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1.
Therap Adv Gastroenterol ; 17: 17562848241258021, 2024.
Article in English | MEDLINE | ID: mdl-38846173

ABSTRACT

Background: Given the growing problem of antibiotic resistance, it is crucial to improve Helicobacter pylori (H. pylori) treatment interventions or provide adjunctive therapy. The objective of this meta-analysis was to evaluate whether Lactobacillus reuteri (L. reuteri) could improve H. pylori eradication rate, reduce the incidence of adverse events (AEs), and alleviate gastrointestinal symptoms. Design: A meta-analysis of randomized controlled trials (RCTs) comparing L. reuteri supplementation therapy with placebo was conducted. Sources and methods: We retrieved relevant studies from PubMed, Embase, and the Cochrane Library. The primary outcome was H. pylori eradication rate, and the scores on the Gastrointestinal Symptom Rating Scale and AEs were secondary outcomes. Results: Eight RCTs including 1087 patients were included in this analysis. The L. reuteri supplementation group showed significantly higher H. pylori eradication rates in both intention-to-treat (ITT) and per-protocol (PP) analysis [ITT: 80.0% versus 72.6%; p = 0.005, relative risk (RR): 1.10; 95% confidence interval (CI): 1.03-1.17; number needed to treat (NNT) = 14; PP: 81.8% versus 75.0%; p = 0.006, RR: 1.09; 95% CI: 1.03-1.16; NNT = 15]. Patients treated with L. reuteri showed greater improvements in gastrointestinal symptoms (pooled mean difference: -2.43, 95% CI: -4.56 to -0.29, p = 0.03). The incidence of AEs was significantly reduced in the L. reuteri supplementation group based on ITT and PP analysis (ITT: p < 0.00001, RR: 0.72, 95% CI: 0.67-0.78; PP: p < 0.00001, RR: 0.70, 95% CI: 0.65-0.77). Conclusion: The present meta-analysis demonstrated that supplementation with L. reuteri was beneficial for improving the eradication rate of H. pylori, reducing the overall incidence of side effects, and relieving gastrointestinal symptoms in patients during treatment. The findings provide new insights into clinical decision-making. Trial registration PROSPERO: CRD42023424052.


Lactobacillus reuteri compared with placebo as an adjuvant in Helicobacter pylori eradication therapy: a meta-analysis of randomized controlled trials Given the growing problem of antibiotic resistance, it is crucial to improve Helicobacter pylori (H. pylori) treatment interventions or provide adjunctive therapy. Eight randomized controlled trials (RCTs) including 1087 patients were included in this analysis. The present meta-analysis demonstrated that supplementing with L. reuteri tends to increase the eradication rate of H. pylori, reduce the overall incidence of antibiotic-related side effects, and alleviate gastrointestinal symptoms in patients during treatment, providing new insights for clinical decision-making.

2.
Gut ; 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906695

ABSTRACT

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. METHODS: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. RESULTS: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). CONCLUSIONS: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. TRIAL REGISTRATION NUMBER: ChiCTR2300074693.

3.
Food Chem X ; 20: 100913, 2023 Dec 30.
Article in English | MEDLINE | ID: mdl-38144747

ABSTRACT

This study aimed to evaluate the efficacy of amylase in hydrolyzing complex carbohydrates of different parts of Ganoderma spp. The aqueous extracts of the Ganoderma samples were analyzed for their selected nutritional composition and physicochemical properties. The purified extracts were also structurally characterized. The aqueous canopy extracts of red-purple Ganoderma had a notably higher total sugar and saponin content than their stalks, but not for the black-type Ganoderma. The enzymatic extraction effectively improved the extraction yields, whereas the amounts of sugars and saponins in some extracts were increased after the enzymatic treatment. The results also showed that only those enzyme-treated cultivated black Ganoderma canopy had increased total sugar and total saponin content. The antioxidant activities of all stalk extracts were higher than the canopy extracts. Their emulsifying properties were comparable with lecithin due to their high saponin content. Therefore, these extracts are new natural emulsifiers.

