Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 425
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
Cell ; 182(3): 685-712.e19, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32645325

RESUMO

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Pneumonia Viral/metabolismo , Proteômica/métodos , Células A549 , Enzima de Conversão de Angiotensina 2 , Animais , Antivirais/farmacologia , COVID-19 , Células CACO-2 , Caseína Quinase II/antagonistas & inibidores , Caseína Quinase II/metabolismo , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Fosforilação , Pneumonia Viral/virologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Receptor Tirosina Quinase Axl
2.
Blood ; 143(21): 2166-2177, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38437728

RESUMO

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Current treatments, based on intensive chemotherapy regimens provide overall survival rates of ∼85% in children and <50% in adults, calling the search of new therapeutic options. We previously reported that targeting the T-cell receptor (TCR) in T-ALL with anti-CD3 (αCD3) monoclonal antibodies (mAbs) enforces a molecular program akin to thymic negative selection, a major developmental checkpoint in normal T-cell development; induces leukemic cell death; and impairs leukemia progression to ultimately improve host survival. However, αCD3 monotherapy resulted in relapse. To find out actionable targets able to re-enforce leukemic cells' vulnerability to αCD3 mAbs, including the clinically relevant teplizumab, we identified the molecular program induced by αCD3 mAbs in patient-derived xenografts derived from T-ALL cases. Using large-scale transcriptomic analysis, we found prominent expression of tumor necrosis factor α (TNFα), lymphotoxin α (LTα), and multiple components of the "TNFα via NF-κB signaling" pathway in anti-CD3-treated T-ALL. We show in vivo that etanercept, a sink for TNFα/LTα, enhances αCD3 antileukemic properties, indicating that TNF/TNF receptor (TNFR) survival pathways interferes with TCR-induced leukemic cell death. However, suppression of TNF-mediated survival and switch to TNFR-mediated cell death through inhibition of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) with the second mitochondrial-derived activator of caspases (SMAC) mimetic birinapant synergizes with αCD3 to impair leukemia expansion in a receptor-interacting serine/threonine-protein kinase 1-dependent manner and improve mice survival. Thus, our results advocate the use of either TNFα/LTα inhibitors, or birinapant/other SMAC mimetics to improve anti-CD3 immunotherapy in T-ALL.


Assuntos
Complexo CD3 , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Fator de Necrose Tumoral alfa , Humanos , Animais , Camundongos , Complexo CD3/imunologia , Complexo CD3/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Imunoterapia/métodos , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico
3.
J Biol Chem ; 300(5): 107217, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522512

RESUMO

Sensor-effector proteins integrate information from different stimuli and transform this into cellular responses. Some sensory domains, like red-light responsive bacteriophytochromes, show remarkable modularity regulating a variety of effectors. One effector domain is the GGDEF diguanylate cyclase catalyzing the formation of the bacterial second messenger cyclic-dimeric-guanosine monophosphate. While critical signal integration elements have been described for different phytochromes, a generalized understanding of signal processing and communication over large distances, roughly 100 Å in phytochrome diguanylate cyclases, is missing. Here we show that dynamics-driven allostery is key to understanding signal integration on a molecular level. We generated protein variants stabilized in their far-red-absorbing Pfr state and demonstrated by analysis of conformational dynamics using hydrogen-deuterium exchange coupled to mass spectrometry that single amino acid replacements are accompanied by altered dynamics of functional elements throughout the protein. We show that the conformational dynamics correlate with the enzymatic activity of these variants, explaining also the increased activity of a non-photochromic variant. In addition, we demonstrate the functional importance of mixed Pfr/intermediate state dimers using a fast-reverting variant that still enables wild-type-like fold-changes of enzymatic stimulation by red light. This supports the functional role of single protomer activation in phytochromes, a property that might correlate with the non-canonical mixed Pfr/intermediate-state spectra observed for many phytochrome systems. We anticipate our results to stimulate research in the direction of dynamics-driven allosteric regulation of different bacteriophytochrome-based sensor-effectors. This will eventually impact design strategies for the creation of novel sensor-effector systems for enriching the optogenetic toolbox.


