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1.
Cancer Med ; 13(14): e70023, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39001679

RESUMEN

BACKGROUND: Meta-analyses have primarily focused on the effects of exercise-based prehabilitation on postoperative outcomes and ignored the role of nutritional intervention. In this study, we filled this gap by investigating the effect of nutrition-based prehabilitation on the postoperative outcomes of patients who underwent esophagectomy and gastrectomy. METHODS: Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched. Adults diagnosed with esophagogastric cancer who were scheduled to undergo surgery and had undergone uni- or multimodal prehabilitation, with at least a week of mandatory nutritional intervention, were included. Forest plots were used to extract and visualize the data from the included studies. The occurrence of any postoperative complication was considered the primary endpoint. RESULTS: Eight studies met the eligibility criteria, with five randomized controlled trials (RCTs) and three cohort studies. In total, 661 patients were included. Any prehabilitation, that is, unimodal (only nutrition) and multimodal prehabilitation, collectively decreased the risk of any postoperative complication by 23% (95% confidence interval [CI] = 0.66-0.90). A similar effect was exclusively observed for multimodal prehabilitation (risk ratio [RR] = 0.78, 95% CI = 0.66-0.93); however, it was not significant for unimodal prehabilitation. Any prehabilitation significantly decreased the length of hospital stay (LOS) (weighted mean difference = -0.77, 95% CI = -1.46 to -0.09). CONCLUSIONS: Nutrition-based prehabilitation, particularly multimodal prehabilitation, confers protective effects against postoperative complications after esophagectomy and gastrectomy. Our findings suggest that prehabilitation slightly decreases LOS; however, the finding is not clinically significant. Therefore, additional rigorous RCTs are warranted for further substantiation.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Gastrectomía , Complicaciones Posoperatorias , Ejercicio Preoperatorio , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/cirugía , Neoplasias Gástricas/cirugía , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Esofagectomía/efectos adversos , Esofagectomía/rehabilitación , Gastrectomía/efectos adversos , Resultado del Tratamiento , Tiempo de Internación , Cuidados Preoperatorios/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estado Nutricional
2.
J Med Microbiol ; 73(7)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38973691

RESUMEN

Introduction. Aminoglycoside antibiotics such as amikacin and kanamycin are important components in the treatment of Mycobacterium tuberculosis (Mtb) infection. However, more and more clinical strains are found to be aminoglycoside antibiotic-resistant. Apramycin is another kind of aminoglycoside antibiotic that is commonly used to treat infections in animals.Hypothesis. Apramycin may have in vitro activity against Mtb.Aim. This study aims to evaluate the efficacy of apramycin against Mtb in vitro and determine its epidemiological cut-off (ECOFF) value.Methodology. One hundred Mtb isolates, including 17 pansusceptible and 83 drug-resistant tuberculosis (DR-TB) strains, were analysed for apramycin resistance using the MIC assay.Results. Apramycin exhibited significant inhibitory activity against Mtb clinical isolates, with an MIC50 of 0.5 µg ml-1 and an MIC90 of 1 µg ml-1. We determined the tentative ECOFF value as 1 µg ml-1 for apramycin. The resistant rates of multidrug-resistant tuberculosis (MDR-TB), pre-extensively drug-resistant (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains were 12.12 % (4/33), 20.69 % (6/29) and 66.67 % (14/21), respectively. The rrs gene A1401G is associated with apramycin resistance, as well as the cross-resistance between apramycin and other aminoglycosides.Conclusion. Apramycin shows high in vitro activity against the Mtb clinical isolates, especially the MDR-TB clinical isolates. This encouraging discovery calls for more research on the functions of apramycin in vivo and as a possible antibiotic for the treatment of drug-resistant TB.


