1.Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling.
Jing-Yi WEN ; Hui-Xi PENG ; Dan WANG ; Zhi-Min WEN ; Yu-Tong LIU ; Jian QU ; Hong-Xuan CUI ; Yu-Ying WANG ; Yan-Lin DU ; Ting WANG ; Cong GENG ; Bing XU
Journal of Geriatric Cardiology 2023;20(11):801-812
BACKGROUND:
Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.
METHODS:
In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot.
RESULTS:
The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.
CONCLUSIONS
These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.
2.Electrotaxis of alveolar epithelial cells in direct-current electric fields.
Chao-Yue YANG ; Jian-Hui SUN ; Kan ZHU ; Juan DU ; Ying ZHANG ; Cong-Hua LU ; Wen-Yi LIU ; Ke-Jun ZHANG ; An-Qiang ZHANG ; Ling ZENG ; Jian-Xin JIANG ; Li LI
Chinese Journal of Traumatology 2023;26(3):155-161
PURPOSE:
This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.
METHODS:
AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis.
RESULTS:
The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.
CONCLUSION
EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.
Humans
;
Rats
;
Animals
;
Alveolar Epithelial Cells
;
Lung
;
Lung Injury
;
Cell Movement/physiology*
3. Bioinformatics analysis on structure and function and expression vector construction of SARS-CoV-2 related protein TMPRSS2
Ben-Jin XU ; Hong-Rong YAN ; Miao DU ; Yan XUAN ; Yan-Xiang HOU ; Ya-Nan YANG ; Ling LIU ; Zhuo-Xi LI ; Lei FAN ; Jing LI ; Xiao-Cong CHEN ; Wen-Ting TANG ; Jun-Xiao YU ; Jie MEN ; Bin-Yu SONG ; Xiao-Liang LIU
Chinese Pharmacological Bulletin 2022;38(8):1218-1226
Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.
4. Mitochondrial Fission Protein 1 (FIS1) Overexpression in Human Cervical Cancer Cells Promotes Mitochondrial Fission and Reduces Cell Proliferation and Migration Capacity
Rui CONG ; Xing-Yu LI ; Nan HUO ; Xiang ZHU ; Chun-Yuan XUE ; Liao-Xin FANG ; Xiao-Feng KANG ; Jun-Wen ZHU ; Yi-Meng DU ; Xiao-Jie XU
Chinese Journal of Biochemistry and Molecular Biology 2022;38(7):926-935
Mitochondria are dynamic organelles that continuously divide and fuse. In recent years, in addition to the studies related to mitochondrial metabolism, the unique dynamics of mitochondria have gradually attracted researchers' attention. A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells. Mitochondrial fission proteins (mitochondrial fission protein 1, FIS1) mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission. They are important proteins in the process of mitochondrial fusion and fission. However, few studies have revealed the expression and role of FIS1 in human cervical cancer. In this study, the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared. The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues (P<0. 01). Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions. Subsequently, HeLa cells with overexpressed FIS1 were investigated for their proliferation, migration, mitochondrial fission and ROS levels. The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability, enhanced mitochondrial fission and higher ROS levels. In conclusion, the expression of FIS1 in human cervical cancer cells was attenuated, while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells. Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.
5.Characteristics and disease burden of injury among residents in Jiangsu Province, 2017
Wen-cong DU ; Hao YU ; Jin-yi ZHOU ; Ming WU
Shanghai Journal of Preventive Medicine 2021;33(9):813-817
Objective:To analyze the injury characteristics and the burden of disease for developing an injury prevention strategy. Methods:Data derived from the ‘National Injury Monitoring Report Card’ and the Global Burden of Diseases Study 2017(GBD 2017) was analyzed for the relevant indicators including proportion, disability adjusted of life years(DALY), DALY rate,et al. Results:The information of 91 507 cases was analyzed. Male cases were more than the females with sex ratio of 1.5∶1. The highest injury rate (38.1%) was in the group of 25-44 years old. The major career structure was production and transportation (25.5%). The education level of most injured people was middle school. The top two causes of injuries were falls and traffic-related. In 2017, a total of 44 725 people died of injury and the crude death rate of injury was 54.77/105, 64.51/105 in male and 44.85/105 in female. In 2017, the DALY and DALY rate caused by injuries was 217.8 thousand person-years and 2 667.27/105. The top two injuries of DALYs were road traffic accidents and falls, followed by suicide, drowning and mechanical injury. Conclusion:Targeted prevention and control measures for road traffic injury and falls injury should be in place to reduce the burden of injury.
