3.Negative modulation of NO for diaphragmatic contractile reduction induced by sepsis and restraint position.
Jian XIANG ; Su-Dong GUAN ; Xiang-He SONG ; Hui-Yun WANG ; Zhen-Yong GU
Journal of Forensic Medicine 2014;30(3):161-165
In practice of forensic medicine, potential disease can be associated with fatal asphyxia in restraint position. Research has demonstrated that nitric oxide (NO) and nitric oxide synthase (NOS) are plentifully distributed in skeletal muscle, contributing to the regulation of contractile and relaxation. In the current study, respiratory functions, indices of diaphragmatic biomechanical functions ex vivo, as well as NO levels in serum, the expressions of diaphragmatic inducible NOS (iNOS) mRNA, and the effects of L-NNA on contractility of the diaphragm were observed in sepsis induced by cecal ligation and puncture (CLP) under the condition of restraint position. The results showed that in the CLP12-18h rats, respiratory dysfunctions; indices of diaphragmatic biomechanical functions (Pt, +dT/dt(max), -dT/dt(max), CT, Po, force over the full range of the force-frequency relationship and fatigue resistance) declined progressively; the NO level in serum, and iNOS mRNA expression in the diaphragm increased progressively; force increased significantly at all stimulation frequencies after L-NNA pre-incubation. Restraint position 1 h in CLP12 h rats resulted in severe respiratory dysfunctions after relative stable respiratory functions, almost all the indices of diaphragmatic biomechanical functions declined further, whereas little change took place in NO level in serum and diaphragmatic iNOS mRNA expression; and the effects of L-NNA were lack of statistical significance compared with those of CLP12 h, but differed from CLP18 h group. These results suggest that restraint position and sepsis act together in a synergistic manner to aggravate the great reduction of diaphragmatic contractility via, at least in part, the negative modulation of NO, which may contribute to the pathogenesis of positional asphyxia.
Animals
;
Asphyxia
;
Diaphragm/physiology*
;
Muscle Contraction
;
Muscle, Skeletal
;
Nitric Oxide/metabolism*
;
Nitric Oxide Synthase
;
Nitric Oxide Synthase Type II
;
Rats
;
Respiration Disorders
;
Restraint, Physical
;
Sepsis
4.Biomechanical study on a net-fixation of Kirschner wire in treating depressed tibial plateau fractures.
Zhao-Xiang CHEN ; Wei ZHANG ; Hong-Hui HE ; Ming-Jiang LIU ; De-Hui ZENG
China Journal of Orthopaedics and Traumatology 2014;27(5):418-421
OBJECTIVETo evaluate the biomechanical properties of tibial plateau depressed fracture fixed with a net-fixation of Kirschner wires.
METHODSTwenty homemade fracture models were fixed with eight 1.5 mm Kirschner wires in a net-fixation; 20 homemade fracture models were fixed with two 3.5 mm cortical screws. Plane-compressed and dot-compressed test were made on each 10 models of the two groups. The maximal force of anti-ompress and stiffness were measured and evaluated.
RESULTSIn plane-compressed test,mean maximal force of anti-compress and stiffness for screw fixation was (1,925.31 +/- 444.26) N and (2.28 +/- 0.53) N/mm2, respectively, for net-fixation was (1,609.62 +/- 277.72) N and (1.90 +/- 0.33) N/mm2, respectively. There was no statistical difference between the two fixation methods (P > 0.05). In dot-compressed test,mean maximal force of anti-compress and stiffness for screw fixation was (411.13 +/- 233.88) N and (2.66 +/- 1.52) N/mm2,respectively,for net-fixation was (1,105.58 +/- 290.66) N and (7.18 +/- 1.89) N/mm2,respectively,the net-fixation was better than that of the screw fixation (P< 0.01).
CONCLUSIONTreatment of tibial plateau depressed fracture with a net-fixation of Kirschner wires is a biological fixation and is a reliably method.
Biomechanical Phenomena ; Bone Screws ; Fracture Fixation, Internal ; instrumentation ; Mechanical Phenomena ; Tibial Fractures ; surgery
5.Research progress of small molecular drugs targeting RNA
Xiao-li DU ; Hui-hui CHEN ; Xiang-yang YE ; Tian XIE ; Xing-rui HE
Acta Pharmaceutica Sinica 2022;57(10):2902-2913
At present, majority of the small molecular drugs used in clinics target proteins, they exert the efficacy through the binding to specific sites on the target protein. However, the "druggable" protein targets account for a small portion of the total number of proteins, and "non-druggable" proteins account for 80%, because of not having suitable drug binding sites. In the central rule, RNA is located in the upstream of proteins and controls the transcription of proteins. The research of small molecule drugs targeting RNA can solve the problem of protein "undruggable proteins" in some extent. This review summarizes the representative research achievements of small molecular drugs targeting RNA in recent years, and the screening methods applied to this field, with the focuses on the latest progress of small molecular drugs targeting novel coronavirus RNA.