Assuntos
Luz , Fósforo-Oxigênio Liases , Fitocromo , Regulação Alostérica , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Fósforo-Oxigênio Liases/metabolismo , Fósforo-Oxigênio Liases/química , Fósforo-Oxigênio Liases/genética , Fitocromo/metabolismo , Fitocromo/química , Fitocromo/genética , Multimerização Proteica , Luz Vermelha , Alteromonadaceae/enzimologia , Modelos Moleculares
4.
Cell Mol Life Sci ; 81(1): 207, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709385

RESUMO

The co-localization of the lysosomal protease cathepsin B (CTSB) and the digestive zymogen trypsinogen is a prerequisite for the initiation of acute pancreatitis. However, the exact molecular mechanisms of co-localization are not fully understood. In this study, we investigated the role of lysosomes in the onset of acute pancreatitis by using two different experimental approaches. Using an acinar cell-specific genetic deletion of the ras-related protein Rab7, important for intracellular vesicle trafficking and fusion, we analyzed the subcellular distribution of lysosomal enzymes and the severity of pancreatitis in vivo and ex vivo. Lysosomal permeabilization was performed by the lysosomotropic agent Glycyl-L-phenylalanine 2-naphthylamide (GPN). Acinar cell-specific deletion of Rab7 increased endogenous CTSB activity and despite the lack of re-distribution of CTSB from lysosomes to the secretory vesicles, the activation of CTSB localized in the zymogen compartment still took place leading to trypsinogen activation and pancreatic injury. Disease severity was comparable to controls during the early phase but more severe at later time points. Similarly, GPN did not prevent CTSB activation inside the secretory compartment upon caerulein stimulation, while lysosomal CTSB shifted to the cytosol. Intracellular trypsinogen activation was maintained leading to acute pancreatitis similar to controls. Our results indicate that initiation of acute pancreatitis seems to be independent of the presence of lysosomes and that fusion of lysosomes and zymogen granules is dispensable for the disease onset. Intact lysosomes rather appear to have protective effects at later disease stages.


Assuntos
Catepsina B , Lisossomos , Pancreatite , Vesículas Secretórias , Proteínas rab de Ligação ao GTP , proteínas de unión al GTP Rab7 , Animais , Lisossomos/metabolismo , Pancreatite/metabolismo , Pancreatite/patologia , Pancreatite/genética , Catepsina B/metabolismo , Catepsina B/genética , Camundongos , Vesículas Secretórias/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , proteínas de unión al GTP Rab7/metabolismo , Doença Aguda , Células Acinares/metabolismo , Células Acinares/patologia , Tripsinogênio/metabolismo , Tripsinogênio/genética , Ceruletídeo , Precursores Enzimáticos/metabolismo , Precursores Enzimáticos/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout
5.
Langenbecks Arch Surg ; 409(1): 27, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183462

RESUMO

BACKGROUND: Substernal (ST) and posterior mediastinal (PM) routes are the two most common for reconstruction after esophagectomy with cervical anastomosis. Recent evidence showed similar outcomes between the routes; thus, the superior choice remained controversial. This study aimed to compare the short-term outcomes of the ST to the PM route for reconstruction after esophagectomy for esophageal cancer (EC). METHOD: This retrospective cohort study included 132 patients who underwent McKeown minimally invasive esophagectomy (MIE) with gastric conduit for EC between March 2015 and December 2022. Among these, 89 and 43 patients received the ST route and PM route for reconstruction, respectively. Short-term outcomes including operative characteristics, postoperative morbidity, and mortality were evaluated. RESULT: There was no conversion from ST to PM route. The ST group had longer operating time (375 min vs. 341 min). Oral feeding initiation, postoperative hospital stays, and overall complication rates were comparable in the two groups. The rate and severity of anastomotic leakage were similar between the groups. The ST group had a significantly lower incidence of postoperative ICU admission and pneumonia compared to the PM group (5.6% vs. 16.3% and 19.1% vs. 37.2%, respectively). Azygos vein bleeding, obstruction at feeding jejunostomy site, and conduit-trachea fistula were severe complications that only occurred in PM route. CONCLUSION: ST route was superior to PM route in term of postoperative ICU admission and pneumonia. This route may prevent severe complications that only occur in PM route. ST route can be favorable option for reconstruction after McKeown MIE for EC.


