ABSTRACT
Objective To investigate whether levosimendan can inhibit the apoptosis of C2C12 cells induced by lipopolysaccharide(LPS)through the PTEN/Akt pathway.Methods C2C12 cells were randomly divided into four groups:blank control group,control group comprising cells treated with levosimendan only,LPS-treated group,and a group comprising cells pretreated with levosimendan for 24 h a subsequently treated with LPS for 48 h.The survival rate of C2C12 cells was determined via the CCK-8 method,and cell apoptosis was assessed via Hoechst 33342 staining.The mRNA and protein expression levels of PTEN/Akt pathway components were evaluated via RT-qPCR and Western blotting,respectively.C2C12 cells were also transfected with siRNA to knockdown the PTEN gene,and the effect on the protein expression of apoptotic pathway components was determined.Results Levosimendan increased the survival rate and decreased the apoptosis rate of C2C12 cells after LPS treatment.PTEN gene expression was inhibited by siRNA and the mRNA and protein levels of PTEN/Akt signaling pathway components changed correspondingly.Furthermore,the apoptosis rate of C2C12 cells decreased.Conclusion Levosimendan can inhibit LPS-induced C2C12 cell apoptosis via the PTEN/Akt pathway.
ABSTRACT
To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.
Subject(s)
Animals , Male , Rats , Bleomycin/pharmacology , Cytokines , Drugs, Chinese Herbal , Glutathione , Idiopathic Pulmonary Fibrosis/drug therapy , Inflammation , Lung/pathology , Network Pharmacology , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Transforming Growth Factor beta/pharmacologyABSTRACT
Objective To explore the effect of vascular stress changes on endothelial function recovery and vascular restenosis inhibition in dynamic degradation process of the degradable stent. Methods The material parameters of the hyper-elastic vascular constitutive relationship was fitted, and the stress distribution on the intima of the blood vessel before stent implantation and during dynamic degradation was calculated by numerical simulation. In vitro culture experiments were carried out, and the stretch ratios of the silicon chambers were 0%, 5%, 10% and 15%, respectively, to simulate the mechanical environment at different degradation stages, and to explore the effects of different stretch ratios on growth state of the endothelial cells (ECs). Results After the stent was completely degraded, the circumferential intimal stress and strain of the vessel were restored to 0.137 MPa and 5.5%, which were close to the physiological parameters (0.122 MPa, 4.8%) before stent implantation. In vitro experiments showed that the survival rate of ECs was the highest under the condition of 0.1 MPa circumferential stress and 5% strain, and adhesion growth could be achieved. Conclusions With the occurrence of stent degradation process, the circumferential stress and strain of the intima were restored to a range close to physiological parameters, which promoted the growth of ECs. The recovery of intimal function could effectively inhibit the process of vascular restenosis. The results can provide the theoretical basis and experimental platform for studying coronary intervention for the treatment of vascular restenosis.
