1.Exploring the Mechanism of Action of Jintiange Capsules in Regulating SMSC-Exos miRNA and Articular Chondrocytes mRNA for the Treatment of Osteoarthritis in Rats Based on Transcriptome
Zhichao WANG ; Xue ZHANG ; Xiaofei ZHANG ; Yajun SHI ; Dongyan GUO ; Fei LUAN ; Bingtao ZHAI ; Junbo ZOU ; Puwei YUAN
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1464-1475
		                        		
		                        			OBJECTIVE 
		                        			To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology.
METHODS 
Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA.
RESULTS 
Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA.
CONCLUSION 
Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.
		                        		
		                        		
		                        		
		                        	
2.Correlations of preoperative serum V-set and immunoglobulin domain 4 and long chain non-coding ribonucleic acid SBF2-antisense RNA1 with acute kidney injury after percutaneous nephrolithotomy in patients with renal calculus
Junbo YAO ; Bo JIA ; Jiayuan LIU ; Yiming ZOU ; Siwen DENG
Journal of Clinical Medicine in Practice 2024;28(10):29-34
		                        		
		                        			
		                        			Objective To investigate the relationships of preoperative serum V-set and immunoglobulin domain 4 (VSIG4) and long chain non-coding ribonucleic acid (LncRNA) SBF2 antisense RNA1 (SBF2-AS1) with acute kidneyinjury (AKI) after percutaneous nephrolithotomy in patients with renal calculus. Methods A total of 109 patients with renal calculus in the hospital from January 2020 to December 2022 were selected as research objects. Serum VSIG4 level and LncRNA SBF2-AS1 expression were detected in all the patients before operation, and incidence of AKI was recorded after operation. Multiple Logistic regression model was used to analyze the factors affecting AKI after percutaneous nephrolithotomy in patients with renal calculus; the receiver operating characteristic (ROC) curve was used to analyze the values of VSIG4 and LncRNA SBF2-AS1 in predicting AKI after percutaneous nephrolithotomy in patients with renal calculus. Results In this study, 16 cases had AKI after operation. The serum VSIG4 level in the AKI group was significantly lower than that in the non-AKI group, while the LncRNA SBF2-AS1 expression was significantly higher than that in the non-AKI group (
		                        		
		                        	
3.Study on the Serum TWEAK and SREBP-1 Levels in Patients with Prostate Cancer and Their Relationship with Clinical Pathological Characteristics and Progression Free Survival Prognosis
Junbo YAO ; Bo JIA ; Jiayuan LIU ; Yiming ZOU ; Siwen DENG
Journal of Modern Laboratory Medicine 2024;39(3):136-141
		                        		
		                        			
		                        			Objective To investigate the serum tumor necrosis factor like weak inducer of apoptosis(TWE AK),sterol regulatory element-binding protein 1(SREBP-1)levels in patients with prostate cancer(PC)and their relationship with clinical pathological characteristics and progression free survival prognosis.Method A total of 94 PC patients who underwent PC radical surgery in Wuhan Dongxihu District People's Hospital from January 2018 to January 2020 were selected as the PC group.Meanwhile,50 patients with benign prostatic hyperplasia(BPH)during the same period were selected as the BPH group,and 50 healthy individuals who underwent physical examination during the same period were selected as the control group.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of serum TWEAK and SREBP-1.Kaplan-Meier survival analysis was used to analyze the effects of serum TWEAK and SREBP-1 on the progression free survival in prostate cancer patients.Multivariate COX regression analysis was used to analyze factors affecting the prognosis of progression free survival in prostate cancer patients.Results The serum TWEAK(77.14±15.46 ng/L)and SREBP-1(334.14±33.81 ng/L)levels in the PC group were higher than those in the BPH group(38.69±10.58 ng/L,201.69±28.74 ng/L)and control group(36.26±10.27 ng/L,189.51±27.65 ng/L),with significant differences(t=23.752,25.249;34.636,37.821,all P<0.05).There was a positive correlation between serum TWEAK and SREBP-1 expression in PC patients(r=0.668,P=0.001).The serum TWEAK and SREBP-1 levels in PC patients with Gleason score>7,TNM stage Ⅲ,and preoperative prostate specific antigen(PSA)level ≥ 20 ng/ml were higher than those with Gleason score≤7,TNM stage Ⅰ~Ⅱ,and preoperative PSA level<20ng/ml,with significance differences(t=8.465~16.597,all P<0.05).The 3-year overall progression free survival rates of the TWEAK high expression and low expression groups were 60.42%(29/48)and 86.96%(40/46),respectively.The 3-year overall progression free survival rates of the SREBP-1 high expression and low expression groups were 57.78%(26/45)and 87.76%(43/49),respectively.The 3-year cumulative progression free survival rates of the TWEAK high expression group and the SREBP-1 high expression group were lower than those of the TWEAK low expression group and the SREBP-1 low expression group,and the differences were significant(Log rankx2=8.125,9.547,P=0.004,0.002).TNM stage Ⅲ(OR=1.448,P<0.001),Gleason score>7(OR=1.401,P<0.001),preoperative PSA ≥ 20 ng/ml(OR=1.353,P<0.001),serum TWEAK(OR=1.338,P<0.001),and SREBP-1(OR=1.293,P<0.001)were independent risk factors affecting the progression free survival prognosis of PC patients.Conclusion Serum TWEAK and SREBP-1 in prostate cancer patients were increased,and they were correlated with the clinical pathological characteristics of PC.They could be serum biomarkers for evaluating the prognosis of progression free survival.
		                        		
