Liver Stiffness Measurement is Useful in Predicting Type 2 Diabetes Mellitus Among Nonalcohol Fatty Liver Disease Patients.

Background: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely related conditions. Aim: This study investigated a group of individuals with NAFLD to evaluate if liver fibrosis, identified by FibroScan, correlated with T2DM. Methods: 154 NAFLD patients obtained FibroScan, liver ultrasonography (US), and a thorough assessment of clinical implications and chemical biomarkers. Results: In comparison to the NAFLD without T2DM group, the hemoglobin A1c(HBA1c)(mmol/mol%), homeostasis model of assessment for insulin resistance index (HOMA-IR), gamma-glutamyl transferase (GGT), fibrosis indices, and liver stiffness measurement (LSM) values were all considerably higher in the NAFLD with T2DM group. Patients with NAFLD and T2DM had considerably lower serum uric acid(SUA) levels than those with NAFLD alone.Those with severe fibrosis (79.3%, 23/29) in the NAFLD group showed a greater frequency of T2DM than those with mild fibrosis (45.6%, 21/46) or no fibrosis (27.85%, 22/79) (P=0.000). LSM value and elements of the metabolic syndrome (MetS) were independent risk factors for incident T2DM among NAFLD patients (OR=1.466, 95% CI [1.139-1.888], P=0.003; and OR=0.273, 95% CI [0.081-0.916], P=0.036). Conclusion: FibroScan can identify significant fibrosis, which is independently linked to a higher prevalence of T2DM. As a result, it is crucial to make use of this technology to predict T2DM in NAFLD patients.

Neutrophil extracellular traps mediate neuro-immunothrombosis.

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammatory reactions. Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms. Histones, von Willebrand factor, fibrin, and many other factors participate in the interplay between inflammation and thrombosis. Neuro-immunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases, providing cutting-edge insights into post-neurotrauma thrombotic events. The blood-brain barrier defends the brain and spinal cord against external assaults, and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases. Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis, but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis, and identified modulators of neuro-immunothrombosis. However, these neurological diseases occur in blood vessels, and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury. This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

Clinical Classification of Obesity and Implications for Metabolic Dysfunction-Associated Fatty Liver Disease and Treatment.

Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM.

FIB-4 is closer to FibroScan screen results to detecting advanced liver fibrosis and maybe facilitates NAFLD warning.

To assess the relationship between clinical biochemical characteristics and steatosis or fibrosis by Fibroscan in non-alcoholic fatty liver disease (NAFLD) patients in order to seek the simple effective screening method closed to the results of the fibroScan measurement. A cross-sectional study was conducted on 188 patients with NAFLD who underwent FibroScan examinations. Demographic data and clinical biochemical characteristics were collected and analyzed. The result showed elevated serum uric acid (SUA) (P = .023, odds ratio [OR = 1.005, 95% CI (1.001-1.009) and metabolic syndrome (MetS) (P = .000, OR = 4.549, 95%CI (1.974-10.484) were associated with severe steatosis (controlled attenuation parameter, CAP ≥ 300 dB/m). The magnitude of liver stiffness measured using FibroScan was positively correlated with aspartate transaminase/alanine aminotransferase (AST/ALT) ratio (R = 0.419, P = .000), AST to platelet ratio index (APRI) score (R = 0.309, P = .000), and Fibrosis-4 score (FIB-4) (R = 0.507, P = .000). The areas under the receiver operating curve (ROC) of AST/ALT, APRI, and FIB-4 for mild or severe fibrosis were 0.563, 0.696, and 0.728, respectively, and those for advanced fibrosis were 0.648, 0.750, and 0.821, respectively. The FIB-4 index cutoff value was 1.65 with a sensitivity of 68.3% and specificity of 89.8% during the diagnosis of advanced fibrosis. MetS and elevated SUA are associated with severe steatosis according to the CAP value screen, whereas FIB-4, as the fibrosis score method, is closer to the liver stiffness measurement results from FibroScan, which may facilitate early warning of NAFLD in the community or in remote areas.

Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1α/ASK1/JNK signaling pathway in mice with traumatic brain injury.

