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2.
Redox Biol ; 47: 102172, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34678655

RESUMO

Innate immunity is the first line of host defense against pathogens. This process is modulated by multiple antiviral protein modifications, such as phosphorylation and ubiquitination. Here, we showed that cellular S-nitrosoglutathione reductase (GSNOR) is actively involved in innate immunity activation. GSNOR deficiency in mouse embryo fibroblasts (MEFs) and RAW264.7 macrophages reduced the antiviral innate immune response and facilitated herpes simplex virus-1 (HSV-1) and vesicular stomatitis virus (VSV) replication. Concordantly, HSV-1 infection in Gsnor-/- mice and wild-type mice with GSNOR being inhibited by N6022 resulted in higher mortality relative to the respective controls, together with severe infiltration of immune cells in the lungs. Mechanistically, GSNOR deficiency enhanced cellular TANK-binding kinase 1 (TBK1) protein S-nitrosation at the Cys423 site and inhibited TBK1 kinase activity, resulting in reduced interferon production for antiviral responses. Our study indicated that GSNOR is a critical regulator of antiviral responses and S-nitrosation is actively involved in innate immunity.


Assuntos
Álcool Desidrogenase/metabolismo , Cisteína , Herpesvirus Humano 1 , Imunidade Inata , Animais , Camundongos , Nitrosação , /genética
4.
Mol Neurobiol ; 58(9): 4628-4638, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34148215

RESUMO

Drug addiction is a global health problem and continues to place an enormous financial burden on society. This addiction is characterized by drug dependence sensitization and craving. Morphine has been widely used for pain relief, but chronic administration of morphine causes analgesic tolerance, hyperalgesia, and addiction, all of which limit its clinical usage. Alterations of multiple molecular pathways have been reported to be involved in the development of drug addiction, including mitochondrial dysfunction, excessive oxidative stress and nitric oxide stress, and increased levels of apoptosis, autophagy, and neuroinflammation. Preclinical and clinical studies have shown that the co-administration of melatonin with morphine leads to a reversal of these affected pathways. In addition, murine models have shown that melatonin improves morphine-induced analgesic tolerance and addictive behaviors, such as behavioral sensitization, reward effect, and physical dependence. In this review, we attempt to summarize the recent findings about the beneficial effect and molecular mechanism of melatonin on mitochondrial dysfunction, uncontrolled autophagy, and neuroinflammation in morphine addiction and morphine analgesic tolerance. We propose that melatonin might be a useful supplement in the treatment opiate abuse.


Assuntos
Tolerância a Medicamentos , Melatonina/farmacologia , Dependência de Morfina/fisiopatologia , Morfina/farmacologia , Fármacos Neuroprotetores/farmacologia , Autofagia/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Medição da Dor
5.
Redox Biol ; 34: 101560, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32413745

RESUMO

Morphine is frequently used for pain relief, but long-term morphine therapy in patients with chronic pain results in analgesic tolerance and hyperalgesia. There are no effective therapeutic treatments that limit these detrimental side effects. We found pretreatment with melatonin could decrease morphine-induced analgesic tolerance. There was a significant activation of the NLRP3 inflammasome in the prefrontal cortex and the peripheral blood of morphine-treated mice compared to control animals, which could be blocked by melatonin. The inflammasome activation induced by morphine was mediated by the microglia. SiRNA knockdown or pharmacological inhibition of the NLRP3 abolished the morphine-induced inflammasome activation. Co-administration of melatonin and low-dose morphine had better analgesia effects in the murine models of pain and led to a lower NLRP3 inflammasome activity in brain tissues. Mice deficient for Nlrp3 had a higher nociceptive threshold and were less sensitive to develop morphine-induced analgesic tolerance and acetic acid-induced pain relative to wild-type animals. Concordantly, we observed a significantly elevated level of serum IL-1ß, which indicates an increase of NLRP3 inflammasome activity associated with the reduced level of serum melatonin, in heroin-addicted patients relative to healthy individuals. Our results provide a solid basis for conducting a clinical trial with the co-administration of melatonin and morphine for the relief of severe pain.