Assuntos
Neoplasias Esofágicas , Pneumonia , Humanos , Esofagectomia , Estudos Retrospectivos , Neoplasias Esofágicas/cirurgia , Anastomose Cirúrgica
6.
Public Health ; 227: 250-258, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38262230

RESUMO

OBJECTIVES: Rapid internet penetration and technological advancements have facilitated accessibility to internet-enabled devices globally. Since Asia lacks comprehensive data on internet addiction among college students, this review aims to estimate its pooled prevalence. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: Searches were conducted in PubMed, Scopus, CINAHL, and MEDLINE from their inception through August 2022 using terms appropriate to internet addiction and Asian countries/territorial for publications in English peer-reviewed journals. The studies included those done on current college students and provided unambiguous indicators of the threshold of internet addiction. The pooled prevalence was calculated through a random-effects meta-analysis by RStudio software, and I2 statistic was used to assess heterogeneity. The Joanna Briggs Institute critical appraisal checklist was used for quality assessment. RESULTS: Overall, between 2007 and 2021, 39 papers comprising 45 effect sizes and totaling 58,058 participants met the inclusion criteria. The pooled prevalence of internet addiction among Asian college students was 24.3% (95% confidence interval: 19.8%-29.5%, Q = 6234, df = 44, τ2 = 0.79, I2 = 99.29%), and strikingly, this percentage increased over time. A high degree of heterogeneity was seen, and no publication bias was found. CONCLUSIONS: To our knowledge, this is the first comprehensive review report on Asian college students, which found that one-fifth suffer from internet addiction. The findings emphasize the significance of multidisciplinary prevention and management strategies to mitigate the harmful effects of internet addiction. Further research is warranted to develop a standardized diagnostic tool for a more precise estimation of internet addiction among this population.


Assuntos
Comportamento Aditivo , Transtorno de Adição à Internet , Humanos , Prevalência , Comportamento Aditivo/epidemiologia , Estudantes , Ásia , Internet
7.
Psychol Health Med ; : 1-18, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700271

RESUMO

Antibiotic resistance (AR) rates in Vietnam are among the highest in Asia, and recent infections due to multi-drug resistance in the country have caused thousands of deaths each year. This study investigated a Vietnamese community's preferences for antibiotic treatment and its knowledge and attitudes regarding antibiotics. A discrete choice experiment-based survey was developed and administered to the population of interest. The respondents were given sociodemographic-, knowledge- and attitude-related items and 17 pairs of choice tasks. Two hypothetical options were included in each choice task. Latent class analysis was conducted to determine the differences among the respondents' preferences. Among 1,014 respondents, 805 (79.4%) gave valid questionnaires. A three-latent-class model with four covariates (age, healthcare-related education or career, occupation, and attitude classifications) was used in the analysis. All five attributes significantly influenced the respondents' decisions. The majority, including young employed respondents with non-healthcare-related work or education, found treatment failure more important. Older respondents who had healthcare-related education/careers and/or appropriate antibiotic use- and antibiotics resistance-related attitudes, regarded contribution to antibiotic resistance as an important attribute in selecting antibiotic treatments. Unemployed individuals with correct knowledge identified the cost of antibiotic treatment as the most essential decision-making factor. Findings suggest minimal antibiotic impact on resistance; only 7.83% view it as amajor concern. The respondents exhibited substantial preference heterogeneity, and the general Vietnamese public had poor knowledge of and attitudes toward antibiotic use and antibiotic resistance. This study emphasizes the need for individual responsibility for antibiotic resistance and appropriate antibiotic use.

