Sinomenine Attenuated Capsaicin-Induced Increase in Cough Sensitivity in Guinea Pigs by Inhibiting SOX5/TRPV1 Axis and Inflammatory Response.

BACKGROUND: Chronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood. RESULTS: Capsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5. CONCLUSION: These results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.

Efficacy and Safety of Traditional Chinese Medicine in Idiopathic Pulmonary Fibrosis: A Meta-Analysis.

Objective: To evaluate the efficacy and safety of traditional Chinese medicine (TCM) on lung function and quality of life of idiopathic pulmonary fibrosis (IPF) patients by meta-analysis. Methods: Randomized controlled trials (RCTs) related to TCM and IPF were searched on PubMed, EMBASE Cochrane Library, ClinicalTrials, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chin VIP Information (VIP), and Chinese Biomedical Database (CBM) until December 2018. Standard mean difference (SMD) and 95% CI were calculated for the measurements related to lung function (FEV1/FVC, FVC%, FEV1%, TLC%, DLCO% or DLCO, and VC%) and other parameters (PO2, 6MWD, and SGRQ) when comparing TCM treatment to the control group. Relative risk (RR) and 95% CI of adverse events (AEs) were calculated to assess the safety of TCM. Results: A total of 40 RCTs comparing TCM to western medicine (WM) and involving 3194 IPF patients were eligible for the meta-analysis. The pooled results showed that TCM treatment improved significantly PO2 (SMD = 0.80, 95% CI 0.54 to 1.06, p < 0.001), FEV1% (SMD = 0.57, 95% CI 0.42 to 0.71, p < 0.001), DLCO% (SMD = 0.38, 95% CI 0.28 to 0.48, p < 0.001), 6MWD (SMD = 0.70, 95% CI 0.56 to 0.84, p < 0.001) and other measurements and reduced SGRQ scores (SMD = −0.51, 95% CI −0.70 to −0.22, p < 0.001). Subgroup analysis of different study durations (3 months, ≥ 6 months) and comparison models (TCM vs. WM, TCM + WM vs. WM or TCM vs. placebo) showed similar results. No significant difference of risk of AEs was observed between both groups (RR = 0.66, 95% CI: 0.27­1.60, p=0.352). There was no obvious publication bias, and the pooled results were stable according to sensitivity analysis. Conclusion: To the best of our knowledge, the present study had the largest sample size. Our results indicated that TCM treatment may help provide benefit to the lung function, exercise capacity, and quality of life of IPF patients, alone or combined with WM, when compared to WM. More rigorous RCTs were needed in the future.

Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway.

Matrine (C15 H24 N2 O), an alkaloid that is one of the main active components from Sophora flavescens. Matrine has been demonstrated to have therapeutic effects on various solid tumors, including breast cancer, but the mechanism still needs further study. Endoplasmic reticulum (ER)-positive Michigan Cancer Foundation cells were cultured, and matrine was added in various amounts to measure the dose-dependent and time-dependent cytotoxicity. Hoechst 33258 staining was used to observed nuclear morphological changes. Apoptosis was measured by AnnexinV/PI double staining assay kit. Intracellular adenosine triphosphate and glycometabolism were detected by assay kit. The protein levels GRP78, p-eIF2α, CHOP, cytochrome c, and HexokinaseII were analyzed. Mechanistic investigations revealed that matrine treatment causes ER dilation and up-regulated the expression of ER stress markers GRP78, eIF2α, and CHOP, increases the levels of apoptotic in Michigan Cancer Foundation cells, subsequently, blocking the ER stress-mediated apoptosis pathway, significantly decreased matrine-induced apoptotic but still has significant difference between control group. In addition, matrine not only promoted the occurrence of ER stress but also inhibited the expression of hexokinase II, down-regulated energy metabolism. In summary, the present study suggests that the induction of ER stress-mediated apoptosis by matrine and down-regulated energy metabolism may account for its cytotoxic effects in human breast cancer cells. Copyright © 2017 John Wiley & Sons, Ltd.

Association of coffee consumption with risk of colorectal cancer: a meta-analysis of prospective cohort studies.

A meta-analysis was performed to assess the association of coffee consumption with colorectal cancer and to investigate the shape of the association. Relevant prospective cohort studies were identified by a comprehensive search of the PubMed, Embase and Web of Science databases from their inception through August 2015. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. Linear and nonlinear dose-response meta-analyses were also performed. Nineteen prospective cohort studies involving 2,046,575 participants and 22,629 patients with colorectal cancer were included. The risk of colon cancer was decreased by 7% for every 4 cups per day of coffee (RR=0.93, 95%CI, 0.88-0.99; P=0.199). There was a threshold approximately five cups of coffee per day, and the inverse association for colorectal cancer appeared to be stronger at a higher range of intake. However, a nonlinear association of rectal cancer with coffee consumption was not observed (P for nonlinearity = 0.214). In conclusion, coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption. The findings support the recommendations of including coffee as a healthy beverage for the prevention of colorectal cancer.