6.Efficacy of bilayer artificial dermis graft plus single layer dermal template for repair of lower extremity wounds with large area of exposed bone
Xin CHEN ; Weili DU ; Chunquan WEN ; Cong ZHANG ; Peng TIAN
Chinese Journal of Trauma 2021;37(6):519-525
Objective:To compare the efficacy of bilayer artificial dermis graft plus single layer dermal template and bilayer artificial dermis graft only in repairing lower extremity wounds with large area of exposed bone.Methods:A retrospective case-control study was conducted to analyze the clinical data of 34 patients with 37 wounds of the lower extremity involving large area of exposed bone admitted to Beijing Jishuitan Hospital from November 2009 to November 2020. There were 27 males and 7 females, aged 9-67 years [35.5(29, 45)years]. The exposed bone in the lower leg, ankle and foot was greater than 10 cm 2 in size (the shortest distance from edge to edge of bony exposure was more than 2 cm). At the first stage, the wounds were grafted with bilayer type artificial dermis only for 21 wounds of 20 patients in Group A, and grafted with bilayer type artificial dermis plus single layer dermal template for 16 wounds of 14 patients in Group B. At the second stage, the auto-skin graft was performed in the two groups. The wound healing rate was observed in all patients, and was compared between the two groups at 2 weeks and 2 months after the second stage operation. At the same time, the interval between first stage and second stage surgery was measured. The Vancouver Scar Scale (VSS) was used to evaluate the scar in the skin grafting area in the two groups at 5-6 months after the second stage operation. Results:All patients were followed up for 1 to 24 months [5(2, 7.5)months]. The total excellent and good wound healing rate in all patients was 81%(30/37) at 2 weeks and 97%(36/37) at 2 months. There was no significant difference between the Group A and Group B in the excellent and good wound healing rate at 2 weeks [(76%(16/21) vs. 88%(14/16)] and at 2 months [95%(20/21) vs. 100%(16/16)] ( P>0.05). In Group A, the bilayer artificial dermis was grafted into 4 wounds again to complete exposed bone coverage. However, all wounds in Group B were covered initially without re-grafting. The interval between the two-stage operation was 20(16, 21)days in Group A after the 4 patients who underwent secondary artificial dermal transplantation were excluded, showing no significant difference from 21(21, 23)days in Group B ( P>0.05). At 5-6 months after the second stage operation, the VSS score in Group B [(8.0±1.2)points] was significant less than that in Group A [(9.2±1.1)days] ( P<0.05). In the sub-index of VSS, the score of color and softness of scar in Group B [(2.0±0.6)points, (1.6±0.5)points] were significantly improved compared to those in Group A [(2.5±0.5)points, (2.2±0.7)points] ( P<0.05). Conclusions:The artificial dermis grafting is effective in treatment of lower extremity wounds with large area of exposed bone. However, the bilayer artificial dermis graft plus single layer dermal template can avoid artificial dermal re-graft in repair of large area of exposed bone, and the interval between two-stage operation is not significantly prolonged. Moerover, the color and texture of scar after skin grafting and wound repair efficiency and quality are improved.
