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1.
Gut ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906695

RESUMEN

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.

2.
Helicobacter ; 28(2): e12947, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36650673

RESUMEN

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.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Hipersensibilidad , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Amoxicilina/uso terapéutico , Estudios de Factibilidad , Antibacterianos/uso terapéutico , Tetraciclina/uso terapéutico , Penicilinas/uso terapéutico , Quimioterapia Combinada , Resultado del Tratamiento , Claritromicina/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico
3.
Helicobacter ; 26(4): e12804, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33860967

RESUMEN

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.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/farmacología , Amoxicilina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Beijing , Claritromicina/farmacología , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/efectos de los fármacos , Humanos , Metronidazol/farmacología , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos
4.
Environ Sci Technol ; 53(14): 8324-8332, 2019 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-31241322

RESUMEN

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.


Asunto(s)
Mercurio , Catálisis , Calor , Peróxido de Hidrógeno , Oxidación-Reducción
5.
J Biol Chem ; 291(8): 4236-46, 2016 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-26742839

RESUMEN

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.


Asunto(s)
Antígenos CD/biosíntesis , Filaminas/metabolismo , Regulación de la Expresión Génica , VIH-1/metabolismo , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismo , Proteínas Reguladoras y Accesorias Virales/metabolismo , Liberación del Virus/fisiología , Antígenos CD/genética , Filaminas/genética , Proteínas Ligadas a GPI/biosíntesis , Proteínas Ligadas a GPI/genética , Células HEK293 , VIH-1/genética , Células HeLa , Proteínas del Virus de la Inmunodeficiencia Humana/genética , Humanos , Proteínas Reguladoras y Accesorias Virales/genética
6.
Biochim Biophys Acta Gen Subj ; 1861(5 Pt A): 1140-1151, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28188859

RESUMEN

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.


Asunto(s)
Calmodulina/metabolismo , Senescencia Celular/fisiología , Litchi/metabolismo , Metionina/metabolismo , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo/fisiología , Metionina/análogos & derivados , Metionina Sulfóxido Reductasas/metabolismo , Oxidación-Reducción , Proteínas de Plantas/metabolismo , Unión Proteica/fisiología , Especies Reactivas de Oxígeno/metabolismo
7.
Zhonghua Yi Xue Za Zhi ; 96(4): 265-9, 2016 Jan 26.
Artículo en Zh | MEDLINE | ID: mdl-26879785

RESUMEN

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.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Anticuerpos Antibacterianos , Pruebas Respiratorias , Úlcera Duodenal , Gastritis , Gastroscopía , Humanos , Úlcera Péptica , Urea
8.
Zhonghua Yi Xue Za Zhi ; 94(8): 567-71, 2014 Mar 04.
Artículo en Zh | MEDLINE | ID: mdl-24762682

RESUMEN

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.


Asunto(s)
Amoxicilina , Antibacterianos , Furazolidona , Infecciones por Helicobacter/tratamiento farmacológico , Adulto , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Femenino , Furazolidona/administración & dosificación , Furazolidona/efectos adversos , Furazolidona/uso terapéutico , Helicobacter pylori , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
9.
J Infect Dis ; 207(7): 1171-80, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23303812

RESUMEN

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.


Asunto(s)
Membrana Celular/metabolismo , Virus GB-C/metabolismo , VIH-1/metabolismo , Proteínas del Envoltorio Viral/metabolismo , Ensamble de Virus , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo , Recuento de Linfocito CD4 , Membrana Celular/virología , Coinfección/virología , Virus GB-C/genética , Glicosilación , Células HEK293 , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/genética , VIH-1/patogenicidad , Células HeLa , Humanos , Plásmidos/genética , Plásmidos/metabolismo , Estructura Terciaria de Proteína , Transporte de Proteínas , Transfección , Proteínas del Envoltorio Viral/genética , Carga Viral , Liberación del Virus , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética
10.
Therap Adv Gastroenterol ; 17: 17562848241258021, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846173

RESUMEN

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.