Assuntos
Melatonina , Morfina , Analgésicos , Animais , Humanos , Inflamassomos , Melatonina/farmacologia , Camundongos , Morfina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
6.
Autophagy ; 16(1): 52-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30898012

RESUMO

Alzheimer disease (AD) is the most common neurodegenerative disease. An imbalance between the production and clearance of Aß (amyloid beta) is considered to be actively involved in AD pathogenesis. Macroautophagy/autophagy is a major cellular pathway leading to the removal of aggregated proteins, and upregulation of autophagy represents a plausible therapeutic strategy to combat overproduction of neurotoxic Aß. PPARA/PPARα (peroxisome proliferator activated receptor alpha) is a transcription factor that regulates genes involved in fatty acid metabolism and activates hepatic autophagy. We hypothesized that PPARA regulates autophagy in the nervous system and PPARA-mediated autophagy affects AD. We found that pharmacological activation of PPARA by the PPARA agonists gemfibrozil and Wy14643 induces autophagy in human microglia (HM) cells and U251 human glioma cells stably expressing the human APP (amyloid beta precursor protein) mutant (APP-p.M671L) and this effect is PPARA-dependent. Administration of PPARA agonists decreases amyloid pathology and reverses memory deficits and anxiety symptoms in APP-PSEN1ΔE9 mice. There is a reduced level of soluble Aß and insoluble Aß in hippocampus and cortex tissues from APP-PSEN1ΔE9 mice after treatment with either gemfibrozil or Wy14643, which promoted the recruitment of microglia and astrocytes to the vicinity of Aß plaques and enhanced autophagosome biogenesis. These results indicated that PPARA is an important factor regulating autophagy in the clearance of Aß and suggested gemfibrozil be assessed as a possible treatment for AD.Abbreviation: Aß: amyloid beta; ACTB: actin beta; ADAM10: ADAM metallopeptidase domain 10; AD: Alzheimer disease; AIF1/IBA1: allograft inflammatory factor 1; ANOVA: analysis of variance; APOE: apolipoprotein E; APP: amyloid beta precursor protein; APP-PSEN1ΔE9: APPswe/PSEN1dE9; BAFA1: bafilomycin A1; BDNF: brain derived neurotrophic factor; BECN1: beclin 1; CD68: CD68 molecule; CREB1: cAMP responsive element binding protein 1; DAPI: 4',6-diamidino-2-phenylindole; DLG4/PSD-95: discs large MAGUK scaffold protein 4; DMSO: dimethyl sulfoxide; ELISA: enzyme linked immunosorbent assay; FDA: U.S. Food and Drug Administration; FKBP5: FK506 binding protein 5; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; gemfibrozil: 5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid; GFAP: glial fibrillary acidic protein; GLI2/THP1: GLI family zinc finger 2; HM: human microglia; IL6: interleukin 6; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; NC: negative control; OQ: opposite quadrant; PPARA/PPARα, peroxisome proliferator activated receptor alpha; PSEN1/PS1: presenilin 1; SEM: standard error of the mean; SQSTM1: sequestosome 1; SYP: synaptophysin; TFEB: transcription factor EB; TNF/TNF-α: tumor necrosis factor; TQ: target quadrant; WT: wild type; Wy14643: 2-[4-chloro-6-(2,3-dimethylanilino)pyrimidin-2-yl]sulfanylacetic acid.


