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BACKGROUND: As an important place of material exchange, the homeostasis of the pulmonary circulation environment and function lays an essential foundation for the normal execution of various physiological functions of the body. Small metabolic molecules in the circulation can reflect the corresponding state of the pulmonary circulation. METHODS: We enrolled patients with Patent Foramen Ovale and obtained blood from the pulmonary arteries and veins through heart catheterization. UPLC-MS based untargeted metabolomics was used to compare the changes and metabolic differences of plasma between pulmonary vein and pulmonary artery. RESULTS: The plasma metabolomics revealed that pulmonary artery had a different metabolomic profile compared to venous. 1060 metabolites were identified, and 61 metabolites were differential metabolites. Purine, Amino acids, Nicotinamide, Tetradecanedioic acid and Bile acid were the most markedly. CONCLUSION: The differential metabolites are mostly related to immune inflammation and damage repaired. It is suggested that the pulmonary circulation is always in a steady state of injury and repair while pathological changes may be triggered when the homeostasis is broken. These changes play an important role in revealing the development process and etiology of lung homeostasis and related diseases. Relevant metabolites can be used as potential targets for further study of pulmonary circulation homeostasis.
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BACKGROUND & AIMS: At present, increasing reports have shown that pretreatment platelet count was associated with the prognosis of many types of cancer. We performed rounded analysis to comprehensively analyze and evaluate the prognostic significance of pretreatment thrombocytosis for patients with gastric cancer. METHODS: We identified relevant studies by searching database including PubMed, Embase, Cochrane Library and Web of Science. The relative risk (RR) with its 95% confidence interval (CI) was used to assess the correlation between thrombocytosis and overall survival (OS) of gastric cancer patients. We also conducted subgroup analysis and sensitivity analysis for the prognostic effect of thrombocytosis on OS. The analysis was performed and assessed using Review Manager 5.2. RESULTS: A total of nine studies including 7158 participants were included in this systematic review. Analysis results showed that pretreatment thrombocytosis had a close relationship with 1, 3 and 5 years survival of gastric cancer, with the pooled RRs being 0.80 (95% CI 0.71-0.90; Pâ¯=â¯0.0004), 0.65 (95% CI 0.45-0.92; Pâ¯=â¯0.02) and 0.64 (95% CI 0.47-0.87; Pâ¯=â¯0.004) respectively. CONCLUSIONS: The present rounded analysis suggests that pretreatment thrombocytosis may have significant association with poor survival of patients with gastric cancer.
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Neoplasias Gástricas/mortalidad , Trombocitosis/complicaciones , Humanos , PronósticoRESUMEN
OBJECTIVE: There are currently no specific strategies for the treatment or prevention of vascular dementia. White matter lesions, a common pathology in cerebral small vessel disease, are a major cause of vascular dementia. We investigated whether apoptosis signal-regulating kinase 1 (ASK1) might be a key molecule in cerebral hypoperfusion, associated with blood-brain barrier breakdown and white matter lesions. APPROACH AND RESULTS: A mouse model of cognitive impairment was developed by inducing chronic cerebral hypoperfusion in white matter including the corpus callosum via bilateral common carotid artery stenosis (BCAS) surgery. BCAS-induced white matter lesions caused cognitive decline in C57BL/6J (wild-type) mice but not in ASK1-deficient (ASK1(-/-)) mice. Phosphorylated ASK1 increased in wild-type mouse brains, and phosphorylated p38 and tumor necrosis factor-α expression increased in corpus callosum cerebral endothelial cells after BCAS in wild-type mice but not in ASK1(-/-) mice. BCAS decreased claudin-5 expression and disrupted blood-brain barrier in the corpus callosum of wild-type but not ASK1(-/-) mice. Cerebral nitrotyrosine was increased in wild-type and ASK1(-/-) BCAS mice. Cerebral phosphorylated ASK1 did not increase in wild-type mice treated with NADPH-oxidase inhibitor. A p38 inhibitor and NADPH-oxidase inhibitor mimicked the protective effect of ASK1 deficiency against cognitive impairment. Specific ASK1 inhibitor prevented cognitive decline in BCAS mice. In vitro oxygen-glucose deprivation and tumor necrosis factor-α stimulation caused the disruption of endothelial tight junctions from wild-type mice but not ASK1(-/-) mice. CONCLUSIONS: Oxidative stress-ASK1-p38 cascade plays a role in the pathogenesis of cognitive impairment, through blood-brain barrier breakdown via the disruption of endothelial tight junctions. ASK1 might be a promising therapeutic target for chronic cerebral hypoperfusion-induced cognitive impairment.