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1.
Toxicol Appl Pharmacol ; 481: 116767, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38007073

RESUMO

Current treatments for stomach cancer are often effective in curing cancer. However, these treatments can also have significant side effects, and they may not be effective in all cases. Hence synthetic compounds exhibit promise as potential agents for cancer treatment. In a previous study, we identified (E)-N'- (2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) as a novel antimycobacterial derivative of isoniazid with cytotoxic effects on the MCF-7 breast cancer cell line. This led us to investigate the potential anti-cancer properties of ITHB4 against adenocarcinoma gastric (AGS) cell line. The cytotoxic effect of ITHB4 has been determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and further confirmed for anticancer properties by means of apoptosis, reactive oxygen species (ROS), nuclear fragmentation, lactate dehydrogenase (LDH), caspases, cytokines and morphological including phenotypic changes of cells assay. The ITHB4 demonstrated a lower IC50 in inhibiting growth of AGS cells at 24 h compared to 48 and 72 h. ITHB4 has also shown no toxicity human immune cells. Treatment of ITHB4 against AGS for 24 h eventually lead to formation of early apoptotic AGS cells, reduced mitochondrial membrane potential, nuclear condensation, and nuclear fragmentation lastly increased in ROS levels together with the release of LDH, and secretion of caspases. The altered cytokine profile in ITHB4 treated AGS hints at the possibility that ITHB4 may possess anti-tumor and anti-inflammatory properties. Our results in this study demonstrate that ITHB4 has almost similar chemotherapeutic properties against gastric adenocarcinoma cells compared to breast cancer cell. This is suggesting that the anticancer capabilities of this compound should be in vivo and clinically assessed.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Mama , Neoplasias Gástricas , Humanos , Feminino , Neoplasias Gástricas/metabolismo , Isoniazida/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Apoptose , Caspases , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Adenocarcinoma/metabolismo , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células
2.
BMC Med Educ ; 23(1): 310, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147649

RESUMO

BACKGROUND: Academic failure is common among medical schools worldwide. However, the process behind this failure itself is underexplored. A deeper understanding of this phenomenon may avert the vicious cycle of academic failure. Hence, this study investigated the process of academic failure among medical students in Year 1. METHODS: This study employed a document phenomenological approach, which is a systematic process to examine documents, interpret them to attain understanding, and develop empirical knowledge of the phenomenon studied. Using document analysis, interview transcripts and reflective essays of 16 Year 1 medical students who experienced academic failure were analysed. Based on this analysis, codes were developed and further reduced into categories and themes. Thirty categories in eight themes were linked to make sense of the series of events leading to academic failure. RESULTS: One or more critical incidents commenced during the academic year, which led to possible resulting events. The students had poor attitudes, ineffective learning methods, health problems or stress. Students progressed to mid-year assessments and reacted differently to their results in the assessments. Afterwards, the students tried different types of attempts, and they still failed the end-of-year assessments. The general process of academic failure is illustrated in a diagram describing chronological events. CONCLUSION: Academic failure may be explained by a series of events (and consequences) of what students experience and do and how they respond to their experiences. Preventing a preceding event may prevent students from suffering these consequences.


Assuntos
Estudantes de Medicina , Humanos , Fracasso Acadêmico , Ansiedade , Atitude , Análise Documental
3.
Clin Oral Investig ; 26(5): 4161-4172, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35257247

