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COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of COPD includes sustained airway inflammation and the eventual destruction of lung tissue structure. While multiple risk factors are implicated in the disease's progression, the underlying mechanisms remain largely elusive. The perpetuation of inflammation is pivotal to the advancement of COPD, emphasising the importance of investigating these self-sustaining mechanisms for a deeper understanding of the pathogenesis. Autoimmune responses constitute a critical mechanism in maintaining inflammation, with burgeoning evidence pointing to their central role in COPD progression; yet, the intricacies of these mechanisms remain inadequately defined. This review elaborates on the evidence supporting the presence of autoimmune processes in COPD and examines the potential mechanisms through which autoimmune responses may drive the chronic inflammation characteristic of the disease. Moreover, we attempt to interpret the clinical manifestations of COPD through autoimmunity.
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Doença Pulmonar Obstrutiva Crônica , Humanos , Autoimunidade , Pulmão/patologia , Fatores de Risco , InflamaçãoRESUMO
This study aimed to explore the efficacy and mechanism of combined rhein and emodin in the treatment of ulcerative colitis(UC) from the aspects of network pharmacology, animal inflammation improvement and molecular mechanism. Network pharmacology predicted that combined rhein and emodin acted on 52 potential targets, mainly participating in signaling pathways such as cancer, PI3 K/AKT, microRNAs in cancer and apoptosis. PI3 K/AKT signaling pathway has been reported to be closely related to UC, and the optimal candidate pathway for combined therapy. The UC mice model was established by dextran sodium sulfate, and then the modeled mice were randomly divided into control group, model group, rhein group, emodin group, rhein+emodin group and sulfasalazine group. After administration, compared with the conditions in model group, body weight, disease activity index(DAI) score, colon length, TNF-α, IL-6, IL-1ß and myeloperoxidase(MPO) of mice in rhein+emodin group were improved(P<0.01); colonic mucosal injury was significantly reduced; the expression of p-PI3 K/PI3 K and p-AKT/AKT proteins were down-regulated(P<0.01). All the above indices were better than those in the rhein/emodin group alone. The Jin's Q-values of the effect of combined rhein and emodin on colon length, TNF-α, IL-6, IL-1ß, MPO, p-PI3 K/PI3 K and p-AKT/AKT were all greater than 1.15, which indicated that there was obvious synergistic effect between rhein and emodin. In all, rhein and emodin have synergistic effect in the treatment of UC, and the mechanism may be related to the inhibition of PI3 K/AKT signaling pathway and the down-regulation of proinflammatory factors. They are the new components in the treatment of UC, which is worthy of attention.
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Colite Ulcerativa , Emodina , Rheum , Animais , Antraquinonas , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Modelos Animais de Doenças , Emodina/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
[This corrects the article DOI: 10.3389/fimmu.2021.594330.].
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OBJECTIVE: Autophagy was prominently activated by cerebral ischaemia. This study was to investigate the exact role of autophagy in ischaemic stroke. METHODS: Two rat models of transient middle cerebral artery occlusion (tMCAO) and permanent MCAO (pMCAO) were prepared. The brain tissues in the penumbra were obtained to observe the dynamic variations of autophagy activity with Beclin1 and LC3 antibodies by Western blotting. At the characteristic time points, when autophagy activity was markedly elevated or reduced, the autophagy activation signaling was intervened with rapamycin and 3-methyladenine, respectively. Thereafter, key proteins in the autopahgic/lysosomal pathway were detected with the antibodies of LC3, p62, ubiquitin, LAMP-1 and cathepsin B. Meanwhile, TTC staining, neurological score and immunofluorescence were performed to evaluate brain infarct volume, neurological deficit and neuron survival, respectively. RESULTS: Both Beclin1 and LC3 expression levels were remarkably altered at 6 h, 12 h, 2 days and 7 days after tMCAO. Interestingly, the dynamic changes of autophagy activity following pMCAO were identical to those after tMCAO. Neither autophagy induction nor autophagy inhibition was able to ameliorate the pMCAO-induced neurological injury due to lysosomal dysfunction, as indicated by low levels of LAMP-1 and cathepsin B, accompanied with the accumulation of LC3-II, ubiquitin and insoluble p62. Comparatively, autophagy induction elicited overt neuroprotection at 2 and 7 days after tMCAO, and this neuroprotection might be elicited by the enhancement of autophagy flux. CONCLUSION: Our study suggests that autophagy confers neuroprotection at the subacute phase of tMCAO but has few effects on neurological outcomes after pMCAO.