8.
Community Ment Health J ; 60(4): 629-634, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38324069

RESUMO

Managing waitlists for outpatient mental health services particularly in community health settings is difficult to standardize, poses an administrative burden, and are barriers rather than gateways to access to care particularly for low-income communities. While telehealth has initially expanded access to mental healthcare at the onset of the COVID-19 pandemic, it has not resolved the challenges associated with the increasing demand for services and the shortage of available providers. This commentary explores the intricate interconnections between wait times, readiness for and appropriateness of therapy, and engagement in treatment. Drawing on insights from waiting line theory to question the attachment to and utility of waitlists for non-emergency, outpatient mental healthcare, this commentary questions the utility and efficacy of waitlists. Alternative solutions that capitalize on community resources and collaboration and harness patients' agency for change are discussed.


Assuntos
COVID-19 , Serviços de Saúde Mental , Telemedicina , Humanos , Listas de Espera , Pandemias
9.
Mol Cancer ; 22(1): 12, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-36650499

RESUMO

The acquisition of genetic abnormalities engendering oncogene dysregulation underpins cancer development. Certain proto-oncogenes possess several dysregulation mechanisms, yet how each mechanism impacts clinical outcome is unclear. Using T-cell acute lymphoblastic leukemia (T-ALL) as an example, we show that patients harboring 5'super-enhancer (5'SE) mutations of the TAL1 oncogene identifies a specific patient subgroup with poor prognosis irrespective of the level of oncogene dysregulation. Remarkably, the MYB dependent oncogenic 5'SE can be targeted using Mebendazole to induce MYB protein degradation and T-ALL cell death. Of note Mebendazole treatment demonstrated efficacy in vivo in T-ALL preclinical models. Our work provides proof of concept that within a specific oncogene driven cancer, the mechanism of oncogene dysregulation rather than the oncogene itself can identify clinically distinct patient subgroups and pave the way for future super-enhancer targeting therapy.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteína 1 de Leucemia Linfocítica Aguda de Células T/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Mebendazol
10.
Ann Surg Oncol ; 30(4): 2278-2289, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36469222

RESUMO

BACKGROUND: Laparoscopic gastrectomy for advanced gastric cancer (GC) has been applied more frequently worldwide but is still controversial for patients with serosal invasion (T4a). This study compared short- and long-term outcomes of laparoscopic distal radical gastrectomy (LDG) with open distal gastrectomy (ODG) for T4a GC. PATIENTS AND METHODS: We retrospectively studied 472 patients with T4a gastric adenocarcinoma in the lower or middle third of the stomach: 231 underwent LDG and 241 underwent ODG between 2013 and 2020. Short-term outcomes included operative characteristics and complications. Long-term outcomes included overall survival (OS) and disease-free survival (DFS). Propensity score-matched (PSM) analysis was used to adjust for imbalances in baseline characteristics between groups. RESULTS: The PSM strategy resulted in 294 patients (147 in each group). The LDG group had a significantly longer operating time (mean: 200 vs 190 min, p = 0.001) but reduced blood loss (mean: 50 vs 100 ml, p = 0.001). The LDG group had a higher rate of any postoperative complication (23.1% vs 12.2%, p = 0.021) but most were classified as grades I-II according to Clavien-Dindo classification. Grade III-V complications were similar between groups. Five-year OS was 69% versus 60% (p = 0.109) and 5-year DFS was 58% vs 53% (p = 0.3) in LDG and ODG groups, respectively. For tumor size < 5 cm, LDG was better in reduction of blood loss, postoperative hospital length of stay, and OS. CONCLUSIONS: LDG is feasible and safe for patients with T4a GC and is comparable to ODG regarding short- and long-term outcomes. Furthermore, LDG can be a favorable option for T4a GC smaller than 5 cm.


