Fourth-generation quinolones in the treatment of Helicobacter pylori infection: A meta-analysis.

AIM: To assess the efficacy and safety of fourth-generation quinolones for Helicobacter pylori (H. pylori) eradication, we conducted this systematic review and meta-analysis of randomized clinical trials. METHODS: Major literature databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) were searched for relevant articles published prior to February 2018. We performed a meta-analysis of all randomized clinical trials that examined the efficacy of H. pylori eradication therapies and included fourth-generation quinolones in the experimental arm. Subgroup analyses by regions and different types of fourth-generation quinolones were also performed. RESULTS: Ten studies including a total of 2198 patients were assessed. A meta-analysis of randomized controlled trials showed that the eradication rate of therapies containing non-fourth-generation quinolones was significantly lower than that of therapies containing fourth-generation quinolones by intention-to-treat (ITT) analysis [75.4% vs 81.8%; odds ratio (OR) = 0.661; 95% confidence interval (CI): 0.447-0.977; P = 0.038]. This analysis also showed that the eradication rate of the therapies containing non-fourth-generation quinolones was inferior to that of therapies containing fourth-generation quinolones by per-protocol analysis (79.1% vs 84.7%; OR = 0.663; 95%CI: 0.433-1.016; P = 0.059). Moreover, the occurrence of side effects was significantly different between the control and experimental groups by ITT analysis (30.6% vs 19.5%; OR = 1.874; 95%CI: 1.120-3.137; P = 0.017). The sub-analyses also showed significant differences in moxifloxacin therapies vs other fourth-generation quinolone therapies (84.3% vs 71.9%) and in Asian vs European groups (76.7% vs 89.1%). CONCLUSION: Therapies containing fourth-generation quinolones achieved a poor eradication rate in the treatment of H. pylori infection. Such regimens might be useful as a rescue treatment based on antimicrobial susceptibility testing. Different antibiotics should be chosen in different regions.

[Effects of wine processed Rheum palmatum on tissue distribution of aloe-emodin, rhein and emodin in rats].

Under the traditional processing theory "wine processing could promote the efficacy", Rhubarb after wine processing could treat the upper energizer diseases such as red swelling, and breath sores. Processing changes the medicinal properties of rhubarb, and thus results in different focuses in clinical application. In this study, a sensitive and specific method was developed for the determination of aloe-emodin, rhein and emodin in rats tissue. Rhubarb raw materials and its wine processed decoction were given to SD rats respectively by gavage administration, and then the contents of aloe-emodin, rhein and emodin in the tissues (heart, lung, brain, liver, kidney) were determined by HPLC-MS to explore the effect of wine processing on free anthraquinones in rat tissues. Experimental results showed that wine processing can significantly change the distribution of aloe emodin, rhein and emodin in rats in vivo, and the distribution of these components was increased in heart and lung tissues.There was no significant change of distribution in the liver and the kidney as compared with raw product group, and these three ingredients were not detected in the brain, indicating that aloe-emodin, rhein, emodin can not pass through the blood brain barrier.Therefore, wine processing had greater effect on distribution of free anthraquinones in rat tissues.This also verified the theory of traditional Chinese medicine, providing experimental basis for rhubarb processing mechanism.

Forsythoside A exerts an anti-endotoxin effect by blocking the LPS/TLR4 signaling pathway and inhibiting Tregs in vitro.

Endotoxins, also referred to as lipopolysaccharides (LPS), are powerful immunostimulators involved in a number of severe diseases. Forsythoside A (FTA), a monomer of phenethyl alcohol glycosides extracted from Forsythia suspensa, has been shown to possess anti-bacterial and immunomodulatory properties. However, it is currently not known whether FTA can counter the adverse effects of endotoxins. We investigated the effect of FTA on LPS-stimulated RAW264.7 cells and primary lymphocytes to determine its molecular mechanism of action. RAW264.7 cells and primary lymphocytes were incubated with or without LPS (100 ng/ml) in the presence or absence of FTA or polymyxin B. We found that FTA increased the viability of LPS-treated RAW264.7 cells and primary lymphocytes suggesting that FTA effectively counters the adverse effects of endotoxins. FTA decreased the percentage of regulatory T cells (Tregs) and inhibited the TLR4/MyD88/NF-κB signaling pathway, downregulating Foxp3, IL-10 and TGF-ß1, molecules involved in the immunosuppressive function of Tregs. These findings elucidate the molecular mechanism underlying the anti-endotoxin effects of FTA and suggest its use as a new treatment for LPS-induced diseases.