RESUMO

OBJECTIVE: This study investigated the subgingival microbial profile of rheumatoid arthritis (RA) patients and its associations with disease parameters and the inflammation-related antimicrobial peptide, LL-37. METHODS: RA and non-RA (NRA) patients were assessed for periodontal status and divided into periodontitis (CP), gingivitis (G), and healthy (H) groups. Subgingival plaque 16s rRNA gene sequencing data was processed and analyzed using the CLC Genomic Workbench (Qiagen). Bacterial diversity and co-occurrence patterns were examined. Differential abundance between groups was also investigated. Associations between bacterial genera with disease parameters and LL-37 levels were explored qualitatively using canonical correlation analysis. RESULTS: Subgingival microbial community clustered in CP status. Co-occurrence network in NRA-H was dominated by health-associated genera, while the rest of the networks' key genera were both health- and disease-associated. RA-CP displayed highly inter-generic networks with a statistically significant increase in periodontal disease-associated genera (p<0.05). In NRA-H, disease parameters and LL-37 were correlated positively with disease-associated genera while negatively with health-associated genera. However, in the remaining groups, mixed positive and negative correlations were noted with genera. CONCLUSION: RA patients demonstrated subgingival microbial dysbiosis where the bacteria networks were dominated by health- and disease-associated genera. Mixed correlations with disease parameters and LL-37 levels were noted. CLINICAL RELEVANCE: The subgingival microbial dysbiosis in RA may predispose these patients to developing periodontal inflammation with an associated detrimental effect on host immune responses. Routine periodontal assessment may allow initiation of treatment strategies to minimize the effects of gingival inflammation on the existing heightened immune response present in RA patients.


Assuntos
Artrite Reumatoide , Gengivite , Periodontite , Artrite Reumatoide/complicações , Bactérias , Disbiose/complicações , Disbiose/microbiologia , Gengivite/complicações , Humanos , Inflamação , Periodontite/microbiologia , RNA Ribossômico 16S/genética
4.
Microb Pathog ; 152: 104614, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33202254

RESUMO

Candidiasis is the most common fungal infection associated with high morbidity and mortality among immunocompromised patients. The ability to form biofilm is essential for Candida albicans pathogenesis and drug resistance. In this study, the planktonic cell and biofilm proteomes of C. albicans SC5314 strain analyzed using Liquid Chromatography-Mass Spectrometry (LC-MS) were compared. In total, 280 and 449 proteins are annotated from the planktonic cell and biofilm proteomes, respectively. The biofilm proteome demonstrated significantly higher proportion of proteins associated with the endomembrane system, mitochondrion and cytoplasm than planktonic proteome. Among proteins detected, 143 and 207 biological processes are annotated, of which, 38 and 102 are specific to the planktonic cell and biofilm proteomes, respectively, while 105 are common biological processes. The specific biological processes of C. albicans planktonic cell proteome are associated with cell polarity, energy metabolism and nucleotide (purine) metabolism, oxido-reduction coenzyme metabolic process, monosaccharide and amino acid (methionine) biosynthesis, regulation of anatomical structure morphogenesis and cell cycling, and single organism reproduction. Meanwhile, regulation of cellular macromolecule biosynthesis and metabolism, transcription and gene expression are major biological processes specifically associated with C. albicans biofilm proteome. Biosynthesis of leucine, isoleucine, and thiocysteine are highlighted as planktonic-related pathways, whereas folate metabolism, fatty acid metabolism and biosynthesis of amino acids (lysine, serine and glycine) are highlighted as biofilm-related pathways. In summary, LC-MS-based proteomic analysis reveals different adaptative strategies of C. albicans via specific biological and metabolic processes for planktonic cell and biofilm lifestyles. The mass spectrometry data are available via ProteomeXchange with identifiers PXD007830 (for biofilm proteome) and PXD007831 (for planktonic cell proteome).


Assuntos
Fenômenos Biológicos , Candida albicans , Antifúngicos , Biofilmes , Cromatografia Líquida , Humanos , Proteômica , Espectrometria de Massas em Tandem
5.
Microb Pathog ; 161(Pt A): 105231, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34619310

RESUMO

The interplay of immune mediators is paramount to optimal host anti-viral immune responses, especially against chronic hepatitis B virus (HBV) infection. Here, we investigated the dynamic changes in host immune responses in chronic HBV-infected individuals with and without liver cirrhosis by examining the signatures of apoptosis and plasma levels of pro-inflammatory cytokines, chemokines, and cytotoxic proteins. A total of 40 chronic HBV patients with and without liver cirrhosis were studied for plasma levels of immune mediators, and signatures of apoptosis in peripheral blood mononuclear cells (PBMCs). The intracellular concentrations of reactive oxygen species (ROS) in patients with chronic HBV with liver cirrhosis was relatively higher as compared to chronic HBV patients. The onset of apoptosis was sustained due to ongoing liver inflammation in concert with plasma TNF-α and IL-6 levels. Plasma VEGF was upregulated among chronic HBV patients with liver cirrhosis, whereas CCL2, CCL5 and granzyme B levels were down-regulated. High levels of ROS, IL-6 and TNF-α correlated with ongoing inflammation among chronic HBV patients with liver cirrhosis, which likely attributed to the expression of biosignatures of apoptosis and activation in immune cells.