Asunto(s)
Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Nebramicina , Nebramicina/análogos & derivados , Nebramicina/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Humanos , Antituberculosos/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Farmacorresistencia Bacteriana Múltiple
3.
Diagn Microbiol Infect Dis ; 110(2): 116435, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39032320

RESUMEN

PURPOSE: Mycobacterium abscessus complex (MABC) infections are increasing worldwide. Furthermore, these infections have a low treatment success rate due to their resistance to many current antibiotics. This study aimed to determine the overall in vitro activity of the tetracyclines doxycycline (DOX), minocycline (MIN), and tigecycline (TGC) against MABC clinical isolates. PATIENTS AND METHODS: A systematic review of PubMed/MEDLINE, Web of Science, and Embase was conducted up to August 28, 2023. Studies applying the drug susceptibility testing standards of the Clinical and Laboratory Standards Institute were considered. A random effects model was used to assess the total in vitro resistance rates of the MABC clinical isolates to DOX, MIN, and TGC. The I2 and Cochran's Q statistics were employed to evaluate the origins of heterogeneity. All analyses were conducted using CMA V.3 software. RESULTS: Twenty-six publications (22, 12, and 11 studies on DOX, MIN, and TGC, respectively) were included. The pooled in vitro resistance rates of the MABC clinical isolates to DOX and MIN at the breakpoint of 8 µg/mL were 93.0 % (95 % CI, 89.2 %-95.5 %) and 87.2 % (95 % CI, 76.5 %-93.4 %), respectively. In the case of TGC, the breakpoints of 2, 4, and 8 µg/mL were associated with pooled resistance rates of 2.5 % (95 % CI, 0.5 %-11.6 %), 7.2 % (95 % CI, 4.0 %-12.5 %), and 16.8 % (95 % CI, 4.7 %-45.0 %), respectively. CONCLUSION: Among the three examined tetracyclines, MABC exhibited extremely high resistance rates to DOX and MIN, thereby limiting their use in treating MABC infections. Conversely, MABC showed an increased susceptibility rate to TGC, highlighting TGC administration as a viable treatment option for patients with MABC infections.

4.
Clin Pharmacokinet ; 63(7): 1055-1063, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38990504

RESUMEN

INTRODUCTION: Isoniazid is a first-line antituberculosis agent with high variability, which would profit from individualized dosing. Concentrations of isoniazid at 2 h (C2h), as an indicator of safety and efficacy, are important for optimizing therapy. OBJECTIVE: The objective of this study was to establish machine learning (ML) models to predict the C2h, that can be used for establishing an individualized dosing regimen in clinical practice. METHODS: Published population pharmacokinetic (PopPK) models for adults were searched based on PubMed and ultimately four reliable models were selected for simulating individual C2h datasets under different conditions (demographics, genotype, ethnicity, etc.). Machine learning models were trained on simulated C2h obtained from the four PopPK models. Five different algorithms were used for ML model building to predict C2h. Real-world data were used for predictive performance evaluations. Virtual trials were used to compare ML-optimized doses with PopPK model-optimized doses. RESULTS: Categorical boosting (CatBoost) exhibited the highest prediction ability. Target C2h can be predicted using the ML model combined with the dosing regimen and three covariates (N-acetyltransferase 2 [NAT2] genotypes, weight and race [Asians and Africans]). Real-world data validation results showed that the ML model can achieve an overall prediction accuracy of 93.4%. Using the final ML model, the mean absolute prediction error value decreased by 45.7% relative to the average of PopPK models. Using the ML-optimized dosing regimen, the probability of target attainment increased by 43.7% relative to the PopPK model-optimized dosing regimens. CONCLUSION: Machine learning models were developed with great predictive performance, which can be used to determine the individualized initial dose of isoniazid in adult patients.


Asunto(s)
Antituberculosos , Isoniazida , Aprendizaje Automático , Tuberculosis , Humanos , Isoniazida/farmacocinética , Isoniazida/administración & dosificación , Antituberculosos/farmacocinética , Antituberculosos/administración & dosificación , Tuberculosis/tratamiento farmacológico , Modelos Biológicos , Adulto , Medicina de Precisión/métodos , Relación Dosis-Respuesta a Droga , Arilamina N-Acetiltransferasa/genética , Algoritmos
5.
J Med Microbiol ; 73(7)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39028256