Assuntos
Doença de Alzheimer/patologia , Autofagia/fisiologia , PPAR alfa/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Autofagia/genética , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Humanos , Camundongos , Microglia/metabolismo , Doenças Neurodegenerativas/metabolismo , PPAR alfa/genética , Placa Amiloide/metabolismo
7.
J Alzheimers Dis ; 61(3): 1015-1028, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29332044

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease with increasing incidence across the world and no cure at the present time. An ideal animal model would facilitate the understanding of the pathogenesis of AD and discovery of potential therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a closer genetic affinity to primates relative to rodents, and can attain ages of 8 years or older, which represents another advantage for the study of neurodegenerative diseases such as AD compared to primates. Here, we analyzed 131 AD-related genes in the Chinese tree shrew brain tissues based on protein sequence identity, positive selection, mRNA, and protein expression by comparing with those of human, rhesus monkey, and mouse. In particular, we focused on the Aß and neurofibrillary tangles formation pathways, which are crucial to AD pathogenesis. The Chinese tree shrew had a generally higher sequence identity with human than that of mouse versus human for the AD pathway genes. There was no apparent selection on the tree shrew lineage for the AD-related genes. Moreover, expression pattern of the Aß and neurofibrillary tangle formation pathway genes in tree shrew brain tissues resembled that of human brain tissues, with a similar aging-dependent effect. Our results provided an essential genetic basis for future AD research using the tree shrew as a viable model.


Assuntos
Doença de Alzheimer/genética , Modelos Animais de Doenças , Tupaia/genética , Sequência de Aminoácidos , Animais , Pesquisa Biomédica , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos
8.
Mol Biol Evol ; 35(1): 149-158, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087519

RESUMO

The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.


Assuntos
Filogeografia/métodos , Ratos/genética , África , Animais , Ásia Sudeste/epidemiologia , Evolução Biológica , Europa (Continente) , Evolução Molecular , Variação Genética/genética , Genética Populacional , Genoma/genética , Oriente Médio , Filogenia , Sequenciamento Completo do Genoma/métodos
9.
Mol Biol Evol ; 34(12): 3148-3153, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961982

RESUMO

The laboratory rat, widely used in biomedical research, is domesticated from wild brown rat. The origin and genetic mechanism underlying domestication of the laboratory rat remain largely elusive. In the present study, large scale genomes supported a single origin for the laboratory rat, possibly from a sister group to wild rats from Europe/Africa/Middle East. Genomic and transcriptomic analyses uncovered many artificially selected genes (e.g., FOXP2, B3GAT1, and CLOCK) involved in the nervous system. These genes associate with learning ability and regulation of circadian rhythm, which likely enabled the successful domestication of the laboratory rat. Particularly, many genes, including mitochondrial genes responsible for energy metabolism, displayed a substantially increased expression in the brain of laboratory rats compared with wild rats. Our findings demystify the origin and evolution of this model animal, and provide insight into the process of its domestication.


Assuntos
Animais Domésticos/genética , Ratos/genética , Animais , Evolução Biológica , Proteínas CLOCK/genética , Domesticação , Metabolismo Energético/genética , Evolução Molecular , Fatores de Transcrição Forkhead/genética , Genoma/genética , Genômica/métodos , Aprendizagem/fisiologia , Filogenia , Seleção Genética/genética
10.
Autophagy ; 13(9): 1496-1511, 2017 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-28722508

RESUMO

The molecular basis of chronic morphine exposure remains unknown. In this study, we hypothesized that macroautophagy/autophagy of dopaminergic neurons would mediate the alterations of neuronal dendritic morphology and behavioral responses induced by morphine. Chronic morphine exposure caused Atg5 (autophagy-related 5)- and Atg7 (autophagy-related 7)-dependent and dopaminergic neuron-specific autophagy resulting in decreased neuron dendritic spines and the onset of addictive behaviors. In cultured primary midbrain neurons, morphine treatment significantly reduced total dendritic length and complexity, and this effect could be reversed by knockdown of Atg5 or Atg7. Mice deficient for Atg5 or Atg7 specifically in the dopaminergic neurons were less sensitive to developing a morphine reward response, behavioral sensitization, analgesic tolerance and physical dependence compared to wild-type mice. Taken together, our findings suggested that the Atg5- and Atg7-dependent autophagy of dopaminergic neurons contributed to cellular and behavioral responses to morphine and may have implications for the future treatment of drug addiction.