		                        		
		                        		
		                        	
4.Historical Evolution and Modern Research Progress of Processing of Notoginseng Radix et Rhizoma
Yazhen GAO ; Junbo ZOU ; Ming YANG ; Fengqin LI ; Xing LEI ; Weijie WEN ; Haizhen LIU ; Hao LU ; Yan ZHANG ; Fang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):212-220
		                        		
		                        			
		                        			By reviewing the relevant literature of ancient herbal works and modern codices, this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis, the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology, chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma, some existing problems were analyzed in this paper, such as not many ancient processing methods used in modern time, lack of standardized research on processing technology. And saponins, polysaccharides, amino acids, flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing, which was the main reason for the difference of efficacy before and after processing. However, the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products, resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference, and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated, which is not conducive to the standardized clinical use of drugs. Therefore, it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products, and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity, so as to clarify the processing mechanism for providing scientific basis for its standardized processing, quality control and clinical rational use. 
		                        		
		                        		
		                        		
		                        	
5.Effect of Integration of Habitat Processing and Pieces Processing on Anti-inflammatory of Cortex Fraxini
Chongbo ZHAO ; Jing WANG ; Junbo ZOU ; Jian-Hua WU ; Xiaoyao LI ; Yajun SHI ; Changli WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(6):1040-1046
		                        		
		                        			
		                        			Objective: To compare the anti-inflammatory effect of Fraxini Cortex pieces between integrated production process and traditional processing method. Methods: The model of rat paw swelling induced by carrageenan was used to study the anti-inflammatory and swelling reliving effects of water extracts of Cortex Fraxini with different methods. The main chemical components of the 2 kinds of Cortex Fraxini herbal pieces were determined by high performance liquid phase. Results: Compared with the blank group, the water extracts of the 2 kinds of Cortex Fraxini could reduce the swelling of the rats and improve the various indicators of inflammation. However, the anti-inflammatory and swelling reliving effects of the integrated processing of Cortex Fraxini were more significant. The contents of 4 main active ingredients of esculine, fraxin, aesculetin and fraxetin in the integrated processing of Cortex Fraxini were higher than that of the traditionally processed Cortex Fraxini. The total amount of 4 kinds of coumarins in the integrated Cortex Fraxini was about 1.5 times that of the traditionally processed water extract of Cortex Fraxini. Conclusion: The integrated processing and traditional processing of Cortex Fraxini have similar effects on anti-inflammatory effects, and have the superiority of reducing the loss of active ingredients, which is worthy of popularization and application.
		                        		
		                        		
		                        		
		                        	
6.Angiotensin II type 1 receptor is required for the cardiac fibrosis triggered by mechanical stress independent of Ang II in mice
Yong YE ; Hui GONG ; Jian WU ; Zhiwen DING ; Yi SHEN ; Peipei YIN ; Xingxu WANG ; Jieyun YOU ; Shijun WANG ; Jie YUAN ; Guoliang JIANG ; Jiayuan HUANG ; Weijing ZHANG ; Junbo GE ; Yunzeng ZOU
Chinese Journal of Pathophysiology 2016;32(8):1500-1500
		                        		
		                        			
		                        			AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.
		                        		
		                        		
		                        		
		                        	
7.The Alteration of Circulating Dendritic Cells and Subtypes in ST-Elevated Acute Myocardial Infarction
Hao LU ; Kang YAO ; Dong HUANG ; Chenguang LI ; Shufu CHANG ; Yuxiang DAI ; Aijun SUN ; Yunzeng ZOU ; Juying QIAN ; Junbo GE
Chinese Journal of Clinical Medicine 2015;(3):291-297
		                        		