Assuntos
Hepatite B Crônica , Citocinas , Vírus da Hepatite B , Hepatite B Crônica/complicações , Humanos , Leucócitos Mononucleares , Cirrose Hepática
6.
Genomics ; 112(1): 501-512, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980902

RESUMO

Differences in expression of potential virulence and survival genes were associated with B. pseudomallei colony morphology variants. Microarray was used to investigate B. pseudomallei transcriptome alterations among the wild type and small colony variant (SCV) pre- and post-exposed to A549 cells. SCV pre- and post-exposed have lower metabolic requirements and consume lesser energy than the wild type pre- and post-exposed to A549. However, both the wild type and SCV limit their metabolic activities post- infection of A549 cells and this is indicated by the down-regulation of genes implicated in the metabolism of amino acids, carbohydrate, lipid, and other amino acids. Many well-known virulence and survival factors, including T3SS, fimbriae, capsular polysaccharides and stress response were up-regulated in both the wild type and SCV pre- and post-exposed to A549 cells. Microarray analysis demonstrated essential differences in bacterial response associated with virulence and survival pre- and post-exposed to A549 cells.


Assuntos
Burkholderia pseudomallei/genética , Burkholderia pseudomallei/patogenicidade , Células A549 , Apoptose , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/metabolismo , Farmacorresistência Bacteriana/genética , Perfilação da Expressão Gênica , Humanos , Viabilidade Microbiana , RNA Bacteriano/isolamento & purificação , Estresse Fisiológico/genética , Virulência , Fatores de Virulência/genética
7.
BMC Med Educ ; 21(1): 320, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090439

RESUMO

BACKGROUND: Self-regulated learning (SRL) is an important contributing element to the academic success of students. Literature suggests that the understanding of SRL among medical students is obscure as there is still some uncertainty about whether high performing medical students use SRL. This study explored the characteristics of high performing medical students from the SRL perspective to gain a better understanding of the application of SRL for effective learning. METHODS: Twenty-one students who scored at the 90th percentile in written knowledge-based assessment consented to participate in this study. Each student wrote a guided reflective journal and subsequently attended a semi-structured interview. Students were prompted to explain the rationales for their answers. The data were then analysed using thematic analysis to identify patterns among these students from the SRL perspective. Two coders analysed the data independently and discussed the codes to reach a consensus. RESULTS: High performing students set goals, made plans, and motivated themselves to achieve the goals. They put consistent efforts into their studies and applied effective learning strategies. They also employed coping mechanisms to deal with challenges. High performing students regularly evaluated their performance and adopted new strategies. CONCLUSIONS: This study reported that high performing students applied SRL and described the rationales of practice. Medical schools could design SRL-driven interventions to enhance the learning experiences of medical students. Recommendations are made for students on how to apply SRL.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Competência Clínica , Humanos , Aprendizagem , Pesquisa Qualitativa
8.
Microbiol Immunol ; 64(2): 87-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31769530

RESUMO

Burkholderia cepacia complex (Bcc) are opportunistic pathogens implicated with nosocomial infections, and high rates of morbidity and mortality, especially in individuals with cystic fibrosis (CF). B. cepacia are naturally resistant to different classes of antibiotics, and can subvert the host innate immune responses by producing quorum sensing (QS) controlled virulence factors and biofilms. It still remains a conundrum as to how exactly the bacterium survives the intracellular environment within the host cells of CF patients and immunocompromised individuals although the bacterium can invade human lung epithelial cells, neutrophils, and murine macrophages. The mechanisms associated with intracellular survival in the airway epithelial cells and the role of QS and virulence factors in B. cepacia infections in cystic fibrosis remain largely unclear. The current review focuses on understanding the role of QS-controlled virulence factors and biofilms, and provides additional impetus to understanding the potentials of QS-inhibitory strategies against B. cepacia.