4.
J Acquir Immune Defic Syndr ; 94(2S): S42-S46, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37707847

ABSTRACT

BACKGROUND: The Southern region of the United States has the highest HIV incidence, and new infections disproportionately affect Black Americans. The Tennessee Center for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) program supports the training of individuals from groups underrepresented in medicine and science in multiple areas of research to increase the pool of HIV-focused investigators at early educational and career stages. SETTING: The Tennessee CFAR is a partnership between Vanderbilt University Medical Center, Meharry Medical College (one of the oldest historically Black medical colleges), Tennessee Department of Health, and Nashville Community AIDS Resources, Education and Services (a sophisticated community service organization, which emphasizes research training responsive to regional and national priorities). METHODS: The Tennessee CFAR CDEIPI program leverages existing Vanderbilt University Medical Center and Meharry Medical College structured biomedical training programs for high school and undergraduate students to provide an intensive, mentored, HIV research experience augmented by CFAR resources situating this training within the broader history, scientific breadth, and societal and political aspects of the HIV epidemic. RESULTS: The first year of the Tennessee CFAR CDEIPI program trained 3 high school and 3 undergraduate students from underrepresented in medicine and science backgrounds in basic, clinical/translational, and community-focused research projects with a diverse group of 9 mentors. All students completed the program, and evaluations yielded positive feedback regarding mentoring quality and effectiveness, and continued interest in HIV-related research. CONCLUSIONS: The Tennessee CFAR CDEIPI program will continue to build upon experience from the first year to further contribute to national efforts to increase diversity in HIV-related research.


Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Humans , Tennessee/epidemiology , HIV Infections/epidemiology , HIV Infections/prevention & control , Schools , Students
5.
Therap Adv Gastroenterol ; 16: 17562848231190976, 2023.
Article in English | MEDLINE | ID: mdl-37664169

ABSTRACT

Background: With the increase in antibiotic resistance, the success rate of Helicobacter pylori (H. pylori) eradication therapy has declined in recent years. Vonoprazan-amoxicillin (VA) dual therapy has been reported to be a promising regimen. Objectives: To compare the efficacy and safety of VA dual therapy and bismuth quadruple therapy containing amoxicillin and clarithromycin for H. pylori first-line eradication, and to further analyze the effects of clarithromycin resistance on eradication rate. Design: This study was a single-center, open-label, randomized controlled trial. Methods: Treatment-naïve H. pylori-infected patients were randomly allocated 1:1 to the VA group (vonoprazan 20 mg twice daily and amoxicillin 750 mg four times daily, for 14 days) or the RBAC group (rabeprazole 10 mg, bismuth potassium citrate 220 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily, for 14 days). H. pylori clarithromycin resistance and CYP2C19 gene polymorphisms were detected with real-time polymerase chain reaction (PCR) technique. The eradication rates and adverse events were analyzed. Results: A total of 151 patients were enrolled. The intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) eradication rates and their 95% confidence intervals (95% CIs) were 94.6% (86.0-98.3%), 98.6% (91.3-99.9%), and 98.5% (90.9-99.9%) for VA group and 87.0% (77.0-93.3%), 91.8% (82.3-96.6%), and 93% (83.7-97.4%) for RBAC group. The eradication rate of the VA group was noninferior to the RBAC group in ITT, mITT, and PP analyses (p < 0.0001). In patients infected with strains of clarithromycin resistance point mutation, the eradication rate of the RBAC group decreased to lower than 90%, but the difference from the VA group did not achieve statistical significance (ITT eradication rate: 81.5% in the RBAC group and 96.2% in the VA group, p = 0.192). The incidence of adverse events in the VA group was 39.2%, which was significantly lower than that in the RBAC group (79.2%, p = 0.000). Conclusion: The efficacy of VA dual therapy is noninferior to RBAC in H. pylori first-line eradication, with fewer adverse reactions. Registration: This study was registered at the Chinese Clinical Trial Registry (ChiCTR2100052550) on 30 October 2021.