7.Loss of MicroRNA-137 Impairs the Homeostasis of Potassium in Neurons via KCC2
Ting-Wei MI ; Xiao-Wen SUN ; Zhi-Meng WANG ; Ying-Ying WANG ; Xuan-Cheng HE ; Cong LIU ; Shuang-Feng ZHANG ; Hong-Zhen DU ; Chang-Mei LIU ; Zhao-Qian TENG
Experimental Neurobiology 2020;29(2):138-149
Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.
8.Different level of fasting blood glucose and cardiovascular risk factors clustering among population of Jiangsu Province
Wei-gang MIAO ; Yu QIN ; Jian SU ; Lan CUI ; Peng-fei LUO ; Wen-cong DU ; Jin-yi. ZHOU
Chinese Journal of Disease Control & Prevention 2019;23(4):436-440
Objective To analyze the clustering of major cardiovascular risk factors among population with different level of fasting blood glucose (FBG) in Jiangsu provincial communities. Methods A population-based screening project was conducted during 2015-2017, with 83 522 residents aged 35-75 years from 6 areas included in the study. Prevalence and the clustering of four cardiovascular risk factors (hypertension, obesity, dyslipidemia and smoking) were analyzed. Binary Logistic regression analysis was performed to explore the relationship between FBG and cardiovascular risk factor clustering. Results The prevalence of diabetes was 18.9% among adults aged 35-75 years in Jiangsu province, and 41.4% of them were aware of their disease. Among undiagnosed population, the odd ratios (OR) of cardiovascular risk factors clustering in impaired fasting glucose (IFG) and hyperglycemia group was 1.29 (OR=1.29,95% CI:1.24-1.36,P<0.001) and 1.99 (OR=1.99,95% CI:1.89-2.08,P<0.001), compared with normal FBG group. The control rate of FBG was 15.5% among diagnosed cases. There was no difference in the risk clustering between diabetes patient with and without control of FBG. Conclusions Hyperglycemia and IFG increase the risk of cardiovascular risk factor clustering. Comprehensive interventions should be served as an important role to keep blood glucose at a normal level in high-risk population.
9.Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer's disease.
Xiao-Cong PANG ; De KANG ; Jian-Song FANG ; Ying ZHAO ; Lv-Jie XU ; Wen-Wen LIAN ; Ai-Lin LIU ; Guan-Hua DU
Chinese Journal of Natural Medicines (English Ed.) 2018;16(1):53-62
Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.
Alzheimer Disease
;
drug therapy
;
pathology
;
physiopathology
;
Autoanalysis
;
Biological Availability
;
Biomarkers
;
Biomarkers, Pharmacological
;
Databases, Chemical
;
Drug Combinations
;
Drug Discovery
;
methods
;
Drugs, Chinese Herbal
;
chemistry
;
pharmacology
;
therapeutic use
;
Humans
;
Machine Learning
;
Molecular Docking Simulation
;
Neural Networks, Computer
;
Peptide Fragments
;
chemistry
;
Permeability
10.Network pharmacology study of Chinese medicine Xiao-Xu-Ming decoction based on vasoconstrictor related GPCR targets
LU WEN-DAN ; Li LI ; Yan-Jia SHEN ; Rui ZHOU ; Xiao-Cong PANG ; Guan-Hua DU
Chinese Journal of Pharmacology and Toxicology 2018;32(4):296-296
OBJECTIVE Using bioinformatics methods, to establish Xiao-Xu-Ming decoction (XX-MD)"compound-vasoconstriction G Protein-Coupled Receptors(GPCR)targets"network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD. METHODS Ac-cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da-ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1AR,5-HT1BR),AT1R,β2-AR,hUTR and ETB were retrieved from Bank Pro-tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col-lected and analyzed. The collected data were further used to construct and analyze the network. RE-SULTS 859 single compound structures information in XXMD were generalized following the screen-ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors. Most of the chemical composition effects were associated with different vasoconstric-tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi-ple targets,but also from the interaction between some effective component and multiple targets.

Result Analysis
Print
Save
E-mail