RESUMEN

Introduction. Pre-existing fluoroquinolones (FQs) resistance is a major threat in treating multidrug-resistant (MDR) tuberculosis. Sitafloxacin (Sfx) is a new broad-spectrum FQ.Hypothesis. Sfx is more active against drug-resistant Mycobacterium tuberculosis (Mtb) isolates.Aim. To determine whether there is cross-resistance between Sfx and ofloxacin (Ofx), levofloxacin (Lfx) and moxifloxacin (Mfx) in MDR Mtb.Methods. A total of 106 clinical Mtb isolates, including 23 pan-susceptible and 83 MDR strains, were analysed for Sfx, Lfx and Mfx resistance using MIC assay. The isolates were also subjected to whole-genome sequencing to analyse drug-resistant genes.Results. Sfx exhibited the most robust inhibition activity against Mtb clinical isolates, with a MIC50 of 0.0313 µg ml-1 and MIC90 of 0.125 µg ml-1, which was lower than that of Mfx (MIC50 = 0.0625 µg ml-1, MIC90 = 1 µg ml-1) and Lfx (MIC50 = 0.125 µg ml-1, MIC90 = 2 µg ml-1). We determined the tentative epidemiological cut-off values as 0.5 µg ml-1 for Sfx. Also, 8.43% (7/83), 43.37% (36/83), 42.17% (35/83) and 51.81% (43/83) MDR strains were resistant to Sfx, Mfx, Lfx and Ofx, respectively. Cross-resistance between Ofx, Lfx and Mfx was 80.43% (37/46). Only 15.22% (7/46) of the pre-existing FQs resistance isolates were resistant to Sfx. Among the 30 isolates with mutations in gyrA or gyrB, 5 (16.67%) were Sfx resistant. The combination of Sfx and rifampicin could exert partial synergistic effects, and no antagonism between Sfx and six clinically important anti-Mtb antibiotics was evident.Conclusion. Sfx exhibited superior activity against MDR isolates comparing to Lfx and Mfx, and could potentially overcome the majority pre-existing FQs resistance in Mtb strains.


Asunto(s)
Antituberculosos , Farmacorresistencia Bacteriana Múltiple , Fluoroquinolonas , Levofloxacino , Pruebas de Sensibilidad Microbiana , Moxifloxacino , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Fluoroquinolonas/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Moxifloxacino/farmacología , Levofloxacino/farmacología , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/farmacología , Secuenciación Completa del Genoma
6.
Heliyon ; 10(11): e31757, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38845977

RESUMEN

Background: The prevalence of nontuberculous mycobacterial (NTM) disease in children is increasing worldwide. The clinical manifestations of pediatric NTM patients are significantly different from those of adult patients, but the knowledge of the disease is generally poor. Methods: English databases (PubMed, Web of Science, Embase, BIOSIS) and Chinese databases (CNKI, Wanfan, VIP) were searched on October 15th, 2022. All the articles of cross-sectional and cohort studies reporting the species composition and lesion site of the NTM disease in children using well-recognized NTM species identification methods were taken into account. Using a random effects model, we assessed the disease lesion sites and the prevalence of different NTM species in pediatric NTM disease. Sources of heterogeneity were analyzed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. Results: The prevalence rates of NTM disease in children ranged between 0.6 and 5.36/100,000 in different countries, and Europe reported the highest prevalence rate. The most common clinical lesion site was lymph node, accounting for 71.1 % (55.0 %-83.2 %), followed by lung (19.3 %, 9.8%-34.4 %)and then skin and soft tissue (16.6 %,13.5%-20.3 %). Mycobacterium avium complex (MAC) was the most isolated NTM pathogen in children, accounting for 54.9 % (39.4%-69.6 %). Inconsistent with adult patients, Mycobacterium avium accounted for a dominant proportion in MAC than Mycobacterium intracellulare. Conclusions: The lymph node was the most affected organ in pediatric NTM disease, while Mycobacterium avium was the most isolated pathogenic species in children.