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Autofagia/genética , Encéfalo/metabolismo , Ataque Isquêmico Transitório/metabolismo , AVC Isquêmico/metabolismo , Neurônios/metabolismo , Animais , Encéfalo/patologia , Modelos Animais de Doenças , Humanos , Infarto da Artéria Cerebral Média , Ataque Isquêmico Transitório/genética , Ataque Isquêmico Transitório/patologia , AVC Isquêmico/genética , AVC Isquêmico/patologia , Lisossomos/genética , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Neurônios/patologia , Neuroproteção/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteína Sequestossoma-1/genética , Transdução de Sinais/genéticaRESUMO
Cigarette smoke (CS)-induced macrophage activation and airway epithelial injury are both critical for the development of chronic obstructive pulmonary disease (COPD), while the eventual functions of autophagy in these processes remain controversial. We have recently developed a novel COPD mouse model which is based on the autoimmune response sensitized by CS and facilitated by elastin. In the current study, we therefore utilized this model to investigate the roles of autophagy in different stages of the development of bronchitis-like airway inflammation. Autophagic markers were increased in airway epithelium and lung tissues, and Becn+/- or Lc3b-/- mice exhibited reduced neutrophilic airway inflammation and mucus hyperproduction in this COPD mouse model. Moreover, treatment of an autophagic inhibitor 3-methyladenine (3-MA) either during CS-initiated sensitization or during elastin provocation significantly inhibited the bronchitis-like phenotypes in mice. Short CS exposure rapidly induced expression of matrix metallopeptidase 12 (MMP12) in alveolar macrophages, and treatment of doxycycline, a pan metalloproteinase inhibitor, during CS exposure effectively attenuated the ensuing elastin-induced airway inflammation in mice. CS extract triggered MMP12 expression in cultured macrophages, which was attenuated by autophagy impairment (Becn+/- or Lc3b-/-) or inhibition (3-MA or Spautin-1). These data, taken together, demonstrate that autophagy mediates both the CS-initiated MMP12 activation in macrophages and subsequent airway epithelial injury, eventually contributing to development COPD-like airway inflammation. This study reemphasizes that inhibition of autophagy as a novel therapeutic strategy for CS-induced COPD.
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Autofagia , Bronquite/etiologia , Bronquite/metabolismo , Elastina/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Biomarcadores , Bronquite/patologia , Linhagem Celular , Células Cultivadas , Modelos Animais de Doenças , Suscetibilidade a Doenças , Elastina/genética , Expressão Gênica , Humanos , Imuno-Histoquímica , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , CamundongosRESUMO
Asthma is a chronic inflammatory disease of the lungs that poses a considerable health and socioeconomic burden. Several risk factors work synergistically to affect the progression of asthma. Lipid metabolism, especially in distinct cells such as T cells, macrophages, granulocytes, and non-immune cells, plays an essential role in the pathogenesis of asthma, as lipids are potent signaling molecules that regulate a multitude of cellular response. In this review, we focused on the metabolic pathways of lipid molecules, especially fatty acids and their derivatives, and summarized their roles in various cells during the pathogenesis of asthma along with the current pharmacological agents targeting lipid metabolism.