Assuntos
Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/metabolismo , Autofagia , Comportamento Animal , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Morfina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/deficiência , Proteína 7 Relacionada à Autofagia/deficiência , Forma Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Mesencéfalo/citologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Nociceptividade/efeitos dos fármacos , Células PC12 , Ratos
11.
J Mol Cell Biol ; 8(6): 542-552, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27744377

RESUMO

Body size is the most important economic trait for animal production and breeding. Several hundreds of loci have been reported to be associated with growth trait and body weight in chickens. The loci are mapped to large genomic regions due to the low density and limited number of genetic markers in previous studies. Herein, we employed comparative population genomics to identify genetic basis underlying the small body size of Yuanbao chicken (a famous ornamental chicken) based on 89 whole genomes. The most significant signal was mapped to the BMP10 gene, whose expression was upregulated in the Yuanbao chicken. Overexpression of BMP10 induced a significant decrease in body length by inhibiting angiogenic vessel development in zebrafish. In addition, three other loci on chromosomes 1, 2, and 24 were also identified to be potentially involved in the development of body size. Our results provide a paradigm shift in identification of novel loci controlling body size variation, availing a fast and efficient strategy. These loci, particularly BMP10, add insights into ongoing research of the evolution of body size under artificial selection and have important implications for future chicken breeding.


Assuntos
Animais Domésticos/genética , Tamanho Corporal/genética , Galinhas/genética , Genética Populacional , Animais , Pareamento de Bases/genética , Proteínas Morfogenéticas Ósseas/genética , Cromossomos/genética , Loci Gênicos , Genômica , Neovascularização Fisiológica/genética , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/genética
12.
Cell Res ; 26(5): 556-73, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27033669

RESUMO

As noted by Darwin, chickens have the greatest phenotypic diversity of all birds, but an interesting evolutionary difference between domestic chickens and their wild ancestor, the Red Junglefowl, is their comparatively weaker vision. Existing theories suggest that diminished visual prowess among domestic chickens reflect changes driven by the relaxation of functional constraints on vision, but the evidence identifying the underlying genetic mechanisms responsible for this change has not been definitively characterized. Here, a genome-wide analysis of the domestic chicken and Red Junglefowl genomes showed significant enrichment for positively selected genes involved in the development of vision. There were significant differences between domestic chickens and their wild ancestors regarding the level of mRNA expression for these genes in the retina. Numerous additional genes involved in the development of vision also showed significant differences in mRNA expression between domestic chickens and their wild ancestors, particularly for genes associated with phototransduction and photoreceptor development, such as RHO (rhodopsin), GUCA1A, PDE6B and NR2E3. Finally, we characterized the potential role of the VIT gene in vision, which experienced positive selection and downregulated expression in the retina of the village chicken. Overall, our results suggest that positive selection, rather than relaxation of purifying selection, contributed to the evolution of vision in domestic chickens. The progenitors of domestic chickens harboring weaker vision may have showed a reduced fear response and vigilance, making them easier to be unconsciously selected and/or domesticated.


Assuntos
Animais Domésticos/genética , Evolução Biológica , Galinhas/genética , Domesticação , Aves Domésticas/genética , Seleção Genética , Visão Ocular/genética , Animais , Técnicas de Silenciamento de Genes , Genoma , Camundongos , Morfolinos/farmacologia , Peixe-Zebra/genética
13.
Autophagy ; 11(10): 1745-59, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26292069