BACKGROUND: Neuroinflammation is one of the most important pathogeneses in secondary brain injury after traumatic brain injury (TBI). Neutrophil extracellular traps (NETs) forming neutrophils were found throughout the brain tissue of TBI patients and elevated plasma NET biomarkers correlated with worse outcomes. However, the biological function and underlying mechanisms of NETs in TBI-induced neural damage are not yet fully understood. Here, we used Cl-amidine, a selective inhibitor of NETs to investigate the role of NETs in neural damage after TBI. METHODS: Controlled cortical impact model was performed to establish TBI. Cl-amidine, 2'3'-cGAMP (an activator of stimulating Interferon genes (STING)), C-176 (a selective STING inhibitor), and Kira6 [a selectively phosphorylated inositol-requiring enzyme-1 alpha [IRE1α] inhibitor] were administrated to explore the mechanism by which NETs promote neuroinflammation and neuronal apoptosis after TBI. Peptidyl arginine deiminase 4 (PAD4), an essential enzyme for neutrophil extracellular trap formation, is overexpressed with adenoviruses in the cortex of mice 1 day before TBI. The short-term neurobehavior tests, magnetic resonance imaging (MRI), laser speckle contrast imaging (LSCI), Evans blue extravasation assay, Fluoro-Jade C (FJC), TUNEL, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative-PCR were performed in this study. RESULTS: Neutrophils form NETs presenting in the circulation and brain at 3 days after TBI. NETs inhibitor Cl-amidine treatment improved short-term neurological functions, reduced cerebral lesion volume, reduced brain edema, and restored cerebral blood flow (CBF) after TBI. In addition, Cl-amidine exerted neuroprotective effects by attenuating BBB disruption, inhibiting immune cell infiltration, and alleviating neuronal death after TBI. Moreover, Cl-amidine treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization at 3 days after TBI. Mechanistically, STING ligand 2'3'-cGAMP abolished the neuroprotection of Cl-amidine via IRE1α/ASK1/JNK signaling pathway after TBI. Importantly, overexpression of PAD4 promotes neuroinflammation and neuronal death via the IRE1α/ASK1/JNK signaling pathway after TBI. However, STING inhibitor C-176 or IRE1α inhibitor Kira6 effectively abolished the neurodestructive effects of PAD4 overexpression after TBI. CONCLUSION: Altogether, we are the first to demonstrate that NETs inhibition with Cl-amidine ameliorated neuroinflammation, neuronal apoptosis, and neurological deficits via STING-dependent IRE1α/ASK1/JNK signaling pathway after TBI. Thus, Cl-amidine treatment may provide a promising therapeutic approach for the early management of TBI.

Neutrophil extracellular traps aggravate neuronal endoplasmic reticulum stress and apoptosis via TLR9 after traumatic brain injury.

Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis play an important role during secondary brain damage after traumatic brain injury (TBI). Increased neutrophil extracellular traps (NETs) formation has been demonstrated to be associated with neurological damage after TBI. However, the correlation between ER stress and NETs remains unclear, and the specific function of NETs in neurons has not been defined. In this study, we found that the levels of NETs circulating biomarkers were remarkably elevated in the plasma of TBI patients. We then inhibited NETs formation by peptidylarginine deiminase 4 (PAD4, a critical enzyme for NETs formation) deficiency and discovered that ER stress activation and ER stress-mediated neuronal apoptosis were reduced. The degradation of NETs via DNase I showed similar outcomes. Furthermore, overexpression of PAD4 aggravated neuronal ER stress and ER stress-associated apoptosis, while TLR9 antagonist administration abrogated the damage caused by NETs. In addition to in vivo experiments, in vitro experiments revealed that treatment with a TLR9 antagonist alleviated NETs-induced ER stress and apoptosis in HT22 cells. Collectively, our results indicated that ER stress as well as the accompanying neuronal apoptosis can be ameliorated by disruption of NETs and that suppression of the TLR9-ER stress signaling pathway may contribute to positive outcomes after TBI.

Inhibition of neutrophil extracellular trap formation attenuates NLRP1-dependent neuronal pyroptosis via STING/IRE1α pathway after traumatic brain injury in mice.