11.
J Virol ; 86(20): 11242-53, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22875976

RESUMEN

Adaptor protein complex 3 (AP-3) is a heterotetramer that is involved in signal-mediated protein sorting to endosomal-lysosomal organelles. AP-3 deficiency in humans, induced by mutations in the AP3B1 gene, which encodes the ß3A subunit of the AP-3 complex, results in Hermansky-Pudlak syndrome 2 (HPS2), which is a rare genetic disorder with defective lysosome-related organelles. In a previous study, we identified the AP-3 complex as an important contributor to HIV-1 assembly and release. We hypothesized that cells from patients affected by HPS2 should demonstrate abnormalities of HIV-1 assembly. Here we report that HIV-1 particle assembly and release are indeed diminished in HPS2 fibroblast cultures. Transient or stable expression of the full-length wild-type ß3A subunit in HPS2 fibroblasts restored the impaired virus assembly and release. In contrast, virus-like particle release mediated by MA-deficient Gag mutants lacking the AP-3 binding site was not altered in HPS2 cells, indicating that the MA domain serves as the major viral determinant required for the recruitment of the AP-3 complex. AP-3 deficiency decreased HIV-1 Gag localization at the plasma membrane and late endosomes and increased the accumulation of HIV-1 Gag at an intermediate step between early and late endosomes. Blockage of the clathrin-mediated endocytic pathway in HPS2 cells did not reverse the inhibited virus assembly and release imposed by the AP-3 deficiency. These results demonstrate that the intact and stable AP-3 complex is required for HIV-1 assembly and release, and the involvement of the AP-3 complex in late stages of the HIV-1 replication cycle is independent of clathrin-mediated endocytosis.


Asunto(s)
Complejo 3 de Proteína Adaptadora/metabolismo , Subunidades delta de Complexo de Proteína Adaptadora/metabolismo , VIH-1/fisiología , Síndrome de Hermanski-Pudlak , Ensamble de Virus , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo , Complejo 3 de Proteína Adaptadora/deficiencia , Complejo 3 de Proteína Adaptadora/genética , Subunidades delta de Complexo de Proteína Adaptadora/deficiencia , Subunidades delta de Complexo de Proteína Adaptadora/genética , Membrana Celular/metabolismo , Membrana Celular/virología , Células Cultivadas , Clatrina/antagonistas & inhibidores , Endocitosis , Fibroblastos/virología , VIH-1/metabolismo , Síndrome de Hermanski-Pudlak/genética , Síndrome de Hermanski-Pudlak/metabolismo , Síndrome de Hermanski-Pudlak/virología , Humanos , Mutación , Transducción de Señal , Piel/virología , Liberación del Virus/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética
12.
Therap Adv Gastroenterol ; 16: 17562848231190976, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37664169

RESUMEN

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.

13.
Food Chem ; 417: 135786, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-36921365

RESUMEN

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.


Asunto(s)
Frutas , Passiflora , Frutas/química , Cloruro de Calcio , Passiflora/química
14.
Food Chem X ; 20: 100913, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-38144747

RESUMEN

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.

15.
J Acquir Immune Defic Syndr ; 94(2S): S42-S46, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37707847

RESUMEN

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.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Tennessee/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Instituciones Académicas , Estudiantes
16.
J Biol Chem ; 286(32): 28498-510, 2011 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-21705339

RESUMEN

HIV-1 Gag precursor directs virus particle assembly and release. In a search for Gag-interacting proteins that are involved in late stages of the HIV-1 replication cycle, we performed yeast two-hybrid screening against a human cDNA library and identified the non-muscle actin filament cross-linking protein filamin A as a novel Gag binding partner. The 280-kDa filamin A regulates cortical actin network dynamics and participates in the anchoring of membrane proteins to the actin cytoskeleton. Recent studies have shown that filamin A facilitates HIV-1 cell-to-cell transmission by binding to HIV receptors and coreceptors and regulating their clustering on the target cell surface. Here we report a novel role for filamin A in HIV-1 Gag intracellular trafficking. We demonstrate that filamin A interacts with the capsid domain of HIV-1 Gag and that this interaction is involved in particle release in a productive manner. Disruption of this interaction eliminated Gag localization at the plasma membrane and induced Gag accumulation within internal compartments. Moreover, blocking clathrin-dependent endocytic pathways did not relieve the restriction to particle release induced by filamin A depletion. These results suggest that filamin A is involved in the distinct step of the Gag trafficking pathway. The discovery of the Gag-filamin A interaction may provide a new therapeutic target for the treatment of HIV infection.


