RESUMO
INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created many challenges for Hong Kong residents attempting to maintain healthy lifestyle habits. This study aimed to measure the prevalences of unhealthy dietary habits and physical inactivity levels in Hong Kong Chinese, identify associated factors, and conduct a time trend analysis during the third wave of the COVID-19 pandemic. METHODS: A cross-sectional telephone survey was conducted in Hong Kong by simple random sampling. The survey comprised socio-demographic characteristics, clinical information, the Hong Kong Diet Score (HKDS), smoking and alcohol consumption, and a Chinese version of the International Physical Activity Questionnaire Short Form. The composite outcome was low HKDS, physical inactivity, smoking, and alcohol consumption. We used 14 Health Behaviour Survey reports from 2003 to 2019 to establish a trend analysis regarding fruit and vegetable consumption, physical activity level, smoking, and alcohol consumption. RESULTS: We performed 1500 complete telephone surveys with a response rate of 58.8%. Most participants were older adults (≥65 years, 66.7%), women (65.6%), and married (77.9%). The HKDS was significantly lower in men, single individuals, low-income participants, alcohol drinkers, and patients with diabetes mellitus or renal disease. Participants who were single, undergoing long-term management of medical diseases, or had diabetes or renal diseases exhibited greater likelihood of physical inactivity. CONCLUSION: Prevalences of unhealthy lifestyle habits were high among men, single individuals, and chronic disease patients during the third wave of the COVID-19 pandemic in Hong Kong. The adoption of physical activity habits tended to decrease in the past two decades.
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COVID-19 , Pandemias , Masculino , Humanos , Feminino , Idoso , Estudos Transversais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Exercício Físico , Hong Kong/epidemiologia , Comportamento AlimentarRESUMO
INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.
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Infecções por Clostridium/terapia , Diarreia/terapia , Transplante de Microbiota Fecal , Idoso , Colonoscopia , Endoscopia do Sistema Digestório , Fezes/microbiologia , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75â years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.
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Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/normas , Idoso , Ásia , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The detection of microRNA (miRNA) dysregulation in stool is a novel approach for the diagnosis of colorectal carcinoma (CRC). The aim of this study is to investigate the use of miR-221 and miR-18a in stool samples as non-invasive biomarkers for CRC diagnosis. METHODS: A miRNA expression array containing 667 miRNAs was performed to identify miRNA dysregulation in CRC tissues. We focused on miR-221 and miR-18a, two significantly upregulated miRNAs which were subsequently verified in 40 pairs of CRC tissues and 595 stool samples (198 CRCs, 199 polyps and 198 normal controls). RESULTS: miR-221 and miR-18a were upregulated in the miRNA expression array. miR-221 and miR-18a levels were also significantly higher in 40 CRC tumours compared with their respective adjacent normal tissues. In stool samples, miR-221 and miR-18a showed a significant increasing trend from normal controls to late stages of CRC (P<0.0001). The levels of stool miR-221 and miR-18a were both significantly higher in subjects with stages I+II (miR-221: P<0.0001, miR-18a: P<0.0001) and stages III+IV of CRC (miR-221: P=0.0004, miR-18a: P<0.0001) compared with normal controls. The AUC of stool miR-221 and miR-18a were 0.73 and 0.67 for CRC patients as compared with normal controls, respectively. No significant differences in stool miR-221 and miR-18a levels were found between patients with proximal and distal CRCs. The use of antibiotics did not influence stool miRNA-221 and miRNA-18a levels. CONCLUSIONS: Stool-based miR-221 can be used as a non-invasive biomarker for the detection of CRC.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Fezes/química , MicroRNAs/genética , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Curva ROCRESUMO
BACKGROUND AND STUDY AIMS: Capsule endoscopy may play a role in the evaluation of patients presenting with acute upper gastrointestinal hemorrhage in the emergency department. PATIENTS AND METHODS: We evaluated adults with acute upper gastrointestinal hemorrhage presenting to the emergency departments of two academic centers. Patients ingested a wireless video capsule, which was followed immediately by a nasogastric tube aspiration and later by esophagogastroduodenoscopy (EGD). We compared capsule endoscopy with nasogastric tube aspiration for determination of the presence of blood, and with EGD for discrimination of the source of bleeding, identification of peptic/inflammatory lesions, safety, and patient satisfaction. RESULTS: The study enrolled 49 patients (32 men, 17 women; mean age 58.3â±â19 years), but three patients did not complete the capsule endoscopy and five were intolerant of the nasogastric tube. Blood was detected in the upper gastrointestinal tract significantly more often by capsule endoscopy (15â/18 [83.3â%]) than by nasogastric tube aspiration (6â/18 [33.3â%]; Pâ=â0.035). There was no significant difference in the identification of peptic/inflammatory lesions between capsule endoscopy (27â/40 [67.5â%]) and EGD (35â/40 [87.5â%]; Pâ=â0.10, OR 0.39 95â%CI 0.11â-â1.15). Capsule endoscopy reached the duodenum in 45â/46 patients (98â%). One patient (2.2â%) had self-limited shortness of breath and one (2.2â%) had coughing on capsule ingestion. CONCLUSIONS: In an emergency department setting, capsule endoscopy appears feasible and safe in people presenting with acute upper gastrointestinal hemorrhage. Capsule endoscopy identifies gross blood in the upper gastrointestinal tract, including the duodenum, significantly more often than nasogastric tube aspiration and identifies inflammatory lesions, as well as EGD. Capsule endoscopy may facilitate patient triage and earlier endoscopy, but should not be considered a substitute for EGD.
