Objective To study the protective effect of Tripterygium wilfordii polycoride (TWP) against TNBS/ethanol-induced ulcerative colitis (UC) rat model. Methods TNBS and ethanol enema were adopted to build TNBS/ethanol-induced UC rat model. Ninety male Wistar rats were divided into six groups: normal, model, low-, medium-, high-dose TWP and azathioprine (AZA) groups, each for 15 rats. All rats were administered by corresponding medicine for 14 d. After 14 d, corresponding colon tissues underwent general and microscopic evaluation. Blood samples were taken from heart and serum was separated by centrifugation. MDA, SOD, GSH, IL-1β and TNF-α levels in serum were tested by ELISA. Colonic samples underwent RT-PCR and Western blotting analysis. Results DAI, general and microscopic evaluation all showed that TWP could promote colonic mucosa healing and such effect was equal to AZA. ELISA results about lipid peroxidation indicated that TWP could decrease MDA level and increase SOD and GSH levels in a dose-dependent manner. TWP with high dose could strongly decrease the MDA level and increase the SOD and GSH levels (P < 0.01). ELISA results about inflammatory cytokines indicated that TWP could inhibit the expression of IL-1β and TNF-α in a dose-dependent manner. Western blotting analysis and RT-PCR all indicated that no matter in mRNA level or protein level, TWP could inhibit the expression of NF-κB, TNF-α IL-1β and IFN-γ in a dose-dependent manner. The inhibitory effect of AZA towards NF-κB was slightly weaker than TWP with high dose (P > 0.05), whereas slightly stronger towards terminal inflammatory cytokines (P > 0.05). Conclusion TWP could significantly lower the infiltration of inflammatory cells under microscope, eventually led to mucosa healing, the mechanism of which was to inhibit lipid peroxidation, then further inhibit NF-κB activation, eventually lower the expression of inflammatory meditors locally and systemically.

Objective To control stem blight disease of Schizonepeta tenuifolia caused by Phytophthora nicotianae.Methods The antagonist effect of 13 Trichoderma strains(including T.viride and T.hamianum)was evaluated upon mycelia growth of P.nicotianae.Trichoderma strains with high antagonistic activities against the pathogen were used to control stem blight of S.tenuifolia in the field.Results Of 13 Trichoderma strains tested,T.viride strain M3 showed maximum mycelia growth inhibition(83.2%)to the pathogen,followed by T.viride strain Tv04-2(78.2%)and then T.harziamum strain ThB(65.0%),in vitro.Fungal cell wall degrading enzymes,protease,and β-1,3-glueanase were analyzed qualitatively and quantitatively in further study.T.viride strains M3,Tv04-2,and T.harzianum strain ThB efficiently against P.nicotianae were used to control stem blight of S.tenuifolia in the field,and T.viride strain M3 showed the best biocontrol potential.Conclusion Trichoderma spp.can be used as alternatives of pesticides to control stem blight,one of the serious soilhome diseases of S.tenuifolia caused by P.nicotianae.However,though T.viride strains Tv04-2 aad T.harzianum strain ThB are also highly against P.nicotianae in vitro,the controlling efficacy of them on stem blight disease is not as excellent as T.viride strains M3 in the field.

Objective To investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the left ventricular structure and function of MHD patients with resistant hypertension. Methods This study was a prospective, randomized, controlled clinical trial. 65 MHD patients with resistant hypertension of our hospital were enrolled and then randomly divided into Group HD+HP and Group HD. The follow-up study was 12 months. The major outcome measures were related to the cardiac structure and function, and the serum inflammatory factors. Results No statistical differences of related factors such as blood pressure and cardiac function was observed in HD group. The serum concentration of inflammatory factors was higher after one-year HD treatment alone. But the serum concentration of inflammatory related factors , blood pressure, cardiac function and related indexes were lower in HD + HP than in Group HD (P < 0.05);HD + HP group had higher ejection fraction (EF) and SV, which demonstrated the improved cardiac function (P < 0.05). Conclusions HD + HP was superior to HD in the treatment in alleviating cardiac after-load and improving the left ventricular structure and function of MHD patients with resistance hypertension.

Objective To identify the role of phosphatidylinositol-3-kinase(PI3K) in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) and the involved mechanism.Methods Knockdown of p110α,receptor-interacting protein 1(RIP1) or both p110αand RIP1 was mediated by the specific short hairpin RNA (shRNA) lentivirus and verified by RT-PCR or Western blotting .In addition , Western blotting was used to detect phosphorylation of mixed lineage kinase domain-like protein(MLKL) and protein kinase B(AKT) or tetramerization of MLKL.Cell death was measured by micros-copy and flow cytometry.Results AKT phosphorylation and TNFα-induced necroptosis of L929 cells were suppressed by the inhibitors of PI3K or AKT, as well as p110αknockdown.Moreover, RIP1 knockdown did not inhibit L929 cell death induced by TNFαplus Z-VAD, but the RIP1-independent necroptosis was inhibited by p 110αknockdown.In addition, p110αknockdown suppressed MLKL phosphorylation and tetramerization induced by TNFαwith Z-VAD in L929 cells. Conclusion PI3K mediates necroptosis of L929 cells induced by TNFαby activating AKT and MLKL, respectively.