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Asma/metabolismo , Granulócitos/imunologia , Metabolismo dos Lipídeos/imunologia , Macrófagos/imunologia , Linfócitos T/imunologia , Animais , Asma/tratamento farmacológico , Asma/epidemiologia , Ácidos Graxos/metabolismo , Humanos , Imunidade Celular , Terapia de Alvo Molecular , Fatores de Risco , Transdução de SinaisRESUMO
Autophagy is crucial for maintaining cellular homeostasis, and can be activated after ischemic stroke. It also participates in nerve injury and repair. The purpose of this study was to investigate whether an enriched environment has neuroprotective effects through affecting autophagy. A Sprague-Dawley rat model of transient ischemic stroke was prepared by occlusion of the middle cerebral artery followed by reperfusion. One week after surgery, these rats were raised in either a standard environment or an enriched environment for 4 successive weeks. The enriched environment increased Beclin-1 expression and the LC3-II/LC3-I ratio in the autophagy/lysosomal pathway in the penumbra of middle cerebral artery-occluded rats. Enriched environment-induced elevations in autophagic activity were mainly observed in neurons. Enriched environment treatment also promoted the fusion of autophagosomes with lysosomes, enhanced the lysosomal activities of lysosomal-associated membrane protein 1, cathepsin B, and cathepsin D, and reduced the expression of ubiquitin and p62. After 4 weeks of enriched environment treatment, neurological deficits and neuronal death caused by middle cerebral artery occlusion/reperfusion were significantly alleviated, and infarct volume was significantly reduced. These findings suggest that neuronal autophagy is likely the neuroprotective mechanism by which an enriched environment promotes recovery from ischemic stroke. This study was approved by the Animal Ethics Committee of the Kunming University of Science and Technology, China (approval No. 5301002013855) on March 1, 2019.
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It is currently not understood whether cigarette smoke exposure facilitates sensitisation to self-antigens and whether ensuing auto-reactive T cells drive chronic obstructive pulmonary disease (COPD)-associated pathologies.To address this question, mice were exposed to cigarette smoke for 2â weeks. Following a 2-week period of rest, mice were challenged intratracheally with elastin for 3â days or 1â month. Rag1-/- , Mmp12-/- , and Il17a-/- mice and neutralising antibodies against active elastin fragments were used for mechanistic investigations. Human GVAPGVGVAPGV/HLA-A*02:01 tetramer was synthesised to assess the presence of elastin-specific T cells in patients with COPD.We observed that 2â weeks of cigarette smoke exposure induced an elastin-specific T cell response that led to neutrophilic airway inflammation and mucus hyperproduction following elastin recall challenge. Repeated elastin challenge for 1â month resulted in airway remodelling, lung function decline and airspace enlargement. Elastin-specific T cell recall responses were dose dependent and memory lasted for over 6â months. Adoptive T cell transfer and studies in T cells deficient Rag1-/- mice conclusively implicated T cells in these processes. Mechanistically, cigarette smoke exposure-induced elastin-specific T cell responses were matrix metalloproteinase (MMP)12-dependent, while the ensuing immune inflammatory processes were interleukin 17A-driven. Anti-elastin antibodies and T cells specific for elastin peptides were increased in patients with COPD.These data demonstrate that MMP12-generated elastin fragments serve as a self-antigen and drive the cigarette smoke-induced autoimmune processes in mice that result in a bronchitis-like phenotype and airspace enlargement. The study provides proof of concept of cigarette smoke-induced autoimmune processes and may serve as a novel mouse model of COPD.