6.
Food Chem ; 417: 135786, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-36921365

ABSTRACT

This study aimed to systematically investigate the changes in peel color, physicochemical characteristics, textural properties, and peel ultrastructure between CaCl2-treated and water-soaked passion fruit under short-term storage at room temperature (20 °C) for eight days. The fruit peel was further analyzed and compared for the differences in calmodulin (CaM) gene expression between the two groups. The data were analyzed using principal component analysis. The results confirmed that CaCl2 treatment effectively maintained the appearance and color of passion fruit, inhibited peel browning, and improved fruit quality. The treatment had an effect on maintaining the physiological properties of passion fruit parenchyma, effectively delayed the passion fruit senescence, and kept the structural integrity of the fruit peel. The relative expression of PeCaM gene in the CaCl2-treated fruit peels was higher than that of the control peels. The Ca2+ stimulated the relative expression of the PeCaM gene, which delayed the senescence of passion fruit.


Subject(s)
Fruit , Passiflora , Fruit/chemistry , Calcium Chloride , Passiflora/chemistry
7.
Helicobacter ; 28(2): e12947, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36650673

ABSTRACT

BACKGROUND: The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin. OBJECTIVE: To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies. DESIGN: Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13 C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing. RESULTS: A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline. CONCLUSIONS: For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Hypersensitivity , Humans , Helicobacter Infections/drug therapy , Amoxicillin/therapeutic use , Feasibility Studies , Anti-Bacterial Agents/therapeutic use , Tetracycline/therapeutic use , Penicillins/therapeutic use , Drug Therapy, Combination , Treatment Outcome , Clarithromycin/therapeutic use , Proton Pump Inhibitors/therapeutic use
8.
Front Plant Sci ; 13: 965345, 2022.
Article in English | MEDLINE | ID: mdl-36035718

ABSTRACT

Postharvest quality of litchi reduces rapidly during storage at room temperature. This study aimed to investigate the effect of melatonin treatment on postharvest quality and oxidative stress markers of litchi fruit during cold storage. The "Feizixiao" litchi was treated with melatonin solution concentrations of 0.2 and 0.6 mmol·L-1 and then stored at 4°C for 12 days. The results confirmed that the melatonin treatment effectively maintained the appearance and color of the litchi fruit, suppressed the peel browning, and improved the litchi quality. The treatment also significantly enhanced the levels of endogenous melatonin, antioxidant components (total phenolics, flavonoids, and anthocyanin), and antioxidant enzyme activities of the fruit. It also inhibited the other oxidative stress markers, such as O 2 - , H2O2, MDA, and protein carbonyl content, and upregulated the expressions of antioxidant and Msr-related genes. Correlation and principal component analyses further confirmed that the melatonin treatment effectively delayed the fruit senescence by enhancing the antioxidant enzyme activities and modulating peel browning and reactive oxygen species metabolism of the litchi fruit via regulating gene expression of the related enzymes (SOD and PPO). These findings suggested that the exogenous application of melatonin to litchi during the postharvest is an ideal way to preserve the fruit quality and delay fruit senescence.

9.
Helicobacter ; 26(4): e12804, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33860967

ABSTRACT

BACKGROUND: Antibiotic resistance is the main cause of Helicobacter pylori (H. pylori) treatment failure. This study aimed to explore the characteristics of antibiotic resistance of H. pylori isolates in Beijing in the last 8 years and to estimate the impact of previous eradication failure on resistance patterns. MATERIALS AND METHODS: This retrospective study included data from a single center in Beijing from 2013 to 2020. Antibiotic susceptibility of 365 clinical H. pylori isolates was tested for amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline. The characteristics of the included patients and their previous eradication history were collected. Primary and secondary resistance rates of H. pylori to the six antibiotics and the impact of previous eradication failure on antibiotic resistance patterns were analyzed. RESULTS: The overall primary resistance rates of amoxicillin, clarithromycin, metronidazole, levofloxacin, moxifloxacin, and tetracycline were 0.7%, 55.2%, 68.0%, 49.7%, 64.5%, and 0%, with no significant increase during the observed period; while the secondary resistance rates were 3.2%, 96.7%, 90.7%, 93.1%, 80.0%, and 0%, respectively. The secondary resistance rate of clarithromycin (p < .001), metronidazole (p = .001), and levofloxacin (p < .001) significantly increased to 100% as the number of previous eradication therapies increased and exhibited a linear association. For strains naive to eradication, only 6.8% were susceptible to all the antibiotics, while 32.4% were single resistant, and 60.8% dual or multiple resistant. Clarithromycin+metronidazole+fluoroquinolone multiple resistance was the predominant pattern (0 course: 21.6%, 1 course: 37.5%, 2 courses: 56.1%, ≥3 courses: 71.1%; p < .001) for patients with treatment failure. The prevalence of dual or multiple-resistance patterns increased significantly as the number of previous therapies increased. CONCLUSIONS: The prevalence of primary and secondary resistance rates of clarithromycin, metronidazole, moxifloxacin, and levofloxacin were high in Beijing. Multiple-resistance patterns were common after treatment failure. Resistance rates of amoxicillin and tetracycline remained low and stable.