RESUMO

Autophagy is involved in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). However, little is known about the regulation of autophagy in neurodegenerative process. In this study, we characterized aberrant activation of autophagy induced by neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and demonstrated that melatonin has a protective effect on neurotoxicity. We found an excessive activation of autophagy in monkey brain tissues and C6 cells, induced by MPTP, which is mediated by CDK5 (cyclin-dependent kinase 5). MPTP treatment significantly reduced total dendritic length and dendritic complexity of cultured primary cortical neurons and melatonin could reverse this effect. Decreased TH (tyrosine hydroxylase)-positive cells and dendrites of dopaminergic neurons in the substantia nigra pars compacta (SNc) were observed in MPTP-treated monkeys and mice. Along with decreased TH protein level, we observed an upregulation of CDK5 and enhanced autophagic activity in the striatum of mice with MPTP injection. These changes could be salvaged by melatonin treatment or knockdown of CDK5. Importantly, melatonin or knockdown of CDK5 reduced MPTP-induced SNCA/α-synuclein aggregation in mice, which is widely thought to trigger the pathogenesis of PD. Finally, melatonin or knockdown of CDK5 counteracted the PD phenotype in mice induced by MPTP. Our findings uncover a potent role of CDK5-mediated autophagy in the pathogenesis of PD, and suggest that control of autophagic pathways may provide an important clue for exploring potential target for novel therapeutics of PD.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Autofagia/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Melatonina/farmacologia , alfa-Sinucleína/metabolismo , Animais , Autofagia/fisiologia , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Haplorrinos , Camundongos , Neurotoxinas/farmacologia , Doença de Parkinson/metabolismo
14.
Asian Pac J Cancer Prev ; 15(19): 8197-201, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25339005

RESUMO

BACKGROUND: Telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes located on chromosome 5p15.33 are known to influence the susceptibility to various cancers. Here, we examined the association of TERT and CLPTM1L single nucleotide polymorphisms (SNPs) with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Genotyping of TERT SNP rs2736098 and CLPTM1L SNP rs401681 was performed using TaqMan allelic discrimination assays in a case-control study of 201 HCC cases and 210 controls in a Chinese male population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analyses. RESULTS: Both the rs2736098 T allele of TERT and the rs401681 T allele of CLPTM1L were associated with a significantly increased risk of HCC (adjusted odds ratio [OR]=1.605, 95% confidence interval [CI]=1.164-2.213; adjusted OR=1.399, 95%CI=1.002-1.955, respectively). Individuals carrying both TERT and CLPTM1L risk genotypes had an even higher risk of HCC (adjusted OR=4.420, 95%CI= 2.319-8.425). The TERT rs2736098 T allele was also significantly associated with the level of the HCC clinical indicator alpha-fetoprotein (P=0.026). CONCLUSIONS: Our results show that genetic variants of TERT and CLPTM1L may contribute to HCC susceptibility in Chinese males.


Assuntos
/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Polimorfismo Genético/genética , Telomerase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Reação em Cadeia da Polimerase , Prognóstico
15.
Autophagy ; 9(9): 1395-406, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23800874

RESUMO

Drug addiction is a chronic brain disease that is a serious social problem and causes enormous financial burden. Because mitochondrial abnormalities have been associated with opiate addiction, we examined the effect of morphine on mtDNA levels in rat and mouse models of addiction and in cultured cells. We found that mtDNA copy number was significantly reduced in the hippocampus and peripheral blood of morphine-addicted rats and mice compared with control animals. Concordantly, decreased mtDNA copy number and elevated mtDNA damage were observed in the peripheral blood from opiate-addicted patients, indicating detrimental effects of drug abuse and stress. In cultured rat pheochromocytoma (PC12) cells and mouse neurons, morphine treatment caused many mitochondrial defects, including a reduction in mtDNA copy number that was mediated by autophagy. Knockdown of the Atg7 gene was able to counteract the loss of mtDNA copy number induced by morphine. The mitochondria-targeted antioxidant melatonin restored mtDNA content and neuronal outgrowth and prevented the increase in autophagy upon morphine treatment. In mice, coadministration of melatonin with morphine ameliorated morphine-induced behavioral sensitization, analgesic tolerance and mtDNA content reduction. During drug withdrawal in opiate-addicted patients and improvement of protracted abstinence syndrome, we observed an increase of serum melatonin level. Taken together, our study indicates that opioid addiction is associated with mtDNA copy number reduction and neurostructural remodeling. These effects appear to be mediated by autophagy and can be salvaged by melatonin.