7.
Front Plant Sci ; 15: 1377793, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38855463

RESUMEN

The mutualistic plant rhizobacteria which improve plant development and productivity are known as plant growth-promoting rhizobacteria (PGPR). It is more significant due to their ability to help the plants in different ways. The main physiological responses, such as malondialdehyde, membrane stability index, relative leaf water content, photosynthetic leaf gas exchange, chlorophyll fluorescence efficiency of photosystem-II, and photosynthetic pigments are observed in plants during unfavorable environmental conditions. Plant rhizobacteria are one of the more crucial chemical messengers that mediate plant development in response to stressed conditions. The interaction of plant rhizobacteria with essential plant nutrition can enhance the agricultural sustainability of various plant genotypes or cultivars. Rhizobacterial inoculated plants induce biochemical variations resulting in increased stress resistance efficiency, defined as induced systemic resistance. Omic strategies revealed plant rhizobacteria inoculation caused the upregulation of stress-responsive genes-numerous recent approaches have been developed to protect plants from unfavorable environmental threats. The plant microbes and compounds they secrete constitute valuable biostimulants and play significant roles in regulating plant stress mechanisms. The present review summarized the recent developments in the functional characteristics and action mechanisms of plant rhizobacteria in sustaining the development and production of plants under unfavorable environmental conditions, with special attention on plant rhizobacteria-mediated physiological and molecular responses associated with stress-induced responses.

8.
Cell Death Discov ; 10(1): 240, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38762546

RESUMEN

Interactions of tumor cells with immune cells in the tumor microenvironment play an important role during malignancy progression. We previously identified that GAS5 inhibited tumor development by suppressing proliferation of tumor cells in non-small cell lung cancer (NSCLC). Herein, we discovered a tumor-suppressing role for tumor cell-derived GAS5 in regulating tumor microenvironment. GAS5 positively coordinated with the infiltration of macrophages and T cells in NSCLC clinically, and overexpression of GAS5 promoted macrophages and T cells recruitment both in vitro and in vivo. Mechanistically, GAS5 stabilized p53 by directly binding to MYBBP1A and facilitating MYBBP1A-p53 interaction, and enhanced p53-mediated transcription of IRF1, which activated type I interferon signaling and increased the production of downstream CXCL10 and CCL5. We also found that activation of type I interferon signaling was associated with better immunotherapy efficacy in NSCLC. Furthermore, the stability of GAS5 was regulated by NAT10, the key enzyme responsible for N4-acetylcytidine (ac4C) modification, which bound to GAS5 and mediated its ac4C modification. Collectively, tumor cell-derived GAS5 could activate type I interferon signaling via the MYBBP1A-p53/IRF1 axis, promoting immune cell infiltration and potentially correlating with immunotherapy efficacy, which suppressed NSCLC progression. Our results suggested GAS5 as a promising predictive marker and potential therapeutic target for combination therapy in NSCLC. A schematic diagram demonstrating the regulatory effect of GAS5 on immune cell infiltration by activating type I interferon signaling via MYBBP1A-p53/IRF1 axis in non-small cell lung cancer. IFN, interferon.

9.
Microbiol Spectr ; 12(6): e0385923, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38738892

RESUMEN

This study aimed to assess the possible causes of discordant results between Xpert MTB/RIF (Xpert) and Bactec MGIT 960 Culture System (MGIT960) regarding rifampicin (RIF) susceptibility in Mycobacterium tuberculosis. Patients with previous RIF-resistant tuberculosis who were admitted to Wenzhou Central Hospital from January 2020 to December 2022 were enrolled. The isolates obtained from these patients were subjected to RIF susceptibility tests using Xpert and MGIT960, and the minimum inhibitory concentration (MIC) of RIF was determined by the MYCOTB MIC plate test. Additionally, molecular docking and molecular dynamics (MD) simulations were performed to evaluate the binding efficacy of rpoB and RIF based on rpoB mutations detected in the isolates with discordant RIF susceptibility results. A total of 28 isolates with discordant RIF susceptibility test results were detected, 15 of them were RIF susceptible with MICs ≤ 0.5 µg/mL. Twelve out of 15 isolates contained borderline RIF resistance-associated mutations [L430P (n = 6), H445N (n = 6)], 1 isolate had D435Y and Q429H double mutation, and the remaining 2 isolates had a silent (Q432Q) mutation. Compared with the affinity of RIF toward the wild type (WT) (-45.83 kcal/mol) by MD, its affinity toward L452P (-55.52 kcal/mol), D435Y (-47.39 kcal/mol), L430P (approximately -69.72 kcal/mol), H445N (-49.53 kcal/mol), and Q429H (-55.67 kcal/mol) increased. Borderline RIF resistance-associated mutations were the main cause for the discordant RIF susceptibility results between Xpert and MGIT960, and the mechanisms of the resistance need further investigated.IMPORTANCEThis study is aimed at assessing discordant results between Xpert MTB/RIF (Xpert) assay and Bactec MGIT 960 Culture System (MGIT960) regarding the detection of rifampicin (RIF)-resistant Mycobacterium tuberculosis isolates in Wenzhou, China. The discordant results of RIF between these two assays were mainly caused by borderline RIF resistance-associated mutations, subsequently by silent mutations of rpoB. Borderline RIF resistance- associated mutations detected in our study were demonstrated to not be affected by the affinity of rpoB and RIF by molecular dynamics, and the mechanism of resistance was needed to be clarified. For the discordant results of RIF by Xpert and MGIT960 that occurred, rpoB DNA sequencing was recommended to investigate its association with resistance to RIF.