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Elastina , Doença Pulmonar Obstrutiva Crônica , Animais , Autoimunidade , Modelos Animais de Doenças , Humanos , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Fumaça/efeitos adversos , Fumar/efeitos adversosRESUMO
Particulate matter (PM) is able to induce airway epithelial injury, while the detailed mechanisms remain unclear. Here we demonstrated that PM exposure inactivated MTOR (mechanistic target of rapamycin kinase), enhanced macroautophagy/autophagy, and impaired lysosomal activity in HBE (human bronchial epithelial) cells and in mouse airway epithelium. Genetic or pharmaceutical inhibition of MTOR significantly enhanced, while inhibition of autophagy attenuated, PM-induced IL6 expression in HBE cells. Consistently, club-cell-specific deletion of Mtor aggravated, whereas loss of Atg5 in bronchial epithelium reduced, PM-induced airway inflammation. Interestingly, the augmented inflammatory responses caused by MTOR deficiency were markedly attenuated by blockage of downstream autophagy both in vitro and in vivo. Mechanistically, the dysregulation of MTOR-autophagy signaling was partially dependent on activation of upstream TSC2, and interacted with the TLR4-MYD88 to orchestrate the downstream NFKB activity and to regulate the production of inflammatory cytokines in airway epithelium. Moreover, inhibition of autophagy reduced the expression of EPS15 and the subsequent endocytosis of PM. Taken together, the present study provides a mechanistic explanation for how airway epithelium localized MTOR-autophagy axis regulates PM-induced airway injury, suggesting that activation of MTOR and/or suppression of autophagy in local airway might be effective therapeutic strategies for PM-related airway disorders.Abbreviations: ACTB: actin beta; AKT: AKT serine/threonine kinase; ALI: air liquid interface; AP2: adaptor related protein complex 2; ATG: autophagy related; BALF: bronchoalveolar lavage fluid; COPD: chronic obstructive pulmonary disease; CXCL: C-X-C motif chemokine ligand; DOX: doxycycline; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPS15: epidermal growth factor receptor pathway substrate 15; HBE: human bronchial epithelial; H&E: hematoxylin & eosin; IKK: IKB kinase; IL: interleukin; LAMP2: lysosomal-associated membrane protein 2; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTEC: mouse tracheal epithelial cells; MTOR: mechanistic target of rapamycin kinase; MYD88: MYD88 innate immune signal transduction adaptor; NFKB: nuclear factor of kappa B; NFKBIA: NFKB inhibitor alpha; PM: particulate matter; PtdIns3K: phosphatidylinositol 3-kinase; Rapa: rapamycin; RELA: RELA proto-oncogene, NFKB subunit; SCGB1A1: secretoglobin family 1A member 1; siRNA: small interfering RNAs; SQSTM1: sequestosome 1; TEM: transmission electronic microscopy; TLR4: toll like receptor 4; TSC2: TSC complex subunit 2.
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Autofagia , Células Epiteliais/patologia , Material Particulado/toxicidade , Pneumonia/induzido quimicamente , Pneumonia/patologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteína 5 Relacionada à Autofagia/metabolismo , Brônquios/patologia , Linhagem Celular , Citocinas/metabolismo , Endocitose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Deleção de Genes , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/deficiência , Proteínas Associadas aos Microtúbulos/metabolismo , Modelos Biológicos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Ligação Proteica/efeitos dos fármacos , Proto-Oncogene Mas , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/metabolismoRESUMO
BACKGROUND: Colorectal cancer is one of the most common malignancies in the world, and about 25% of colorectal cancer patients present with colorectal cancer liver metastases (CRCLM) even at new diagnosis. The study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) alternating with mFOLFOX6 in Chinese patients with unresectable CRCLM. MATERIALS AND METHODS: In this study, by combining the systemic and regional treatment, the resectability rate, overall survival, and progression-free survival were measured with addition of TACE. Included patients had Eastern Cooperative Oncology Group performance status 0-2. Sixty-two patients received mFOLFOX6 plus one TACE after 2 weeks of chemotherapy; after 2 weeks, the next periodical treatment repeated. Patients received operation when the liver metastases were converted to resectability or severe tumor-associated complications occurred. RESULTS: We found that 28 patients (45.2%) patients received operation after the treatment of TACE combined with systemic chemotherapy. The median time from initial treatment to the operation was 6 months. The median follow-up period was 41 months in all the patients. The 3-year survival rate of resected patients and unresected patients was 54% and 17%, respectively. Post-TACE syndrome was the major adverse reaction (81%). Other adverse reactions were neutropenia, nausea, and neurotoxicity. No patient died of the adverse reactions. The resection rate was related to hepatic segments and vasculature involvement. CONCLUSION: Taken together, TACE alternating with mFOLFOX6 has been proved to be safe and effective for CRCLM treatment to improve resection rate and prolong the survival time.