Subject(s)
Drug Resistance, Multiple, Bacterial , Helicobacter Infections , Helicobacter pylori , Amoxicillin/pharmacology , Amoxicillin/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Beijing , Clarithromycin/pharmacology , Drug Resistance, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/drug effects , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter pylori/drug effects , Humans , Metronidazole/pharmacology , Microbial Sensitivity Tests , Retrospective Studies
10.
Environ Sci Technol ; 53(14): 8324-8332, 2019 Jul 16.
Article in English | MEDLINE | ID: mdl-31241322

ABSTRACT

A novel method of ultraviolet-heat synergistically catalyzing H2O2-X (X: NaCl, NaBr, HCl, and HBr) for removal of elemental mercury (Hg0) was developed. In terms of Hg0 removal efficiency and economy, HCl and HBr were the suitable additives. Hg0 removal efficiencies reached 93.6% for H2O2-HCl and 91.4% for H2O2-HBr, the concentrations of H2O2, HCl and HBr were 1 M, 4.2 mM and 0.5 mM. The doses of gaseous Cl and Br-oxidants were 6.27 and 0.75 ppm. The costs by using H2O2-HCl and H2O2-HBr were 1,180 USD/lb-Hg0 and 1,170 USD/lb-Hg0. The best temperature for heat catalysis was 413 K. Hg0 removal was enhanced by 500 mg/m3 SO2 and 300 mg/m3 NO due to the formation of sulfuric and NO2. Mercury distribution analyses indicated that 500 mg/m3 SO2, 300 mg/m3 NO, and 6% O2 favored KCl retaining Hg2+. When the H2O2 concentration was adjusted to 3 M, the simultaneous removal efficiencies of NO and Hg0 reached 83.7% and 99.2% for H2O2-HCl, and 82.8% and 98.8% for H2O2-HBr. Electron spin resonance demonstrated that ClOH•-/BrOH•- and Cl2•-/Br2•- played leading roles in Hg0 oxidation, besides Cl2/Br2. The mercury forms in spent KCl were HgCl2, HgBr2, and HgNO3, according to X-ray photoelectron spectroscopy.


Subject(s)
Mercury , Catalysis , Hot Temperature , Hydrogen Peroxide , Oxidation-Reduction
11.
Food Sci Nutr ; 7(4): 1417-1425, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31024715

ABSTRACT

Isolated peanut protein (PPI) dispersions were pretreated by high pressure at 100, 300, and 500 MPa prior to enzymatic hydrolysis with alkaline protease (Alcalase). The degree of hydrolysis (DH) was determined by the pH-stat method, the hydrolysates profiles were analyzed by high-performance liquid chromatography (HPLC), the molecular weight distribution (MWD) was analyzed by gel filtration chromatogram (GFC), and content of SH/S-S and antioxidant activity of hydrolysates were evaluated. Results showed that HP pretreatment improved effectively the enzymatic hydrolysis of PPI, with an effective sequence of 300 > 100 > 500 MPa. However, no significant differences were observed in the peak pattern of HPLC profiles, but the peak times were earlier in HPLC profiles of the HP-treated protein. GFC analysis showed that more peptide fractions with low molecular weight appeared in the hydrolysates of the HP-treated PPI with increasing pressure. Moreover, the level of free SH of hydrolysates of the HP-treated PPI was relatively higher than non-HP-treated PPI. The hydrolysates of the HP-treated PPI exerted higher antioxidant activity (reducing power and DPPH radical scavenging) than the hydrolysates of non-HP-treated PPI. The results indicated that high pressure treatment affected the enzymatic hydrolysis of peanut protein and some protein structure properties and improved antioxidant activity of PPI hydrolysates.