Asunto(s)
Proteínas Bacterianas , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/farmacología , Humanos , China , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Antituberculosos/farmacología , ARN Polimerasas Dirigidas por ADN/genética , Farmacorresistencia Bacteriana/genética , Simulación del Acoplamiento Molecular
11.
Food Chem ; 450: 139352, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38640532

RESUMEN

Gelatin (GL) and carboxymethyl cellulose (CMC) are common natural components for edible films, but their water barrier performance are finite as hydrophilic polymers. In this study, a GL/CMC water barrier film was prepared, characterized and applied. The microstructure results showed that complex coacervation at pH 2.0 and cross-linking effect of sodium benzoate resulted in strong interaction forces and dense structure of this film. Compared with pure GL or CMC film, this novel composite film decreased water vapor permeability by approximately 90%, and possessed applicable water solubility (51.5%) and stronger barrier to oxygen and UV light. Acidic environment and sodium benzoate endowed antibacterial activity. Furthermore, the water barrier coating film decreased water loss by 47.8% and improved overall quality of fresh strawberries stored at 25 °C for 6 d. Therefore, the novel water barrier film based on complex coacervation and cross-linking is promising to control the postharvest quality of perishable berries.


Asunto(s)
Carboximetilcelulosa de Sodio , Embalaje de Alimentos , Conservación de Alimentos , Fragaria , Gelatina , Permeabilidad , Agua , Fragaria/química , Fragaria/efectos de los fármacos , Gelatina/química , Carboximetilcelulosa de Sodio/química , Embalaje de Alimentos/instrumentación , Agua/química , Conservación de Alimentos/métodos , Conservación de Alimentos/instrumentación , Electricidad Estática , Frutas/química , Frutas/efectos de los fármacos , Solubilidad
12.
J Glob Antimicrob Resist ; 37: 135-140, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561143

RESUMEN

OBJECTIVE: This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections. METHODS: We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. RESULTS: A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively. CONCLUSION: This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.


Asunto(s)
Antituberculosos , Diarilquinolinas , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Complejo Mycobacterium avium , Diarilquinolinas/farmacología , Humanos , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/genética , Mycobacterium abscessus/aislamiento & purificación , Complejo Mycobacterium avium/efectos de los fármacos , Complejo Mycobacterium avium/aislamiento & purificación , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Infección por Mycobacterium avium-intracellulare/microbiología
13.
J Infect ; 88(5): 106149, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38574774

RESUMEN

BACKGROUND: Distinguishing between nontuberculous mycobacterial (NTM) lung infections and pulmonary tuberculosis becomes challenging due to their similar clinical manifestations and radiological images. Consequently, instances of delayed diagnosis or misdiagnosis are highly frequent. A feasible and reliable indicator of the existence of NTM in the early stages of the disease would help to solve this dilemma. METHODS: In this study, we evaluated the potential of smear-positive and Xpert assay (Cepheid, USA) negative outcomes as an early indicator of possible NTM infection in a high TB-burden setting retrospectively and prospectively. RESULTS: During the study period, 12·77% (138/1081) of the smear-positive cases yielded negative outcomes with the simultaneous Xpert assay. From the 110 patients who yielded smear-positive/Xpert-negative outcomes and cultivated strain as well, 105 (95·45%) were proved to have NTM isolated. By incorporating an additional criterion of a negative result from the Interferon-gamma release assay, the accuracy of the screening method reached 100%. Regarding the NTM presence prediction value, smear-positive/Xpert-negative has a sensitivity of 24·86% (45/181) in all NTM isolated cases but 93·75-96·55% accuracy in retrospective study or 93·75% accuracy in prospective study in smear-positive NTM isolated cases. In addition, the specificity was ∼99·47% (943/948) in smear-positive tuberculosis cases. CONCLUSION: The clue of the presence of NTM could be obtained on the first day of the hospital visit due to the point of care (POC) feature of smear testing and Xpert assay. About one-fourth of the NTM-isolated patients would benefit from this rapid, convenient, and reliable screening strategy in the given circumstance. Smear-positive/Xpert-negative outcome is an early, trustable indicator that is indicative of NTM isolation.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Sensibilidad y Especificidad , Humanos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Masculino , Femenino , Estudios Retrospectivos , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/genética , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Adulto , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Esputo/microbiología , Ensayos de Liberación de Interferón gamma/métodos , Diagnóstico Diferencial , Anciano de 80 o más Años
14.
Mol Nutr Food Res ; 68(9): e2400147, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38643378