Introduction: Increased neutrophil extracellular trap (NET) formation has been reported to be associated with cerebrovascular dysfunction and neurological deficits in traumatic brain injury (TBI). However, the biological function and underlying mechanisms of NETs in TBI-induced neuronal cell death are not yet fully understood. Methods: First, brain tissue and peripheral blood samples of TBI patients were collected, and NETs infiltration in TBI patients was detected by immunofluorescence staining and Western blot. Then, a controlled cortical impact device was used to model brain trauma in mice, and Anti-Ly6G, DNase, and CL-amidine were given to reduce the formation of neutrophilic or NETs in TBI mice to evaluate neuronal death and neurological function. Finally, the pathway changes of neuronal pyroptosis induced by NETs after TBI were investigated by administration of peptidylarginine deiminase 4 (a key enzyme of NET formation) adenovirus and inositol-requiring enzyme-1 alpha (IRE1α) inhibitors in TBI mice. Results: We detected that both peripheral circulating biomarkers of NETs and local NETs infiltration in the brain tissue were significantly increased and had positive correlations with worse intracranial pressure (ICP) and neurological dysfunction in TBI patients. Furthermore, the depletion of neutrophils effectively reduced the formation of NET in mice subjected to TBI. we found that degradation of NETs or inhibition of NET formation significantly inhibited nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 1 (NLRP1) inflammasome-mediated neuronal pyroptosis after TBI, whereas these inhibitory effects were abolished by cyclic GMP-AMP (cGAMP), an activator of stimulating Interferon genes (STING). Moreover, overexpression of PAD4 in the cortex by adenoviruses could aggravate NLRP1-mediated neuronal pyroptosis and neurological deficits after TBI, whereas these pro-pyroptotic effects were rescued in mice also receiving STING antagonists. Finally, IRE1α activation was significantly upregulated after TBI, and NET formation or STING activation was found to promote this process. Notably, IRE1α inhibitor administration significantly abrogated NETs-induced NLRP1 inflammasome-mediated neuronal pyroptosis in TBI mice. Discussion: Our findings indicated that NETs could contribute to TBI-induced neurological deficits and neuronal death by promoting NLRP1-mediated neuronal pyroptosis. Suppression of the STING/ IRE1α signaling pathway can ameliorate NETs-induced neuronal pyroptotic death after TBI.

Activation of Sigma-1 Receptor Alleviates ER-Associated Cell Death and Microglia Activation in Traumatically Injured Mice.

BACKGROUND: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) is associated with neuroinflammation and subsequent cell death following traumatic brain injury (TBI). The sigma-1 receptor (Sig-1R) acts as a dynamic pluripotent modulator of fundamental cellular processes at the mitochondria-associated membranes (MAMs). The activation of Sig-1R is neuroprotective in a variety of central nervous system diseases, but its impact on ER stress induced by traumatic brain injury is not known. This study investigated the role of Sig-1R in regulating the ER stress-mediated microglial activation and programmed cell death (apoptosis and pyroptosis) induced by TBI. METHODS: Ten human brain tissues were obtained from The Tianjin Medical University General Hospital. Four normal brain tissues were obtained from patients who underwent surgery for cerebral vascular malformation, through which peripheral brain tissues were isolated. Six severe TBI tissues were from patients with brain injury caused by accidents. None of the patients had any other known neurological disorders. Mice with Sig-1R deletion using CRISPR technology were subjected to controlled cortical impact-induced injury. In parallel, wild type C57BL/6J mice were analyzed for outcomes after they were exposed to TBI and received the Sig-1R agonist PRE-084 (10 mg/kg daily for three days) either alone or in combination with the Sig-1R antagonist BD-1047 (10 mg/kg). RESULTS: The expression of Sig-1R and the 78 kDa glucose-regulated protein, a known UPR marker, were significantly elevated in the injured cerebral tissues from TBI patients and mice subjected to TBI. PRE-084 improved neurological function, restored the cerebral cortical perfusion, and ameliorated and brain edema in C57BL/6J mice subjected to TBI by reducing endoplasmic reticulum stress-mediated apoptosis, pyroptosis, and microglia activation. The effect of PRE-084 was abolished in mice receiving Sig-1R antagonist BD-1047. CONCLUSIONS: ER stress and UPR were upregulated in TBI patients and mice subjected to TBI. Sig-1R activation by the exogenous activator PRE-084 attenuated microglial cells activation, reduced ER stress-associated programmed cell death, and restored cerebrovascular and neurological function in TBI mice.

Role of platelet-derived extracellular vesicles in traumatic brain injury-induced coagulopathy and inflammation.

Extracellular vesicles are composed of fragments of exfoliated plasma membrane, organelles or nuclei and are released after cell activation, apoptosis or destruction. Platelet-derived extracellular vesicles are the most abundant type of extracellular vesicle in the blood of patients with traumatic brain injury. Accumulated laboratory and clinical evidence shows that platelet-derived extracellular vesicles play an important role in coagulopathy and inflammation after traumatic brain injury. This review discusses the recent progress of research on platelet-derived extracellular vesicles in coagulopathy and inflammation and the potential of platelet-derived extracellular vesicles as therapeutic targets for traumatic brain injury.