Assuntos
Biofilmes , Infecções por Burkholderia , Burkholderia cepacia/patogenicidade , Fibrose Cística/microbiologia , Percepção de Quorum/imunologia , Animais , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Infecções por Burkholderia/etiologia , Infecções por Burkholderia/imunologia , Burkholderia cepacia/crescimento & desenvolvimento , Complexo Burkholderia cepacia/patogenicidade , Doenças Transmissíveis Emergentes , Infecção Hospitalar/imunologia , Fibrose Cística/complicações , Fibrose Cística/imunologia , Síndrome da Liberação de Citocina , Farmacorresistência Bacteriana Múltipla , Humanos , Evasão da Resposta Imune , Hospedeiro Imunocomprometido , Inflamação , Lipase/metabolismo , Lipopolissacarídeos/metabolismo , Pulmão/microbiologia , Macrófagos/microbiologia , Metaloendopeptidases/metabolismo , Camundongos , Neutrófilos/imunologia , Sideróforos/metabolismo , Fatores de Virulência/metabolismo
9.
J Antimicrob Chemother ; 74(1): 11-16, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30403784

RESUMO

Objectives: Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors. Methods: Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection). Results: Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects. Conclusions: Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.


Assuntos
Antibacterianos/uso terapêutico , Citocromo P-450 CYP2C19/genética , Resistência Microbiana a Medicamentos , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Polimorfismo Genético , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada/métodos , Feminino , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
10.
Cell Microbiol ; 19(12)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28776327

RESUMO

Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas da Membrana Bacteriana Externa/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/fisiologia , Helicobacter pylori/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Western Blotting , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Deleção de Genes , Helicobacter pylori/química , Humanos , Espectrometria de Massas , Proteoma/análise , Fatores de Virulência/análise
11.
BMC Infect Dis ; 18(1): 455, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185168

RESUMO

BACKGROUND: Burkholderia pseudomallei is the causative agent of melioidosis, which is a potentially life threatening disease endemic in Southeast Asian countries. In Malaysia, cystic fibrosis (CF) is an uncommon condition. The association between CF and B.pseudomallei infections has been reported previously. However, this is the first case report of a pediatric melioidosis relapse and co-infection with other Gram-negative bacteria in Malaysia. CASE PRESENTATION: A 14-year-old Chinese Malaysian boy presented with a history of recurrent pneumonia, poor growth and steatorrhoea since childhood, and was diagnosed with CF. B. pseudomallei was cultured from his sputum during three different admissions between 2013 and 2016. However, the patient succumbed to end stage of respiratory failure in 2017 despite antibiotics treatment against B.pseudomallei. The isolates were compared using multilocus-sequence typing and repetitive-element polymerase chain reaction (PCR), and confirmed that two of the isolates were of same sequence type, which may indicate relapse. CONCLUSIONS: CF patients should be aware of melioidosis in endemic regions, as it is an emerging infectious disease, especially when persistent or recurrent respiratory symptoms and signs of infection occur. The high prevalence rates of melioidosis in Malaysia warrants better management options to improve quality of life, and life expectancy in patients with CF. Travel activities to endemic regions should also be given more consideration, as this would be crucial to identify and initiate appropriate empiric treatment.


