ABSTRACT
Objective:To investigate the role and mechanisms of fibulin-1 in senescence-related calcification of rat vascular smooth muscle cells induced by high-concentrationphosphate treatment.Methods:From September 2020 to September 2021, rat primary vascular smooth muscle cells were extracted from the thoracic aorta and abdominal aorta of 10 male SD rats aged 6 to 8 weeks.Phosphate(2.5 mmol/L Pi)was used to stimulate the calcification of vascular smooth muscle cells(VSMCs)in a model of stress-induced senescence-related calcification.Cellular senescence was assessed by SA-β-gal staining.Cellular calcification was determined by alizarin red staining and quantification of calcium deposition.Phenotypic transformation indexes and the expression of fibulin-1 during the process of calcification were detected by Western blot.The expression of fibulin-1 in primary rat vascular smooth muscle cells was knocked down by siRNA, the expression of pSmad3 was detected by immunofluorescence, and the effects of fibulin-1 on phenotypic transformation indexes of smooth muscle cells were detected by Western blot.The cells were cultured with recombinant fibulin-1 while transforming growth factor beta(TGF-β)inhibitor A83-01 and pSmad3 inhibitor SIS3 were also added.The senescence and calcification indexes of smooth muscle cells were detected by Western blot.Results:In the stress-induced aging model with phosphate stimulation of calcification in rat VSMCs, the expression of fibulin-1 was up-regulated( t=11.20, P<0.01), the expressions of MHC and SM22α was down-regulated( t=7.97, P<0.01; t=10.27, P<0.01), and the expression of osteoblastic phenotype markers OPN and Bmp2 and senescence marker P53 was up-regulated( t=4.79, P<0.01; t=9.56, P<0.01; t=14.07, P<0.01). Knockdown of fibulin-1 attenuated the degree of senescence and calcium deposition in VSMCs( t=12.90, P<0.05)and decreased the expression of OPN, Bmp2 and P53( t=5.92, P<0.05; t=10.15, P<0.01; t=8.28, P<0.01), at the same time, and TGF-β and pSmad3 expression was inhibited( t=12.90, P<0.01; t=7.46, P<0.01). After the addition of TGF-β/ smad3 pathway inhibitors, the stimulatory effect of recombinant fibulin-1 on phenotypic transformation and senescence protein expression inVSMCs was significantly reduced( t=4.52, P<0.01; t=9.82, P<0.01; t=3.85, P<0.05). Conclusions:Fibulin-1 can promote aging-related calcification of vascular smooth muscle cells through the TGF-β/smad3 signaling pathway.
ABSTRACT
Objective:To analyze the composition and functional characteristics of the intestinal microflora in novel coronavirus pneumonia patients with arterial stiffness, in order to provide empirical evidence for rational use of intestinal microecological modulators.Methods:Patients with novel coronavirus pneumonia admitted to our hospital between April 5 and April 19, 2020 were enrolled as research subjects.They were divided into the stiffness group and the control group according to the results of arterial stiffness.Stool samples were collected within 7 days of admission.Intestinal flora DNA was analyzed and entered into a database, shotgun metagenomic sequencing was performed, and bioinformatics analysis was conducted based on sequencing results.Results:A total of 16 patients with novel coronavirus pneumonia were included in this study, including 7 in the stiffness group and 9 in the control group.Brachial-ankle pulse wave velocity and blood pressure were higher in the stiffness group than in the control group( P<0.05). Beta diversity analysis at the phylum level showed that there were significant differences in the composition of the intestinal flora between the two groups( P<0.05). Patients with arterial stiffness had a lower relative abundance than the controls in fecal Holdemanella, Mitsuokella, Deinococcus, Lachnospira, Turicibacter, Butyrivibrio, Sporomusa, and Halanaerobium, species associated with the production of short-chain fatty acids(SCFAs), regulation of energy metabolism, anti-radiation, anti-oxidative stress and anti-inflammatory effects.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that the intestinal flora in the control group was mainly involved in the pathways of lipopolysaccharide biosynthesis, metabolism of SCFA and other amino acids, and membrane transport, while the intestinal flora in the stiffness group was mostly concerned with the pathways of amino acid metabolism and DNA damage repair. Conclusions:The use of microbial agents capable of increasing short-chain fatty acids in patients with novel caronavirus infection may contribute to the restoration of intestinal flora homeostasis.
ABSTRACT
Objective To analyze the effect of Xuebijing injection on inflammatory response in patients after hepatobiliary and pancreatic surgeries, and to evaluate its safety and clinical value. Methods A retrospective cohort study was conducted. 708 patients received hepatobiliary and pancreatic surgeries of Nanfang Hospital, Southern Medical University from January 2015 to September 2017 were enrolled and divided into Xuebijing treatment group and conventional treatment group according to whether they were treated with Xuebijing injection or not. The inflammatory response indexes included white blood cell count (WBC), neutrophil (NE), C-reactive protein (CRP), body temperature, which were compared between the two groups at 1, 3, and 5 days after operation. The incidence of adverse reactions, the length of postoperative hospital stays and hospitalization costs were compared. Results A total of 209 patients were prescribed with Xuebijing injection, and 499 patients were allocated into conventional treatment group. The two groups were stratified by liver, biliary and pancreatic surgery types, and further 1:1 propensity score matching was performed. After propensity score match, 189 patients were included in each group, with 101, 46, and 42 patients undergoing liver, biliary, and pancreas surgery, respectively. There were no significant differences in baseline data such as gender, age and inflammatory response indexes before surgery between the two groups. In both groups, the WBC and NE showed a gradual decline after operation, CRP were increased gradually and then decreased after 3 days. Compared with the conventional treatment group, Xuebijing treatment group showed obvious anti-inflammatory effect from 3 days after operation [WBC (×109/L): 10.1±4.0 vs. 11.0±3.5, NE: 0.71±0.10 vs. 0.76±0.12, CRP (mg/L): 73.1±38.7 vs. 82.2±41.8, all P < 0.05]. On the 5th day, it still showed a strong anti-inflammatory trend [WBC (×109/L): 7.0±2.8 vs. 7.9±2.6, NE: 0.62±0.10 vs. 0.68±0.12, CRP (mg/L): 43.4±31.0 vs. 50.9±25.3, all P < 0.05]. The cases of postoperative fever in the Xuebijing treatment group were significantly less than that in the conventional treatment group (cases:98 vs. 119, χ2＝4.711, P＝0.029). There was no significant different in the total incidence of adverse drug reactions such as rash, nausea and vomiting (5.0% vs. 3.2%), the length of postoperative hospital stays [days: 9.3 (6.1, 13.5) vs. 9.1 (5.5, 13.3)] and hospitalization costs [wanyuan: 5.8 (3.6, 9.5) vs. 5.7 (3.5, 9.8)] between Xuebijing treatment group and conventional treatment group (all P > 0.05). Conclusions Xuebijing injection has a good anti-inflammatory effect on patients undergoing hepatobiliary and pancreatic surgeries. Xuebijing injection has good safety and can be applied to the prevention and treatment of excessive inflammatory reaction after hepatobiliary and pancreatic surgeries.