Asunto(s)
Proteínas Contráctiles/metabolismo , Infecciones por VIH/mortalidad , VIH-1/fisiología , Proteínas de Microfilamentos/metabolismo , Ensamble de Virus/fisiología , Clatrina/genética , Clatrina/metabolismo , Proteínas Contráctiles/genética , Endocitosis/genética , Filaminas , Biblioteca de Genes , Infecciones por VIH/genética , Infecciones por VIH/transmisión , VIH-1/patogenicidad , Células HeLa , Humanos , Proteínas de Microfilamentos/genética , Transporte de Proteínas/genética , Saccharomyces cerevisiae , Técnicas del Sistema de Dos Híbridos , Ensamble de Virus/efectos de los fármacos , Productos del Gen gag del Virus de la Inmunodeficiencia Humana
17.
Anal Bioanal Chem ; 402(3): 1347-54, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22105299

RESUMEN

Fusarium proliferatum was isolated as a major pathogen causing the Fusarium disease in harvested banana fruit. One of its major compounds, fusaric acid, was identified by high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS). Because the light intensity of the luminescent bacterium Vibrio qinghaiensis sp. Nov. Q67 can be inhibited by fusaric acid, the fusaric acid content of F. proliferatum was assessed and compared by both the HPLC and luminescent bacterium methods. Although both methods afforded almost similar values of fusaric acid, the latter indicated slightly lower content than the former. Czapek medium was more suitable for the growth of F. proliferatum and fusaric acid production than modified Richard medium, with an optimum pH of approximately 7.0. However, no significant (P < 0.05) correlation was obtained between the fusaric acid production and growth of mycelia of F. proliferatum. The study suggests that the bioevaluation by use of the luminescent bacterium was effective in monitoring fusaric acid production by F. proliferatum without expensive equipment.


Asunto(s)
Ácido Fusárico/aislamiento & purificación , Fusarium/aislamiento & purificación , Mediciones Luminiscentes/métodos , Musa/microbiología , Enfermedades de las Plantas/microbiología , Vibrio/química , Cromatografía Líquida de Alta Presión/métodos , Ácido Fusárico/metabolismo , Fusarium/metabolismo , Espectrometría de Masa por Ionización de Electrospray/métodos
18.
Front Plant Sci ; 13: 965345, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36035718

RESUMEN

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.

19.
Molecules ; 15(2): 680-8, 2010 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-20335938

RESUMEN

Harvested longan (Dimocarpus longan Lour.) fruit are susceptible to decay caused by both bacterial and fungal infections. Ochratoxin A (OTA) is a kind of mycotoxin produced by a number of fungi. In this study, OTA was extracted from longan fruit pulp by 80% methanol and then loaded on C-18 solid-phase extraction columns. The extract solution was then analyzed by high-performance liquid chromatography - fluorescence detection (HPLC-FD) and an electron spray ionization-mass spectrometry (ESI-MS), respectively. The HPLC-FD analysis showed that a compound similar to OTA might exist in longan fruit pulp, but further analysis by the ESI-MS method demonstrated that OTA was not present in the longan pulp, indicating that the presence of OTA in longan fruit pulp detected by the HPLC-FD analysis needed to be confirmed by the ESI-MS method.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Frutas/química , Ocratoxinas/análisis , Extractos Vegetales/química , Sapindaceae/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Fluorescencia , Ocratoxinas/química , Estándares de Referencia
20.
Helicobacter ; 14(2): 128-33, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19298340

RESUMEN

BACKGROUND: The prevalence of Helicobacter pylori is higher in developing countries such as China. The aim of this study was to investigate the prevalence of H. pylori in one rural and one urban region of Beijing, China. MATERIALS AND METHODS: Healthy individuals in rural Pinggu and urban Haidian voluntarily participated in this study. The diagnosis of H. pylori infection was reached using the (13)C-urea breath test. Associations between H. pylori and sex, age, living area (i.e. rural vs urban), education level, smoking, and alcohol consumption were evaluated. RESULTS: Of the 1232 included subjects, 54.7% of tested individuals residing in Pinggu and 41.3% in Haidian were positive for H. pylori. In urban region, more individuals were negative for H. pylori (429 of 731), whereas in the rural region, more individuals were positive for H. pylori (p < .05). Univariate analysis identified geographic area and lower education and annual income as significant factors associated with H. pylori. Men in rural areas were more likely than women in rural areas to be infected, and both men and women in the rural area were more likely to be positive for H. pylori than men and women in the urban area (all p < .05). CONCLUSIONS: H. pylori infection is common in both rural and urban regions of Beijing. Residing in a rural area, having a lower family income, and lower education level are significant risk factors associated with infection.


Asunto(s)
Infecciones por Helicobacter/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , China/epidemiología , Femenino , Infecciones por Helicobacter/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Salud Rural , Salud Urbana , Adulto Joven
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