Assuntos
Fibrose Cística/diagnóstico , Melioidose/diagnóstico , Adolescente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/genética , Burkholderia pseudomallei/isolamento & purificação , Doença Crônica , Fibrose Cística/complicações , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Humanos , Malásia , Masculino , Melioidose/complicações , Melioidose/tratamento farmacológico , Tipagem de Sequências Multilocus , Pneumonia/complicações , Pneumonia/diagnóstico , Recidiva , Escarro/microbiologia , Tomografia Computadorizada por Raios X
13.
Cell Immunol ; 313: 1-9, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28104239

RESUMO

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-ß1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Imunossenescência , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/virologia , Células Cultivadas , Receptores Coestimuladores e Inibidores de Linfócitos T/genética , Receptores Coestimuladores e Inibidores de Linfócitos T/metabolismo , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Carga Viral , Adulto Jovem
14.
Helicobacter ; 22(1)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27258354

RESUMO

BACKGROUND: Helicobacter pylori colonizes almost half of the human population worldwide. H. pylori strains are genetically diverse, and the specific genotypes are associated with various clinical manifestations including gastric adenocarcinoma, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). However, our current knowledge of the H. pylori metabolism is limited. To understand the metabolic differences among H. pylori strains, we investigated four Malaysian H. pylori clinical strains, which had been previously sequenced, and a standard strain, H. pylori J99, at the phenotypic level. MATERIALS AND METHODS: The phenotypes of the H. pylori strains were profiled using the Biolog Phenotype Microarray system to corroborate genomic data. We initiated the analyses by predicting carbon and nitrogen metabolic pathways from the H. pylori genomic data from the KEGG database. Biolog PM aided the validation of the prediction and provided a more intensive analysis of the H. pylori phenomes. RESULTS: We have identified a core set of metabolic nutrient sources that was utilized by all strains tested and another set that was differentially utilized by only the local strains. Pentose sugars are the preferred carbon nutrients utilized by H. pylori. The amino acids l-aspartic acid, d-alanine, and l-asparagine serve as both carbon and nitrogen sources in the metabolism of the bacterium. CONCLUSION: The phenotypic profile based on this study provides a better understanding on the survival of H. pylori in its natural host. Our data serve as a foundation for future challenges in correlating interstrain metabolic differences in H. pylori.


Assuntos
Helicobacter pylori/metabolismo , Redes e Vias Metabólicas , Análise em Microsséries , Fenótipo , Carbono/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Humanos , Malásia , Nitrogênio/metabolismo
15.
Helicobacter ; 22 Suppl 12017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28891140

RESUMO

The current article is a review of the most important and relevant literature published in 2016 and early 2017 on non-Helicobacter pylori Helicobacter infections in humans and animals, as well as interactions between H. pylori and the microbiota of the stomach and other organs. Some putative new Helicobacter species were identified in sea otters, wild boars, dogs, and mice. Many cases of Helicobacter fennelliae and Helicobacter cinaedi infection have been reported in humans, mostly in immunocompromised patients. Mouse models have been used frequently as a model to investigate human Helicobacter infection, although some studies have investigated the pathogenesis of Helicobacters in their natural host, as was the case for Helicobacter suis infection in pigs. Our understanding of both the gastric and gut microbiome has made progress and, in addition, interactions between H. pylori and the microbiome were demonstrated to go beyond the stomach. Some new approaches of preventing Helicobacter infection or its related pathologies were investigated and, in this respect, the probiotic properties of Saccharomyces, Lactobacillus and Bifidobacterium spp. were confirmed.


Assuntos
Microbioma Gastrointestinal , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/veterinária , Helicobacter/classificação , Helicobacter/isolamento & purificação , Animais , Modelos Animais de Doenças , Humanos , Interações Microbianas , Probióticos/administração & dosagem
16.
Nucleic Acids Res ; 43(1): 324-35, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25452339

RESUMO

The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host-pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner.


