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1.
Zool Res ; 42(2): 250-251, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33738990

RESUMO

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

2.
Zool Res ; 41(1): 3-19, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31840949

RESUMO

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macacafascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3ß,5,6ß-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.


Assuntos
Androstanóis/farmacologia , Hipóxia/veterinária , Macaca fascicularis , Doenças dos Macacos/prevenção & controle , Progesterona/farmacologia , Transcriptoma , Androstanóis/administração & dosagem , Animais , Encefalopatias/prevenção & controle , Encefalopatias/veterinária , Cálcio/metabolismo , Regulação da Expressão Gênica , Hipóxia/patologia , Leucócitos/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Pressão , Progesterona/administração & dosagem
3.
Mil Med Res ; 5(1): 33, 2018 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-30268159

RESUMO

BACKGROUND: Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease (COPD). Thus far, little advancement in countering hypoxic damage has been achieved, and one of the main reasons is the absence of an ideal algorithm or calculation method to normalize hypoxia tolerance scores when evaluating an animal model. In this study, we improved a traditional calculation formula for assessment of hypoxia tolerance. METHODS: We used a sealed bottle model in which the oxygen is gradually consumed by a mouse inside. To evaluate the hypoxia tolerance of mice, the survival time (ST) of the mouse is recorded and was used to calculate standard hypoxia tolerance time (STT) and adjusted standard hypoxia tolerance time (ASTT). Mice administered with methazolamide and saline were used as positive and negative controls, respectively. RESULTS: Since mice were grouped according to either body weight (BW) or bottle volume, we found a strongly negative correlation between STT and BW instead of between STT and bottle volume, suggesting that different BWs could cause false positive or negative errors in the STT results. Furthermore, both false positive and negative errors could be rectified when ASTT was used as the evaluation index. Screening for anti-hypoxic medicines by using mice as the experimental subjects would provide more credible results with the improved ASTT method than with the STT method. CONCLUSION: ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.


Assuntos
Peso Corporal , Hipóxia/fisiopatologia , Oxigênio/análise , Animais , Modelos Animais de Doenças , Reações Falso-Positivas , Masculino , Camundongos , Fatores de Tempo
4.
Mol Med Rep ; 16(5): 6828-6836, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901489

RESUMO

Hypoxic preconditioning (HPC) is well­known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra­performance liquid chromatography­quadrupole time­of­flight mass spectrometry (UPLC­QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.


Assuntos
Cromatografia Líquida de Alta Pressão , Hipóxia , Espectrometria de Massas por Ionização por Electrospray , Aminoácidos/sangue , Animais , Análise Discriminante , Modelos Animais de Doenças , Precondicionamento Isquêmico , Análise dos Mínimos Quadrados , Lisofosfatidilcolinas/sangue , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Palmitoilcarnitina/sangue , Análise de Componente Principal
5.
Am J Cancer Res ; 6(5): 1141-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27294006

RESUMO

ATPase inhibitory factor 1 (IF1), an inhibitor of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase, is putatively involved in tumor progression. This study aimed to evaluate the expression levels of IF1 in non-small cell lung cancer (NSCLC) and the prognostic value for the patients. IF1 protein expression levels were detected in 149 cases of NSCLC by using immunohistochemistry. Kaplan-Meier analysis showed that NSCLC patients with high expression of IF1 possessed poorer outcome than those with low expression of IF1 (P=0.007). Moreover, IF1 was also prognostic in the patients with early stages (stage I/II) (P=0.042) and low grade (grade I/II) (P=0.002). Multivariable Cox-regression analysis showed that high expression of IF1 (HR=1.67, P=0.034), tumor size (HR=1.79, P=0.001), and lymph node metastasis (HR=2.66, P=0.000) were independent indicators for NSCLC patients. In conclusion, our study demonstrated that elevated expression of IF1 may associated with lymph node metastasis of NSCLC and served as an independent prognostic and recurrent indicator for the patients.

6.
Sci Rep ; 6: 22589, 2016 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26940428

RESUMO

The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia.


Assuntos
Adaptação Fisiológica , Doença da Altitude/diagnóstico , Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo , Hipóxia/diagnóstico , Doença Aguda , Suscetibilidade a Doenças , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Redes e Vias Metabólicas , Metabolômica , Prognóstico , Adulto Jovem
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