Diagnosis and prognosis potential of four gene promoter hypermethylation in prostate cancer.

The current prostate special antigen (PSA) test causes the overtreatment of indolent prostate cancer (PCa). It also increases the risk of delayed treatment of aggressive PCa. DNA methylation aberrations are important events for gene expression dysregulation during tumorigenesis and have been suggested as novel candidate biomarkers for PCa. This may improve the diagnosis and prognosis of PCa. This study assessed the differential methylation and messenger RNA (mRNA) expression between normal and PCa samples. Correlation between promoter methylation and mRNA expression was estimated using Pearson's correlation coefficients. Moreover, the diagnostic potential of candidate methylation markers was estimated by the receiver operating characteristic (ROC) curve using continuous beta values. Survival and Cox analysis was performed to evaluate the prognostic potential of the candidate methylation markers. A total of 359 hypermethylated sites 3435 hypomethylation sites, 483 upregulated genes, and 1341 downregulated genes were identified from The Cancer Genome Atlas database. Furthermore, 17 hypermethylated sites (covering 13 genes), including known genes associated with hypermethylation in PCa (e.g., AOX1 and C1orf114), showed high discrimination between adjacent normal tissues and PCa samples with the area under the ROC curve from 0.88 to 0.94. Notably, ANXA2, FGFR2, HAAO, and KCNE3 were identified as valuable prognostic markers of PCa through the Kaplan-Meier analysis. Using gene methylation as a continuous variable, four promoter hypermethylation was significantly associated with disease-free survival in univariate Cox regression and multivariate Cox regression. This study identified four novel diagnostic and prognostic markers for PCa. The markers provide important strategies for improving the timely diagnosis and prognosis of PCa.

PAR-2 promotes invasion and migration of esophageal cancer cells by activating MEK/ERK and PI3K/Akt signaling pathway.

Protease-activated receptor 2 (PAR-2) has been demonstrated to promote invasion and metastasis of certain cancer cells. This study aimed to investigate the mechanism by which PAR-2 regulated invasion and migration of esophageal cancer (EC) cells EC109. A successfully constructed PAR-2 shRNA lentiviral vector (Lenti-PAR-2 shRNA) was stably transfected into EC109 cells, and the expression of PAR-2 in infected cells was detected by quantitative real-time PCR (qRT-PCR) and western blotting. Specific inhibitors, PD98059 (for MEK/ERK) and LY294002 (for PI3K/Akt), were used to confirm the role of MEK/ERK and PI3K/Akt signaling pathways, respectively, in PAR-2-regulated invasion and migration of EC109 cells. A significant decrease in PAR-2 mRNA and protein expression was detected in EC109 cells stably transfected with Lenti-PAR-2 shRNA. The PAR-2 agonist could dramatically promote cell invasion and migration, up-regulate the expression of MMP-9 and TM4SF3, and activate MEK/ERK and PI3K/Akt signaling pathways. However, PAR-2 gene silencing attenuated PAR-2-mediated enhancement of invasion and migration of EC109 cells, significantly down-regulated the mRNA and protein expression of MMP-9 and TM4SF3, and inhibited ERK (Try202/204) and Akt (Ser473) phosphorylation. An effect similar to PAR-2 silencing could be achieved with the two specific MEK/ERK and PI3K/Akt pathway inhibitors. Consequently, these results demonstrated that PAR-2 promoted invasion and migration of esophageal cancer cells EC109 by activating MEK/ERK and PI3K/Akt signaling pathways, which was accompanied by up-regulation of MMP-9 and TM4SF3 expression. Hence, PAR-2 may be a potential candidate for anti-metastasis treatment of EC.

Sex Differences in the Prevalence of and Risk Factors for Nonvascular Cognitive Function in Rural, Low-Income Elderly in Tianjin, China.

