RESUMEN
Trueperella pyogenes (T. pyogenes) is a common opportunistic pathogen of many livestock and play an important regulation role during multibacterial infection and interaction with the host by its primary virulence factor pyolysin (PLO). The purpose of this study was to investigate the regulation role of PLO which serve as a combinational pathogen with lipopolysaccharide (LPS) during endometritis. In this study, the expression of bioactive recombinant PLO (rPLO) in a prokaryotic expression system and its purification are described. Moreover, we observed that rPLO inhibited the innate immune response triggered by LPS and that methyl-ß-cyclodextrin (MBCD) abrogated this inhibitory effect in goat endometrium stromal cells (gESCs). Additionally, we show from pharmacological and genetic studies that rPLO-induced autophagy represses gene expression by inhibiting NLRP3 inflammasome activation. Importantly, this study reported that ATF6 serves as a primary regulator of the cellular inflammatory reaction to rPLO. Overall, these observations suggest that T. pyogenes PLO could create an immunosuppressive environment for other pathogens invasion by regulating cellular signaling pathways.
Asunto(s)
Factor de Transcripción Activador 6/metabolismo , Autofagia/efectos de los fármacos , Proteínas Bacterianas/farmacología , Toxinas Bacterianas/farmacología , Endometrio/citología , Proteínas Hemolisinas/farmacología , Lipopolisacáridos/farmacología , Actinomycetaceae/patogenicidad , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Femenino , Cabras , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Inflamación , Mediadores de Inflamación/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismoRESUMEN
This study aimed to explore the correlation of kinesin family member 2A (KIF2A) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML), and investigate the effect of KIF2A knockdown on AML cell activities in vitro. Bone marrow samples were collected from 176 AML patients and 40 healthy donors, and KIF2A expression was measured by real-time quantitative polymerase chain reaction. Treatment response, event-free survival (EFS), and overall survival (OS) were assessed in AML patients. In vitro, KIF2A expression in AML cell lines and CD34+ cells (from healthy donors) was measured, and the effect of KIF2A knockdown on AML cell proliferation and apoptosis in HL-60 and KG-1 cells was detected. KIF2A expression was greater in AML patients compared to healthy donors, and receiver operating characteristic curve indicated that KIF2A expression predicted increased AML risk (area under curve: 0.793 (95%CI: 0.724-0.826)). In AML patients, KIF2A expression positively correlated with white blood cells, monosomal karyotype, and high risk stratification. Furthermore, no correlation of KIF2A expression with complete remission or hematopoietic stem cell transplantation was found. Kaplan-Meier curves showed that KIF2A expression was negatively correlated with EFS and OS. In vitro experiments showed that KIF2A was overexpressed in AML cell lines (KG-1, HL-60, ME-1, and HT-93) compared to CD34+ cells, moreover, cell proliferation was reduced but apoptosis was increased by KIF2A knockdown in HL-60 and KG-1 cells. In conclusion, KIF2A showed potential to be a biomarker and treatment target in AML.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Cinesinas/genética , Biomarcadores de Tumor/genética , Tasa de Supervivencia , Factores de Riesgo , Apoptosis , Células HL-60 , Proliferación Celular , Técnicas de Silenciamiento del GenRESUMEN
This study aimed to explore the correlation of kinesin family member 2A (KIF2A) expression with disease risk, clinical characteristics, and prognosis of acute myeloid leukemia (AML), and investigate the effect of KIF2A knockdown on AML cell activities in vitro. Bone marrow samples were collected from 176 AML patients and 40 healthy donors, and KIF2A expression was measured by real-time quantitative polymerase chain reaction. Treatment response, event-free survival (EFS), and overall survival (OS) were assessed in AML patients. In vitro, KIF2A expression in AML cell lines and CD34+ cells (from healthy donors) was measured, and the effect of KIF2A knockdown on AML cell proliferation and apoptosis in HL-60 and KG-1 cells was detected. KIF2A expression was greater in AML patients compared to healthy donors, and receiver operating characteristic curve indicated that KIF2A expression predicted increased AML risk (area under curve: 0.793 (95%CI: 0.724-0.826)). In AML patients, KIF2A expression positively correlated with white blood cells, monosomal karyotype, and high risk stratification. Furthermore, no correlation of KIF2A expression with complete remission or hematopoietic stem cell transplantation was found. Kaplan-Meier curves showed that KIF2A expression was negatively correlated with EFS and OS. In vitro experiments showed that KIF2A was overexpressed in AML cell lines (KG-1, HL-60, ME-1, and HT-93) compared to CD34+ cells, moreover, cell proliferation was reduced but apoptosis was increased by KIF2A knockdown in HL-60 and KG-1 cells. In conclusion, KIF2A showed potential to be a biomarker and treatment target in AML.