RESUMEN

SCOPE: Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. METHODS AND RESULTS: This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. CONCLUSION: This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.


Asunto(s)
Ácidos y Sales Biliares , Dieta Alta en Grasa , Suplementos Dietéticos , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Farmacología en Red , Receptores Citoplasmáticos y Nucleares , Ubiquinona , Ubiquinona/análogos & derivados , Ubiquinona/farmacología , Ácidos y Sales Biliares/metabolismo , Animales , Receptores Citoplasmáticos y Nucleares/metabolismo , Masculino , Receptores Acoplados a Proteínas G/metabolismo , Ratones
15.
Antimicrob Agents Chemother ; 68(5): e0134823, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38572960

RESUMEN

Mycobacterium abscessus (M. abscessus) inherently displays resistance to most antibiotics, with the underlying drug resistance mechanisms remaining largely unexplored. Efflux pump is believed to play an important role in mediating drug resistance. The current study examined the potential of efflux pump inhibitors to reverse levofloxacin (LFX) resistance in M. abscessus. The reference strain of M. abscessus (ATCC19977) and 60 clinical isolates, including 41 M. abscessus subsp. abscessus and 19 M. abscessus subsp. massilense, were investigated. The drug sensitivity of M. abscessus against LFX alone or in conjunction with efflux pump inhibitors, including verapamil (VP), reserpine (RSP), carbonyl cyanide 3-chlorophenylhydrazone (CCCP), or dicyclohexylcarbodiimide (DCC), were determined by AlarmarBlue microplate assay. Drug-resistant regions of the gyrA and gyrB genes from the drug-resistant strains were sequenced. The transcription level of the efflux pump genes was monitored using qRT-PCR. All the tested strains were resistant to LFX. The drug-resistant regions from the gyrA and gyrB genes showed no mutation associated with LFX resistance. CCCP, DCC, VP, and RSP increased the susceptibility of 93.3% (56/60), 91.7% (55/60), 85% (51/60), and 83.3% (50/60) isolates to LFX by 2 to 32-fold, respectively. Elevated transcription of seven efflux pump genes was observed in isolates with a high reduction in LFX MIC values in the presence of efflux pump inhibitors. Efflux pump inhibitors can improve the antibacterial activity of LFX against M. abscessus in vitro. The overexpression of efflux-related genes in LFX-resistant isolates suggests that efflux pumps are associated with the development of LFX resistance in M. abscessus.


Asunto(s)
Antibacterianos , Levofloxacino , Pruebas de Sensibilidad Microbiana , Mycobacterium abscessus , Reserpina , Levofloxacino/farmacología , Antibacterianos/farmacología , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/genética , Reserpina/farmacología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbonil Cianuro m-Clorofenil Hidrazona/farmacología , Girasa de ADN/genética , Girasa de ADN/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Farmacorresistencia Bacteriana/genética , Humanos , Verapamilo/farmacología
16.
Front Plant Sci ; 15: 1326917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38516657

