The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity. METHODS: Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite). RESULTS: Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes. CONCLUSION: We identified 14 MRP genes as HCC diagnostic markers. We investigated FRG and m6A modification-related gene expression profiles and immune features in patients with HCC, and developed and validated a model incorporating MRP and FRG expression that accurately and reliably predicts HCC prognosis and may predict disease progression and treatment response.

The mechanism of VCP-mediated metastasis of osteosarcoma based on cell autophagy and the EMT pathway.

OBJECTIVE: Study of the molecular mechanisms of metastasis is still the research focus for osteosarcoma (OS) prevention. This study investigates the mechanism of valosin-containing protein (VCP) promoting OS metastasis in vitro through autophagy and epithelial-mesenchymal transition (EMT). METHODS: Different cell lines of osteosarcoma (143B and MG63) were adopted in this study. The level of VCP expression in osteosarcoma cells was changed, and the level of autophagy and the progression of the epithelial-mesenchymal transition (EMT) were observed. Then autophagy and EMT in OS cells were changed artificially, and proliferation and migration ability were observed. RESULTS: The expression of LC3II/I was decreased, but the insolubilized P62 protein expression was increased in the VCP inhibiting group and the autophagy inhibitor treatment group. Simultaneously, E-cadherin protein expression increased while N-cadherin protein expression decreased in the VCP inhibiting group but increased in the TGF-ß1 treatment group. In addition, suppressing VCP can cause a decrease in Transforming Growth Factor ß1 (TGF-ß1), smad2, smad3, phosphorylated smad2 (p-smad2), and phosphorylated smad3 (p-smad3). Autophagy inhibitors and agonists have no significant effect on the migration and invasion of OS cells but can significantly affect the ability of cells to resist anoikis. EMT inhibitors and agonists have a proportional effect on the migration and invasion of OS cells. CONCLUSION: VCP is likely to promote the migration and invasion of OS cells by inducing EMT, possibly via TGF-ß1/smad2/3 signaling pathway. In this process, VCP-mediated autophagy may contribute to successful distant metastasis of tumor cells indirectly.

Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial, 2020

[RESUMO]. • Cerca de ¼ dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). • Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. • É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. • A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. • Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. • É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

[ABSTRACT]. • About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). • There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. • Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. • Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. • Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. • Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

[RESUMEN]. • Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). • Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. • La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. • La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. • La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. • Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020

[RESUMEN]. • Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). • Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. • La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. • La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. • La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. • Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

[ABSTRACT]. • About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). • There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. • Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. • Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. • Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. • Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

[RESUMO]. • Cerca de ¼ dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). • Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. • É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. • A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. • Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. • É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020 / São Paulo call to action for the prevention and control of high blood pressure: 2020 / Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial, 2020

RESUMEN Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

ABSTRACT About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

RESUMO Cerca de » dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

Llamado a la acción de San Pablo para la prevención y el control de la hipertensión arterial, 2020 / São Paulo call to action for the prevention and control of high blood pressure: 2020 / Chamado à ação de São Paulo para prevenção e controle da hipertensão arterial, 2020

RESUMEN Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

ABSTRACT About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

RESUMO Cerca de » dos adultos têm hipertensão arterial, que é o fator de risco isolado mais importante para morte (incluídas as mortes por cardiopatia e acidente vascular cerebral). Existem políticas eficazes que poderiam facilitar escolhas pessoais saudáveis para evitar a elevação da pressão arterial e, se plenamente implementadas, podem prevenir a ocorrência da hipertensão arterial. É fácil rastrear e tratar a hipertensão, MAS somente cerca de 50% dos adultos hipertensos estão cientes de sua condição, e apenas cerca de 1 em cada 7 é tratado adequadamente. A prevenção e controle da hipertensão é o principal mecanismo de prevenção e controle das doenças não transmissíveis e um modelo para outros riscos de doenças não transmissíveis. Tratamentos eficazes com mudanças de estilo de vida e medicamentos poderiam prevenir e controlar a hipertensão arterial na maioria das pessoas se aplicados sistematicamente à população; as intervenções simples são viáveis em todos os ambientes e podem melhorar a atenção primária. É necessária a ação continuada e urgente a fim de obter mudanças efetivas nas políticas públicas e no sistema de saúde para prevenir e controlar a hipertensão arterial.

A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve.

