that C/EBPβ and AP-1 could directly bind the S100A12 gene promoter. We also found that the transcriptional activity and expression levels of C/EBPβ and AP-1 could positively regulate each other. Furthermore, the promoter activity of the S100A12 gene was higher when C/EBPβ and AP-1 were cotransfected than when they were transfected individually. We concluded that the S100A12 gene was cooperatively and positively regulated by C/EBPβ and AP-1 in pigs. Our study offers new insight into the transcriptional regulation of the S100A12 gene.

The predictive ability of National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol and Montreal Cognitive Assessment (MoCA) administered sub-acutely and at the convalescent phase after stroke for significant vascular cognitive impairment (VCI) at 1 year is unknown. We compared prognostic values of these tests.

Cardiovascular diseases are positively correlated with periodontal disease. However, the molecular mechanisms linking atherosclerosis and periodontal infection are not clear. This study aimed to determine whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) altered the expression of genes regulating cholesterol metabolism in macrophages in the presence of low-density lipoprotein (LDL).

Autophagy is involved in both innate and adaptive immune regulation. We propose that autophagy regulates activation of TLR3 in macrophages and is thereby essential for development of pristane-induced arthritis. We found that pristane treatment induced autophagy in macrophages in vitro and in vivo, in spleen cells from pristane injected rats. The induced autophagy was associated with STAT1 phosphorylation and expression of IRF1 and TLR3. Blocking the pristane activated autophagy by Wortmannin and Bafilomycin A1 or by RNAi of Becn1 led to a downregulation of the associated STAT1-IRF1-TLR3 pathway. Most importantly, the development of arthritis was alleviated by suppressing either autophagy or TLR3. We conclude that pristane enhanced autophagy, leading to a STAT1-IRF1 controlled upregulation of TLR3 expression in macrophages, is a pathogenic mechanism in the development of arthritis.

The anthracnose caused by Colletotrichum species is an important disease that primarily causes fruit rot in pepper. Eighty-eight strains representing seven species of Colletotrichum were obtained from rotten pepper fruits in Sichuan Province, China, and characterized according to morphology and the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) sequence. Fifty-two strains were chosen for identification by phylogenetic analyses of multi-locus sequences, including the nuclear ribosomal internal transcribed spacer (ITS) region and the β-tubulin (TUB2), actin (ACT), calmodulin (CAL) and GAPDH genes. Based on the combined datasets, the 88 strains were identified as Colletotrichum gloeosporioides, C. siamense, C. fructicola, C. truncatum, C. scovillei, and C. brevisporum, and one new species was detected, described as Colletotrichum sichuanensis. Notably, C. siamense and C. scovillei were recorded for the first time as the causes of anthracnose in peppers in China. In addition, with the exception of C. truncatum, this is the first report of all of the other Colletotrichum species studied in pepper from Sichuan. The fungal species were all non-host-specific, as the isolates were able to infect not only Capsicum spp. but also Pyrus pyrifolia in pathogenicity tests. These findings suggest that the fungal species associated with anthracnose in pepper may inoculate other hosts as initial inoculum.

Cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent high-risk human papillomavirus (HPV) infection. HPV genotype prevalence varies with severity of cervical lesions, patient age and geographical location. The aim of this study was to investigate HPV genotypes prevalence and attribution according to the severity of cervical lesions among Chinese women.

The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line.

Three new myrsinol diterpenes were isolated from the roots of Euphorbia prolifera. Their structures were elucidated as 2α-O-isobutyryl-3β,5α,7β,10,15β-penta-O-acetyl-14α-O-benzoyl-10,18-dihydromyrsinol (1), 2α-O-isobutyryl-3β-O-propion-yl-5α,7β,10,15β-tetra-O-acetyl-10,18-dihydromyrsinol (2), and 2α,14α-di-O-benzoyl-3β,5α,7β,10,15β-penta-O-acetyl-10,18-dihydromyrsinol (3) on the basis of spectroscopic data analyses (IR, ESI-MS, HR-ESI-MS, and 1D and 2D NMR). Their neuroprotective activities were evaluated and compounds 1 and 2 showed neuroprotective effects against MPP+ -induced neuronal cell death in SH-SY5Y cells.

CD44 is a major cell surface receptor for the glycosaminoglycan hyaluronan (HA). Native high molecular weight hyaluronan (nHA) and oligosaccharides of hyaluronan (oHA) provoke distinct biological effects upon binding to CD44. Despite the importance of such interactions, however, the feature of binding with CD44 at the cell surface and the molecular basis for functional distinction between different sizes of HA is still unclear. In this study we investigated the effects of high and low molecular weight hyaluronan on CD44 clustering. For the first time, we provided direct evidence for a strong relationship between HA size and CD44 clustering in vivo. In CD44-transfected COS-7 cells, we showed that exogenous nHA stimulated CD44 clustering, which was disrupted by oHA. Moreover, naturally expressed CD44 was distributed into clusters due to abundantly expressed nHA in HK-2 cells (human renal proximal tubule cells) and BT549 cells (human breast cancer cell line) without exogenous stimulation. Our results suggest that native HA binding to CD44 selectively induces CD44 clustering, which could be inhibited by oHA. Finally, we demonstrated that HA regulates cell adhesion in a manner specifically dependent on its size. oHA promoted cell adhesion while nHA showed no effects. Our results might elucidate a molecular- and/or cellular-based mechanism for the diverse biological activities of nHA and oHA.

Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.