RESUMEN

Introduction: Endophytes play a significant role in regulating plant root development and facilitating nutrient solubilization and transportation. This association could improve plant growth. The present study has uncovered a distinct phenotype, which we refer to as "white root", arising from the intricate interactions between endophytic fungi and bacteria with the roots in a sugarcane and bamboo fungus (Dictyophora indusiata) intercropping system. Methods: We investigated the mechanisms underlying the formation of this "white root" phenotype and its impact on sugarcane yield and metabolism by metabarcoding and metabolome analysis. Results and Discussion: Initial analysis revealed that intercropping with D. indusiata increased sugarcane yield by enhancing the number of viable tillers compared with bagasse and no input control. Metabarcoding based on second-generation and third-generation sequencing indicated that D. indusiate and Bacillus aryabhattai dominates the fungal and bacterial composition in the "white root" phenotype of sugarcane root. The coexistence of D. indusiata and B. aryabhattai as endophytes induced plant growth-promoting metabolites in the sugarcane root system, such as lysoPC 18:1 and dihydrobenzofuran, probably contributing to increased sugarcane yield. Furthermore, the association also enhanced the metabolism of compounds, such as naringenin-7-O-glucoside (Prunin), naringenin-7-O-neohesperidoside (Naringin)*, hesperetin-7-O-neohesperidoside (Neohesperidin), epicatechin, and aromadendrin (Dihydrokaempferol), involved in flavonoid metabolism during the formation of the endophytic phenotype in the sugarcane root system. These observations suggest that the "white root" phenotype promotes sugarcane growth by activating flavonoid metabolism. This study reports an interesting phenomenon where D. indusiata, coordinate with the specific bacteria invade, forms a "white root" phenotype with sugarcane root. The study also provides new insights into using D. indusiata as a soil inoculant for promoting sugarcane growth and proposes a new approach for improve sugarcane cultivation.

17.
Food Funct ; 15(8): 4154-4169, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38482844

RESUMEN

The consumption of dietary fiber is beneficial for gut health, but the role of bound polyphenols in dietary fiber has lacked systematic study. The aim of this study is to evaluate the ameliorative effect of mung bean coat dietary fiber (MDF) on DSS-induced ulcerative colitis in mice in the presence and absence of bound polyphenols. Compared to polyphenol-removed MDF (PR-MDF), MDF and formulated-MDF (F-MDF,backfilling polyphenols by the amount of extracted from MDF into PR-MDF) alleviated symptoms such as weight loss and colonic injury in mice with colitis, effectively reduced excessive inflammatory responses, and the bound polyphenols restored the integrity of the intestinal barrier by promoting the expression of tight junction proteins. Additionally, bound polyphenols restored the expression of autophagy-related proteins (mTOR, beclin-1, Atg5 and Atg7) and inhibited the excessive expression of apoptotic-related proteins (Bax, caspase-9, and caspase-3). Furthermore, bound polyphenols could ameliorate the dysregulation of the intestinal microbiota by increasing the abundance of beneficial bacteria and inhibiting the abundance of harmful bacteria. Thus, it can be concluded that the presence of bound polyphenols in MDF plays a key role in the alleviation of DSS-induced ulcerative colitis.


Asunto(s)
Colitis Ulcerosa , Sulfato de Dextran , Fibras de la Dieta , Microbioma Gastrointestinal , Polifenoles , Vigna , Animales , Polifenoles/farmacología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Fibras de la Dieta/farmacología , Sulfato de Dextran/efectos adversos , Vigna/química , Masculino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Humanos
18.
Front Microbiol ; 15: 1287806, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384275

RESUMEN

Objectives: Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a potent tool for detecting drug resistance in tuberculosis (TB); however, concerns about its reliability have been raised. In this study, we assessed the reliability of MassARRAY (Sequenom, Inc.), which is a MALDI-TOF MS-based method, by comparing it to the well-established GeneXpert assay (Cepheid) as a reference method. Methods: A retrospective study was conducted using laboratory data retrieved from Henan Chest Hospital (Zhengzhou, China). To ensure a rigorous evaluation, we adopted a comprehensive assessment approach by integrating multiple outcomes of the Xpert assay across various specimen types. Results: Among the 170 enrolled TB cases, MassARRAY demonstrated significantly higher sensitivity (85.88%, 146 of 170) compared to the Xpert assay (76.62%, 118 of 154) in TB diagnosis (p < 0.05). The concordance in detecting rifampicin resistance between MassARRAY and the combined outcomes of the Xpert assay was 90%, while it was 97.37% (37 of 38) among smear-positive cases and 89.06% (57 of 64) among culture-positive cases. When compared to the phenotypic susceptibility outcomes of the 12 included drugs, consistency rates of 81.8 to 93.9% were obtained, with 87.9% for multiple drug resistance (MDR) identification. Conclusion: MassARRAY demonstrates high reliability in detecting rifampicin resistance, and these findings may offer a reasonable basis for extrapolation to other drugs included in the test panel.