Rapid CO breath test screening of drugs for protective effects on ribavirin-induced hemolysis in a rabbit model: a pilot study.

Hemolytic anemia is a major side effect of ribavirin antiviral treatment for chronic hepatitis C. Ribavirin dose reduction may compromise the antiviral response and erythropoietin can take several weeks to alleviate anemia. The purpose of the present study was to screen potentially protective drugs against ribavirin-induced hemolytic anemia in a rabbit model, using our modified CO breath test for measuring erythrocyte (RBC) lifespan, the gold standard diagnostic index of hemolysis. Fifteen rabbits were divided randomly into five groups (N = 3/group): one vehicle control group, one ribavirin (only)-treated (RBV) group, and three groups initially treated with ribavirin only, followed by a combination of ribavirin with prednisone (RBV + Pred), polyene phosphatidyl choline (RBV + PPC), or reduced glutathione (RBV + GSH). RBC lifespan was calculated from accumulated CO measured in a closed rebreath apparatus, blood volume measured by the Evan's blue dye (EBD) dilution test, and hemoglobin concentration data. The RBC lifespan was normal in the vehicle control group (44-60 d), but reduced significantly in all of the ribavirin-treated groups before the addition of screened drugs (17-35 d). RBC lifespan rebounded significantly with the addition of glutathione, but not with the addition of prednisone or polyene phosphatidyl choline. A similar overall drug effect pattern was seen in the hemoglobin concentration and reticulocyte count data. In conclusion, the results of this pilot study indicate that reduced glutathione can attenuate ribavirin-induced hemolytic anemia, and that the RBC lifespan measured with our modified rapid CO breath test is feasible and reliable for use in animal studies.

Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid ß-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPK.

Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced A ß 25 ‒ 35-induced cytotoxicity in PC12 cells. Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro. Pretreatment of cells with D diminished intracellular generation of ROS in response to A ß 25 ‒ 35. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against A ß 25 ‒ 35-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in A ß 25 ‒ 35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury. Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression. While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells. Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against A ß 25 ‒ 35-induced cell death. These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from A ß 25 ‒ 35-induced oxidative cytotoxicity.

[Clinical study on treatment of acute biliary tract infection with biliary drainage via endoscope combined with Chinese drug medication].

OBJECTIVE: To observe the curative effects of biliary drainage via endoscope (ENBD) combined with Chinese drug medication on acute biliary tract infection (ABTI) and the influence of treatment on complement 3 (C3), C-reactive protein (CRP) and interleukin-6 (IL-6). METHODS: Sixteen patients with ABTI were randomly assigned to two groups: the 9 patients in the combined treatment group (CTG) treated with ENBD combined with Chinese medicine and the 7 patients in routine treatment group (RTG) treated with ENBD alone. Another 18 patients with simple gallbladder stone were taken as the control group (CG). The curative effect was observed and the serum concentrations of C3, CRP and IL-6 were determined before and after treatment. RESULTS: Before treatment, the concentrations of CRP and IL-6 were significantly higher and C3 lower in all ABTI patients than those in patients with simple gallbladder stone (P < 0.05 or P < 0.01). After treatment, the general condition of patients was improved, the recovery time of intestinal tract function was shortened and the concentrations of C3, CRP and IL-6 significantly decreased in CTG, with the effects better than those in RTG respectively (P < 0.01 or P < 0.05). CONCLUSION: ENBD combined with Chinese drug medication shows favorable curative effects on ABTI. Treatment with Chinese medicine according to syndrome differentiation could decrease blood level of pro-inflammatory cytokines and promote recovery of the injured immune function.

Clinical study on treatment of acute biliary tract infection with biliary drainage via endoscope combined with Chinese drug medication / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the curative effects of biliary drainage via endoscope (ENBD) combined with Chinese drug medication on acute biliary tract infection (ABTI) and the influence of treatment on complement 3 (C3), C-reactive protein (CRP) and interleukin-6 (IL-6).</p><p><b>METHODS</b>Sixteen patients with ABTI were randomly assigned to two groups: the 9 patients in the combined treatment group (CTG) treated with ENBD combined with Chinese medicine and the 7 patients in routine treatment group (RTG) treated with ENBD alone. Another 18 patients with simple gallbladder stone were taken as the control group (CG). The curative effect was observed and the serum concentrations of C3, CRP and IL-6 were determined before and after treatment.</p><p><b>RESULTS</b>Before treatment, the concentrations of CRP and IL-6 were significantly higher and C3 lower in all ABTI patients than those in patients with simple gallbladder stone (P < 0.05 or P < 0.01). After treatment, the general condition of patients was improved, the recovery time of intestinal tract function was shortened and the concentrations of C3, CRP and IL-6 significantly decreased in CTG, with the effects better than those in RTG respectively (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>ENBD combined with Chinese drug medication shows favorable curative effects on ABTI. Treatment with Chinese medicine according to syndrome differentiation could decrease blood level of pro-inflammatory cytokines and promote recovery of the injured immune function.</p>