Assuntos
Laparoscopia , Neoplasias Gástricas , Humanos , Estudos de Coortes , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Pontuação de Propensão , Laparoscopia/métodos , Gastrectomia/métodos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
11.
Microb Pathog ; 175: 105986, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36638852

RESUMO

In 2021, pomelo (Citrus grandi) trees grown in Tuyen Quang and Phu Tho in northern Vietnam suffered from leaf yellowing, gummosis on stems, brown rot on fruit, and black rot on roots. Based on morphological and sequence analysis of the ITS and cox1 gene regions, the pathogen causing gummosis and root rot of citrus trees was identified as Phytophthora parvispora. Pathogenicity assays using mycelial plugs and zoospore suspension showed that P. parvispora induces disease symptoms on both the upper and lower parts of various citrus trees, including pomelo, orange (C. sinensis), and lime (C. aurantiifolia). This is the first report of P. parvispora as the causative agent of gummosis and root rot on various citrus trees in South-East Asia as well as in Vietnam. Further, P. parvispora was sensitive to all tested fungicides, including mancozeb, chlorothalonil, fosetyl aluminium, potassium phosphonate, and dimethomorph. These findings will have important implications for the effective management of gummosis and root rot disease of citrus trees.


Assuntos
Citrus , Fungicidas Industriais , Phytophthora , Fungicidas Industriais/farmacologia , Phytophthora/genética , Árvores , Virulência
12.
Langmuir ; 39(39): 13897-13907, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37738086

RESUMO

It is essential to develop novel catalysts with high catalytic activity, strong durability, and good stability for further application in methanol fuel cells. In this work, we present for the first time the effect of the chemical functional groups (thiol and amine) with different electron affinity in reduced graphene oxide supports on the morphology and catalytic activity of platinum nanoparticles for the methanol oxidation reaction. Hydroxyl groups on graphene oxide were initially brominated and then transformed to the desired functional groups. The good dispersion of metal nanoparticles over functionalized carbon substrates (particle size less than 5 nm) with good durability, even at a limited functionalization degree (less than 7%) has been demonstrated by morphological and structural studies. The durability of the catalysts was much improved via strong coordination between the metal and nitrogen or sulfur atoms. Impressively, the catalytic activity of platinum nanoparticles on aminated reduced graphene oxide was found to be much better than that on thiolated graphene oxide despite the weaker affinity between amine and noble metals. These findings support further developing new graphene derivatives with the desired functionalization for electronics and energy applications..

13.
Med Mycol ; 61(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37771088

RESUMO

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group. Participants were matched by age, sex, HIV serostatus, and CD4 count in the HIV-positive group. Plasma immunoglobulin (Ig) levels, including IgG1, IgG2, IgM, and IgA, Cryptococcus spp. glucuronoxylomannan (GXM)- and laminarin (branched ${\rm{\beta }}$-[1-3]-glucan)-binding IgG, IgM, IgA levels, and peripheral blood B cell subsets were measured. Logistic regression, principal component, and mediation analyses were conducted to assess associations between antibody, B cell levels, and CM. The results showed that GXM-IgG levels were higher and IgG1 and IgG2 were lower in CM cases than controls, regardless of HIV status. In HIV-negative individuals, IgG2 mediated an inverse association between CD19+CD27+CD43+CD5- (B-1b-like) cells and CM. In HIV-positive individuals, lower levels of IgA, laminarin-IgA, and CD19+CD27+IgM+IgD- (IgM+ memory B) cells were each associated with CM. The shared and distinct antibody and B cell profiles identified in HIV-negative and HIV-positive CM cases may inform the identification of non-T-cell markers of CM risk or unsuspected disease, particularly in HIV-negative individuals.