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Endoscopia por Cápsula , Hemorragia Gastrointestinal/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência , Endoscopia do Sistema Digestório , Estudos de Viabilidade , Feminino , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Projetos Piloto , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Trato Gastrointestinal SuperiorRESUMO
BACKGROUND AND STUDY AIMS: Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated. PATIENTS AND METHODS: In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed. RESULTS: 20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up. CONCLUSION: These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.
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Hemostase Endoscópica , Hemostáticos/administração & dosagem , Úlcera Péptica Hemorrágica/terapia , Pós/administração & dosagem , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NanopartículasRESUMO
OBJECTIVE: Our study aimed to assess the effectiveness of esomeprazole or rabeprazole in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in Hong Kong non-ulcer dyspepsia (NUD) patients. METHODS: A prospective clinical trial was conducted at the Alice Ho Miu ling Nethersole Hospital outpatient endoscopy center from June 2004 to December 2005. Participants received amoxicillin 1 g, clarithromycin 500 mg, and, esomeprazole 20 mg (EAC) or rabeprazole 20 mg (RAC), all given twice daily for 1 week. The H. pylori status was determined by the [13C] urea breath test at least 4 weeks after completion of the treatment. Mutation status of CYP2C19 in exon 4 and exon 5 associated with the poor metabolizer phenotype was determined. RESULTS: The intention-to-treat eradication rates in patients treated with RAC and EAC were 77% and 84.6% respectively, and per protocol-based eradication rates were 83.7% and 88.9% respectively. The eradication rates did not vary with CYP2C19 phenotype found. For clarithromycin-sensitive strains, the cure rates were statistically significant regardless of CYP2C19 polymorphism (P < 0.0001). CONCLUSION: Triple therapy with either EAC or RAC is effective for Hong Kong Chinese NUD patients with H. pylori infection. Success eradication was related to clarithromycin resistance and not CYP2C19 genotype.
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2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Antibacterianos/uso terapêutico , Esomeprazol/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , 2-Piridinilmetilsulfinilbenzimidazóis/administração & dosagem , Adulto , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Hidrocarboneto de Aril Hidroxilases/genética , Povo Asiático/genética , Testes Respiratórios/métodos , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Citocromo P-450 CYP2C19 , Farmacorresistência Bacteriana , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Esomeprazol/administração & dosagem , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Farmacogenética , Polimorfismo Genético , Estudos Prospectivos , Rabeprazol , Ureia/metabolismoRESUMO
BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.
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Hepatite B Crônica/complicações , Cirrose Hepática/etiologia , Síndrome Metabólica/complicações , Adulto , Distribuição por Idade , Biópsia , Índice de Massa Corporal , Técnicas de Imagem por Elasticidade , Métodos Epidemiológicos , Feminino , Hepatite B Crônica/epidemiologia , Hong Kong/epidemiologia , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis. METHODS: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro. RESULTS: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar. CONCLUSION: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.