Asunto(s)
Cinesinas/genética , Leucemia Mieloide Aguda , Adulto , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Femenino , Técnicas de Silenciamiento del Gen , Células HL-60 , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Aggrecanase-2 (ADAMTS5) gene is responsible for aggrecan degradation that may contribute to cartilage destruction in a mouse osteoarthritis (OA) model. We aimed to investigate the effects of ADAMTS5 gene polymorphisms on OA risk in a Chinese population. A total of 300 OA patients and 300 controls were recruited and their genotypes for ADAMTS5 gene rs226794 and rs2830585 polymorphisms were determined using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ kit. ADAMTS5-associated genes were identified by co-expression analysis and their functions were investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Bioinformatics analysis showed that ADAMTS5 was significantly related to the components, structural constituent, and organization of the extracellular matrix. The rs2830585 polymorphism, but not rs226794 polymorphism, was significantly associated with an increased risk of knee OA. Stratified analysis further confirmed this significant association in patients at age ≥55 years. In conclusion, the ADAMTS5 rs2830585 polymorphism may be involved in the development of knee OA by destroying the extracellular matrix, but this finding should be further confirmed by larger studies.
Asunto(s)
Proteína ADAMTS5/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Osteoartritis de la Rodilla/genética , Polimorfismo Genético/genética , Anciano , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Humanos , MasculinoRESUMEN
Aggrecanase-2 (ADAMTS5) gene is responsible for aggrecan degradation that may contribute to cartilage destruction in a mouse osteoarthritis (OA) model. We aimed to investigate the effects of ADAMTS5 gene polymorphisms on OA risk in a Chinese population. A total of 300 OA patients and 300 controls were recruited and their genotypes for ADAMTS5 gene rs226794 and rs2830585 polymorphisms were determined using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ kit. ADAMTS5-associated genes were identified by co-expression analysis and their functions were investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Bioinformatics analysis showed that ADAMTS5 was significantly related to the components, structural constituent, and organization of the extracellular matrix. The rs2830585 polymorphism, but not rs226794 polymorphism, was significantly associated with an increased risk of knee OA. Stratified analysis further confirmed this significant association in patients at age ≥55 years. In conclusion, the ADAMTS5 rs2830585 polymorphism may be involved in the development of knee OA by destroying the extracellular matrix, but this finding should be further confirmed by larger studies.
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Polimorfismo Genético/genética , Variación Genética/genética , Osteoartritis de la Rodilla/genética , Predisposición Genética a la Enfermedad/genética , Proteína ADAMTS5/genética , Ensayo de Inmunoadsorción Enzimática , Estudios de Casos y Controles , GenotipoRESUMEN
A majority of emerging infectious diseases in humans are zoonoses. Understanding factors that influence the emergence and transmission of zoonoses is pivotal for their prevention and control. Toxoplasma gondii is one of the most widespread zoonotic pathogens known today. Whereas only a few genotypes of T. gondii dominate in the Northern Hemisphere, many genotypes coexist in South America. Furthermore, T. gondii strains from South America are more likely to be virulent than those from the Northern Hemisphere. However, it is not clear what factor(s) shaped modern-day genetic diversity and virulence of T. gondii Here, our analysis suggests that the rise and expansion of farming in the past 11,000 years established the domestic cat/mouse transmission cycle for T. gondii, which has undoubtedly played a significant role in the selection of certain linages of T. gondii Our mathematical simulations showed that within the domestic transmission cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive advantage and eventually become dominant due to a balance between lower host mortality and the ability to superinfect mice previously infected with a less virulent T. gondii strain. Our analysis of the global type II lineage of T. gondii suggests its Old World origin but recent expansion in North America, which is likely the consequence of global human migration and trading. These results have significant implications concerning transmission and evolution of zoonotic pathogens in the rapidly expanding anthropized environment demanded by rapid growth of the human population and intensive international trading at present and in the future.