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OBJECTIVE: To investigate drug knowledge of middle school students in HIV prone areas in Liangshan of Sichuan Province. METHODS: Students were randomly selected from the middle schools located in the HIV prone areas in Liangshan. A questionnaire survey was conducted. Drug knowledge of the respondents and associated factors were analyzed. RESULTS: Of the 10 749 respondents,10.1% had wrong knowledge about drugs. The respondents of male gender and minority ethnicity in the region and those who were in a lower grade,had poor academic records,more sisters,and a schoolmate taking drugs,and lived in a family with HIV infected member were more likely to had poor drug knowledge. By contrast,the respondents who had a peasant father,lived with both parents,resided in a city or township,self-rated in the middle and low 1/3 of wealth,lived in a community with >50% school attendance,and had a family member taking drugs were less likely to have wrong drug knowledge. CONCLUSION: Middle school students in the HIV prone areas in Liangshan have poor drug knowledge. Socioeconomic factors influence the drug knowledge of students,which require systematic interventions.
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Conhecimentos, Atitudes e Prática em Saúde , Drogas Ilícitas , Estudantes , China , Feminino , Infecções por HIV , Humanos , Masculino , Instituições Acadêmicas , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To determine the prevalence and determinants of smoking in middle school students in priority areas for HIV control in Liangshan of Sichuan Province. METHODS: Students were randomly selected in all of the schools located in the priority areas for HIV control in Liangshan. A questionnaire survey was conducted,collecting data in relation to socio-demographic characteristics of the participants,their smoking behavior,drug abuse in family members,and HIV infections in family members. Risk factors associated with smoking were identified using univariate and multivariate statistical analyses. RESULTS: About 21.3% of respondents were smoking at the time of survey; 33.4% attempted smoking; 5% were heavy smokers; and 16.8% started smoking before 13 years old. The Logistic regression analysis identified male gender,senior high school students,poor academic records,low household income,rural residency,family drug abuse and HIV infections as predictors of attempted smoking. Male gender,minority ethnicity,average academic records,broken family,medium and high household income,family drug abuse and HIV infections were identified as predictors of smoking. Male gender,senior high school students,low or medium academic records,rural residency,and family drug abuse were identified as predictors of heavy smoking. Male gender,broken family,average academic records,medium or high household income,family drug abuse and HIV infections were associated with smoking before thirteen. CONCLUSION: Smoking rate in middle school students in the priority areas for HIV control in Liangshan is high. They start smoking at a young age. School smoking control programs should place priorities on those who are in the groups of boys,minority ethnicity,senior high school students,rural residency,poor academic records,and those with family drug abuse and HIV infections.
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Infecções por HIV/epidemiologia , Fumar/epidemiologia , Inquéritos e Questionários , Adolescente , Família , Feminino , Humanos , Renda , Masculino , Prevalência , Fatores de Risco , População Rural , Instituições Acadêmicas , Estudantes , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Whether they thrive as they grow must be determined for all constantly expanding networks. However, few studies have focused on this important network feature or the development of quantitative analytical methods. Given the formation and growth of the global container-shipping network, we proposed the concept of network temporal robustness and quantitative method. As an example, we collected container liner companies' data at two time points (2004 and 2014) and built a shipping network with ports as nodes and routes as links. We thus obtained a quantitative value of the temporal robustness. The temporal robustness is a significant network property because, for the first time, we can clearly recognize that the shipping network has become more vulnerable to damage over the last decade: When the node failure scale reached 50% of the entire network, the temporal robustness was approximately -0.51% for random errors and -12.63% for intentional attacks. The proposed concept and analytical method described in this paper are significant for other network studies.
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We evaluate the performance of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis (EPTB) in China. The performance of Xpert was evaluated compared to the composite reference standard (CRS), drug susceptibility testing (DST), and imaging examination. The overall sensitivity and specificity of Xpert were 64.1% (195/304) and 100% (24/24), respectively, using CRS as the gold standard. The sensitivity was significantly higher than that of culture for pus (P<0.05). The proportion of EPTB-positive cases diagnosed by imaging was two times more than that diagnosed using Xpert; however, 6 out of 19 cases may have been overdiagnosed by imaging. Compared to phenotypic DST, the sensitivity and specificity of Xpert were 80% (12/15) and 100% (75/75), respectively. Considering its high sensitivity and specificity, Xpert MTB/RIF may be used as a rapid initial test for EPTB diagnosis, and may also support a quicker decision on the treatment regimen. The combination of imaging and Xpert testing could provide high efficiency and accurate diagnosis of suspected EPTB.