BACKGROUND: At the global level, dementia is the leading cause of dependence and disability among the elderly. Although the preponderant prevalence in women has been identified, the sex differences in risk factors were unclear. We aimed to evaluate the sex differences in the prevalence of nonvascular cognitive impairment and the risk factors among the elderly in rural China screened with the Mini-Mental State Examination (MMSE). METHODS: Between 2014 and 2015, a population-based cross-section study was conducted to collect basic information among the elderly aged 60 years and over. Those participants with the previous history of stroke or heart disease were excluded in this study. Nonvascular cognitive impairment was assessed using the MMSE scores. RESULTS: The prevalence of cognitive impairment was 32.4% overall, 25.6% in men and 38.1% in women. In the multivariate analysis, older age and lower education were risk factors both in men and in women; older, large waist circumference was a protective factor for cognitive function in men; higher blood pressure was the risk factor in women. CONCLUSION: These findings suggest that it is crucial to manage and control hypertension and improve educational attainment in order to reduce the prevalence and burden of nonvascular cognitive impairment among low-income residents, both men and women, in rural China.

Effects of SDF-1/CXCR4 on the Repair of Traumatic Brain Injury in Rats by Mediating Bone Marrow Derived Mesenchymal Stem Cells.

Our study aims to investigate the effects of the SDF-1/CXCR4 axis on the repair of traumatic brain injury (TBI) in rats by mediating bone marrow derived from mesenchymal stem cells (BMSCs). Healthy male SD rats were collected, their tibiofibulars were removed, cultured, and BMSCs were collected. The expression of cell-surface molecular proteins was examined using flow cytometry. The mRNA and protein expression of CXCR4 in cells were tested using qRT-PCR and western blotting analysis. An electronic brain injury instrument was utilized to build TBI rat models and each rat was assigned into the experiment, positive control and control groups (10 rats in each group). The morris water maze was used to calculate the escape latency and number of times rats in each group crossed the platform. Neurological severity scores (NSS) was calculated to evaluate the recovery of neurological functioning. The distribution of neuronal nuclear antigens was detected using double-labeling immunohistochemistry. The morphological changes in the hippocampal neuronal and the number of BrdU-positive cells were observed through Nissl's staining and high magnification. The mRNA and protein expressions of CXCR4 were gradually increased as SDF-1 concentration increased. NGF and BDNF positive cells were expressed in each group. The distribution of neuronal nuclear antigens in the experiment group was elevated compared to the control and positive control groups. Among the three groups, the experimental group had the shortest escape latency and the highest number platform crossings. The difference in NSS among the three groups was significant. The experimental group had better cell morphology and a higher number of BrdU-positive cells than the other groups. The present study demonstrates that transplanting BMSCs with SDF-1-induced CXCR4 expression can promote the repair of TBI. This is expected to become a new treatment regimen for TBI.

Overexpressed MALAT1 promotes invasion and metastasis of gastric cancer cells via increasing EGFL7 expression.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in various cancers. Here, the role and its potential mechanism of MALAT1 in invasion and migration of gastric cancer (GC) were investigated. METHODS: Gastric adenocarcinoma tissues and matched normal adjacent tissues were isolated from 25 patients with GC. The expression of epidermal growth factor-like domain-containing protein 7 (EGFL7) was detected in the normal gastric mucosa epithelial GES-1 cell line and three different differentiation GC cell lines, including MKN28 (well-differentiated adenocarcinoma), SGC7901 (moderately differentiated adenocarcinoma) and BGC823 (poorly differentiated adenocarcinoma). Tumor xenotransplant mouse model was established with the injection of cell line pretreated with lentiviral vectors for si-MALAT1 or si-control. RESULTS: The expression of MALAT1 was up-regulated in GC tissues and three cell lines. Si-MALAT1/pcDNA-MALAT1 induced the decrease of cell invasion and migration, while the effects were reversed by the transfection of pcDNA-EGFL7/si-EGFL7. ChIP assay showed that MALAT1 regulated EGFL7 expression by altering the level of H3 histone acetylation in EGFL7 promoter. In tumor xenotransplant mice, down-regulated MALAT1 contributed to the inhibition of tumor metastasis. CONCLUSIONS: Up-regulated MALAT1 promoted the invasion and metastasis of GC, and the increase of EGFL7 expression was a potential mechanism via altering its H3 histone acetylation level.

Hypothalamic paraventricular nucleus stimulation reduces intestinal injury in rats with ulcerative colitis.

