THRIL mediates endothelial progenitor cells autophagy via AKT pathway and FUS.

BACKGROUND: This study focused on the roles of lncRNA THRIL in coronary atherosclerotic heart disease (CAD) through regulating AKT signaling pathway and directly interacting with FUS. METHODS: QRT-PCR was conducted to detect the expression of THRIL in CAD blood samples and endothelial progenitor cells (EPCs). Cell autophagy of EPCs was examined through Cyto-ID Autophagy Detection Kit. CCK-8 assay and flow cytometry were carried out to assess cell viability and apoptosis under various interference conditions. Western blotting was conducted to detect the expression of interest proteins. The expression levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by qRT-PCR. The direct interactions between HCG18 and FUS was confirmed through RNA electrophoretic mobility shift assay (RNA EMSA) and RNA immunoprecipitation (RIP) assay. RESULTS: THRIL was upregulated in CAD blood samples and EPCs. Knockdown of THRIL in EPCs promoted cell viability, inhibited cell autophagy and further suppressed the development of CAD. Over-expression of THRIL induced inactivation of AKT pathway, while knockdown of THRIL played reversed effects. THRIL directly interacted with FUS protein and knockdown of FUS reversed the over-expressing effect of THRIL on cell proliferation, autophagy and the status of AKT pathway. CONCLUSION: THRIL inhibits the proliferation and mediates autophagy of endothelial progenitor cells via AKT pathway and FUS.

Ultrasound Detection of Epicardial Adipose Tissue Combined With Ischemic Modified Albumin in the Diagnosis of Coronary Heart Disease.

OBJECTIVE: To evaluate the value of epicardial adipose tissue (EAT) thickness combined with serum ischemic modified albumin (IMA) concentration in the diagnosis of coronary heart disease. METHODS: A total of 180 patients with coronary heart disease from May 2017 to December 2018 were selected as the case group. After the examination of Judkins coronary angiography, they were grouped according to the results of angiography, including 60 patients in a single-vessel group, 60 patients in a double-vessel group, and 60 patients in a multi-vessel group. Sixty healthy people with physical examinations at our hospital at the same time were selected as the control group. All selected participants were tested for epicardial adipose tissue thickness by echocardiography and serum IMA concentration by albumin cobalt ion binding test. RESULTS: The EAT thickness and IMA concentration in the single-vessel disease group, double-vessel disease group, and multi-vessel disease group significantly were higher than those in the control group (P < .01). The ROC curve shows that the sensitivity is 53.33% and the specificity is 87.6%, when the EAT thickness is 6.12 mm. The sensitivity is 76.0% and the specificity is 72.3%, when the serum IMA concentration is 72 U/L. When the two were combined, the sensitivity was 40.15% and the specificity was 96.89%. In the parallel test, the sensitivity was 88.3% and the specificity was 65.44%. CONCLUSION: Ultrasound detection of EAT thickness and serum IMA concentration has certain reference value for the diagnosis of coronary heart disease. Combined diagnosis can significantly improve the diagnosis rate and accuracy of coronary heart disease.

Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose depletion in a murine cancer cachexia model.

Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril would further attenuate cancer cachexia in vivo. After injection with colon-26 adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following four treatment groups for 7 days (n = 8 per group): (1) placebo, (2) RGZ, (3) imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose mass, serum metabolic markers and cytokines, and the expression of nuclear factor-κB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From days 14 to 16, all treatments significantly reduced tumor volume (P < 0.05). From days 10 to 16, improvements in the tumor-free body weight were observed in the RGZ and RGZ+imidapril groups. In addition, significant improvements in both gastrocnemius muscle and epididymal adipose mass were observed in all treatment groups (all, P < 0.05). Furthermore, all treatments significantly increased tumor necrosis factor alpha levels as compared to those observed in the healthy control animals (P < 0.001). Insulin levels significantly increased in the placebo group as compared to those in the healthy control group (P < 0.05), which were reduced in all the treatment groups (P < 0.05). Finally, whereas all treatments significantly reduced atrogin-1 levels as compared to the placebo group (all, P < 0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and RGZ+imidapril groups (both, P < 0.05). Thus, all three treatments reduce tumor growth and alleviate cancer cachexia; however, synergistic effects of RGZ+imidapril combination therapy were not observed.

Seasonal variation in C:N:P stoichiometry, nonstructural carbohydrates, and carbon isotopes of two coniferous pioneer tree species in subtropical China.

The characteristics of C:N:P stoichiometry, nonstructural carbohydrate (NSC) content, and C stable isotopes and their relationships affect plant responses to environmental changes and are critical to understanding the ecosystem carbon and water cycles. We investigated the water use strategies and physiological changes of two pioneer tree species (Pinus armandii and Pinus yunnanensis) in response to seasonal drought in subtropical China. The seasonal variation in needle δ13C values, C:N:P stoichiometry, and NSC contents of the two tree species were studied in 25-year-old plantation in central Yunnan Province. The needle δ13C values of both species were highest in summer. Soluble sugars, starch and NSC content of the two tree species decreased from spring to winter, while there was no significant difference in the seasonal variation of soluble sugars/starch in P. armandii needles, the maximum soluble sugars/starch in P. yunnanensis needles was in autumn. In addition, the C, N, and P contents of the needles and the C:N and C:P ratios of the two species showed different seasonal fluctuations, whereas the N:P ratio decreased with the season. The C:N:P stoichiometry and NSC content of the needles showed significant correlations, whereas the needle δ13C was weakly correlated with C:N:P stoichiometry and NSC content. Phenotypic plasticity analysis and principal component analysis revealed that the needle nutrient characteristics (NSC and P contents and N:P ratio) and needle δ13C values were critical indicators of physiological adaptation strategies of P. armandii and P. yunnanensis for coping with seasonal variation. These results increase our understanding of the water-use characteristics of the two pioneer tree species and the dynamic balance between the NSC, C, N, and P contents of the needles.

Rational administration sequencing of immunochemotherapy elicits powerful anti-tumor effect.

As a research hotspot, immune checkpoint inhibitors (ICIs) is often combined with other therapeutics in order to exert better clinical efficacy. To date, extensive laboratory and clinical investigations into the combination of ICIs and chemotherapy have been carried out, demonstrating augmented effectiveness and broad application prospects in anti-tumor therapy. However, the administration of these two treatment modalities is usually randomized or fixed to a given chronological order. Nevertheless, the pharmacological effect of drug is closely related to its exposure behavior in vivo, which may consequently affect the synergistic outcomes of a combined therapy. In this study, we prepared a lipid nanoparticle encapsulating docetaxel (DTX-VNS), and associated it with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) for the treatment of malignant tumors. To identify the optimum timing and sequencing for chemotherapy and immunotherapy, we designed three administration regimes, including the simultaneous delivery of DTX-VNS and αPD-1(DTX-VNS@αPD-1), DTX-VNS delivery before (DTX-VNS plus αPD-1) or post (αPD-1 plus DTX-VNS) PD-1 blockade with an interval of two days. Analysis from mass spectrometry, multi-factor detection and other techniques indicated that DTX-VNS plus αPD-1 initiated a powerful anti-tumor response in multiple tumor models, contributing to a remarkably reshaped tumor microenvironment landscape, which may attribute to the maximum therapeutic additive effects arise from a concomitant exposure of DTX-VNS and αPD-1 at the tumor site. By profiling the exposure kinetics of nanoparticles and αPD-1 in vivo, we defined the administration schedule with utmost therapeutic benefits, which may provide a valuable clinical reference for the rational administration of immunochemotherapy.