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Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Testes Diagnósticos de Rotina/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/farmacologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Proteínas de Bactérias/metabolismo , China , RNA Polimerases Dirigidas por DNA/metabolismo , Testes Diagnósticos de Rotina/instrumentação , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Estudos Retrospectivos , Sensibilidade e Especificidade , Escarro , TuberculoseRESUMO
Bone and Joint tuberculosis (BJTB) constitutes about 10% of total extra-pulmonary TB cases. Since the BJTB is a paucibacillary condition, there has been no systematic study on the bacterial characterization, especially the epidemiological feature. Here we collected the mycobacterial clinical isolates, analyzed the clinical features and the bacteriological characteristics from 113 BJTB cases reported in China. The mean age of the cases was 40.33 years while most of the patients fell into the 20-29 year age group; local pain was the most common onset symptom of BJTB cases; mean time from symptom onset to BJTB diagnosis was 13.16 months. 31 isolates were defined as drug resistant, including 15 multidrug resistant (MDR) and 2 extensively drug resistant (XDR) isolates according to the drug susceptibility test outcomes; after spoligotyping, 87.6% (99/113) isolates were categorized as Beijing family. In contrast to the isolates from pulmonary tuberculosis patients, here the MIRU-VNTR assay did not find anything significant. A prolonged time span for BJTB diagnosis highlights the requirement of paying further attention to BJTB infection in China. This study provides essential insights into the demographic and microbial characteristics of BJTB cases in China.
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Osso e Ossos/microbiologia , Articulações/microbiologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Osteoarticular/microbiologia , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Osso e Ossos/patologia , Criança , China , DNA Intergênico/genética , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Humanos , Articulações/patologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética , Estudos Retrospectivos , Tuberculose Osteoarticular/tratamento farmacológico , Tuberculose Osteoarticular/patologia , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/patologia , Adulto JovemRESUMO
A clinical isolate from a patient was identified as Mycobacterium chimaera, a recently identified species of nontuberculous Mycobacteria. The biochemical and molecular identity, drug sensitivity and virulence of this isolated strain were investigated. 16S rRNA, the 16S-23S ITS, hsp65 and rpoB were amplified, and their sequence similarities with other mycobacteria were analyzed. The minimum inhibitory concentrations of 22 anti-microbial agents against this isolate were established, and the virulence of the isolate was evaluated by intravenous injection into C57BL/6 mice using Mycobacterium tuberculosis H37Rv as a control strain. Growth and morphological characteristics and mycolic acid profile analysis revealed that this isolated strain was a member of the Mycobacterium avium complex. BLAST analysis of the amplified sequences showed that the isolated strain was closely related to M. chimaera. Susceptibility testing showed that the isolate was sensitive to rifabutin, rifapentine, clarithromycin, azithromycin, imipenem and cefoxitin. Bacterial load determination and tissue histopathology of the infected mice indicated that the isolate was highly virulent. The first case of M. chimaera infection in China was evaluated. The information derived from this case may offer valuable guidance for clinical diagnosis and treatment.
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Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/classificação , Mycobacterium/isolamento & purificação , Adulto , Animais , Anti-Infecciosos/farmacologia , Carga Bacteriana , Proteínas de Bactérias/genética , Técnicas de Tipagem Bacteriana , Chaperonina 60/genética , China , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , RNA Polimerases Dirigidas por DNA/genética , Modelos Animais de Doenças , Histocitoquímica , Humanos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Mycobacterium/efeitos dos fármacos , Mycobacterium/crescimento & desenvolvimento , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , VirulênciaRESUMO
OBJECTIVE: To evaluate the reliability of thiophen-2-carboxylic acid hydrazine (TCH) test for identification of Mycobacterium bovis (M. bovis). METHODS: A total of 4069 clinically isolated strains were identified by P-Nitrobenzoic acid medium (500 mg/L) and TCH medium (5 mg/L). Mycobacterium tuberculosis (M. tuberculosis) complex strains susceptible to 5 mg/L TCH were further tested for susceptibility to 2 mg/L TCH. Spacer oligonucleotide typing (spoligotyping) and multi-loci PCR were also performed to identify TCH susceptible strains. RESULTS: Among the 4069 isolated strains there were 3929 strains belonging to M. tuberculosis complex (MTBC) of which 245 were susceptible to 5 mg/L TCH. Of these 245 strains, 20 were also susceptible to 2 mg/L TCH, while only 1 strain was identified to be M. bovis by both spoligotyping and multi-loci PCR. CONCLUSION: TCH susceptibility test (either 5 mg/L or 2 mg/L) is not a reliable method for identification of M. bovis.