Antagonistic mechanisms of Trichoderma viride M3, Tv04-2, and T. harzianum ThB, were studied against Phytophthora nicotianae, the pathogen of stem blight disease on Schizonepeta tenuifolia by dual-culture, hydrolase activity, volatile and nonvolatile substances. Results indicated that competitive, mycoparasitism and antagonism were the antagonistic mechanisms of three Trichoderma spp. against P. nicotianae. Hydrolase activity showed that M3 was the highest for beta-1, 3-glucanases activity while ThB was the highest for proteases activity among the three T. strains, and they could produce volatile and non-volatile substances, also.
Fungal Proteins ; metabolism ; Hydrolases ; metabolism ; Lamiaceae ; parasitology ; Peptide Hydrolases ; metabolism ; Pest Control, Biological ; Phytophthora ; microbiology ; physiology ; Plant Diseases ; parasitology ; Trichoderma ; enzymology ; physiology

OBJECTIVETo investigate whether analgesic effect of electroacupuncture (EA) is affected by p38 mitogen-activated protein kinase (p38 MAPK) on microglia.

METHODSThere were two experiments. The experiment 1: 40 male Sprague-Dawley (SD) rats were randomly divided into the normal, surgery, EA and sham EA groups, and the L5 spinal nerve ligation (SNL) on the right side was used to establish neuropathic pain model. EA was applied to bilateral Zusanli (ST36) and Kunlun (BL60) at 24, 48 and 72 h after SNL for 30 min, once per day. The paw withdrawal thresholds (PWTs) were measured before surgery (as base) and at 24, 25, 49 and 73 h after surgery. Phospho-p38 MAPK (p-p38 MAPK), oxycocin-42 (OX-42, marker of microglia), and glial fibrillary acidic protein (GFAP, marker of astrocyte) in bilateral spinal cord dorsal horn (SCDH) were detected by immunofluorescence, respectively. The experiment 2: 40 male SD rats were cannulated for SNL-induced neuropathic pain, and then were randomly divided into the dimethyl sulfoxide (DMSO), EA plus DMSO, 4-(4-fluorophenyl)-2-(4-methylsulfonylpheny)-5-(4-pyridyl)-1H-imidazole (SB203580) and EA plus SB203580 groups. SB203580 (30 nmol/L) was administered 5 min prior to EA treatment. The PWTs and OX-42 in bilateral SCDH were measured as mentioned above.

RESULTSSNL-induced neuropathic pain reduced PWTs and increased the expression of p-p38 MAPK and OX-42 in bilateral lumbar SCDH of rats (P<0.01). Spinal p-p38 MAPK was only co-localized with OX-42 in our study. EA treatment significantly alleviated SNL-mediated mechanical hyperalgesia, and suppressed the expression of p-p38 MAPK and OX-42 in lumbar SCDH (P<0.05 or P<0.01). Intrathecal injection of low dose SB203580 had no influence on PWTs (P>0.05), but significantly inhibited the expression of OX-42 positive cells in bilateral SCDH (P<0.01 or P<0.05). EA plus SB203580 synergistically increased PWTs, and reduced the expression of bilateral spinal OX-42 (P<0.01 or P<0.05).

CONCLUSIONSThe central mechanism of EA-induced anti-hyperalgesia may be partially associated with the reduced expression of p-p38 MAPK, and subsequently reducing the activation of OX-42 in neuropathic pain. Therefore, EA may be a new complementary and alternative therapy for neuropathic pain.

Animals ; Biomarkers ; metabolism ; CD11b Antigen ; metabolism ; Electroacupuncture ; Fluorescent Antibody Technique ; Hyperalgesia ; pathology ; therapy ; Imidazoles ; pharmacology ; Ligation ; Male ; Microglia ; drug effects ; enzymology ; pathology ; Neuroglia ; drug effects ; metabolism ; Phosphorylation ; drug effects ; Posterior Horn Cells ; drug effects ; enzymology ; pathology ; Pyridines ; pharmacology ; Rats, Sprague-Dawley ; Spinal Nerves ; drug effects ; pathology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Dihydroorotate dehydrogenase is a flavin-dependent mitochondrial enzyme to catalyze the fourth step of the de novo synthesis of pyrimidine and to oxidize dihydroorotate to orotate. By selectively inhibiting dihydroorotate dehydrogenase, thereby inhibiting pyrimidine synthesis, the enzyme has been developed for the treatment of cancer, autoimmune diseases, bacterial or viral infections, parasitic diseases and so on. The development of inhibitory drugs requires a detailed understanding of the structural characteristics and catalytic cycle mechanism of dihydroorotate dehydrogenase. Therefore, this paper reviews these two aspects, and indicates perspectives of these inhibitors in clinical application.
Catalysis ; Mitochondria/metabolism* ; Oxidation-Reduction ; Oxidoreductases Acting on CH-CH Group Donors/metabolism*

OBJECTIVE: To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis. METHODS: Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO. RESULTS: A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process. CONCLUSIONS CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.
Fatty Acids ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Humans ; Metabolomics ; T-Lymphocytes ; Tongue

Acquired Immunodeficiency Syndrome ; DNA ; Diagnostic Tests, Routine ; Humans ; Leukoencephalopathy, Progressive Multifocal ; Polyomavirus

BACKGROUND: Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs. METHODS: We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%. RESULTS: At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group. CONCLUSIONS: The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.
Adult ; Anti-HIV Agents/adverse effects* ; Antiretroviral Therapy, Highly Active ; China ; Drug Therapy, Combination ; HIV Infections/drug therapy* ; HIV-1 ; Humans ; Maleimides ; Peptides ; Ritonavir/therapeutic use* ; Treatment Outcome ; Viral Load