Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis.

BACKGROUND: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. METHODS: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. RESULTS: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk. CONCLUSION: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.

Analysis of the utilization value of different tissues of Taxus×Media based on metabolomics and antioxidant activity.

BACKGROUND: Taxaceae, is a class of dioecious and evergreen plant with substantial economic and ecology value. At present many phytochemical analyses have been performed in Taxus plants. And various biological constituents have been isolated from various Taxus species. However, the difference of compounds and antioxidant capacity of different tissues of T. media is not clear. RESULTS: In the present study, we investigated the metabolites and antioxidant activity of four tissues of T. media, including T. media bark (TB), T. media fresh leaves (TFL), T. media seeds (TS), T. media aril (TA). In total, 808 compounds, covering 11 subclasses, were identified by using UPLC-MS/MS. Paclitaxel, the most popular anticancer compound, was found to accumulate most in TS, followed by TB, TFL and TA in order. Further analysis found that 70 key differential metabolites with VIP > 1.0 and p < 0.05, covering 8 subclasses, were screened as the key differential metabolites in four tissues. The characteristic compounds of TFL mainly included flavonoids and tanninsis. Alkaloids and phenolic acids were major characteristic compounds of TS and TB respectively. Amino acids and derivatives, organic acids, saccharides and lipids were the major characteristic compounds of TA. Additionally, based on FRAP and ABTS method, TS and TFL exhibited higher antioxidant activity than TB and TA. CONCLUSION: There was significant difference in metabolite content among different tissues of T. media. TFL and TS had higher metabolites and antioxidant capacity than other tissues, indicating that TFL and TS were more suitable for the development and utilization of T. media in foods and drinks.

Th17 cells are involved in mouse chronic obstructive pulmonary disease complicated with invasive pulmonary aspergillosis.

BACKGROUND: The incidence of chronic obstructive pulmonary disease (COPD) complicated with invasive pulmonary aspergillosis (IPA) has increased in the last two decades. The mechanism underpinning susceptibility to and high mortality of COPD complicated with IPA is unclear, and the role of T helper cells 17 (Th17 cells) in the compound disease remains unknown. Therefore, this study aimed to assess the function of Th17 cells in COPD combined with IPA. METHODS: COPD, IPA, and COPD+IPA mouse models were established in male wild type C57/BL6 mice. The amounts of Th17 cells and retinoic acid-related orphan receptors γt (RORγt) were tested by flow cytometry. Then, serum interleukin (IL)-17 and IL-23 levels were detected by enzyme-linked immunosorbent assay (ELISA) in the control, COPD, IPA and COPD+IPA groups. In addition, COPD+IPA was induced in IL-17 knockout (KO) mice, for determining the role of Th17 cells in COPD+IPA. RESULTS: Compared with the COPD group, the COPD+IPA group showed higher amounts of blood RORγt ([35.09 ±â€Š16.12]% vs. [17.92 ±â€Š4.91]%, P = 0.02) and serum IL-17 (17.96 ±â€Š9.59 pg/mL vs. 8.05 ±â€Š4.44 pg/mL, P = 0.02), but blood ([5.18 ±â€Š1.09]% vs. [4.15 ±â€Š0.87]%, P = 0.28) and lung levels of Th17 cells ([1.98 ±â€Š0.83]% vs. [2.03 ±â€Š0.98]%, P = 0.91), lung levels of RORγt ([9.58 ±â€Š6.93]% vs. [9.63 ±â€Š5.98]%, P = 0.49) and serum IL-23 (51.55 ±â€Š27.82 pg/mL vs. 68.70 ±â€Š15.20 pg/mL, P = 0.15) showed no significant differences. Compared with the IPA group, the COPD+IPA group displayed lower amounts of blood ([5.18 ±â€Š1.09]% vs. [9.21 ±â€Š3.56]%, P = 0.01) and lung Th17 cells ([1.98 ±â€Š0.83]% vs. [6.29 ±â€Š1.11]%, P = 0.01) and serum IL-23 (51.55 ±â€Š27.82 pg/mL vs. 154.90 ±â€Š64.60 pg/mL, P = 0.01) and IL-17 (17.96 ±â€Š9.59 pg/mL vs. 39.81 ±â€Š22.37 pg/mL, P = 0.02), while comparable blood ([35.09 ±â€Š16.12]% vs. [29.86 ±â€Š15.42]%, P = 0.25) and lung levels of RORγt ([9.58 ±â€Š6.93]% vs. [15.10 ±â€Š2.95]%, P = 0.18) were found in these two groups. Finally, Aspergillus load in IL-17 KO COPD+IPA mice was almost 2 times that of COPD+IPA mice (1,851,687.69 ±â€Š944,480.43 vs. 892,958.10 ±â€Š686,808.80, t = 2.32, P = 0.02). CONCLUSION: These findings indicate that Th17 cells might be involved in the pathogenesis of COPD combined with IPA, with IL-17 likely playing an antifungal role.

High-Flow Nasal Cannula: A Promising Oxygen Therapy for Patients with Severe Bronchial Asthma Complicated with Respiratory Failure.

Severe bronchial asthma complicated with respiratory failure, a common critical illness in respiratory medicine, may be life-threatening. High-flow nasal cannula (HFNC) is a novel oxygen therapy technique developed in recent years. HFNC was applied in this study for treating adult patients with severe bronchial asthma complicated with respiratory failure. Its efficacy was analyzed comparatively to conventional oxygen therapy (COT). HFNC and COT were randomly performed based on conventional treatment. The HFNC group was similar to COT-treated patients in terms of response rate, with no significant difference in efficacy between the two groups. In patients with bronchial asthma, effectively increased PO2 and reduced PCO2 were observed after treatment in both groups. However, HFNC was more efficient than COT in elevating PO2 in patients with severe bronchial asthma complicated with respiratory failure, while no statistically significant difference in PCO2 reduction was found between the two groups. Heart rate (HR) and respiratory rate (RR) between the two groups on admission (0 h) and at 2, 8, 24, and 48 h after admission were compared. Both indicators significantly decreased with time. No significant differences in HR and RR were found between the groups at 0, 2, and 8 h after admission. However, these indicators were significantly lower in the HFNC group compared with the COT group at 24 and 48 h after admission. HFNC could significantly elevate PO2 and reduce HR and RR. Thus, it is a promising option for patients with severe bronchial asthma complicated with respiratory failure.

Trapidil determines the fate of RHF rats through inhibition of ER stress.

Pulmonary arterial hypertension is a fatal disease, especially when it causes right heart failure (RHF). However, it is difficult to treat. It has been reported that trapidil (Tra) can improve the redox balance and cardiac conditions. In this study, we investigated the effect of Tra on RHF induced by monocrotaline (MCT) in rats. Male Wistar rats were treated with MCT or Tra. Treatment lasted 28 days, then rats were euthanized after echocardiography and catheterization. Subsequently, lungs and right ventricular myocardia were evaluated by hematoxylin and eosin, Masson, and TUNEL staining. Protein expression was detected by western blotting. We found remarkably expanded right ventricle end-diastolic volume, decreased partial pressure of oxygen (PaO2), increased partial pressure of carbon dioxide (PaCO2), right ventricular systolic pressure, mean pulmonary arterial pressure, lung/body weight, and liver/body weight in the RHF rat group, as well as increases in the apoptosis rate and the expression of endoplasmic reticulum stress (ERS)-related proteins. However, these changes were significantly inhibited by Tra. Our data suggested that inhibition of ERS is essential for improving RHF, and that therapeutic intervention of Tra in RHF rats works by reducing ERS.