ABSTRACT
Objective:To explore the relationship between Th17 immunoregulatory system and depression and reveal the mechanism of depression from the perspective of neuroimmunity, as well to look for biomarkers that can be used to diagnose, evaluate and predict recurrence of depression.Methods:A total of 91 patients with depression including 45 first-episode patients (FED group) and 46 recurrent episodes patients (RMDD group) were collected who were admitted to Psychiatry Department of the First Affiliated Hospital of Zhengzhou University from March 2019 to May 2020. And 40 healthy controls matched with depression patients in age, gender and education level were collected as control group (HC group). The levels of eight inflammatory cytokines in Th17 immunoregulatory system (five pro-inflammatory cytokines: IL-1β, IL-6, IL-17A, IL-21, IL-23; three anti-inflammatory cytokines: TGF-β1, IL-10, and IL-27) were measured by enzyme-linked immunosorbent assay (ELISA). Hamilton depression scale-24 (HAMD-24) was used to evaluate the severity of depressive symptoms. Data analyses were performed with SPSS 23.0.Two independent samples t-test, one-way ANOVA, Mann Whitney U test and Kruskal Wallis H test were used for comparison between groups. Results:(1) Comparison of FED group, RMDD group and HC group showed that the levels of pro-inflammatory cytokines IL-1β (5.321(1.317, 21.287)ng/L, 11.277(4.315, 26.167) ng/L, 8.126(1.179, 9.287) ng/L), IL-6(7.787(2.077, 16.778) ng/L, 5.290(2.364.14.475) ng/L, 4.389(1.453, 4.491) ng/L), IL-21 (6.777(6.293, 9.198) ng/L, 7.261(6.293, 25.058)ng/L, 5.097(3.033, 6.507) ng/L) and anti-inflammatory cytokines TGF-β1 (59.098(13.491, 125.368) ng/L, 46.230(18.852, 122.559) ng/L, 25.292(2.716, 31.874) ng/L), IL-10 (226.930(105.117, 449.444) ng/L, 193.929(109.014, 468.269) ng/L, 131.429(77.587, 157.497) ng/L) and IL-27 (0.968(0.651, 1.879)ng/L, 1.859(0.690, 6.221) ng/L, 0.865(0.679, 1.287)ng/L) in plasma were statistically different( H=7.219, 9.482, 18.989, 16.166, 11.511, 6.262, all P<0.05), while the levels of pro-inflammatory cytokines IL-17A (2.175(1.031, 7.975)ng/L, 3.576(1.896, 11.611)ng/L, 3.807(1.301, 4.710)ng/L)and IL-23 (15.708(2.898, 114.175) ng/L, 26.893(9.282, 58.592) ng/L, 17.041(5.027, 23.613)ng/L) were not statistically significant ( H=2.179, 4.305, both P>0.05). Further pairwise comparisons showed that the levels of pro-inflammatory cytokines IL-6, IL-21 and anti-inflammatory cytokines TGF-β1 and IL-10 in plasma of FED group were higher than those of HC group, and the differences were statistically significant (all P<0.05). The levels of pro-inflammatory cytokines IL-1β, IL-6, IL-21 and anti-inflammatory cytokines TGF-β1, IL-10, IL-27 in RMDD group were higher than those in HC group, and the differences were statistically significant (all P<0.05). There were no significant differences in the eight inflammatory cytokines between FED group and RMDD group (all P>0.05). (2) Spearman correlation analysis showed that IL-1β was positively correlated with total score of HAMD-24 ( r=0.286, P<0.05). IL-6 was positively correlated with total score of HAMD-24 and factor score of anxiety or somatization ( r=0.390, 0.291, both P<0.05). TGF-β1 was negatively correlated with total score of HAMD-24 and factor scores of anxiety or somatization and cognitive impairment ( r=-4.200, -0.321, - 0.361, all P<0.05). IL-21 was positively correlated with factor score of sleep ( r=0.319, P<0.05); IL-10 was negatively correlated with total score of HAMD-24 and factor score of cognitive impairment ( r=-0.306, - 0.270, both P<0.05). There was no significant correlation between other inflammatory cytokines and total score of HAMD-24 and seven factor scores (all P>0.05). Conclusion:There is an imbalance in pro-and anti-inflammatory cytokines of Th17 immunoregulatory system in patients with depression, which is more obvious in recurrent episodes patients.The level of immune activation of Th17 immunoregulatory system may be associated with the severity of clinical symptoms, in which the inflammatory cytokine IL-6 may be a biomarker of major depressive disorder; TGF-β1 and IL-21 may be associated with depressive cognitive impairment and sleep.