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Mycobacterium bovis/classificação , Mycobacterium tuberculosis/classificação , Tiofenos/farmacologia , Animais , Técnicas de Tipagem Bacteriana , Bovinos , DNA Bacteriano/genética , Testes de Sensibilidade Microbiana , Mycobacterium bovis/genética , Mycobacterium bovis/isolamento & purificação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Tiofenos/administração & dosagem , Tuberculose/microbiologiaRESUMO
PURPOSE: The purpose of this study was to investigate in vitro osteoblast responses to the thin nano-hydroxyapatite (HA) coating on porous implant surfaces. MATERIALS AND METHODS: Surface characteristics of nano-HA coating were evaluated by x-ray diffractometer (XRD) and Fourier transform infrared spectroscopy (FTIR). Murine preosteoblast cell (MC3T3-E1) proliferation, alkaline phosphatase (ALP) activity, and osteocalcin release on nano-HA coated surfaces were compared with HA-coated surfaces. RESULTS: The XRD pattern demonstrated that the peak of nano-HA coating matched well with the standard HA patterns. FTIR spectra also showed that the coating consisted of pure HA crystals. Significant increases in cell proliferation, total protein on day 7, ALP activity on day 14 and day 21, and osteocalcin production on day 21 (P < .05) were observed for nano-HA coated surfaces. CONCLUSIONS: It was concluded that thin nano-HA coating, deposited by the electrochemical process, improved proliferation and differentiation of osteoblasts.
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Implantes Dentários , Durapatita/química , Osteoblastos/citologia , Osteoblastos/metabolismo , Titânio/química , Fosfatase Alcalina/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Técnicas Eletroquímicas , Teste de Materiais , Camundongos , Nanotecnologia , Osteocalcina/metabolismo , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios XRESUMO
AIM: E-cadherin is unusually highly expressed in most ovarian cancers. This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers. METHODS: Human ovarian adenocarcinoma cell line SKOV-3 was examined. E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi), and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment. E-cadherin-mediated Ca(2+)-dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells. The expression levels of E-cadherin, extracellular signal-related kinase (ERK), phosphorylated ERK (P-ERK) were measured using Western blot assays. RESULTS: Transfection with CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells. E-cadherin-mediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK, but did not modify the expression of ERK protein. The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 (50 µmol/L), but not by the PI3K inhibitor wortmannin (1 µmol/L) or PKA inhibitor H89 (10 µmol/L). CONCLUSION: E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.
Assuntos
Adenocarcinoma/metabolismo , Caderinas/metabolismo , Sistema de Sinalização das MAP Quinases , Neoplasias Ovarianas/metabolismo , Adenocarcinoma/genética , Caderinas/genética , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Neoplasias Ovarianas/genética , Interferência de RNARESUMO
OBJECTIVE: To investigate the risk factors of worsening renal function (WRF) in patients with chronic heart failure (CHF) and WRF influence on prognosis. METHODS: A case-control study were undertaken to analyze independent risk factor statistically related to incidence of WRF, and to assess the influence of WRF on prognosis. RESULTS: The independent predictors of WRF were creatinine level at admission (OR 2.248, 95%CI 1.088 - 4.647, P = 0.029) and NYHA class on admission (OR 2.485, 95%CI 1.385 - 4.459, P = 0.002). The mortality of patient with WRF was obviously higher than that of control group during hospitalization (OR 3.824, 95%CI 2.452 - 5.637, P < 0.015). CONCLUSIONS: WRF is a common complication among patients hospitalized for CHF, and is obviously associated with mortality during hospitalization. Higher creatinine level and weak heart function are independent risk factors for incidence of WRF of patients with CHF.