Tissue metabolic changes for effects of pirfenidone in rats of acute paraquat poisoning by GC-MS.

We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg-1) poisoning group, a pirfenidone (20 mg kg-1) treatment group, and a pirfenidone (40 mg kg-1) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg-1) treatment group was separated farther than the pirfenidone (20 mg kg-1) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning.

Association of asthma with the risk of cardiovascular disease: A Mendelian randomization study.

BACKGROUND: Association of asthma with the risk of cardiovascular disease has not been fully elucidated. So, this study tried to explore the genetic effect of asthma on five cardiovascular diseases and 90 peripheral cardiovascular proteins to answer the above topic. METHODS: Instrumental variables predicting asthma was extracted from its genome-wide association study data. Two-sample and multivariate MR approaches were used to assess the genetic association of exposure factor (i.e., asthma) with outcome factors (i.e., hypertension, atrial fibrillation, angina pectoris, myocardial infarction, heart failure, and 90 peripheral cardiovascular proteins). RESULTS: First, asthma nominally increased the risk of hypertension and atrial fibrillation (OR = 1.009, 95%CI = 1.003-1.016, P = 0.004; OR = 1.074, 95%CI = 1.024-1.127, P = 0.003). Second, of the 90 cardiovascular proteins, asthma was associated with the increased levels of tumor necrosis factor ligand superfamily member 14 and CC motif chemokine 4 (ß = 0.145, 95%CI = 0.077-0.212, P = 2.936e-05; ß = 0.128, 95%CI = 0.063-0.193, P = 1.036e-04). Third, CC motif chemokine 4 increased the risk of hypertension (P = 0.043); and after adjusting for this protein, asthma still increased the risk of hypertension, but the strength of its P-value changed from 0.004 to 0.011. CONCLUSION: Asthma was a risk factor for hypertension and atrial fibrillation at the genetic level, and CC motif chemokine 4 might play a mediating role in the mechanism by which asthma promoted hypertension. Thus, effective control of asthma may help reduce the risk of some cardiovascular diseases in older adults.

Effect of selective sleep deprivation on heart rate variability in post-90s healthy volunteers.

The 5-minute frequency domain method was used to examine the effects of polysomnography (PSG)-guided acute selective sleep deprivation (REM/SWS) on the cardiovascular autonomic nervous system, heart rate, and rhythm in healthy volunteers to understand the relationship between cardiac neuro regulatory homeostasis and cardiovascular system diseases in healthy subjects. The study included 30 healthy volunteers selected through the randomized-controlled method, randomly divided into REM sleep deprivation and SWS sleep deprivation groups. PSG analyses and dynamic electrocardiogram monitoring were done at night, during slow wave sleep or REM sleep. An all-night sleep paradigm, without any interruptions, was tested 3 times for comparison. The frequency domain parameter method was further used to monitor the volunteers 5 min before and after a period of sleep deprivation. According to the characteristics of the all-night sleep scatter plot, healthy volunteers were divided into abnormal and normal scatter plot groups. When compared with the period before sleep deprivation, high frequency (HF) and normalized high-frequency component (HFnu) were found to be decreased. Normalized low-frequency component (LFnu) increased in the abnormal scatter plot group after sleep deprivation, and this difference was statistically significant (P < 0.05). The scatter plot also showed that very low frequency (VLF) increased only in the normal group after deprivation and this difference, as well, was statistically significant (P < 0.05). The increase in diastolic blood pressure in the abnormal group was statistically significant (P < 0.05), but the change in blood pressure in the normal group was not statistically significant (P > 0.05). There are 62.5% of the patients and 20% of the employees that were observed to have abnormal whole-night sleep patterns during the uninterrupted whole-night sleep regime. Patients with atrial or ventricular premature beats (more than 0.1%), and those with ST-t changes during sleep, were all ascertained as abnormal. We concluded that some healthy people could face unstable autonomic nervous functioning related to their long-term tension, anxiety, time urgency, hostility, and other chronic stress states. In the face of acute sleep deprivation selectivity, mild stress based excitability of the vagus nerve is reduced, which diminishes the protective function, making them susceptible to conditions such as premature ventricular arrhythmia.