12.
Sci Rep ; 8(1): 8812, 2018 06 11.
Article in English | MEDLINE | ID: mdl-29891956

ABSTRACT

The association between mucosal microbiota and HIV-1 infection has garnered great attention in the field of HIV-1 research. Previously, we reported a receptor-independent HIV-1 entry into epithelial cells mediated by a Gram-negative invasive bacterium, Porphyromonas gingivalis. Here, we present evidence showing that P. gingivalis outer membrane vesicles (OMVs) promote mucosal transmission of HIV-1. We demonstrated, using the Dynabeads technology, a specific interaction between HIV-1 and P. gingivalis OMVs which led to an OMV-dependent viral entry into oral epithelial cells. HIV-1 was detected in human oral keratinocytes (HOKs) after a 20 minute exposure to the HIV-vesicle complexes. After entry, most of the complexes appeared to dissociate, HIV-1 was reverse-transcribed, and viral DNA was integrated into the genome of HOKs. Meanwhile, some of the complexes exited the original host and re-entered neighboring HOKs and permissive cells of HIV-1. Moreover, P. gingivalis vesicles enhanced HIV-1 infection of MT4 cells at low infecting doses that are not able to establish an efficient infection alone. These findings suggest that invasive bacteria and their OMVs with ability to interact with HIV-1 may serve as a vehicle to translocate HIV through the mucosa, establish mucosal transmission of HIV-1, and enhance HIV-1 infectivity.


Subject(s)
Disease Transmission, Infectious , Epithelial Cells/virology , Extracellular Vesicles/metabolism , HIV Infections/transmission , HIV-1/physiology , Porphyromonas gingivalis/metabolism , Virus Internalization , Cells, Cultured , Humans , Models, Theoretical
13.
Biochim Biophys Acta Gen Subj ; 1861(5 Pt A): 1140-1151, 2017 May.
Article in English | MEDLINE | ID: mdl-28188859

ABSTRACT

Reactive oxygen species (ROS) play a role in aging and senescence in organisms. The oxidation of methionine (Met) residues in proteins to Met sulfoxide by ROS can cause conformational alteration and functional impairments. Met oxidation is reversed by Met sulfoxide reductase (Msr) A and B. Currently, the repair of oxidized proteins by Msr and Msr-mediated physiological functions are not well understood, especially in higher plants. The down-regulated expression of LcMsrA1/B1 may be involved in the senescence of litchi (Litchi chinensis) fruit. We verified that LcCaM1 is a substrate of LcMsrA1 and LcMsrB1 in vitro and in vivo, and oxidized LcCaM1 could be repaired by LcMsrA1 in combination with LcMsrB1. Moreover, LcMsrA1 and LcMsrB1 play important roles in repairing oxidized Met110 and Met125 residues, respectively, in LcCaM1. Furthermore, the Met oxidation in LcCaM1 did not affect its physical interactions with two LcCaM1-binding senescence-related transcription factors LcNAC13 and LcWRKY1, but enhanced their DNA-binding activities. Therefore, we hypothesized that the down-regulated expression of LcMsrA1/B1 results in the accelerated oxidation of LcCaM1, which enhanced the DNA-binding activities of LcNAC13 and LcWRKY1, thereby activating or repressing the expression of senescence-related genes.