ABSTRACT
Objective To design and develop an in vitro simulation device for circumferential stress of mural coronary artery, so as to achieve the in vitro loading of mural circumferential stress under coronary myocardial bridge oppression with different degrees. MethodsUsing the in vitro simulation device for myocardial bridge coronary artery hemodynamics, the in vitro measurement of mural circumferential stress was achieved. Based on the experimental data, the in vitro loading of mural circumferential stress under coronary myocardial bridge oppression with different degrees was achieved. Results The in vitro measurement experiment showed that the maximum, average and fluctuation of circumferential stress at proximal end of mural coronary artery would increase significantly with the increase in the degree of myocardial bridge oppression. The in vitro loading experiment of mural circumferential stress verified that the loading waveform coincided basically with the experimental waveform from in vitro measurement. Conclusions The device could realize the in vitro loading of mural circumferential stress, which provided an in vitro simulation platform which was as close as possible to the in vivo environment, so as to explore the influence from hemodynamic abnormality of proximal mural coronary artery on the occurrence of atherosclerosis and plaque rupture.
ABSTRACT
Wolfram syndrome(WS) is a rare autosomal recessive neurodegenerative disease characterized by diabetes insipidus, onset diabetes mellitus, optic atrophy and sensorineural hearing loss.The syndrome is mainly caused by mutations in the WFS1 gene, and another causative gene, CISD2 gene is responsible for Wolfram syndrome 2 with different phenotypes.The prognosis of WS is poor, 60% of patients die before the age of 35 years old.Currently, there are no effective treatments to delay or reverse the progression of WS, standardized clinical monitoring and supportive care can help alleviate the debilitating symptoms of patients and improve their quality of life.This article reviews the pathogenesis, clinical feature, diagnosis and new treatments of WS.
ABSTRACT
Objective To develop an innovative device for endothelial cell culture in vitro, namely, to develop a vascular endothelial cell culture device based on hemodynamic environment, so as to introduce the development and experimental study of endothelial cell culture device in vitro. Methods A device of dynamic culture system for endothelial cells in vitro on the basis of the existing research was designed with the theory and method of hemodynamics. The shear stress, positive stress and tensile stress existed at the same time in the flow environment. The development and experimental research of the device were described in detail from 5 aspects, such as the development background, structure and composition, design principle, theoretical basis and experimental research. Results The device could accurately simulate the hemodynamic environment of endothelial cells at normal level, with precise control of shear stress in 0-12 Pa range, positive stress in 0-15.96 kPa range, and tensile stress in 0-0.5 MPa range. Conclusions The device can provide a hemodynamic environment which is closer to the physiological conditions of human body, as well as a more ideal experimental environment and means for further exploring the mechanism of vascular intimal injury.
ABSTRACT
Dual-energy computed tomography (CT) reconstruction imaging technology is an important development direction in the field of CT imaging. The mainstream model of dual-energy CT reconstruction algorithm is the basis material decomposition model, and the projection decomposition is the crucial technique. The projection decomposition algorithm based on projection matching was a general method. With establishing the energy spectrum lookup table, we can obtain the stable solution by the least squares matching method. But the computation cost will increase dramatically when size of lookup table enlarges and it will slow down the computer. In this paper, an acceleration algorithm based on projection matching is proposed. The proposed algorithm makes use of linear equations and plane equations to fit the lookup table data, so that the projection value of the decomposition coefficients can be calculated quickly. As the result of simulation experiment, the acceleration algorithm can greatly shorten the running time of the program to get the stable and correct solution.
ABSTRACT
Sterol C24-methyltransferase (SMT) plays multiple important roles in plant growth and development. SMT1, which belongs to the family of transferases and transforms cycloartenol into 24-methylene cycloartenol, is involved in the biosynthesis of 24-methyl sterols. Here, we report the cloning and characterization of a cDNA encoding a sterol C24-methyltransferase from().(GenBank access number KU885950) is a 1530 bp cDNA with a 1041 bp open reading frame predicted to encode a 346-amino acid, 38.62 kDa protein. The polypeptide encoded by thecDNA was expressed and purified as a recombinant protein from() and showed SMT activity. The expression ofwas highly up-regulated incell suspension cultures treated with methyl jasmonate (MeJA). Tissue expression pattern analysis showed higher expression in the phellem layer compared to the other four organs (leaf, stem, xylem and phloem), which is about ten times that of the lowest expression in leaf. The results are meaningful for the study of sterol biosynthesis ofand will further lay the foundations for the research in regulating both the content of other main compounds and growth and development of