Unlike cryptococcal meningitis (CM) in HIV-positive individuals, there are no known biomarkers of risk in HIV-negative individuals and the diagnosis is often not suspected and delayed. This study identified non-T cells, including antibody and B cell CM-associated profiles that may guide cryptococcal antigen testing in HIV-negative individuals.


Assuntos
Cryptococcus neoformans , Infecções por HIV , Meningite Criptocócica , Meningoencefalite , Humanos , Estudos de Casos e Controles , Infecções por HIV/complicações , Infecções por HIV/veterinária , Imunoglobulina M , Imunoglobulina G , Meningoencefalite/veterinária , Imunoglobulina A , Meningite Criptocócica/veterinária
14.
Org Biomol Chem ; 21(44): 8813-8818, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37889185

RESUMO

In four simple steps, a series of 5H-thiazolo[2',3':2,3]imidazo[4,5-b]indole and 11H-benzo[4',5']thiazolo[2',3':2,3]imidazo[4,5-b]indole derivatives were prepared with high yields. The key step in this procedure was demonstrated to be two-fold Cu-catalysed C-N coupling reactions of 5-bromo-6-(2-bromophenyl)imidazo[2,1-b]thiazole and 3-bromo-2-(2-bromophenyl)benzo[d]imidazo[2,1-b]thiazole with various amines.

15.
Appl Microbiol Biotechnol ; 107(17): 5367-5378, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37436482

RESUMO

Fermentation technology using endophytes is considered a potential alternative approach for producing pharmaceutical compounds like podophyllotoxin (PTOX). In this study, fungus TQN5T (VCCM 44284) was selected from endophytic fungi isolated from Dysosma versipellis in Vietnam for PTOX production through TLC. The presence of PTOX in TQN5T was further confirmed by HPLC. Molecular identification indicated TQN5T as Fusarium proliferatum with 99.43% identity. This result was asserted by morphological characteristics such as white cottony, filamentous colony, layer and branched mycelium, and clear hyphae septa. Cytotoxic assay indicated both biomass extract and culture filtrate of TQN5T presented strong cytotoxicity on LU-1 and HepG2 with IC50 of 0.11, 0.20, 0.041, and 0071, respectively, implying anti-cancer compounds were accumulated in the mycelium and secreted into the medium. Further, the production of PTOX in TQN5T was investigated in the fermentation condition supplemented with 10 µg/ml of host plant extract or phenylalanine as elicitors. The results revealed a significantly higher amount of PTOX in the PDB + PE and PDB + PA at all studied time points in comparison with PDB (control). Especially, after 168 h of culture, PTOX content in the PDB with plant extract reached the peak with 314 µg/g DW which is 10% higher than the best yield of PTOX in previous studies, denoting F. proliferatum TQN5T as a promising PTOX producer. This is the first study on enhancing the PTOX production in endophytic fungi by supplementing phenylalanine-a precursor for PTOX biosynthesis in plants into fermented media, suggesting a common PTOX biosynthetic pathway between host plant and endophytes. KEY POINTS: • Fusarium proliferatum TQN5T was proven for PTOX production. • Both mycelia extract and spent broth extract of Fusarium proliferatum TQN5T presented strong cytotoxicity on cancer cell lines LU-1 and HepG2. • The supplementation of 10 µg/ml host plant extract and phenylalanine into fermentation media of F. proliferatum TQN5T improved the yield of PTOX.