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Biomarcadores Tumorais/análise , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Apoptose/fisiologia , Western Blotting , Linhagem Celular Tumoral , Citometria de Fluxo , Expressão Gênica , Humanos , Imuno-Histoquímica , RNA Mensageiro/análise , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos , Ubiquitina-Proteína LigasesRESUMO
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
Assuntos
Alanina Transaminase/sangue , Técnicas de Imagem por Elasticidade , Hepatite B Crônica/patologia , Cirrose Hepática/diagnóstico , Fígado/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To evaluate nucleic acid testing of urine specimens against conventional Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) tests in genital swab specimens in a sexually transmitted infection (STI) clinic setting. METHODS: Genital swab and urine samples were collected from attendees of public STI clinics in Hong Kong from May to June 2007. Swab specimens were subjected to on-site Gram stained microscopy and inoculation onto modified Thayer-Martin medium for NG culture before laboratory processing. CT PCR on genital swabs was performed by the Roche Cobas Amplicor test. Urine samples were tested for CT and NG by the Aptima Combo 2 (AC2) assay. RESULTS: Data from 414 patients were analysed. The sensitivity and specificity of AC2 for NG were 100% (35/35) and 98.4% (373/379), respectively, with culture of genital swab specimens as standard. On-site microscopy provided timely results for empirical antimicrobial therapy, whereas culture yielded bacterial isolates for susceptibility testing and typing studies. Regarding CT, using Amplicor on genital swab specimens as reference, the sensitivity and specificity of AC2 were 98.7% (78/79) and 97.5% (313/321), respectively. Amplicor yielded uninterpretable results in 14 specimens due to PCR inhibitors. CONCLUSIONS: The current STI clinic and laboratory practices were practical and useful for clinical management, even though favourable results were obtained with the AC2 assay, which had streamlined laboratory workflow. The use of a molecular testing strategy may be cost-effective with microscopy and culture being targetted for patient groups with the highest expected yield of positive results.
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Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Gonorreia/diagnóstico , Neisseria gonorrhoeae/isolamento & purificação , Instituições de Assistência Ambulatorial , Infecções por Chlamydia/urina , Feminino , Gonorreia/urina , Hong Kong , Humanos , Masculino , Técnicas de Amplificação de Ácido Nucleico/métodos , Kit de Reagentes para Diagnóstico , Sensibilidade e EspecificidadeRESUMO
A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-alpha and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.
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Receptores do Fator de Necrose Tumoral/química , Receptores do Fator de Necrose Tumoral/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Substituição de Aminoácidos , Antígenos CD/química , Antígenos CD/metabolismo , Apoptose , Sítios de Ligação , Reagentes de Ligações Cruzadas , Dimerização , Transferência de Energia , Fluorescência , Humanos , Ligantes , Substâncias Macromoleculares , Mutação , Conformação Proteica , Estrutura Terciária de Proteína , Receptores Tipo I de Fatores de Necrose Tumoral , Receptores Tipo II do Fator de Necrose Tumoral , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Succinimidas , Células Tumorais CultivadasRESUMO
Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced receptor oligomerization, was found to stem from ligand- independent interaction of wild-type and mutant Fas receptors through a specific region in the extracellular domain. Preassociated Fas complexes were found in living cells by means of fluorescence resonance energy transfer between variants of green fluorescent protein. These results show that formation of preassociated receptor complexes is necessary for Fas signaling and dominant interference in human disease.
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Apoptose , Glicoproteínas de Membrana/metabolismo , Transdução de Sinais , Receptor fas/química , Receptor fas/metabolismo , Animais , Doenças Autoimunes/fisiopatologia , Linhagem Celular , Membrana Celular/metabolismo , Reagentes de Ligações Cruzadas , Proteína Ligante Fas , Humanos , Ligantes , Linfócitos/citologia , Transtornos Linfoproliferativos/fisiopatologia , Substâncias Macromoleculares , Camundongos , Mutação , Mutação Puntual , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Succinimidas , Células Tumorais Cultivadas , Receptor fas/genéticaRESUMO
Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.
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Povo Asiático/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Programas de Rastreamento/métodos , Ásia/epidemiologia , Colonoscopia , Neoplasias Colorretais/etnologia , Medicina Baseada em Evidências , Feminino , Humanos , Incidência , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/etnologia , Masculino , Pessoa de Meia-Idade , Sangue Oculto , SigmoidoscopiaRESUMO
Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.