6.Prediction of CTL epitopes of Tat exon 1 region in HIV-1 CRF07_BC strains in China
Zhiming FANG ; Hui XING ; Zhefeng MENG ; Kunxue HONG ; Lingjie LIAO ; Xiang HE ; Jianxin Lü ; Yiming SHAO
Chinese Journal of Microbiology and Immunology 2010;30(2):135-139
Objective To predict the CTL epitopes of Tat exon 1 region in HIV-1 CRF07_BC strains, which were prevailing in China. Methods Total of 236 plasma samples were from the 3rd National HIV Molecular Epidemic Survey (NMES3). All the subjects were infected with HIV-1 CRF07_BC viruses. The tat exon 1 region was amplified by reverse transcription reaction and nested polymerase chain reaction (nested-PCR), then the PCR products were sequenced. The distribution of CTL epitopes of this region were predicted by on-line software BIMAS HLA Peptide Binding Predictions and statistics software. Results To-tal of 236 CRF07_BC strains were from 16 provinces, mainly in intravenous drug asers(58.9%)and then sex(25.0%). It was showed that there were 12 CTL epitopes of 236 Tat exon 1 region of CRF07_BC strains mainly located in proline-rich region, cysteine-rich region and core-region. Those epitopes were banded by 5 HLA presenting molecules in genotype(A * 2501 ,A * 2902, B * 15,B * 5301 and Cw * 1203) and 6 HLA presenting molecules in serotype (B53, B58 ,B57 ,A3 ,A68 and Cw12). The frequency of single amino acid substitution was more than 50% in 7 CTL epitopes. Conclusion The CTL epitopes in Tat exon 1 of CRF07 _BC strains were located in different functional regions, and there were some amino acid variations in them.
8.Effect of paeoniflorin on oxidative stress and energy metabolism in mice with lipopolysaccharide (LPS)-induced brain injury.
Ling LIU ; Xiang-jun QIU ; Su-na HE ; Hui YANG ; Deng WANG ; Xue-mei YANG
China Journal of Chinese Materia Medica 2015;40(14):2871-2875
Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg · kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg · kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism.
Animals
;
Energy Metabolism
;
drug effects
;
Glucosides
;
pharmacology
;
Heme Oxygenase-1
;
genetics
;
Lipopolysaccharides
;
pharmacology
;
Male
;
Membrane Proteins
;
genetics
;
Mice
;
Mice, Inbred BALB C
;
Monoterpenes
;
pharmacology
;
Oxidative Stress
;
drug effects
;
Sodium-Potassium-Exchanging ATPase
;
metabolism
10.Experimental study on intervention effect of Grifola frondosa on nonalcoholic steatohepatitis.
Xian-wei DAI ; Zhi-yun CHEN ; Mao-xiang YAN ; Bei-hui HE
China Journal of Chinese Materia Medica 2015;40(9):1808-1811
To study the preventive effect of Grifola frondosa on nonalcoholic steatohepatitis (NASH). The rat model of NASH was established by feeding high-fat diets for 12 weeks and intervened with 0.5 g · kg(-1) · d(-1) and 1.0 g · kg(-1) · d(-1) of C. frondosa powder suspensions. The degrees of hepatocyte fatty degeneration and inflammation were observed under the optical microscope with routine HE staining. The NAFLD activity scores (NAS) were calculated. Serum ALT, AST and hepatic TG and CHOL were tested by the biochemical method. The hepatic MDA was examined by thiobarbituric acid method. The hepatic SOD was tested by the xanthine oxidase test. The hepatic GSH-PX activity was determined by the dithio-nitrobenzoic acid method. Hepatic TNF-α and IL-6 were detected by the enzyme-linked immunosorbent assay (ELISA). The NASH model group induced by high-fat diets showed higher hepatic NAS, ser- um ALT, AST, CHOL and hepatic TG, CHOL, MDA, TNF-α, IL-6 (P < 0.01 or P < 0.05) and lower serum TG and hepatic SOD, GSH-PX (P < 0.01, P < 0.05) than the normal control group. After being intervened with different doses of G. frondosa, the NASH group revealed significantly lower hepatic NAS, serum ALT and hepatic TG, CHOL, MDA, TNF-α and IL-6 (P < 0.05) and higher hepatic SOD, GSH-PX (P < 0.05) than the model group. G. frondosa may prevent the further development of NASH by improving the disorder of lipid metabolism in rats with NASH induced by high-fat diets, relieving the level of oxidative stress and reducing the generation of inflammatory cytokines.
Animals
;
Drugs, Chinese Herbal
;
administration & dosage
;
Grifola
;
chemistry
;
Humans
;
Interleukin-6
;
metabolism
;
Liver
;
drug effects
;
metabolism
;
Male
;
Non-alcoholic Fatty Liver Disease
;
drug therapy
;
metabolism
;
Oxidative Stress
;
drug effects
;
Rats
;
Rats, Sprague-Dawley
;
Tumor Necrosis Factor-alpha
;
metabolism