TBX5 has been linked to Holt-Oram syndrome, with congenital heart defect (CHD) and atrial fibrillation (AF) being two major cardiac phenotypes. However, the prevalence of a TBX5 variation in patients with CHD and AF remains obscure. In this research, by sequencing analysis of TBX5 in 178 index patients with both CHD and AF, a novel heterozygous variation, NM_000192.3: c.577G>T; p.(Gly193*), was identified in one index patient with CHD and AF as well as bicuspid aortic valve (BAV), with an allele frequency of approximately 0.28%. Genetic analysis of the proband's pedigree showed that the variation co-segregated with the diseases. The pathogenic variation was not detected in 292 unrelated healthy subjects. Functional analysis by using a dual-luciferase reporter assay system showed that the Gly193*-mutant TBX5 protein failed to transcriptionally activate its target genes MYH6 and NPPA. Moreover, the mutation nullified the synergistic transactivation between TBX5 and GATA4 as well as NKX2-5. Additionally, whole-exome sequencing analysis showed no other genes contributing to the diseases. This investigation firstly links a pathogenic variant in the TBX5 gene to familial CHD and AF as well as BAV, suggesting that CHD and AF as well as BAV share a common developmental basis in a subset of patients.

Brevibacterium metallicus sp. nov., an endophytic bacterium isolated from roots of Prosopis laegivata grown at the edge of a mine tailing in Mexico.

A Gram-positive, aerobic, nonmotile strain, NM2E3(T) was identified as Brevibacterium based on the 16S rRNA gene sequence analysis and had the highest similarities to Brevibacterium jeotgali SJ5-8(T) (97.3 %). This novel bacterium was isolated from root tissue of Prosopis laegivata grown at the edge of a mine tailing in San Luis Potosí, Mexico. Its cells were non-spore-forming rods, showing catalase and oxidase activities and were able to grow in LB medium added with 40 mM Cu(2+), 72 mM As(5+) and various other toxic elements. Anteiso-C15:0 (41.6 %), anteiso-C17:0 (30 %) and iso-C15:0 (9.5 %) were the major fatty acids. MK-8(H2) (88.4 %) and MK-7(H2) (11.6 %) were the major menaquinones. The DNA G + C content of the strain NM2E3(T) was 70.8 mol % (Tm). DNA-DNA hybridization showed that the strain NM2E3(T) had 39.8, 21.7 and 20.3 % relatedness with B. yomogidense JCM 17779(T), B. jeotgali JCM 18571(T) and B. salitolerans TRM 45(T), respectively. Based on the phenotypic and genotypic analyses, the strain NM2E3(T) (=CCBAU 101093(T) = HAMBI 3627(T) = LMG 8673(T)) is reported as a novel species of the genus Brevibacterium, for which the name Brevibacterium metallicus sp. nov., is proposed.

Operative versus nonoperative treatment for displaced midshaft clavicle fractures: a meta-analysis based on current evidence.

Literature searches of the Cochrane Library, PubMed, EMBASE, Web of Science, LILACS, China National Knowledge Infrastructure, and Wanfang Data databases were performed from 1966 to September 2014. Only randomized and quasi-randomized controlled clinical trials comparing operative and nonoperative treatments for displaced midshaft clavicle fractures were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Thirteen studies were considered in the meta-analysis. Constant scores and the Disabilities of the Arm, Shoulder and Hand scores were improved in the operative fixation group at a follow up of one year or more. The nonunion and symptomatic malunion rates were significantly lower in the operative group. Additionally, the nonoperative group had a higher likelihood of neurological symptoms compared with the operative group. A significantly higher risk of complications was found in patients treated conservatively than in those who underwent operative fixation. However, when patients with nonunion and symptomatic malunion were excluded from the analysis, no significant differences in the complication rate were found. We concluded that based on the current clinical reports, operative treatment is superior to nonoperative treatment in the management of displaced midshaft clavicle fractures. However, we do not support the routine use of primary operative fixation for all displaced midshaft clavicle fractures in adults.

Operative versus nonoperative treatment for displaced midshaft clavicle fractures: a meta-analysis based on current evidence

Literature searches of the Cochrane Library, PubMed, EMBASE, Web of Science, LILACS, China National Knowledge Infrastructure, and Wanfang Data databases were performed from 1966 to September 2014. Only randomized and quasi-randomized controlled clinical trials comparing operative and nonoperative treatments for displaced midshaft clavicle fractures were included. Data collection and extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Thirteen studies were considered in the meta-analysis. Constant scores and the Disabilities of the Arm, Shoulder and Hand scores were improved in the operative fixation group at a follow up of one year or more. The nonunion and symptomatic malunion rates were significantly lower in the operative group. Additionally, the nonoperative group had a higher likelihood of neurological symptoms compared with the operative group. A significantly higher risk of complications was found in patients treated conservatively than in those who underwent operative fixation. However, when patients with nonunion and symptomatic malunion were excluded from the analysis, no significant differences in the complication rate were found. We concluded that based on the current clinical reports, operative treatment is superior to nonoperative treatment in the management of displaced midshaft clavicle fractures. However, we do not support the routine use of primary operative fixation for all displaced midshaft clavicle fractures in adults.