AIM: To investigate the effect and mechanism of stimulation of the hypothalamic paraventricular nucleus with glutamate acid in rats with ulcerative colitis (UC). METHODS: The rats were anesthetized with 10% chloral hydrate via abdominal injection and treated with an equal volume of TNBS + 50% ethanol enema, injected into the upper section of the anus with the tail facing up. Colonic damage scores were calculated after injecting a certain dose of glutamic acid into the paraventricular nucleus (PVN), and the effect of the nucleus tractus solitarius (NTS) and vagus nerve in alleviating UC injury through chemical stimulation of the PVN was observed in rats. Expression changes of C-myc, Apaf-1, caspase-3, interleukin (IL)-6, and IL-17 during the protection against UC injury through chemical stimulation of the PVN in rats were detected by Western blot. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in colon tissues of rats were measured by colorimetric methods. RESULTS: Chemical stimulation of the PVN significantly reduced UC in rats in a dose-dependent manner. The protective effects of the chemical stimulation of the PVN on rats with UC were eliminated after chemical damage to the PVN. After glutamate receptor antagonist kynurenic acid was injected into the PVN, the protective effects of the chemical stimulation of the PVN were eliminated in rats with UC. After AVP-Vl receptor antagonist ([Deamino-penl, val4, D-Arg8]-vasopressin) was injected into NTS or bilateral chemical damage to NTS, the protective effect of the chemical stimulation of PVN on UC was also eliminated. After chemical stimulation of the PVN, SOD activity increased, MDA content decreased, C-myc protein expression significantly increased, caspase-3 and Apaf-1 protein expression significantly decreased, and IL-6 and IL-17 expression decreased in colon tissues in rats with UC. CONCLUSION: Chemical stimulation of the hypothalamic PVN provides a protective effect against UC injury in rats. Hypothalamic PVN, NTS and vagus nerve play key roles in this process.

MiR-506 suppresses cell proliferation and tumor growth by targeting Rho-associated protein kinase 1 in hepatocellular carcinoma.

Recent studies have shown that miR-506 plays important roles in human cancer progression. However, little is known about the function of miR-506 in hepatocellular carcinoma (HCC). In this study, we found that miR-506 significantly inhibits HCC cell proliferation in vitro and tumorigenicity in vivo. Moreover, miR-506 induced G1/S cell cycle arrest and apoptosis in HCC cells. Rho-associated protein kinase 1(ROCK1) was identified as a novel target of miR-506; overexpression of ROCK1 reversed the suppressive effects of miR-506 in HCC cells. Additionally, ROCK1 was found up-regulated and inversely correlated with miR-506 in HCC tissues. Therefore, our findings collectively suggest that miR-506 acts as a tumor suppressor via regulation of ROCK1 expression and may thus be a promising therapeutic target for HCC.

Protective effects of BDNF overexpression bone marrow stromal cell transplantation in rat models of traumatic brain injury.

Bone marrow stromal cells (MSCs) were used as cell therapy for various diseases in recent years. Some reports showed that transplanted MSCs promote functional recovery in animal models of brain trauma. But other studies indicate that tissue replacement by this method may not be the main source of therapeutic benefit. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) therapeutic potential may contribute to the recovery of function after trauma. Our previous study showed that BDNF-MSCs could promote the survival of neurons in neuronal injured models in vitro. The present study was undertaken to explore the therapeutic effects of MSCs transfected with BDNF in vivo. After intraventricular injection of MSCs-BDNF, BDNF levels were increased significantly in cerebrospinal fluid by ELISA. Further studies showed that treatment of traumatic brain injury with MSCs-BDNF could attenuate neuronal injury as measurement of biological behavior assessment. These studies demonstrate that by increasing the brain concentration of BDNF, intraventricularly transplanted MSCs-BDNF might play an important role in the treatment of traumatic brain injury and might be an optional therapeutic strategy.

Treatment of injured neurons with bone marrow stem cells cotransfected by hTERT and Ad-BDNF in vitro.

The purpose of this paper is to study the anti-injury effect of bone marrow stromal cells (BMSCs) transfected by human telomerase reverse transcriptase (hTERT) and adenovirous brain-derived neurotrophic factor (Ad-BDNF) in injured neurons. Rat injured neurons were induced in vitro and then cocultured with rBMSCs transfected by hTERT and Ad-BDNF. The anti-injury effect of rBMSCs transfected by hTERT and Ad-BDNF was detected by Western blot for neural apoptosis gene MAP2 and NF-kappaB and lactic dehydrogenase released by injured neurons. Our data demonstrated that graft rBMSCs transfected by hTERT and Ad-BDNF could increase the expression of BDNF in injured neurons and alleviate apoptosis of the injured neurons. According to these data, BDNF-BMSCs demonstrate a tendency to be protection against neuronal death caused by apoptosis which would last a long time after neural injury. The data also show the potential of BDNF-BMSCs as a promising therapeutic strategy that warrants further investigation in patients with traumatic brain injury.