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Proteínas de Ligação ao Cálcio/metabolismo , Metilação de DNA/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Idoso , Compostos Aza/farmacologia , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Neoplasias Gástricas/patologia , Regulação para Cima/efeitos dos fármacosRESUMO
The cell cycle in mammalian cells is regulated by a series of cyclins and cyclin-dependent kinases (CDKs). The G1/S checkpoint is mainly dictated by the kinase activities of the cyclin D-CDK4 and/or cyclin D-CDK6 complex and the cyclin E-CDK2 complex. These G1 kinases can in turn be regulated by cell cycle inhibitors, which may cause the cells to arrest at the G1 phase. In T-cell hybridomas, addition of anti-T-cell receptor antibody results not only in G1 arrest but also in apoptosis. In searching for a protein(s) which might interact with Nur77, an orphan steroid receptor required for activation-induced apoptosis of T-cell hybridomas, we have cloned a novel human and mouse CDK inhibitor, p19. The deduced p19 amino acid sequence consists of four ankyrin repeats with 48% identity to p16. The human p19 gene is located on chromosome 19p13, distinct from the positions of p18, p16, and p15. Its mRNA is expressed in all cell types examined. The p19 fusion protein can associate in vitro with CDK4 but not with CDK2, CDC2, or cyclin A, B, E, or D1 to D3. Addition of p19 protein can lead to inhibition of the in vitro kinase activity of cyclin D-CDK4 but not that of cyclin E-CDK2. In T-cell hybridoma DO11.10, p19 was found in association with CDK4 and CDK6 in vivo, although its association with Nur77 is not clear at this point. Thus, p19 is a novel CDK inhibitor which may play a role in the cell cycle regulation of T cells.
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Proteínas de Transporte/genética , Quinases Ciclina-Dependentes , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas , Sequência de Aminoácidos , Animais , Apoptose , Proteínas de Transporte/metabolismo , Proteínas de Transporte/farmacologia , Ciclo Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 19 , Clonagem Molecular , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Inibidor p16 de Quinase Dependente de Ciclina , Humanos , Hibridização in Situ Fluorescente , Camundongos , Dados de Sequência Molecular , Proteínas Serina-Treonina Quinases/metabolismo , Homologia de Sequência de Aminoácidos , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Receptor interacting protein kinase 3 (RIPK3) is an essential serine/threonine kinase for necroptosis, a type of regulated necrosis. A variety of stimuli can cause RIPK3 activation through phosphorylation. Activated RIPK3 in turn phosphorylates and activates the downstream necroptosis executioner mixed lineage kinase domain-like (MLKL). Necroptosis is a highly inflammatory type of cell death because of the release of intracellular immunogenic contents from disrupted plasma membrane. Indeed, RIPK3-deficient mice exhibited reduced inflammation in many inflammatory disease models. These results have been interpreted as evidence that necroptosis is a key driver for RIPK3-induced inflammation. Interestingly, recent studies show that RIPK3 also regulates NF-κB, inflammasome activation, and kinase-independent apoptosis. These studies also reveal that these nonnecroptotic functions contribute significantly to disease pathogenesis. In this review, we summarize our current understanding of necroptotic and nonnecroptotic functions of RIPK3 and discuss how these effects contribute to RIPK3-mediated inflammation.
Assuntos
Apoptose , Inflamação/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Animais , Humanos , Modelos Biológicos , NecroseRESUMO
BACKGROUND: Non-alcoholic fatty liver disease is prevalent in affluent countries and is strongly associated with metabolic syndrome. AIM: To study the prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. METHODS: 73 consecutive patients with biopsy-proven non-alcoholic fatty liver disease and no history of diabetes underwent comprehensive metabolic screening. Diagnosis of diabetes and impaired glucose regulation was based on the 2006 American Diabetes Association criteria. RESULTS: The prevalence of undiagnosed diabetes and impaired glucose tolerance in non-alcoholic fatty liver disease patients was 33% and 29%, respectively. Among patients with 2-h plasma glucose above 7.8 mm, 47% had normal fasting glucose (below 5.6 mm). Impaired glucose tolerance was more common in patients with non-alcoholic steatohepatitis than those with simple hepatic steatosis (P = 0.036), and 2-h plasma glucose correlated with fibrosis stage (Spearman coefficient: 0.25, P = 0.046). In a binary logistic regression analysis, high fasting glucose and low high-density lipoprotein cholesterol were independent factors associated with diabetes. Nevertheless, if oral glucose tolerance test was only performed in non-alcoholic fatty liver disease patients with impaired fasting glucose, 20.8% of diabetes cases would be missed. CONCLUSIONS: Isolated postchallenge hyperglycaemia is common among Chinese non-alcoholic fatty liver disease patients without history of diabetes. It is associated with histological severe disease, and cannot be accurately predicted by any fasting glucose cut-off.