Subject(s)
Calmodulin/metabolism , Cellular Senescence/physiology , Litchi/metabolism , Methionine/metabolism , Transcription Factors/metabolism , Amino Acid Sequence , DNA-Binding Proteins/metabolism , Down-Regulation/physiology , Methionine/analogs & derivatives , Methionine Sulfoxide Reductases/metabolism , Oxidation-Reduction , Plant Proteins/metabolism , Protein Binding/physiology , Reactive Oxygen Species/metabolism
14.
PLoS One ; 11(2): e0149618, 2016.
Article in English | MEDLINE | ID: mdl-26894834

ABSTRACT

Porphyromonas gingivalis is a keystone pathogen of periodontitis. One of its bacterial characteristics is the ability to invade various host cells, including nonphagocytic epithelial cells and fibroblasts, which is known to facilitate P. gingivalis adaptation and survival in the gingival environment. In this study, we investigated two small compounds, Alop1 and dynasore, for their role in inhibition of P. gingivalis invasion. Using confocal microscopy, we showed that these two compounds significantly reduced invasion of P. gingivalis and its outer membrane vesicles into human oral keratinocytes in a dose-dependent manner. The inhibitory effects of dynasore, a dynamin inhibitor, on the bacterial entry is consistent with the notion that P. gingivalis invasion is mediated by a clathrin-mediated endocytic machinery. We also observed that microtubule arrangement, but not actin, was altered in the host cells treated with Alop1 or dynasore, suggesting an involvement of microtubule in this inhibitory activity. This work provides an opportunity to develop compounds against P. gingivalis infection.


Subject(s)
Hydrazones/pharmacology , Mouth Mucosa/microbiology , Piperidines/pharmacology , Porphyromonas gingivalis/drug effects , Cells, Cultured , Dynamins/antagonists & inhibitors , Endocytosis/drug effects , Humans , Keratinocytes/drug effects , Keratinocytes/microbiology , Microtubules/microbiology , Porphyromonas gingivalis/physiology , Quinolizidines
15.
Zhonghua Yi Xue Za Zhi ; 96(4): 265-9, 2016 Jan 26.
Article in Chinese | MEDLINE | ID: mdl-26879785

ABSTRACT

OBJECTIVE: To evaluate the accuracy and effectiveness of Helicobacter pylori(H.pylori)antibody detection kit (immunoblot) in typing H. pylori strains, and to investigate the relationship between characteristics of H. pylori strains and clinical outcomes. METHODS: A total of 378 patients with upper gastrointestinal symptoms who had received gastroscopy and had pathological results within the period from March to August 2012 were collected from 6 centers in China.In all the patients, H. pylori antibody detection kit was used to detect and type serum H. pylori antibodies.The sensitivity, specificity, and accuracy of immunoblot in diagnosing H. pylori infection were evaluation in comparison to (13)C urea breath test (UBT) as the"gold standard". The results were also compared with those colloidal gold method.The relationship between H. pylori typing and clinical conditions was analyzed. RESULTS: Totally 378 patients were enrolled, in which 257 had H. pylori-positive (13)C UBT results, and 121 were negative.With (13)C UBT as the"gold standard", the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of H. pylori antibodies detection kit(immunoblot)were 97.7%, 86.8%, 94.0%, 94.6%, and 94.2%, respectively; the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of colloidal gold method were 84.4%, 92.6%, 96.0%, 73.7%, and 87.0%, respectively.In patients diagnosed as H. pylori-positive by (13)C UBT and immunoblot, 93.0%(53/57) in H. pylori eradication failure patients and 93.8%(182/194)in untreated patients were infected with type Ⅰ H. pylori as detected by immunoblot, with no statistically significant difference (P=0.764). The type Ⅰ strains positive rate was 94.2%(65/69), 89.9%(62/69)and 98.2% (55/56) in non-atrophy gastritis, atrophy gastritis, and duodenal ulcer untreated patients, respectively, the positive rate of type Ⅰ strains higher in duodenal ulcer cases than in gastritis ones, but with no statistically significant difference(P=0.185). CONCLUSIONS: Compared with the"gold standard"(13)C UBT, the accuracy of H. pylori antibody detection kit (immunoblot) and that of colloidal gold method are both fairly high.Different H. pylori strains may have significantly different potential in causing diseases, as typeⅠtrain appeared to be more virulent than type Ⅱ strain, especially in causing peptic ulcer.There was no obvious difference between eradication failure and untreated patients in terms of positive rate of type Ⅰ H. pylori strains, hence further study is needed to explore the relationship between type Ⅰ H. pylori and eradication rates.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Antibodies, Bacterial , Breath Tests , Duodenal Ulcer , Gastritis , Gastroscopy , Humans , Peptic Ulcer , Urea
16.
J Biol Chem ; 291(8): 4236-46, 2016 Feb 19.
Article in English | MEDLINE | ID: mdl-26742839

