Expressions of toll-like receptors 2 and 4, and relative cellular factors in HIV patients with tuberculosis infection

Purpose: To investigate the expressions of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), tumor necrosis factor alpha (TNF-α), IFN-γ (IFN- gamma), interleukin 2 (IL-2), interleukin 6 (IL-6) and interleukin 10 (IL-10) in human immunodeficiency virus (HIV) patients with tuberculosis (TB) infection.Methods: Two groups of HIV patients (68 in each group) were used for this study. These were HIV with TB (HIV/TB) group and HIV without TB group. A third group (68 healthy people) served as control. Quantitative polymerase chain reaction (qPCR) was adopted to measure TLR-2 and TLR-4 expressions in peripheral blood mononuclear cells (PBMC), while the serum levels of TNF-α, IFN-γ, IL-2, IL-6 and IL-10 were determined by ELISA.Results: The △Ct values of TLR-2 and TLR-4 in HIV/TB and HIV groups were significantly lower than those in the control group (p < 0.05). Compared to control group, the serum levels of TNF-α, IL-6 and IL-10 significantly increased, while IFN-γ and IL-2 in HIV/TB and HIV groups significantly decreased (p < 0.05). However, IFN-γ and IL-2 decreased significantly in HIV/TB group (p < 0.05). Expression of TLR2 correlated positively with serum levels of TNF-α, IL-6 and IL-10, but negatively with IFN-γ and IL-2 (p < 0.05).Conclusion: TLR2 signal pathway plays a role in HIV patients with TB infection by promoting the expressions of TNF-α, IL-6 and IL-10, while inhibiting IFN-γ and IL-2 cellular factors, and thus may provide a new pathway for the treatment of patients with HIV/TB.Keywords: HIV, Tuberculosis, Toll-like receptor, Cellular factors, Tumor necrosis factor, Interleuki

Effect of siRNA interference on nerve growth factor in intervertebral disc inflammation rats

AbstractObjectiveTo investigate the inhibition effect of siRNA interference on NGF induced by inflammatory factor IL-6, and IL-1 so as to provide novel targets for clinical treatment of discogenic low back pain.MethodsThe intervertebral disc nucleus and annulus fibrosus cells of rats were separated. The cells were co-cultured with different concentrations (10 nmol/L, 20 nmol/L, 50 nmol/L, 100 nmol/L) of IL-6 and IL-1β. The NGF-siRNA was leaded into the co-cultured cells with its import ability assessed by flow cytometry instrument tests, before and after which the NGF mRNA expression was detected by real-time Q-PCR and the NGF content was detected by ELISA.ResultsFlow cytometry instrument test results showed that the NGF-siRNA cell conversion rate was 99.8%. Real-time Q-PCR detection results showed that compared with negative control group, the NGF mRNA expression of co-cultured cells treated by 10 nmol/L, 20 nmol/L, 50 nmol/L, 100 nmol/L IL-6 and IL-1β were respectively raised 3.4, 3.7, 4.7, 3.7 times which were all significantly down-regulated after the import of NGF-siRNA. EILSA detection results showed that compared with negative control group, the NGF content of co-cultured medium treated by 10 nmol/L, 20 nmol/L, 50 nmol/L, 100 nmol/L I-L6 and IL-1β were respectively raised 2.9, 3.3, 4.5, 7.4 times which were all significantly decreased after the import of NGF-siRNA.ConclusionsThese molecular biological results suggest that inflammatory factor IL-6 and IL-1β could stimulate NGF on intervertebral disc cells in vitro culture model and its efficiency is concentration dependent, while siRNA interference can inhibit the stimulation effect of IL-6 and IL-1β on intervertebral disc cell, which provides a new targets for the clinical treatment of discogenic low back pain

Adeno-associated virus serotype rh.10 displays strong muscle tropism following intraperitoneal delivery

Recombinant adeno-associated virus (rAAV) is an attractive tool for basic science and translational medicine including gene therapy, due to the versatility in its cell and organ transduction. Previous work indicates that rAAV transduction patterns are highly dependent on route of administration. Based on this relationship, we hypothesized that intraperitoneal (IP) administration of rAAV produces unique patterns of tissue tropism. To test this hypothesis, we investigated the transduction efficiency of 12 rAAV serotypes carrying an enhanced green fluorescent protein (EGFP) reporter gene in a panel of 12 organs after IP injection. Our data suggest that IP administration emphasizes transduction patterns that are different from previously reported intravascular delivery methods. Using this approach, rAAV efficiently transduces the liver, pancreas, skeletal muscle, heart and diaphragm without causing significant histopathological changes. Of note, rAAVrh.10 showed excellent muscle transduction following IP administration, highlighting its potential as a new muscle-targeting vector

Research on Influences of Transient High IOP during LASIK on Retinal Functions and Ultrastructure

Objectives. To study the influences of transient high intraocular pressure(IOP) during LASIK on retinal functions and ultrastructure. Methods. Thirty-two New Zealand white rabbits were randomly divided into normal control, experimental control, negative suction 20 s and negative suction 3 min groups. The experimental control group was treated only by laser. Rabbit eyes received suction for different periods of time (20 s, 3 min) by negative pressure generator in different groups. The changes of neuro-optic and retinal ultrastructure were observed under electron and light microscopes; retinal neurofunctional changes were observed with flash-visual evoked potential (F-VEP) and flash-electroreinogram (F-ERG). Results. There was no obvious change in optic nerve, retina, ERG a-wave and b-wave in normal control and experimental control groups. There were slight changes in tissues of optic nerve and retina at various times of suction 20 s compared with control group, and a sharp change in suction 3 min group within 14d after operation, but these changes recovered at 28d . Amplitude of ERG b-wave observed at different time will decrease with suction periods prolonged. It can recover to normal level with the prolonged recovery periods. Amplitude and incubation period of ERG a-wave and VEP-P did not change significantly after different duration of suction. Conclusions. The transient high IOP during LASIK might have influence on retinal function and ultrastructure, but these changes were reversible

Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A of rat offspring with gestational diabetes mellitus

AbstractObjectiveTo discuss the effect of insulin and metformin on a methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A (PPARGC1A) of rat offspring with gestational diabetes mellitus (GDM).MethodsA total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM. A total of 21 pregnant rats with GDM were randomly divided into three groups, with 7 rats in each group, namely the insulin group, metformin group and control group. Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day. Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day, with the first dose of 300 mg/kg. The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65–7.62 mmol/L. Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day. After the natural delivery of pregnant rats, 10 offspring rats were randomly selected from each group. At birth, 4 wk and 8 wk after the birth of offspring rats, the weight of offspring rats was measured. The blood glucose level of offspring rats was measured at 4 wk and 8 wk, while the level of serum insulin, triglyceride and leptin was measured at 8 wk.ResultsThe weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group (P < 0.05), and there was no significant difference at 4 wk and 8 wk among three groups (P > 0.05). The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group (P < 0.05); there was no significant difference between the insulin group and metformin group (P > 0.05). The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P < 0.05); but there was no significant difference between the insulin group and metformin group (P > 0.05). Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher, while triglyceride was significantly lower than the one in the control group (P < 0.05); triglyceride level in the insulin group was significantly higher than the one in the metformin group (P < 0.05). There was no significant difference in insulin and leptin level between the insulin group and metformin group (P > 0.05).ConclusionsGDM can induce the methylation of PPARGC1A of offspring rats to reduce the expression of PPARGC1A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up; the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1A and thus improve the abnormal glycolipid metabolism of offspring rats

Buyang Huanwu Decoction for Healthcare: Evidence-Based Theoretical Interpretations of Treating Different Diseases with the Same Method and Target of Vascularity

Buyang Huanwu Decoction (BHD) is a famous herbal prescription that has been used to treat stroke for centuries. Recent studies reported that the use of BHD had been extended to treat various kinds of disorders according to the TCM syndrome theory of Treating Different Diseases with the Same Method (TDDSM). Here, an overview of systematic reviews (SRs) of BHD for healthcare was conducted to interpret the TCM theory of TDDSM and its target of vascularity in an evidence-based manner. Literature searches were carried out in 5 databases to search SRs of BHD for any indication up to August 2013. Thirteen eligible SRs were identified which reported a wide range of vascular conditions. Based on the Overview Quality Assessment Questionnaire scores, the quality of included SRs was varied, with an average score of 4 points. We found that there is premature evidence for the use of BHD for healthcare, whereas BHD was well tolerable in all patients. BHD can be used to treat many disorders with the same therapeutic principle of invigorating Qi to activate blood circulation, which is essentially a manifestation of the TDDSM and is likely to account for targeting the specific pathogenesis of vascular diseases

Prognostic value of vitamin D in patients with pneumonia: A systematic review and meta-analysis

Purpose: To investigate the prognostic role of vitamin D in pneumonia patients  through meta-analysis.Methods: PubMed and Embase were systematically searched for relevant studies that assessed the impact of vitamin D on the risk of adverse outcomes among patients with pneumonia. Risk ratios (RR) with 95 % confidence intervals (95 % CI) were pooled using meta-analysis. Q-test and I2 statistics were used to evaluate between-study heterogeneity.Results: Six studies were finally included in the meta-analysis. The results of meta-analysis of these studies indicated that low vitamin D status was associated with higher risk of mortality among pneumonia patients (RR = 2.59, 95 % CI = 1.32-5.08; p = 0.005). Results from meta-analysis of studies with adjusted estimates suggest that low vitamin D status was independently associated with higher risk of mortality among pneumonia patients (RR = 3.15, 95 % CI 1.54-6.44, p = 0.002). There was no significant risk of bias in the meta-analysis.Conclusion: This study demonstrates that low vitamin D level is associated with a higher risk of adverse outcomes in patients with pneumonia.Keywords: Pneumonia, Vitamin D, Prognosis, Meta-analysis, Systematic revie

Podoplanin-positive cancer cells at the edge of esophageal squamous cell carcinomas are involved in invasion

Podoplanin (PDPN) is a well established lymphatic endothelial marker and has frequently been observed in cancer cells at the edge of cancer masses. Previous studies investigating the association between PDPN expression and patient prognosis have had contradictory results. In the present study, it was hypothesized that the different locations of PDPNpositive cells may explain these varying results. The present study aimed to focus on PDPN expression at the edge of esophageal cancer cell nests. In order to analyze the clinical significance of this PDPN expression, immunohistochemistry was performed using esophageal cancer tissue microarrays. PDPN expression at the edge of the cancer cell nest was found to be significantly associated with invasion (P<0.05) and poor prognosis (P<0.001) in patients with cancer. To further investigate the role of PDPN expression in cancer cells, the PDPN gene was cloned and transfected into esophageal squamous cell carcinoma (ESCC) cell lines. PDPN expression was also knocked down using small interfering RNA. PDPNpositive cancer cells were found to exhibit invasion characteristics. Thus, PDPN expression at the edge of a cancer cell nest may indicate invasion and represent a poor prognostic factor for ESCCs.published_or_final_versio