Assuntos
Fusarium , Podofilotoxina , Podofilotoxina/metabolismo , Endófitos/metabolismo , Fusarium/metabolismo , Extratos Vegetais/metabolismo , Plantas/metabolismo
16.
Biol Pharm Bull ; 46(8): 1057-1064, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37532557

RESUMO

Glinus oppositifolius is an endemic herbaceous plant found in tropical Asian countries and is native in Vietnam. It is used in traditional folk medicine because of its flavor and antiseptic and laxative effects. In the current research, the effects of Tox-off, Biovip, and the purified compounds isolated from G. oppositifolius in the previous study were evaluated on the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) in C2C12 myoblasts. In addition, the most potent active compounds, traphanoside-GO1 (TRA-GO1) and TRA-GO5 have validated the reduction of fatty acid synthase (FAS) and sterol regulatory element binding protein (SREBP)-1c in HepG2 cells. We found that Tox-off and Biovip significantly increased the phosphorylation of AMPK and ACC in C2C12 myoblasts. Furthermore, TRA-GO1 and TRA-GO5 significantly increased the AMPK activation and phosphorylation of its downstream substrate ACC in a concentration-dependent way compared to the dimethyl sulfoxide (DMSO) control. Besides, the protein level of FAS and SREBP-1c decreased by TRA-GO1 and TRA-GO5 in a concentration-dependent manner. Taken together, our results showed that the increased AMPK and ACC phosphorylation by active components of G. oppositifolius may activate the AMPK signaling pathways, which are useful for the anti-obesity and its related metabolic disorders.


Assuntos
Proteínas Quinases Ativadas por AMP , Molluginaceae , Humanos , Células Hep G2 , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Metabolismo dos Lipídeos , Ácido Graxo Sintases/metabolismo , Acetil-CoA Carboxilase/metabolismo
17.
Am J Otolaryngol ; 44(4): 103888, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37060780

RESUMO

PURPOSES: The purpose of this study was to present and analyze the etiologic factors, clinical manifestations, bacteriology, and treatment outcomes of nasal septal abscess in a large cohort of adult patients. MATERIAL AND METHODS: Retrospective analysis. RESULTS: 36 adult patients, age from 19 to 85 (mean age, 51.83), with nasal septal abscesses were treated at Ear Nose Throat Hospital of Ho Chi Minh City from January 2020 to August 2022. The most common symptoms were nasal obstruction (75 %), headache/facial pain (58.33 %). Etiologic factors were found in 83.33 % of cases with the most common were diabetes mellitus (47.22 %), nose-picking (44.44 %). 75 % of cases had positive bacterial culture, of which 70.37 % were Staphylococcus aureus. Septal abscess was successfully treated in all cases using our treatment protocol, which involved an extended modified Killian's incision, irrigation with 1 % poviodine, placement of gauze in the abscess pocket, and nasal packing with Merocels. CONCLUSIONS: Diabetes and nose-picking were the most common etiologic factors; Staphylococcus aureus was the most common organism of nasal septal abscess in our study. Our treatment protocol is safe and effective.


Assuntos
Diabetes Mellitus , Obstrução Nasal , Doenças dos Seios Paranasais , Doenças Faríngeas , Infecções Respiratórias , Infecções Estafilocócicas , Humanos , Adulto , Pessoa de Meia-Idade , Septo Nasal , Abscesso/etiologia , Abscesso/terapia , Abscesso/diagnóstico , Estudos Retrospectivos , Obstrução Nasal/complicações , Doenças dos Seios Paranasais/complicações , Staphylococcus aureus , Infecções Respiratórias/complicações , Celulite (Flegmão) , Infecções Estafilocócicas/terapia , Infecções Estafilocócicas/complicações , Doenças Faríngeas/complicações
18.
J Asian Nat Prod Res ; : 1-11, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37889019

RESUMO

Alkaloids are among the most important and best-known secondary metabolites as sources of new drugs from medicinal plants and marine organisms. A phytochemical investigation of the whole plant of Crinum asiaticum var. sinicum resulted in the isolation of seven alkaloids (1-7), including one new dimeric compound, bis-(-)-8-demethylmaritidine (1). Their structures were elucidated using NMR and HR-ESI-MS. The absolute configuration of new compound 1 was established by circular dichroism spectroscopy. All isolated compounds were evaluated for their inhibitory effects on acetylcholinesterase (AChE) activity in vitro. Among them, compound 1 exhibited the most potent AChE inhibition. Moreover, molecular docking and molecular dynamics simulations were carried out for the most active compound to investigate their binding interactions and dynamics behavior of the AChE protein-ligand complex. Therefore, compound 1 may be a potential candidate for effectively treating Alzheimer's disease.