Asunto(s)
Toxoplasma/genética , Toxoplasma/patogenicidad , Toxoplasmosis/genética , Toxoplasmosis/transmisión , Zoonosis/genética , Zoonosis/transmisión , Animales , Gatos , Migración Humana , Humanos , Ratones , América del Sur , Toxoplasmosis/mortalidad , Zoonosis/mortalidadRESUMEN
PURPOSE: To investigate dynamically the X-ray appearance of cervical degenerative disease induced by unbalanced dynamic and static forces in rats. METHODS: A total of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into the one-, three- and six-month post-operative groups. The test group included 10, 15 and 20 rats at the respective corresponding post-operative stage and the control group included five rats at each time-point. By excising cervicodorsal muscles, interspinous ligaments and supraspinous ligament of rats in the test group, the balance of dynamic and static forces on cervical vertebrae was disrupted to establish a rat model of cervical degeneration. Spinal X-ray images were acquired, and intervertebral disc space and intervertebral foramen size were measured at one, three and six months post-operation. The results were analyzed and compared among groups. RESULTS: Cervical dynamic and static imbalance accelerated the appearance of cervical degenerative disease on X-ray. CONCLUSION: Cervical degenerative disease may be induced by unbalanced dynamic and static forces in rats.
Asunto(s)
Degeneración del Disco Intervertebral/diagnóstico por imagen , Animales , Fenómenos Biomecánicos , Modelos Animales de Enfermedad , Degeneración del Disco Intervertebral/etiología , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
Purpose: To investigate dynamically the X-ray appearance of cervical degenerative disease induced by unbalanced dynamic and static forces in rats. Methods: A total of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into the one-, three- and six-month post-operative groups. The test group included 10, 15 and 20 rats at the respective corresponding post-operative stage and the control group included five rats at each time-point. By excising cervicodorsal muscles, interspinous ligaments and supraspinous ligament of rats in the test group, the balance of dynamic and static forces on cervical vertebrae was disrupted to establish a rat model of cervical degeneration. Spinal X-ray images were acquired, and intervertebral disc space and intervertebral foramen size were measured at one, three and six months post-operation. The results were analyzed and compared among groups. Results: Cervical dynamic and static imbalance accelerated the appearance of cervical degenerative disease on X-ray. Conclusion: Cervical degenerative disease may be induced by unbalanced dynamic and static forces in rats.(AU)
Asunto(s)
Animales , Ratas , Rayos X , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/veterinaria , Ratas/anomalíasRESUMEN
Abstract Purpose: To investigate dynamically the X-ray appearance of cervical degenerative disease induced by unbalanced dynamic and static forces in rats. Methods: A total of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into the one-, three- and six-month post-operative groups. The test group included 10, 15 and 20 rats at the respective corresponding post-operative stage and the control group included five rats at each time-point. By excising cervicodorsal muscles, interspinous ligaments and supraspinous ligament of rats in the test group, the balance of dynamic and static forces on cervical vertebrae was disrupted to establish a rat model of cervical degeneration. Spinal X-ray images were acquired, and intervertebral disc space and intervertebral foramen size were measured at one, three and six months post-operation. The results were analyzed and compared among groups. Results: Cervical dynamic and static imbalance accelerated the appearance of cervical degenerative disease on X-ray. Conclusion: Cervical degenerative disease may be induced by unbalanced dynamic and static forces in rats.
Asunto(s)
Animales , Masculino , Ratas , Degeneración del Disco Intervertebral/diagnóstico por imagen , Fenómenos Biomecánicos , Distribución Aleatoria , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Degeneración del Disco Intervertebral/etiologíaRESUMEN
Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii, which can infect warm-blooded animals and humans. The present study was performed to investigate the seroprevalence of T. gondii in horses in Xinjiang, northwestern China. A total of 637 blood samples were collected from seven regions in Changji Hui Autonomous Prefecture, Xinjiang in 2011 and assayed for T. gondiiantibodies using the modified agglutination test (MAT). Risk factors (age, gender, and region) related to seroprevalence were determined by a multivariate logistic regression analysis. A total of 200 horses (31.4%, 95% CI 27.79-35.00) were seropositive for T. gondii. Age, gender, and region present no association with seroprevalence (p>0.05) in the logistic regression analysis. The results indicated that T. gondii is widely prevalent in horses in Xinjiang, northwestern China, representing a serious threat to animal and human health. Therefore, more careful measures should be performed to control and prevent T. gondii infection in horses from Xinjiang, northwestern China.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/epidemiología , Toxoplasma/inmunología , Toxoplasmosis Animal/sangre , Toxoplasmosis Animal/epidemiología , Animales , China/epidemiología , Femenino , Caballos , Masculino , Prevalencia , Estudios SeroepidemiológicosRESUMEN
Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii, which can infect warm-blooded animals and humans. The present study was performed to investigate the seroprevalence of T. gondii in horses in Xinjiang, northwestern China. A total of 637 blood samples were collected from seven regions in Changji Hui Autonomous Prefecture, Xinjiang in 2011 and assayed for T. gondiiantibodies using the modified agglutination test (MAT). Risk factors (age, gender, and region) related to seroprevalence were determined by a multivariate logistic regression analysis. A total of 200 horses (31.4%, 95% CI 27.7935.00) were seropositive for T. gondii. Age, gender, and region present no association with seroprevalence (p>0.05) in the logistic regression analysis. The results indicated that T. gondii is widely prevalent in horses in Xinjiang, northwestern China, representing a serious threat to animal and human health. Therefore, more careful measures should be performed to control and prevent T. gondii infection in horses from Xinjiang, northwestern China.(AU)
A toxoplasmose é uma zoonose global causada pelo Toxoplasma gondii, o qual pode infectar animais de sangue quente e seres humanos. Este estudo foi realizado com o objetivo de investigar a soroprevalência em cavalos para T. gondii, na região de Xinjiang, no Noroeste da China. Em 2011, foram recolhidas 637 amostras de sangue em sete distritos da Prefeitura Autônoma de Changji Hui do Xinjiang, as quais foram testadas para a presença de anticorpos, utilizando-se o teste de aglutinação modificado (MAT). Foram estimados fatores de risco relacionados com a soroprevalência (idade, sexo e distrito), através de uma análise de regressão logística multivariada. Um total de 200 equinos (31,4%, 95% IC 27,79 35,00) foi positivo para T. gondii. Idade, sexo e região estudada não apresentaram associação com a soroprevalência (p>0,05) na análise de regressão logística. Os resultados revelam que a infecção por T. gondii tem uma prevalência generalizada em todo o território de Xinjiang, no Noroeste da China, constituindo uma séria ameaça à saúde de animais e de humanos. Consequentemente, propõe-se que sejam adotadas medidas reforçadas para o controle e prevenção da infecção de cavalos por T. gondii, no Xinjiang, Noroeste da China.(AU)
Asunto(s)
Animales , Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/epidemiología , Toxoplasma/inmunología , Toxoplasmosis Animal/sangre , Toxoplasmosis Animal/epidemiología , China/epidemiología , Estudios Seroepidemiológicos , PrevalenciaRESUMEN
Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii, which can infect warm-blooded animals and humans. The present study was performed to investigate the seroprevalence of T. gondii in horses in Xinjiang, northwestern China. A total of 637 blood samples were collected from seven regions in Changji Hui Autonomous Prefecture, Xinjiang in 2011 and assayed for T. gondiiantibodies using the modified agglutination test (MAT). Risk factors (age, gender, and region) related to seroprevalence were determined by a multivariate logistic regression analysis. A total of 200 horses (31.4%, 95% CI 27.79–35.00) were seropositive for T. gondii. Age, gender, and region present no association with seroprevalence (p>0.05) in the logistic regression analysis. The results indicated that T. gondii is widely prevalent in horses in Xinjiang, northwestern China, representing a serious threat to animal and human health. Therefore, more careful measures should be performed to control and prevent T. gondii infection in horses from Xinjiang, northwestern China.
A toxoplasmose é uma zoonose global causada pelo Toxoplasma gondii, o qual pode infectar animais de sangue quente e seres humanos. Este estudo foi realizado com o objetivo de investigar a soroprevalência em cavalos para T. gondii, na região de Xinjiang, no Noroeste da China. Em 2011, foram recolhidas 637 amostras de sangue em sete distritos da Prefeitura Autônoma de Changji Hui do Xinjiang, as quais foram testadas para a presença de anticorpos, utilizando-se o teste de aglutinação modificado (MAT). Foram estimados fatores de risco relacionados com a soroprevalência (idade, sexo e distrito), através de uma análise de regressão logística multivariada. Um total de 200 equinos (31,4%, 95% IC 27,79 – 35,00) foi positivo para T. gondii. Idade, sexo e região estudada não apresentaram associação com a soroprevalência (p>0,05) na análise de regressão logística. Os resultados revelam que a infecção por T. gondii tem uma prevalência generalizada em todo o território de Xinjiang, no Noroeste da China, constituindo uma séria ameaça à saúde de animais e de humanos. Consequentemente, propõe-se que sejam adotadas medidas reforçadas para o controle e prevenção da infecção de cavalos por T. gondii, no Xinjiang, Noroeste da China.
Asunto(s)
Animales , Masculino , Femenino , Toxoplasma/inmunología , Anticuerpos Antiprotozoarios/sangre , Toxoplasmosis Animal/sangre , Toxoplasmosis Animal/epidemiología , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/epidemiología , Estudios Seroepidemiológicos , China/epidemiología , Prevalencia , CaballosRESUMEN
Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii, which can infect warm-blooded animals and humans. The present study was performed to investigate the seroprevalence of T. gondii in horses in Xinjiang, northwestern China. A total of 637 blood samples were collected from seven regions in Changji Hui Autonomous Prefecture, Xinjiang in 2011 and assayed for T. gondiiantibodies using the modified agglutination test (MAT). Risk factors (age, gender, and region) related to seroprevalence were determined by a multivariate logistic regression analysis. A total of 200 horses (31.4%, 95% CI 27.7935.00) were seropositive for T. gondii. Age, gender, and region present no association with seroprevalence (p>0.05) in the logistic regression analysis. The results indicated that T. gondii is widely prevalent in horses in Xinjiang, northwestern China, representing a serious threat to animal and human health. Therefore, more careful measures should be performed to control and prevent T. gondii infection in horses from Xinjiang, northwestern China.
A toxoplasmose é uma zoonose global causada pelo Toxoplasma gondii, o qual pode infectar animais de sangue quente e seres humanos. Este estudo foi realizado com o objetivo de investigar a soroprevalência em cavalos para T. gondii, na região de Xinjiang, no Noroeste da China. Em 2011, foram recolhidas 637 amostras de sangue em sete distritos da Prefeitura Autônoma de Changji Hui do Xinjiang, as quais foram testadas para a presença de anticorpos, utilizando-se o teste de aglutinação modificado (MAT). Foram estimados fatores de risco relacionados com a soroprevalência (idade, sexo e distrito), através de uma análise de regressão logística multivariada. Um total de 200 equinos (31,4%, 95% IC 27,79 35,00) foi positivo para T. gondii. Idade, sexo e região estudada não apresentaram associação com a soroprevalência (p>0,05) na análise de regressão logística. Os resultados revelam que a infecção por T. gondii tem uma prevalência generalizada em todo o território de Xinjiang, no Noroeste da China, constituindo uma séria ameaça à saúde de animais e de humanos. Consequentemente, propõe-se que sejam adotadas medidas reforçadas para o controle e prevenção da infecção de cavalos por T. gondii, no Xinjiang, Noroeste da China.
RESUMEN
Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii, which can infect warm-blooded animals and humans. The present study was performed to investigate the seroprevalence of T. gondii in horses in Xinjiang, northwestern China. A total of 637 blood samples were collected from seven regions in Changji Hui Autonomous Prefecture, Xinjiang in 2011 and assayed for T. gondiiantibodies using the modified agglutination test (MAT). Risk factors (age, gender, and region) related to seroprevalence were determined by a multivariate logistic regression analysis. A total of 200 horses (31.4%, 95% CI 27.7935.00) were seropositive for T. gondii. Age, gender, and region present no association with seroprevalence (p>0.05) in the logistic regression analysis. The results indicated that T. gondii is widely prevalent in horses in Xinjiang, northwestern China, representing a serious threat to animal and human health. Therefore, more careful measures should be performed to control and prevent T. gondii infection in horses from Xinjiang, northwestern China.
A toxoplasmose é uma zoonose global causada pelo Toxoplasma gondii, o qual pode infectar animais de sangue quente e seres humanos. Este estudo foi realizado com o objetivo de investigar a soroprevalência em cavalos para T. gondii, na região de Xinjiang, no Noroeste da China. Em 2011, foram recolhidas 637 amostras de sangue em sete distritos da Prefeitura Autônoma de Changji Hui do Xinjiang, as quais foram testadas para a presença de anticorpos, utilizando-se o teste de aglutinação modificado (MAT). Foram estimados fatores de risco relacionados com a soroprevalência (idade, sexo e distrito), através de uma análise de regressão logística multivariada. Um total de 200 equinos (31,4%, 95% IC 27,79 35,00) foi positivo para T. gondii. Idade, sexo e região estudada não apresentaram associação com a soroprevalência (p>0,05) na análise de regressão logística. Os resultados revelam que a infecção por T. gondii tem uma prevalência generalizada em todo o território de Xinjiang, no Noroeste da China, constituindo uma séria ameaça à saúde de animais e de humanos. Consequentemente, propõe-se que sejam adotadas medidas reforçadas para o controle e prevenção da infecção de cavalos por T. gondii, no Xinjiang, Noroeste da China.