Assuntos
Genoma Bacteriano , Helicobacter pylori/genética , Enzimas de Restrição-Modificação do DNA/genética , Evolução Molecular , Genes Bacterianos , Genômica , Helicobacter pylori/classificação , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/patogenicidade , Humanos , Malásia , Filogenia , Filogeografia , Virulência
17.
Food Microbiol ; 62: 68-76, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27889168

RESUMO

To date, the exact route and mode of transmission of Helicobacter pylori remains elusive. The detection of H. pylori in food using molecular approaches has led us to postulate that the gastric pathogen may survive in the extragastric environment for an extended period. In this study, we show that H. pylori prolongs its survival by forming biofilm and micro-colonies on vegetables. The biofilm forming capability of H. pylori is both strain and vegetable dependent. H. pylori strains were classified into high and low biofilm formers based on their highest relative biofilm units (BU). High biofilm formers survived longer on vegetables compared to low biofilm formers. The bacteria survived better on cabbage compared to other vegetables tested. In addition, images captured on scanning electron and confocal laser scanning microscopes revealed that the bacteria were able to form biofilm and reside as micro-colonies on vegetable surfaces, strengthening the notion of possible survival of H. pylori on vegetables for an extended period of time. Taken together, the ability of H. pylori to form biofilm on vegetables (a common food source for human) potentially plays an important role in its survival, serving as a mode of transmission of H. pylori in the extragastric environment.


Assuntos
Biofilmes/crescimento & desenvolvimento , Microbiologia de Alimentos , Helicobacter pylori/fisiologia , Verduras/microbiologia , Aderência Bacteriana/fisiologia , Brassica/microbiologia , Humanos , Viabilidade Microbiana , Folhas de Planta/microbiologia , Estômatos de Plantas/microbiologia
18.
Proc Natl Acad Sci U S A ; 111(51): 18321-6, 2014 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-25489084

RESUMO

Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.


Assuntos
Neoplasias Colorretais/microbiologia , Microbiota , Bactérias/classificação , Bactérias/isolamento & purificação , Biofilmes , Colonoscopia , Humanos
19.
Eur J Clin Invest ; 46(2): 170-80, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26681320

RESUMO

BACKGROUND: Mucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. MATERIALS AND METHODS: We investigated the frequency of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. RESULTS: The frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. CONCLUSIONS: Immune exhaustion and senescence of CD8(+) CD161(++) TCR Vα7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Hepatite C Crônica/imunologia , ADP-Ribosil Ciclase 1/imunologia , Adulto , Antígenos CD/imunologia , Biomarcadores , Antígenos CD57/imunologia , Linfócitos T CD8-Positivos/metabolismo , Antígeno CTLA-4/imunologia , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Feminino , Citometria de Fluxo , Antígenos HLA-DR/imunologia , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Imunidade Inata/imunologia , Imunossenescência/imunologia , Cadeias alfa de Integrinas/imunologia , Contagem de Linfócitos , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Subfamília B de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores CCR5/imunologia , Carga Viral , Adulto Jovem
20.
Faraday Discuss ; 191: 465-479, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27430046

RESUMO

We have developed a new class of lanthanide nano-clusters that self-assemble using flexible Schiff base ligands. Cd-Ln and Ni-Ln clusters, [Ln8Cd24(L1)12(OAc)39Cl7(OH)2] (Ln = Nd, Eu), [Eu8Cd24(L1)12(OAc)44], [Ln8Cd24(L2)12(OAc)44] (Ln = Nd, Yb, Sm) and [Nd2Ni4(L3)2(acac)6(NO3)2(OH)2], were constructed using different types of flexible Schiff base ligands. These molecular nano-clusters exhibit anisotropic architectures that differ considerably depending upon the presence of Cd (nano-drum) or Ni (square-like nano-cluster). Structural characterization of the self-assembled particles has been undertaken using crystallography, transmission electron microscopy and small-angle X-ray scattering. Comparison of the metric dimensions of the nano-drums shows a consistency of size using these techniques, suggesting that these molecules may share similar structural features in both solid and solution states. Photophysical properties were studied by excitation of the ligand-centered absorption bands in the solid state and in solution, and using confocal microscopy of microspheres loaded with the compounds. The emissive properties of these compounds vary depending upon the combination of lanthanide and Cd or Ni present in these clusters. The results provide new insights into the construction of novel high-nuclearity nano-clusters and offer a promising foundation for the development of new functional nanomaterials.


Assuntos
Elementos da Série dos Lantanídeos , Nanoestruturas , Bases de Schiff , Ligantes , Compostos Organometálicos
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