ABSTRACT

Tetherin, also known as bone marrow stromal antigen 2 (BST-2), inhibits the release of a wide range of enveloped viruses, including human immunodeficiency virus, type 1 (HIV-1) by directly tethering nascent virions to the surface of infected cells. The HIV-1 accessary protein Vpu counteracts tetherin restriction via sequestration, down-regulation, and/or displacement mechanisms to remove tetherin from sites of virus budding. However, the exact mechanism of Vpu-mediated antagonism of tetherin restriction remains to be fully understood. Here we report a novel role for the actin cross-linking regulator filamin A (FLNa) in Vpu anti-tetherin activities. We demonstrate that FLNa associates with tetherin and that FLNa modulates tetherin turnover. FLNa deficiency was found to enhance cell surface and steady-state levels of tetherin expression. In contrast, we observed that overexpression of FLNa reduced tetherin expression levels both on the plasma membrane and in intracellular compartments. Although FLNb shows high amino acid sequence similarity with FLNa, we reveal that only FLNa, but not FLNb, plays an essential role in tetherin turnover. We further showed that FLNa deficiency inhibited Vpu-mediated enhancement of virus release through interfering with the activity of Vpu to down-regulate cellular tetherin. Taken together, our studies suggest that Vpu hijacks the FLNa function in the modulation of tetherin to neutralize the antiviral factor tetherin. These findings may provide novel strategies for the treatment of HIV-1 infection.


Subject(s)
Antigens, CD/biosynthesis , Filamins/metabolism , Gene Expression Regulation , HIV-1/metabolism , Human Immunodeficiency Virus Proteins/metabolism , Viral Regulatory and Accessory Proteins/metabolism , Virus Release/physiology , Antigens, CD/genetics , Filamins/genetics , GPI-Linked Proteins/biosynthesis , GPI-Linked Proteins/genetics , HEK293 Cells , HIV-1/genetics , HeLa Cells , Human Immunodeficiency Virus Proteins/genetics , Humans , Viral Regulatory and Accessory Proteins/genetics
17.
Microbiologyopen ; 4(1): 53-65, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25524808

ABSTRACT

Porphyromonas gingivalis is a keystone periopathogen that plays an essential role in the progress of periodontitis. Like other gram-negative bacteria, the ability of P. gingivalis to produce outer membrane vesicles is a strategy used to interact with, and survive within its biological niches. Here we compared the protein components associated with vesicles derived from a fimbriated strain (33277) and an afimbriated strain (W83) of P. gingivalis using proteomic analyses. Some well-known virulence factors were identified in vesicles from both strains, such as gingipains and hemagglutinin. In contrast, FimC, FimD, and FimE, minor components of long fimbriae were found exclusively in 33277 vesicles, while proteins with a tetratricopeptide repeat (TPR) domain were unique to W83 vesicles. We found that significantly more 33277 than W83 vesicles were internalized into human oral keratinocytes and gingival fibroblasts. Interestingly, FimA, a well-known adhesin responsible for the attachment and invasion of P. gingivalis into host cells, was not essential for the invasive capabilities of P. gingivalis vesicles. Rather minor components of long fimbriae were required for an efficient invasive activity of vesicles. The most striking finding was that P. gingivalis strains lacking or having a reduced FimA expression showed a significant reduction in vesiculation. These results suggest that production and pathogenicity of P. gingivalis vesicles may largely depend on expression of the fim locus, and that the integration of vesicle production and pathogenicity with fimbrial expression may allow P. gingivalis to confer upon itself certain functional advantages.