19.
Nutr Health ; 29(3): 443-452, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36285514

RESUMO

BACKGROUND: Chronic noncommunicable diseases (NCDs) associated with excess weight as a significant risk factor, but few studies have been sufficient enough to examine the magnitude of excess weight of Vietnamese adults. This review aimed to provide a generalized estimate of the prevalence of excess weight among Vietnamese adults. METHODS: PubMed, Scopus and national database were used to identify articles published up to May 2022. The Newcastle-Ottawa Quality Assessment Scale was used to rate the study quality. The data was analyzed using RStudio software, and the combined effects were estimated using random-effects meta-analysis. The Cochran's Q-test and the I2 test were employed to examine heterogeneity, and subgroups were conducted. Egger's test and visual inspection of the symmetry in funnel plots were used to determine publication bias. RESULTS: 58 studies with 432,585 participants from 1998 to 2020 were suitable for inclusion in the final model after meeting the prerequisites. Over the last three decades, the combined pooled prevalence of excess weight among adults in Vietnam was 20.3% (95% CI: 15.2-26.6). Notably, this proportion has a tendency to go up between 1998 and 2020. Moreover, rates of excess weight were found to be substantially higher in non-national studies (23.1%, 17.3-30.1) compared to national studies (8.4%, 3.6-18.3) and significantly higher when Asian and Pacific cut-offs (27.6%, 20.0-36.7) were used rather than WHO classification (11.2%, 6.7-18.0). CONCLUSION: The findings suggest healthcare professionals and policymakers should focus more on designing and implementing preventive initiatives to lower the rising prevalence of excess weight adults in Vietnam.


Assuntos
Sobrepeso , População do Sudeste Asiático , Adulto , Humanos , Prevalência , Fatores de Risco , Vietnã/epidemiologia , Sobrepeso/epidemiologia
20.
Esophagus ; 20(3): 435-444, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609618

RESUMO

PURPOSE: Colon conduit is an alternative to a gastric conduit for esophagectomy in patients that stomach is not available. Surgical technique is complex and has a high risk of morbidities and mortality. Outcomes of patients are still lacking in the literature, thus aims of this study are to evaluate the safety, feasibility and long-term functional outcomes of patients who underwent esophagectomy for cancer with colon conduit via retrosternal route. METHODS: Twenty-six patients underwent operation between August 2016 and June 2021 for malignancies. Minimally invasive esophagectomy and laparotomy were performed in accordance with the 2017 Japan Esophageal Society's guidelines. Colonic interposition was used for esophageal replacement. Outcomes were technical success, complications assessed using Clavien-Dindo classification, and patient's quality of life (QOL) based on EORTC-QOL-OES18 questionnaire. RESULTS: Mean age was 56.0 ± 9.9 years and 21 patients (80.8%) were men. Mean operating time was 432 ± 66 min. Technical success was 100%. The average number of resected lymph nodes was 26 ± 14. Twelve patients (46.2%) experienced postoperative complications: 7/12 were classified as grade I-II, 3/12 as grade III, 1/12 as grade IV, and 1/12 as grade V (death). Patient's QOL improved during the follow-up period with median (25-75th percentiles) global EORTC-QOL-OES18 score was 29 (17-34); 13 (9-21), and 9 (6-16) at 3, 6, and 12 months, respectively. During the follow-up period, there were 4 late complications, 3 lymphatic recurrences, 5 distant metastases, and 6 deaths. CONCLUSIONS: Colon conduit via retrosternal route after esophagectomy is feasible, safe, and could provide acceptable long-term functional outcomes.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Qualidade de Vida , Neoplasias Esofágicas/patologia , Colo/patologia , Colo/cirurgia , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA