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1.
Braz. j. biol ; 83: e249424, 2023. graf
Article in English | LILACS, VETINDEX | ID: biblio-1345538

ABSTRACT

Abstract Hypoxia is a prominent feature of head and neck cancer. However, the oxygen element characteristics of proteins and how they adapt to hypoxia microenvironments of head and neck cancer are still unknown. Human genome sequences and proteins expressed data of head and neck cancer were retrieved from pathology atlas of Human Protein Atlas project. Then compared the oxygen and carbon element contents between proteomes of head and neck cancer and normal oral mucosa-squamous epithelial cells, genome locations, pathways, and functional dissection associated with head and neck cancer were also studied. A total of 902 differentially expressed proteins were observed where the average oxygen content is higher than that of the lowly expressed proteins in head and neck cancer proteins. Further, the average oxygen content of the up regulated proteins was 2.54% higher than other. None of their coding genes were distributed on the Y chromosome. The up regulated proteins were enriched in endocytosis, apoptosis and regulation of actin cytoskeleton. The increased oxygen contents of the highly expressed and the up regulated proteins might be caused by frequent activity of cytoskeleton and adapted to the rapid growth and fast division of the head and neck cancer cells. The oxygen usage bias and key proteins may help us to understand the mechanisms behind head and neck cancer in targeted therapy, which lays a foundation for the application of stoichioproteomics in targeted therapy and provides promise for potential treatments for head and neck cancer.


Resumo A hipóxia é uma característica proeminente do câncer de cabeça e pescoço. No entanto, as características do elemento oxigênio das proteínas e como elas se adaptam aos microambientes de hipóxia do câncer de cabeça e pescoço ainda são desconhecidas. Sequências do genoma humano e dados expressos de proteínas de câncer de cabeça e pescoço foram recuperados do atlas de patologia do projeto Human Protein Atlas. Em seguida, comparou o conteúdo do elemento de oxigênio e carbono entre proteomas de câncer de cabeça e pescoço, e células epiteliais escamosas da mucosa oral normal, localizações do genoma, vias e dissecção funcional associada ao câncer de cabeça e pescoço também foram estudadas. Um total de 902 proteínas expressas diferencialmente foi observado onde o conteúdo médio de oxigênio é maior do que as proteínas expressas de forma humilde em proteínas de câncer de cabeça e pescoço. Além disso, o conteúdo médio de oxigênio das proteínas reguladas positivamente foi 2,54% maior do que das outras. Nenhum de seus genes codificadores foi distribuído no cromossomo Y. As proteínas reguladas positivamente foram enriquecidas em endocitose, apoptose e regulação do citoesqueleto de actina. O conteúdo aumentado de oxigênio das proteínas altamente expressas e reguladas pode ser causado pela atividade frequente do citoesqueleto e adaptado ao rápido crescimento e divisão das células cancerosas de cabeça e pescoço. O viés do uso de oxigênio e as proteínas-chave podem nos ajudar a entender os mecanismos por trás do câncer de cabeça e pescoço na terapia direcionada, o que estabelece uma base para a aplicação da estequioproteômica na terapia direcionada e oferece uma promessa para potenciais tratamentos para o câncer de cabeça e pescoço.


Subject(s)
Humans , Head and Neck Neoplasms/genetics , Oxygen , Carbon , Proteome/genetics , Tumor Microenvironment
2.
Braz. j. biol ; 83: e245330, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1339394

ABSTRACT

Abstract Background The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.


Resumo Contexto O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.


Subject(s)
Animals , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia , Brain , RNA, Messenger , Cattle , Neuroglobin
3.
Rev. mex. anestesiol ; 45(3): 163-171, jul.-sep. 2022. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1409781

ABSTRACT

Resumen: Las complicaciones neurológicas perioperatorias secundarias a hipoxia durante procedimientos de sedación y anestesia general son frecuentes en cirugía cardiovascular y en pacientes con comorbilidades. Sin embargo, hasta el momento no existe un consenso para el diagnóstico de estas posibles complicaciones. En pacientes con trauma encefálico severo y/o hemorragia subaracnoidea el lactato cerebral no fue útil para predicción de hipoxia cerebral; pese a ello, la relación de lactato/piruvato podría ser una herramienta para diagnóstico intraoperatorio de hipoxia cerebral aguda. Los estudios sugieren que éste debe asociarse a otros marcadores y/o a monitoreo multimodal. Es necesario realizar estudios que evalúen su valor predictivo para hipoxia cerebral.


Abstract: Perioperative neurological complications secondary to hypoxia during sedation and general anesthesia procedures are frequent in cardiovascular surgery, and in patients with comorbidities. However, so far there is no consensus for the diagnosis of these possible complications. In patients with head trauma severe and/or subarachnoid hemorrhage cerebral lactate was not useful for predicting cerebral hypoxia, however the lactate/pyruvate ratio could be a tool for intraoperative diagnosis of acute cerebral hypoxia. Studies suggest that it must be associated with other markers or multimodal monitoring. Further studies are needed to evaluate lactate predictive value for the diagnosis of cerebral hypoxia.

4.
Fisioter. Pesqui. (Online) ; 29(2): 176-180, maio-ago. 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394354

ABSTRACT

ABSTRACT The COVID-19 pandemic has led to a great number of hospitalizations. A considerable number of cases progress to the severe form of the infection and death. Prone positioning is a therapeutic strategy with strong evidence of reduced mortality in patients with acute respiratory distress syndrome (ARDS). This study aims to assess if the prone positioning strategy is used by health professionals in hospitals to treat patients with COVID-19 on invasive mechanical ventilation and the professionals' perception of its effect on the mortality rate. This is a cross-sectional study, with a convenience sample composed of health professionals of both sexes working in hospitals throughout Brazil. Participants answered an online questionnaire composed of 16 questions using Google Forms, from July 2020 to September 2020. A total of 455 questionnaires were answered. Prone positioning is routinely performed in hospitals where 386 (95%) of the responding professionals work. Among them, 374 (96.9%) consider that the prone position strategy reduces hypoxemia and 289 (74.9%) consider that it reduces mortality in patients with COVID-19 and ARDS on invasive mechanical ventilation. Finally, most health professionals working in Brazilian hospitals perform and believe that prone positioning reduces hypoxemia and mortality in patients with COVID-19 on invasive mechanical ventilation.


RESUMO A pandemia de covid-19 gerou um grande número de internações hospitalares e uma quantidade considerável de casos evolui para a forma grave da doença e óbito. A manobra de posição prona é uma estratégia terapêutica com forte evidência de redução da mortalidade em pacientes com síndrome do desconforto respiratório agudo (SDRA). Este estudo teve como objetivo verificar se a manobra de decúbito ventral é realizada como estratégia de tratamento de pacientes com covid-19 em ventilação mecânica invasiva por profissionais de saúde que atuam em ambiente hospitalar e a percepção sobre seu impacto na mortalidade. Trata-se de um estudo transversal, com amostra de conveniência composta por profissionais de saúde que atuam em hospitais de todo o Brasil, de ambos os sexos. Os participantes responderam a um questionário online, composto por 16 questões, elaborado no Google Forms, de julho a setembro de 2020. Quatrocentos e cinquenta e cinco questionários foram respondidos. A manobra da posição prona é realizada rotineiramente em hospitais onde atuam 386 profissionais (95%). Desses, 374 (96,9%) têm a percepção de que a manobra de decúbito ventral reduz a hipoxemia e 289 (74,9%) percebe que ela reduz a mortalidade de pacientes com covid-19 e SDRA em ventilação mecânica invasiva. Em conclusão, a maioria dos profissionais de saúde que atuam em hospitais brasileiros realiza e acredita que a manobra de decúbito ventral reduz a hipoxemia e a mortalidade em pacientes com covid-19 em ventilação mecânica invasiva.


RESUMEN La pandemia del Covid-19 ha generado un incremento de las hospitalizaciones y un gran número de casos de esta enfermedad ha evolucionado a su forma grave y la muerte. El manejo de la posición de decúbito prono es una estrategia terapéutica con sólida evidencia de reducción de la mortalidad en pacientes con síndrome de dificultad respiratoria aguda (SDRA). Este estudio tuvo como objetivo comprobar si la posición de decúbito prono es realizada por los profesionales de la salud que trabajan en un hospital como estrategia para el tratamiento de pacientes con el Covid-19 en ventilación mecánica invasiva y la percepción de estos profesionales sobre el impacto de tal práctica en la mortalidad. Se trata de un estudio transversal, con una muestra de conveniencia compuesta por profesionales de la salud que actúan en hospitales de todo Brasil, de ambos sexos. Los participantes respondieron un cuestionario en línea, con 16 preguntas en Google Forms, en el periodo de julio a septiembre de 2020. Se respondieron 455 cuestionarios. El manejo de la posición de decúbito prono se realiza de forma rutinaria en los hospitales donde trabajan 386 profesionales (95%). De estos, 374 (96,9%) tienen la percepción de que el manejo de la posición de decúbito prono reduce la hipoxemia y 289 (74,9%) perciben que esta práctica reduce la mortalidad de los pacientes con Covid-19 y SDRA en ventilación mecánica invasiva. Se concluye que la mayoría de los profesionales de la salud que actúan en los hospitales brasileños realizan y creen que la posición de decúbito prono reduce la hipoxemia y la mortalidad en pacientes con Covid-19 en ventilación mecánica invasiva.

5.
Rev. bras. cir. cardiovasc ; 37(4): 587-590, Jul.-Aug. 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394717

ABSTRACT

Abstract While the fraternity continues to ponder on the mechanisms by which coronavirus disease (COVID-19) positivity affects the outcome of cardiac surgical subset, we put forth a 3H (Hypoxia-Hemolysis-Hyperinflammation) trilogy aimed at elucidating the liaison between cardiopulmonary bypass (commonly employed for cardiac surgical conduct) and COVID-19 infection. A sound comprehension of the same can doubtlessly assist the perioperative team in staging a well-directed pathophysiology-driven management approach.

6.
Rev. bras. cir. cardiovasc ; 37(3): 370-379, May-June 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1376533

ABSTRACT

ABSTRACT Introduction: The objective of this study is to investigate the protective mechanism of dexmedetomidine (Dex) in myocardial ischemia/reperfusion (MIR)-induced acute lung injury (ALI) of diabetic rats by inhibiting hypoxia-inducible factor-1α (HIF-1α). Methods: Initially, healthy male Sprague Dawley rats were treated with streptozocin to induce diabetes. Then, three weeks after the induction, Dex or lentiviral vector (LV)-HIF-1α was injected into the rats 30 minutes prior to the MIR modeling. After four weeks, lung tissues were harvested for pathological changes observation and the wet/dry weight (W/D) ratio determination. Afterwards, oxidative stress indicators and pro-inflammatory factors were measured. In addition, HIF-1α expression was assessed by immunohistochemistry and western blot analysis. Results: Dex could suppress inflammatory cell infiltration, improve lung tissue structure, reduce pathological score and the W/D ratio, and block oxidative stress and inflammatory response in MIR-induced ALI of diabetic rats. Besides, Dex could also inhibit HIF-1α expression. Moreover, Dex + LV-HIF-1α reversed the protective role of Dex on diabetic MIR-induced ALI. Conclusion: Our study has made it clear that Dex inhibited the upregulation of HIF-1α in diabetic MIR-induced ALI, and thus protect lung functions by quenching the accumulation of oxygen radical and reducing lung inflammatory response.

8.
J. health med. sci. (Print) ; 8(1): 15-20, ene.-mar. 2022. tab
Article in English | LILACS | ID: biblio-1391822

ABSTRACT

The Chilean workforce has over 200,000 people that are intermittently exposed to altitudes over 4000 m. In 2012, the Ministry of Health provided a technical guide for high altitude workers that included a series of actions to mitigate the effects of hypoxia. Previous studies have shown the positive effect of oxygen enrichment at high altitudes. The Atacama Large Millimeter / submillimeter Arrays (ALMA) radiotelescope operate at 5,050 m (Array Operation Site, AOS) and is the only place in the world where Pressure Swing Adsorption (PSA) and Liquid Oxygen technologies have been installed at a large scale. Here we discuss our experience using oxygen supplementation at ALMA, to prevent the malaise and/or risks associated with exposure at 5,050 m. Antenna operators experienced chronic intermittent hypobaric hypoxia (CIHH, shiftwork 8 days HA*6 days rest SL) over 4 years. Studies to define normal O2 saturation values were performed in OSF and AOS by continuous recording during the shift. The outcomes showed no differences between production procedures (PSA or Liquid oxygen) in regulating oxygen availability at AOS facilities. As a result, big-scale installations have difficulties reaching the appropriate oxygen concentration due to leaks in high mobility areas. In addition, the PSA plant requires adequation and maintenance to operate at a very high altitude.


La fuerza laboral chilena cuenta con más de 200.000 personas que están expuestas intermitentemente a altitudes superiores a los 4000 m. En 2012, el Ministerio de Salud entregó una guía técnica para trabajadores de altura que incluía una serie de acciones para mitigar los efectos de la hipoxia. Estudios anteriores han demostrado el efecto positivo del enriquecimiento de oxígeno en altitudes elevadas. El radiotelescopio Atacama Large Millimeter/submillimeter Arrays (ALMA) opera a 5.050 m (Array Operation Site, AOS) y es el único lugar en el mundo donde se han instalado tecnologías de adsorción por cambio de presión (PSA) y oxígeno líquido a gran escala. Aquí discutimos nuestra experiencia usando suplementos de oxígeno en ALMA, para prevenir el malestar y/o los riesgos asociados con la exposición a 5.050 m. Los operadores de antena experimentaron hipoxia hipobárica intermitente crónica (CIHH, trabajo por turnos 8 días HA*6 días descanso SL) durante 4 años. Se realizaron estudios para definir valores normales de saturación de O2 en OSF y AOS mediante registro continuo durante el turno. Los resultados no mostraron diferencias entre los procedimientos de producción (PSA u oxígeno líquido) en la regulación de la disponibilidad de oxígeno en las instalaciones de AOS. Como resultado, las instalaciones a gran escala tienen dificultades para alcanzar la concentración de oxígeno adecuada debido a fugas en áreas de alta movilidad. Además, la planta de PSA requiere de adecuación y mantenimiento para operar a gran altura.


Subject(s)
Humans , Oxygen/administration & dosage , Hypoxia/physiopathology , Blood Pressure/physiology , Models, Molecular , Desert , Absorption , Altitude , Telescopes
9.
An. Fac. Med. (Perú) ; 83(1): 58-64, ene.-mar. 2022.
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1374224

ABSTRACT

RESUMEN Durante el envejecimiento, los factores genéticos y ambientales conllevan un mayor riesgo de enfermedades que facilitan la pérdida de la funcionalidad. El entrenamiento de resistencia de alta intensidad ha demostrado conducir a beneficios para la salud en los adultos mayores, sin embargo, su utilización es limitada en esta población. Recientemente, el entrenamiento de resistencia en hipoxia (ERH) se ha presentado como una alternativa viable en la terapia de rehabilitación para adultos mayores, con todo, la información es escasa al respecto. De esta forma, el objetivo de este estudio fue recopilar el conocimiento actual sobre el ERH en adultos mayores, así como los beneficios para su salud. Para ello, se realizó una búsqueda selectiva de artículos publicados en los últimos 6 años sobre los efectos del ERH en personas mayores en la base de datos Pubmed. La búsqueda resultó en 227 artículos, de los cuales 18 fueron seleccionados para esta revisión. Se identificaron 3 tipos de entrenamiento: terapia de restricción del flujo sanguíneo (TRFS), entrenamiento de resistencia en hipoxia hipobárica (ERHH) y entrenamiento de resistencia en hipoxia normobárica (ERHN). A partir de la información recabada, podemos indicar que el TRFS ofrece mayores efectos positivos sobre la ganancia de fuerza y la hipertrofia muscular, mientras que existe poca evidencia del ERHH y ERHN en personas mayores. Finalmente, manifestamos la necesidad de más estudios que evalúen la seguridad de esta intervención en la salud en este grupo etario.


ABSTRACT During aging, genetic and environmental factors carry an increased risk of diseases that facilitate the loss of function. High-intensity resistance training has been shown to lead to health benefits in older adults, however, its use is limited in this population. Recently, hypoxic resistance training (HRT) has been presented as a viable alternative in rehabilitation therapy for older adults, however, information is scarce in this regard. Thus, the objective of this study was to collect current knowledge about HRT in older adults, as well as the benefits for their health. To do this, a selective search was carried out for articles published in the last 6 years on the effects of HRT in older people in the Pubmed database. The search resulted in 227 articles, of which 18 were selected for this review. Three types of training were identified: blood flow restriction therapy (BFRT), resistance training in hypobaric hypoxia (RTHH), and resistance training in normobaric hypoxia (RTNH). From the information collected, we can indicate that TRFS offers greater positive effects on strength gain and muscle hypertrophy, while there is little evidence of RTHH and RTNH in older people. Finally, we express the need for more studies to evaluate the safety of this intervention in health in this age group.

10.
Braz. arch. biol. technol ; 65: e22210166, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364436

ABSTRACT

Abstract Osteoarthritis (OA) encompasses degeneration of articular cartilage, subchondral bone erosions and sclerosis. Chondrocyte apoptosis and an oxygen-deprived microenvironment are essential factors in OA pathogenesis. PAR-4 (Prostate apoptosis response-4) is a pro-apoptotic protein implicated in many pathologies as well as in chondrocyte cell death mechanism. Vitamin D supplementation has been identified as a therapeutic tool for a variety of inflammatory pathologies. In the present manuscript, we investigated whether first, PAR-4 expression is influenced by chondrocytes in a model of OA, in vitro, and second, whether vitamin D modulates PAR-4 expression in the same model. To test our hypothesis, we used the primary culture of murine chondrocytes isolated from the femoral and tibial condyles of wistar rats. The expression of the pro-inflammatory effect interleukin IL-1β was evaluated in the presence and absence of vitamin D. Western blot and immunofluorescence analysis confirmed protein expression. In the normoxia condition, the chondrocytes expressed PAR-4 in the cell nucleus, and in the hypoxic condition, PAR-4 was expressed in the cell cytoplasm. We disclosed that the treatment with Vitamin D decreased PAR-4 (p= 0.0137) and caspase-3 (p= 0.0007) expression. Thus, the results suggested that PAR-4 and caspase-3 proteins could be potential targets for OA.However, we believe that research is needed to identify the mechanisms implicated in the regulation of PAR-4 in OA.

11.
Article in Chinese | WPRIM | ID: wpr-936323

ABSTRACT

OBJECTIVE@#To investigate the the effects of leptin on the proliferation, differentiation and PTEN expression of rat retinal progenitor cells (RPCs) cultured under hypoxic condition.@*METHODS@#SD rat RPCs were cultured in normoxic conditions or exposed to hypoxia in the presence of 0, 0.3, 1.0, 3.0, 10, and 30 nmol/L leptin for 12, 48 and 72 h, and the cell viability was assessed using cell counting kit 8 (CCK 8) assay. The RPCs in primary culture were divided into control group, hypoxia group, and hypoxia+leptin group, and after 48 h of culture, the cell medium was replaced with differentiation medium and the cells were further cultured for 6 days. Immunofluorescence staining was employed to detect the cells positive for β-tubulin III and GFAP, and Western blotting was used to examine the expression of PTEN at 48 h of cell culture.@*RESULTS@#The first generation of RPCs showed suspended growth in the medium with abundant and bright cellular plasma and formed mulberry like cell spheres after 2 days of culture. Treatment with low-dose leptin (below 3.0 nmol/L) for 48 h obviously improved the viability of RPCs cultured in hypoxia, while at high concentrations (above 10 nmol/L), leptin significantly suppressed the cell viability (P < 0.05). The cells treated with 3.0 nmol/L leptin for 48 h showed the highest viability (P < 0.05). After treatment with 3.0 nmol/L leptin for 48 h, the cells with hypoxic exposure showed similar GFAP and β-tubulin Ⅲ positivity with the control cells (P>0.05), but exhibited an obvious down-regulation of PTEN protein expression compared with the control cells (P < 0.05).@*CONCLUSION@#In rat RPCs with hypoxic exposure, treatment with low dose leptin can promote the cell proliferation and suppress cellular PTEN protein expression without causing significant effects on cell differentiation.


Subject(s)
Animals , Cell Differentiation/drug effects , Cell Hypoxia/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Leptin/pharmacology , PTEN Phosphohydrolase/metabolism , Rats , Rats, Sprague-Dawley , Retina/metabolism , Stem Cells/metabolism , Tubulin
12.
Article in Chinese | WPRIM | ID: wpr-928725

ABSTRACT

OBJECTIVE@#To explore the effect of hypoxia on the chemosensitivity of B-acute lymphoblastic leukemia (B-ALL) cells to Vincristine (VCR) and the mechanisms.@*METHODS@#B-ALL cells SUP-B15, Nalm-6 and RS4;11 were selected as the research objects. The cells were divided into the control group and the hypoxia mimic group (CoCl2 pretreatment). The two groups were treated with VCR at different concentrations for 24 hours, CCK-8 was used to detect cell viability, flow cytometry was used to detect cell apoptosis, and Western bolt method was used to detect hypoxia inducible factor (HIF-1α), BAX, Bcl-2 and β-actin protein expression. Quantitative real-time fluorescent PCR (qRT-PCR) was used to detect BAX and β-actin mRNA levels.@*RESULTS@#CoCl2 could simulate hypoxic environment to induce the expression of HIF-1α. The cells SUP-B15 and RS4;11 of the hypoxia mimic group were lower sensitivity to VCR as compared with the control group; the apoptosis rate of the hypoxia mimic group was lower than that of the control group after 80 nmol/L VCR treatment. The expression levels of BAX protein and mRNA in the hypoxia mimic group were lower than those of the control group, and there was no significant difference in the expression levels of Bcl-2 protein between two groups.@*CONCLUSION@#Under hypoxic conditions, HIF-1α may mediate VCR resistance in B-ALL cells by downregulating the pro-apoptotic protein BAX.


Subject(s)
Actins/pharmacology , Apoptosis , Cell Hypoxia , Humans , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit , Proto-Oncogene Proteins c-bcl-2 , RNA, Messenger , Vincristine/pharmacology , bcl-2-Associated X Protein/pharmacology
13.
China Pharmacy ; (12): 542-547, 2022.
Article in Chinese | WPRIM | ID: wpr-920722

ABSTRACT

OBJECTIVE To explore the effects of acteoside on hypoxia/reoxygena tion(H/R)-induced cardiomyocyte damage by regulating Rho family GTPase 3(Rnd3)/nuclear factor κB(NF-κB)pathway. METHODS The H 9c2 cardiomyocyte were divided into control group (no administration ,no modeling ),H/R group (only modeling ),H/R+AS-L group ,H/R+AS-M group , H/R+AS-H group (10,30,90 μmol/L acteoside for above 3 groups firstly ,and then modeling ),H/R+pcDNA group [transfecting pcDNA (empty vector ) firstly,and then modeling] ,H/R + pcDNA-Rnd 3 group [overexpression of Rnd 3 by transfecting pcDNA-Rnd3(Rnd3 overexpression vector )firstly,and then modeling] ,H/R+AS-H+si-NC group [transfecting si-NC (negative control)firstly,and then giving 90 μmol/L acteoside and modeling],H/R+AS-H+si-Rnd3 group [inhibiting overexpression of Rnd 3 by transfecting si-Rnd 3 (Rnd3 small interfering RNA ) firstly,and then giving 90 μ mol/L acteoside and modeling]. After corresponding treatment ,the apoptotic rate ,release of lactate dehydrogenase (LDH),malondialdehyde(MDA)level,the activity of superoxide dismutase (SOD),the level of tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin- 6(IL-6), mRNA and protein expression of Rnd 3 and NF-κB subunit p65(NF-κB p65),the expression of aspartate proteolytic enzyme 3 (Cleaved Caspase- 3)protein and Cleaved Caspase- 9 protein were detected. RESULTS Different concentrations of acteoside could reduce the apoptotic rate of H/R-induced H 9c2 cardiomyocyte,the protein expressions of Cleaved Caspase- 3 and Cleaved Caspase-9,mRNA and protein expressions of NF-κB p65,the levels of LDH release and MDA ,TNF-α,IL-1β and IL-6,while increase the activity of SOD and mRNA and protein expressions of Rnd 3(P<0.05),in a dose-dependent manner. Overexpression of Rnd 3 could decrease the apoptotic rate of H 9c2 cardiomyocyte,protein expressions of NF-κB p65,Cleaved Caspase- 3 and Cleaved Caspase- 9, the levels of LDH release , MDA, TNF-α,IL-1β and IL-6,while increase the protein expression of Rnd 3 and the activity of SOD (P<0.05). The inhibition overexpression of Rnd 3 could weaken the inhibitory effects of acteoside on H/R-induced apoptosis of H 9c2 cardiomyocyte, oxidative stress and inflammatory reaction (P<0.05). CONCLUSIONS Acteoside could regulate Rnd 3/NF-κ B pathway by promoting the expression of Rnd 3 and inhibiting the expression of NF-κB p65,inhibit cardiomyocyte apoptosis ,oxidative stress and inflammation reaction so as to relieve the H/R-induced cardiomyocyte damage.

14.
International Eye Science ; (12): 357-362, 2022.
Article in English | WPRIM | ID: wpr-920398

ABSTRACT

@#AIM: To investigate the effects of simvastatin(Sim)on human retinal pigment epithelial cells(RPE-19)and the possible mechanisms <i>in vitro</i> under hypoxia. <p>METHODS: RPE-19 cells were divided into three group: control group, hypoxia group(the final concentration of CoCl2 in the medium was 125 μmol/L), and Sim treatment group(3 μmol/L Sim was added in the RPE cells' medium which contain 125 μmol/L CoCl2). After 24h, the morphology of RPE-19 cells were observed, the proliferation of cells were calculated by MTT, the secretion levels and protein expression of hypoxia-inducible factor 1-Alpha(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by enzyme-linked immunosorbent assay(ELISA)and Western blotting. The expression level of autophagy protein was detected by Western blot and apoptosis was detected by TUNEL.<p>RESULTS: The morphology and activity of RPE-19 cells showed an apparent change under hypoxia. The expression of HIF-1α and VEGF protein were increased obviously in the hypoxia group and then significantly decreased after Sim treatment. Beclin1, and LC3B proteins were decreased in the CoCl2+Sim group, and the expression levels were lower than the control and CoCl2 group. Under hypoxia, Sim inhibited RPE cells' proliferation and promoted the apoptosis.<p>CONCLUSION:Sim inhibits RPE cells' proliferation, decreases HIF-1α and VEGF protein, and promotes apoptosis under hypoxia. Our results suggested that the mechanism by which Sim promoted apoptosis in RPE cells may be related to its inhibition of autophagy.

15.
Acta Pharmaceutica Sinica ; (12): 98-108, 2022.
Article in Chinese | WPRIM | ID: wpr-913172

ABSTRACT

Tumor microenvironment (TME) is composed of abnormal tumor vasculature, extracellular matrix components, endothelial cells, pericytes, tumor associated fibroblasts, smooth muscle cells and immune cells, which is characterized by hypoxia, acidosis and high interstitial fluid pressure. Hypoxia and acidosis within the TME trigger an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing tumor growth, angiogenesis, and ultimately, resulting in metastasis. What's more, the components of TME including abnormal tumor vasculature, rich composition of the ECM, and abundant stroma cells impair tumoral distribution and penetration of the drugs. At the same time, this stromal microenvironment plays a vital role in creating an immunosuppressive environment.Over the past years, more and more researches focus on targeting and remolding TME to improve therapeutic effects against tumors. Herein, we reviewed current strategies developed to target and remodel TME, including modulating tumor hypoxia, tumor vasculature, tumor associated fibroblasts, extracellular matrix components, tumor associated macrophage phenotypes and dendritic cells. Also, potential problems and future directions are pointed out in this review.

16.
China Pharmacy ; (12): 13-18, 2022.
Article in Chinese | WPRIM | ID: wpr-907006

ABSTRACT

OBJECTIVE To investigate the e ffects of methyl ferulate (MF) on the mitochondrial function of H 9c2 cardiomyocytes after hypoxia-induced injury. METHODS H9c2 cardiomyocytes were divided into normal group (no administration,no modeling ),hypoxia model group (modeling alone ),MF high-dose ,medium-dose and low-dose groups (40, 20,10 μmol/L)and positive control drug group (cyclosporin A ,1 μmol/L). After drug pretreatment and inducing hypoxia-induced injury,the levels of lactate dehydrogenase (LDH),malondialdehyde(MDA),creatine kinase (CK)and adenosine triphosphate (ATP)were tested. The intracellular reactive oxygen species (ROS),mitochondrial membrane potential (MMP),the opening of mitochondrial membrane permeability transition pore (mPTP) were detected with flow cytometry. RESULTS Compared with hypoxia model group ,the levels of LDH ,MDA,CK and ROS fluorescence intensity were decreased significantly in MF high-dose,medium-dose and low-dose groups ,while the level of ATP was increased significantly (P<0.01 or P<0.05). The red/ green fluorescence intensity ratio of MMP and the green fluorescence intensity of mPTP were increased significantly (P<0.01 or P<0.05). CONCLUSIONS MF can reverse the levels of biochemical indexes in H 9c2 cardiomyocyte after hypoxia-induced injury,keep MMP stable ,reduce the opening of mPTP ,and has an obvious protective effect on the mitochondrial function of H9c2 cardiomyocytes injured by hypoxia ,and this protective effect is dose-dependent.

17.
Article in Chinese | WPRIM | ID: wpr-941023

ABSTRACT

OBJECTIVE@#To investigate effects of physiological hypoxic conditions on suspension and adherence of embryoid bodies (EBs) during differentiation of human induced pluripotent stem cells (hiPSCs) and explore the underlying mechanisms.@*METHODS@#EBs in suspension culture were divided into normoxic (21% O2) and hypoxic (5% O2) groups, and those in adherent culture were divided into normoxic, hypoxic and hypoxia + HIF-1α inhibitor (echinomycin) groups. After characterization of the pluripotency with immunofluorescence assay, the hiPSCs were digested and suspended under normoxic and hypoxic conditions for 5 days, and the formation and morphological changes of the EBs were observed microscopically; the expressions of the markers genes of the 3 germ layers in the EBs were detected. The EBs were then inoculated into petri dishes for further culture in normoxic and hypoxic conditions for another 2 days, after which the adhesion and peripheral expansion rate of the adherent EBs were observed; the changes in the expressions of HIF-1α, β-catenin and VEGFA were detected in response to hypoxic culture and echinomycin treatment.@*RESULTS@#The EBs cultured in normoxic and hypoxic conditions were all capable of differentiation into the 3 germ layers. The EBs cultured in hypoxic conditions showed reduced apoptotic debris around them with earlier appearance of cystic EBs and more uniform sizes as compared with those in normoxic culture. Hypoxic culture induced more adherent EBs than normoxic culture (P < 0.05) with also a greater outgrowth rate of the adherent EBs (P < 0.05). The EBs in hypoxic culture showed significantly up-regulated mRNA expressions of β-catenin and VEGFA (P < 0.05) and protein expressions of HIF-1 α, β-catenin and VEGFA (P < 0.05), and their protein expresisons levels were significantly lowered after treatment with echinomycin (P < 0.05).@*CONCLUSION@#Hypoxia can promote the formation and maturation of suspended EBs and enhance their adherence and post-adherent proliferation without affecting their pluripotency for differentiation into all the 3 germ layers. Our results provide preliminary evidence that activation of HIF-1α/β-catenin/VEGFA signaling pathway can enhance the differentiation potential of hiPSCs.


Subject(s)
Echinomycin/metabolism , Embryoid Bodies/metabolism , Humans , Hypoxia/metabolism , Induced Pluripotent Stem Cells/metabolism , beta Catenin/metabolism
18.
Article in Chinese | WPRIM | ID: wpr-940741

ABSTRACT

ObjectiveTo predict the underlying mechanism of Bushen Huoxuetang in treating osteoporosis related to endocrine therapy in breast cancer by network pharmacology and to verify the results through in vitro cell model. MethodThe main effective components and targets of Bushen Huoxuetang were screened out through network pharmacology, and the targets of osteoporosis related to endocrine therapy in breast cancer were further obtained. The intersected targets were analyzed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Kaplan Meier plotter was used to analyze the survival of crucial targets. Finally, the inhibitory activity against cell proliferation was evaluated by in vitro methye thiazolye telrazlium(MTT) assay. The key targets and pathways were verified by Western blot, and the mRNA expression of the key targets was evaluated by real-time polymerase chain reaction(Real-time PCR). ResultA total of 716 active components and 249 key targets of Bushen Huoxuetang were obtained from network pharmacology. There were 135 common targets, among which protein kinase B(Akt)1 and hypoxia-inducible factor-1α (HIF-1α) were two key targets. Additionally, 531 biological processes, 62 cellular components, 162 molecular functions, and 145 signaling pathways including breast cancer and endocrine resistance were involved. The key targets were effectively enriched in phosphatidylinositol 3-kinases(PI3K)/Akt and HIF-1 signaling pathways. According to the MTT assay, the cell proliferation rate and cell motility of MCF-7 and T47D cells in the luminal A cell line were reduced by Bushen Huoxuetang treatment (22.5, 45, 90 g·L-1, and 45, 90, 180 g·L-1) for 48 h as compared with the blank group. As revealed by Western blot, MCF-7 cells were treated with Bushen Huoxuetang (0, 15, 60 g·L-1) for 48 h, and the relative expression of p-PI3K, PI3K, p-Akt, Akt, and HIF-1α was decreased in a dose-dependent manner as compared with the blank group (P<0.05, P<0.01). Real-time PCR was used to detect the mRNA expression of the key target HIF-1α. The results showed that the mRNA expression of HIF-1α in MCF-7 cells was decreased with the increase in the dose (P<0.01), and the change was in a concentration-dependent manner. ConclusionThe mechanism of Bushen Huoxuetang in the treatment of osteoporosis related to endocrine therapy in breast cancer may be related to the key targets including Akt1 and HIF-1α through the PI3K/Akt/HIF-1α signaling pathway.

19.
Article in Chinese | WPRIM | ID: wpr-940557

ABSTRACT

ObjectiveTo establish blood stasis models in zebrafish using three inducers and select the optimal model for evaluating the activity of Notoginseng Radix et Rhizoma in promoting blood circulation. MethodArachidonic acid (AA), ponatinib, and isoprenaline (ISO) were used to induce blood stasis models in zebrafish. A normal group, a model group, a positive drug group, and Notoginseng Radix et Rhizoma water extract freeze-dried powder groups at different concentrations were set up. The staining intensity of cardiac erythrocytes and the fluorescence intensity of cardiac apoptotic cells were calculated, the anti-thrombotic effect and anti-myocardial hypoxia activity of Notoginseng Radix et Rhizoma were evaluated. The activities of water extract and 70% methanol extract of Notoginseng Radix et Rhizoma were compared based on the preferred AA- and ISO-induced blood stasis models in zebrafish and the difference in the chemical composition was analyzed by UHPLC LTQ-Orbitrap MS/MS. ResultAfter induction by AA and ponatinib, the staining intensity of cardiac erythrocytes was reduced (P<0.01), and the fluorescence intensity of cardiac apoptotic cells increased after the induction by ISO (P<0.01). The freeze-dried powder of the water extract of Notoginseng Radix et Rhizoma could antagonize the thrombosis in the AA-induced model (P<0.01) and the myocardial apoptosis in the ISO-induced model (P<0.05), while no significant improvement in the thrombosis was observed in the ponatinib-induced model. The freeze-dried powder of 70% methanol extract of Notoginseng Radix et Rhizoma could inhibit myocardial apoptosis in the ISO-induced blood stasis model (P<0.01), and the effect was stronger than that of the freeze-dried powder of Notoginseng Radix et Rhizoma water extract. The difference in chemical composition lay in some saponins (such as ginsenoside Re), amino acids, and acetylenic alcohols. ConclusionAA, ponatinib, and ISO all can serve as inducers for the blood stasis model in zebrafish. AA- and ISO-induced models can be used to evaluate the activity of freeze-dried powder of Notoginseng Radix et Rhizoma water extract in promoting blood circulation. The chemical compositions of the freeze-dried powders of Notoginseng Radix et Rhizoma extracted with water and 70% methanol are quite different. For the ISO-induced blood stasis model, the freeze-dried powder of Notoginseng Radix et Rhizoma extracted with 70% methanol has a stronger ability against myocardial hypoxia. Saponins and acetylenic alcohols may be closely related to the effects of promoting blood circulation and resolving blood stasis.

20.
Article in Chinese | WPRIM | ID: wpr-940515

ABSTRACT

ObjectiveTo establish an evaluation method for mitochondrial energy metabolism with Seahorse analyzer and investigate the protective effect of Yiqi Jiedu prescriptions (YQ) on mitochondria in rat adrenal pheochromocytoma (PC12) cells against hypoxia injury. MethodThe PC12 cell injury model was induced in vitro using hypoxic chambers. Five groups were set up, ie, a control group, a model group (model), high- (25 µmol·L-1), medium- (5 µmol·L-1) and low-dose (1 µmol·L-1) YQ groups, and a positive drug trimetazidine (TMZ) group, with three replicate wells in each group. The experiment was repeated three times. The established method for energy metabolism analysis was used to assay the activity of mitochondrial complex in cells and screen the optimal dosing concentration. Subsequently, the YQ group and modified YQ groups were set up, and the aerobic respiration and glycolysis function were assayed by the Seahorse analyzer. According to the non-mitochondrial oxygen consumption, proton leakage, basal respiration, maximum respiration, ATP production, and potentially improved respiration, the effects of modified YQ groups on the aerobic respiration of mitochondria damaged by hypoxia were evaluated by principal component analysis (PCA) and variable importance in projection (VIP). The expression of cytochrome C, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) was detected by Western blot. ResultCompared with the groups of other concentrations, the optimal dosing concentration of carbonyl cyanide-4 (trifluoromethoxy)phenylhydrazone (FCCP) was 2 µmol·L-1. Compared with the model group, the medium-dose YQ group showed enhanced mitochondrial complex activity (P<0.05). The YQ groups were superior to the model group in improvement (P<0.01). The combination of ginsenoside and geniposide showed the optimal effect among the modified YQ groups (P<0.01). VIP analysis revealed that for the improvement of mitochondrial respiratory function, the contribution of geniposide in YQ was the greatest. Compared with the model group, the high-dose YQ group displayed reduced leakage of mitochondrial cytochrome C (P<0.01), decreased expression of Bax protein (P<0.01), and increased expression of Bcl-2 protein (P<0.05, P<0.01). ConclusionA cellular, high-throughput quantitative evaluation method for mitochondrial energy metabolism was established, which demonstrated that YQ could significantly improve the impaired mitochondrial energy metabolism in PC12 cells damaged by hypoxia, and the underlying mechanism might be related to the protection against mitochondrial apoptosis.

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