Subject(s)
Fimbriae, Bacterial/physiology , Porphyromonas gingivalis/physiology , Transport Vesicles/metabolism , Fimbriae Proteins/biosynthesis , Fimbriae Proteins/metabolism , Fimbriae Proteins/physiology , Humans , Porphyromonas gingivalis/genetics , Porphyromonas gingivalis/pathogenicity , Protein Transport , Proteomics
18.
Zhonghua Yi Xue Za Zhi ; 94(8): 567-71, 2014 Mar 04.
Article in Chinese | MEDLINE | ID: mdl-24762682

ABSTRACT

OBJECTIVE: To evaluate the efficacy, compliance and adverse effects of 14-day amoxicillin and furazolidone-based quadruple regimen as rescue treatment for Helicobacter pylori (H.pylori) infection. METHODS: A total of 228 patients positive for H.pylori with previous failed treatment at least once were enrolled into this retrospective study. There were 71 males and 157 females, aged (50 ± 13) years. A 14-day quadruple regimen was administered along with furazolidone, amoxicillin and bismuth citrate in combination with proton pump inhibitors. Adverse effects were recorded at the end of treatment.H.pylori status was assessed by (13)C-urea breath test at 4 weeks after treatment. RESULTS: Among them, 206 patients completed treatment. The H.pylori eradication rates were 91.96% (206/224) and 90.35% (206/228) according to per-protocol (PP) and intention-to-treat (ITT) analyses respectively. Mild and moderate adverse effects such as dizziness, nausea and diarrhea occurred in 43 patients (18.86%). Four of them had to terminate their treatment due to rash, dizziness and headache respectively. CONCLUSIONS: The 14-day quadruple therapy with furazolidone, amoxicillin, bismuth citrate and proton pump inhibitors may be an effective regimen for rescue treatment because of its relatively high eradication rate (>90%). The patients should be watched closely during the treatment since the adverse effects of this regimen happen frequently. Treatment is stopped in events of skin rash, fever or other serious adverse effects.Vitamins B1 and B6 can relieve some discomforts.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Furazolidone , Helicobacter Infections/drug therapy , Adult , Amoxicillin/administration & dosage , Amoxicillin/adverse effects , Amoxicillin/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination , Female , Furazolidone/administration & dosage , Furazolidone/adverse effects , Furazolidone/therapeutic use , Helicobacter pylori , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
19.
J Infect Dis ; 207(7): 1171-80, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23303812

ABSTRACT

GB virus type C (GBV-C) is a single-stranded positive-sense RNA virus classified in the Flaviviridae family. Persistent coinfection with GBV-C is associated with lower human immunodeficiency virus type 1 (HIV-1) load, higher CD4(+) T-cell count, and prolonged survival in HIV-1 coinfected patients. The GBV-C envelope glycoprotein E2 has been reported to interfere with HIV-1 entry. In this study, we showed that the expression of GBV-C E2 inhibited HIV-1 Gag assembly and release. Expression of glycosylated GBV-C E2 inhibited HIV-1 Gag precursor processing, resulting in lower production of CAp24 and MAp17, while the overall expression level of the Gag precursor Pr55 remained unchanged. Membrane floatation gradient and indirect immunofluorescence confocal microscopy analysis showed that glycosylated E2 disrupted HIV-1 Gag trafficking to the plasma membrane, resulting in Gag accumulation in subcellular compartments. This interference in HIV-1 Gag trafficking led to diminished HIV-1 particle production, which is a critical step for HIV-1 to infect new host cells. These findings shed light on a novel mechanism used by GBV-C E2 to inhibit HIV-1 replication and may provide insight into new approaches for suppressing HIV-1 replication.


Subject(s)
Cell Membrane/metabolism , GB virus C/metabolism , HIV-1/metabolism , Viral Envelope Proteins/metabolism , Virus Assembly , gag Gene Products, Human Immunodeficiency Virus/metabolism , CD4 Lymphocyte Count , Cell Membrane/virology , Coinfection/virology , GB virus C/genetics , Glycosylation , HEK293 Cells , HIV Infections/metabolism , HIV Infections/virology , HIV-1/genetics , HIV-1/pathogenicity , HeLa Cells , Humans , Plasmids/genetics , Plasmids/metabolism , Protein Structure, Tertiary , Protein Transport , Transfection , Viral Envelope Proteins/genetics , Viral Load , Virus Release , gag Gene Products, Human Immunodeficiency Virus/genetics
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