19.
Acta Biochim Biophys Sin (Shanghai) ; 56(2): 210-222, 2024 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-38273783

RESUMEN

Lung adenocarcinoma (LUAD) is one of the most aggressive types of lung cancer. The prognosis of LUAD patients remains poor, and the overall efficacy of gemcitabine-based chemotherapy is still unsatisfactory. Long noncoding RNAs (lncRNAs) play important roles in several cancer types by interacting with multiple proteins, RNA, and DNA. However, the relationship between lncRNA dysregulation and gemcitabine resistance in LUAD has not been fully elucidated. In this study, lncRNA CYTOR expression and its association with the prognosis of LUAD patients are assessed by quantitative RT-PCR and Kaplan-Meier survival analysis. In vitro and in vivo functional studies are conducted to evaluate the biological functions of CYTOR in LUAD. The underlying mechanism regarding the tumor-promoting effects of CYTOR is explored using RNA immunoprecipitation, biotin-labelled RNA pulldown, luciferase reporter assays, and western blot analysis. We identify that CYTOR is an oncogenic lncRNA and is apparently upregulated in LUAD by analysing TCGA-LUAD data. High CYTOR expression is a poor prognostic factor for LUAD. Functional studies reveal that CYTOR confers LUAD cells with stronger resistance to gemcitabine treatment and upregulates the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. Mechanically, CYTOR acts as a competitive endogenous RNA (ceRNA) to absorb miR-125a-5p, weakens the antitumor function of miR-125a-5p, and ultimately upregulates ANLN and RRM2 expressions. Taken together, this study explains the mechanism of lncRNA in the gemcitabine resistance of LUAD and formulates a theoretical framework for the in depth study of LUAD.


Asunto(s)
Adenocarcinoma , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Gemcitabina , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proliferación Celular/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Adenocarcinoma/genética , Transición Epitelial-Mesenquimal/genética , Pulmón/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral
20.
Int J Antimicrob Agents ; 63(2): 107061, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38103753

RESUMEN

OBJECTIVES: Patients with Mycobacterium avium complex-pulmonary disease (MAC-PD) can exhibit contraindications in applying the recommended treatment regimens by the guidelines. Clofazimine (CFZ) is considered a promising drug for MAC-PD treatment and is frequently included in alternative regimens; however, its efficacy remains unclear. METHODS: MAC-PD patients, unsuitable for standard regimens, were enrolled continuously in a prospective study at Beijing Chest Hospital. The treatment response of the CFZ-containing regimen was monitored. RESULTS: Fifty patients were enrolled in the initial treatment, and 25 patients had a history of anti-TB treatment. Nodular bronchiectasis was observed in 34 patients, while 8 patients exhibited fibrocavitary changes. Additionally, eight patients displayed a combination of both patterns. In a multivariate analysis, MAC-PD patients with CFZ MIC < 0.25 mg/L were significantly associated with culture conversion [OR 8.415, 95% CI (1.983-35.705); P = 0.004]. Among patients who had previous TB treatment history, patients with CFZ MIC < 0.25 mg/L had a higher chance of acquiring culture conversion outcomes [(OR 7.737, 95% CI 1.032-57.989); P = 0.046]. In contrast, among patients with no previous TB treatment history, the RIF-containing regimen had a higher chance of acquiring culture conversion outcomes [(OR 11.038, 95%CI 1.008-120.888); P = 0.049]. CONCLUSION: MAC-PD patients unsuitable for standard regimens could benefit from a CFZ-containing regimen, especially for patients with previous TB treatment history and baseline CFZ MIC values lower than 0.25 mg/L.


Asunto(s)
Enfermedades Pulmonares , Infección por Mycobacterium avium-intracellulare , Humanos , Clofazimina/uso terapéutico , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Estudios Prospectivos , Quimioterapia Combinada , Enfermedades Pulmonares/tratamiento farmacológico , Antibacterianos/uso terapéutico
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