2-Aminoxazole and 2-Aminothiazole Dasatinib Derivatives as Potent Inhibitors of Chronic Myeloid Leukemia K562 Cells.

Dasatinib is an important drug against chronic myeloid leukemia (CML). In this paper, we describe the preparation and anti-CML activity of 2-aminoxazole and 2-aminothiazole dasatinib derivatives. Biological activity was measured by the inhibition of proliferation of human CML K562 cells. The 2-aminoxazole derivatives had similar activities as the 2-aminothiazole derivatives. All newly synthesized compounds demonstrated more potent antiproliferative activity than imatinib. A few compounds (8b, 8c, 9b) showed nanomolar inhibitory activity, similar to that of dasatinib.

[Effects of extractionfrom raspberry on hippocampus proteomics of mice suffered from ovariectomized-induced AD].

This paper was aimed to investigate the impact of the extraction from raspberry on the Alzheimer disease model protein expression. According to weight, the ovariectomized mice were randomly divided into shame operation group, model group, estrogen positive control group(0.1 g•L⁻¹) and ethyl acetate extraction part control group(in dose of 18 g•kg⁻¹). Each mouse in positive control group was subcutaneous injected of estradiol with 0.2 mL every two days. Raspberry effective parts group were given 0.01 mL•g⁻¹ raspberry ethylacetate extracts, model group and control group were given 0.01 mL•g⁻¹ saline once a day. The drug administration lasted for 32 days. Proteins from mice's hippocampus were extracted, then Nanol-ESI liquid-mass spectrometry system was used for detection and ProteinDiscovery software was used for identification to qualitative analysis different groups of hippocampal proteins by using the software of SIEVE. The results showed that model group compared with the mice of ethyl acetate extraction part control group have 66 differentially expressed proteins including heat shock protein, microtubule protein, protein involved in energy metabolism and protein of brain protection related proteins associated with AD. Those differences protein may be the target that Raspberry prevention and treatment of AD.

[Proteomics research of intervention effect of "Qi enriching" herbs on "Qi deficiency" rats based on technology of NanoLC-LTQ-Orbitrap].

Proteomics method, based on NanoLC-LTQ-Orbitrap technology, was applied to explore the biological basis of intervention effect of "Qi enriching" herbs on "Qi deficiency" rats. The "Qi deficiency" rat model was established with caloric restriction combined with excessive swimming. Muscle proteins of vastus lateralis from the blank group, the model group and the ginseng group were detected by NanoLC-LTQ-Orbitrap system. The data were imported into Protein Discovery software to identify the proteins and all the raw datum were analyzed by SIEVE software. Compared with model group, 26 significant difference proteins were found in ginseng group, which the variation trend was consistent with the blank group. Through the biological function analysis, the found proteins could be classified into proteins involved in energy metabolism, proteins involved in glucose metabolism, electrolyte balance and material transfer related proteins, inflammation related protein and cytoskeleton protein. The above target proteins and their regulation pathways may be the biological basis which ginseng played a role of tonifying "Qi" of "Qi deficiency" symptom.

[The effects and mechanisms of Forsythia suspense on the expression of Foxp3 on splenocytes and level of Treg in peripheral blood in severely burnt rats].

AIM: To explore the immunity modulation function of aqueous of Forsythia suspense (AFS) and its possible mechanisms. METHODS: Rats of burned model group were burned with vapor under 3 mpa pressure and 108 degrees C temperature for 8 seconds to achieve deep partial-thickness burn, to make a thirty percent total body surface area (TBSA) burn. The experiment were divided into five groups: CONTROL GROUP: without any treatment; 8PBH group: 8 h after burn; the rats of AFS1 group, AFS2 group and AFS3 group of them were given AFS 5 g/kg, 2.5 g/kg, 1.25 g/kg once a day by Po. pathway for seven days before burns, respectively. Rats were sacrificed before and 8h after burn, The percentage of Treg cells in CD4(+) T cells was detected by flow cytometry (FCM); the expression of Foxp3 mRNA on splenocytes were measured by RT-PCR, and the protein of Foxp3 activity was evaluated by immunohistochemistry staining. RESULTS: Compared with CONTROL GROUP, the expression of Foxp3 mRNA and protein on the splenocytes were upregulated markedly (P<0.01), and the percentage of Treg were significantly increased (P<0.01) in the 8PBH group. AFS1, AFS2 and AFS3 significantly attenuated these increases (P<0.01), which was dose-dependent. CONCLUSION: AFS has immunity modulation function and mechanism of it is corrected with Foxp3 mRNA on splenocytes.