Assuntos
Autofagia/efeitos dos fármacos , DNA Mitocondrial/sangue , Dosagem de Genes , Hipocampo/metabolismo , Melatonina/farmacologia , Transtornos Relacionados ao Uso de Opioides/sangue , Transtornos Relacionados ao Uso de Opioides/genética , Analgésicos/farmacologia , Animais , Comportamento Animal , Células Cultivadas , DNA Mitocondrial/genética , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Dendritos/patologia , Heroína/farmacologia , Hipocampo/patologia , Humanos , Masculino , Melatonina/sangue , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/ultraestrutura , Modelos Biológicos , Morfina/administração & dosagem , Morfina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Transtornos Relacionados ao Uso de Opioides/patologia , Ratos , Ratos Sprague-Dawley , Síndrome de Abstinência a Substâncias/sangue , Síndrome de Abstinência a Substâncias/genética
16.
PLoS One ; 7(6): e38848, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22719964

RESUMO

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. The high level of inactivation of gene function in M. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. We hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to M. leprae and the onset of clinical leprosy, and this may be reflected by mitochondrial DNA (mtDNA) background and mtDNA copy number. METHODS: We analyzed the mtDNA sequence variation of 534 leprosy patients and 850 matched controls from Yunnan Province and classified each subject by haplogroup. mtDNA copy number, taken to be proportional to mtDNA content, was measured in a subset of these subjects (296 patients and 231 controls) and 12 leprosy patients upon diagnosis. RESULTS: Comparison of matrilineal components of the case and control populations revealed no significant difference. However, measurement of mtDNA copy number showed that lepromatous leprosy patients had a significantly higher mtDNA content than controls (P = 0.008). Past medical treatments had no effect on the alteration of mtDNA copy number. CONCLUSIONS: Our results suggested that mtDNA content, but not haplogroup, affects leprosy and this influence is limited to the clinical subtype of lepromatous leprosy.


Assuntos
DNA Mitocondrial/genética , Dosagem de Genes , Predisposição Genética para Doença , Hanseníase/genética , Sequência de Bases , Estudos de Casos e Controles , China , Primers do DNA , Humanos
17.
Zhonghua Liu Xing Bing Xue Za Zhi ; 25(8): 674-6, 2004 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-15555389

RESUMO

OBJECTIVE: To understand the risk factors on severe acute respiratory syndrome (SARS) among their contacts and to develop effective strategy for its control. METHODS: Available epidemiological data of SARS cases and close contacts were reviewed and analyzed by SPSS. RESULTS: Out of the 2195 close contacts, 138 (6.3%) were diagnosed as SARS. Among colleagues and classmates of SARS patients, the infection rate was 0.36% versus 31.71% in contacts among families and hospitals, 0.77% in schools. No one was infected among 459 close contacts to SARS in the working unit. CONCLUSIONS: Among close contacts, factors that facilitating transmission would include: time, extent, frequency and place of contact to the patients, as well as factors related to close contacts as way, time of isolation and age. One of the epidemiological characteristics was that SARS were as clustered in the family among those close contacts. It is important to control the spread of SARS through supervision on the close contacts to patients.


Assuntos
Busca de Comunicante , Saúde da Família , Quarentena/estatística & dados numéricos , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Adulto , Idoso , China/epidemiologia , Infecção Hospitalar/transmissão , Feminino , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Masculino , Pessoa de Meia-Idade , Isolamento de Pacientes , Estudos Retrospectivos , Fatores de Risco , Síndrome Respiratória Aguda Grave/prevenção & controle
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