[Study on the expression of TLR4 on splenocytes and its relation with CD4(+) CD25(+) regulatory T cells in peripheral blood in severely burnt rats].

AIM: To investigate the expression of Toll like receptor 4(TLR4) on splenocytes and TNF-alpha mRNA, the dynamic changes of CD4(+) CD25(+) regulatory T cell(Treg) and endotoxin(ET) in peripheral blood of burnt rats during the early phase, and to explore the mechanism against inflammatory reaction in intestine-derived infection after burn. METHODS: 64 SD male rats were randomly separated into control group and burn model groups. Rats of burn model group were burnt with vapor under 3 mPa pressure and 108 degrees Celsius temperature for 8 seconds to achieve deep partial-thickness burn, and a 30% total body surface area (TBSA) burn model was made. Rats were sacrificed before and 2, 5, 8, 12, 24, 48 and 72 h after burn, and the TLR4 and TNF-alpha mRNA expression in splenocytes were measured at various intervals by RT-PCR. The expression of TLR4 protein was measured by Western blot, and the percentage of Treg cells in CD4(+) T cells was detected by flow cytometry (FCM), and the LPS concentration of plasma was detected by limulus lysate test. RESULTS: The expression of TLR4 mRNA, TNF-alpha mRNA, TLR4 protein and the levels of Treg, ET were significantly increased at some times points after burn. The expression of TLR4 mRNA and protein reached the peak at 8 h, whereas the TNF-alpha mRNA at 12 h, and Treg and ET at 8 h. The peak values of them were 3.66+/-0.51, 2.27+/-0.19, 1.65+/-0.23, 63.19+/-12.65% and 11.68+/-1.71 Eu/mL respectively, which were of significant difference when compared with the control group (P<0.01). The expression of TLR4 mRNA showed a positive correlation with that of Treg, ET and TNF-alpha mRNA (r=0.898, 0.811, 0.462, P<0.01). CONCLUSION: Treg might play a major role in the process of immune regulation in rats after burn, the mechanism of which may be correlated with the increase of LPS-TLR4 signal transduced by intestine-derived infection.

[Protective effect and mechanism of pharmacologic preconditioning induced by sodium ferulate on primary cultured myocardial cell injury by anoxia/reoxygenation].

AIM: To study the preconditioning effects and mechanism of action of sodium ferulate (SF) on primary cultured myocardial cell injury induced by anoxia/reoxygenation. METHODS: Cultured myocardial cells of neonatal SD rats were randomly divided into ten groups: control group: without any treatment; anoxia/reoxygenation group (A/R), reoxygenation of 1 h following anoxia of 3 h; anoxia preconditioning group (AP), reoxygenation of 30 mins following anoxia of 30 mins, three times before the same procedure as group A/R; SF preconditioning groups, 20 mins of SF (1.68, 0.42, 0.105 mmol x L(-1) in final concentration) preconditioning followed by 10 mins wash out before A/R; K+ATP channel blocker group, NOS inhibitor group and PKC inhibitor group, adding gliberclamide, L-NAME, ploymyxin B at final concentration of 12 g x mL(-1), 50 micromol x L(-1), 50 micromol x L(-1), to culture medium respectively 10 min before the same procedures as SF preconditioning group (1.68 mmol x L(-1)). Myocardial cells pulse rate and rhythm, myocyte viability, the activity of LDH and CK in culture, the contents of intracelluar MDA, LD in myocardial cells, the activity of SOD and GSH-Px of the cultured myocardial cell were measured at the end of experiment. RESULTS: Compared with control group, anoxia/reoxygenation caused great increases of levels of LDH, CK, MDA and LD (P < 0.01), decreases of myocardial cells pulse rate, cell viability, SOD and GSH-Px (P < 0.01); SF preconditioning significantly attenualed these increases and decreases. Glib, L-NAME, and Ploy B partly abolished the effects of SF preconditioning. CONCLUSION: SF preconditioning is effective in protecting myocardial cells from anoxia injury. The cardioprotective effect of SF preconditioning is produced by multiple factors.