		                        			
		                        			Objective:To analyze the frequency and alteration of circulating dendritic cells (DCs) and subtypes in patients with ST‐elevated acute myocardial infarction(AMI) .Methods:A total of 17 patients with ST‐elevated AMI(AMI group) and 14 pa‐tients with stable angina pectoris(SAP) as SAP group and 15 people with normal coronary angiogram with matched age and gender(control group) were enrolled .The absolute number and percentage in peripheral blood mononuclear cells of circulating DCs ,myeloid dendritic cell(mDC) and plasmacytoid dendritic cell(pDC) in the three groups were detected using the 3‐colure staining flow cytometry .The levels of interleukin‐6(IL‐6) and tumor necrosis factor‐α(TNF‐α) were detected with enzyme‐linked immunosorbent assay .In the AMI group ,these indexes were measured on the 7th day after the attack .Results:The per‐centage of circulating DCs in peripheral blood mononuclear cells and the absolute number of DCs ,the percentage of circulating mDC and pDC in peripheral blood mononuclear cells and the absolute numbers of mDC and pDC and mDC/pDC ratio in the AM I group on the day of attack(<24 h) were significantly lower than those in the control group and the SAP group(P<0 .01 or 0 .05) .In the AMI group ,on the 7th day after the attack , the percentages of DCs ,mDC and pDC in peripheral blood mononuclear cells and the absolute numbers of DCs ,mDC and pDC and mDC/pDC ratio were higher than those on the day of attack (P<0 .01 or 0 .05) .The level of IL‐6 and TNF‐αin the AMI group on the day of attack were significantly higher than those in the control group and SAP group(P<0 .05) ,and the level of IL‐6 decreased on the 7th day after the attack in the AMI group (P<0 .05) .But there was no significant difference in the percentage of DCs ,mDC and pDC in peripheral blood mononu‐clear cells and the absolute numbers and mDC/pDC ratio between the control group and the SAP group(P>0 .05) .Conclu‐sions:Circulating mDC and pDC are significantly reduced in patients on the day of attack of AM I ,and it can increase to nearly normal on the 7th day after attack .It indicates that the possibility of DCs recruits into coronary plaques and improve the forma‐tion of unstable plaque .
		                        		
		                        		
		                        		
		                        	
8.Immune maturation of human monocyte-derived dendritic cells induced by angiotensinⅡ
Dong HUANG ; Hao LU ; Kang YAO ; Aijun SUN ; Yunzeng ZOU ; Junbo GE
Chinese Journal of Pathophysiology 2014;33(4):681-685
		                        		
		                        			
		                        			AIM:To investigate the effects of angiotensin II ( Ang II) on the immune maturation and the oxi-dized low-density lipoprotein (Ox-LDL)-uptaking capacity of human monocyte-derived dendritic cells (DCs).METH-ODS:Human peripheral blood mononuclear cells were isolated by density gradient centrifugation , and the monocytes were purified by positive selection with anti-CD14 magnetic beads.After cultured with rhGM-CSF (100 μg/L) and rhIL-4 (50μg/L) for 5 d, the monocytes differentiated into immature DCs .On the 6th day of the culture, the cells were treated with various concentration levels of Ang II or pretreated with losartan .The immunophenotypic expression of HLA-DR and CD83 was analyzed by flow cytometry .The secretion levels of IL-12 and IFN-γin the culture supernatants were measured by ELISA.Furthermore, DCs were incubated with DiI-labelled Ox-LDL.The DiI-Ox-LDL-incorporated fraction was investiga-ted by flow cytometry .The mRNA expression of 3 scavenger receptors , scavenger receptor A ( SR-A) , CD36 and lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), was examined by real-time PCR.RESULTS: Ang II induced the maturation of human monocyte-derived DCs, stimulated the expression of CD83 and HLA-DR, and promoted the secre-tion of IL-12 and IFN-γ, which were suppressed by losartan .Furthermore, Ang II increased the Ox-LDL-uptaking capacity of DCs, which was partially reduced by losartan .The incubation of DCs with Ang II enhanced the mRNA expression of LOX-1 in a dose-dependent manner , which was reduced by losartan .However, the expression of SR-A and CD36 was not changed .CONCLUSION:Ang II promotes the immune maturation of human monocyte-derived DCs and increases the up-take of Ox-LDL probably through the up-regulation of LOX-1 expression.
		                        		
		                        		
		                        		
		                        	
9.Investigation of Circulating Fractalkine and its Receptor CX3CR1 Levels in Patients With Chronic Congestive Heart Failure
Kang YAO ; Shuning ZHANG ; Yan WU ; Hao LU ; Zheyong HUANG ; Juying QIAN ; Yunzeng ZOU ; Junbo GE
Chinese Circulation Journal 2014;(12):992-995
		                        		
		                        			
		                        			Objective: To observe the changes of circulating fractalkine and its receptor CX3CR1 level in patients with chronic congestive heart failure (CHF). 
 Methods: Our work included 2 group, CHF group, n=55 patients and Control group, n=25 healthy subjects. Plasma level of soluble fractalkine (sFKN) was measured by ELISA, CX3CR1 in peripheral blood mononuclear cell was examined by lfow cytometry method. The relationship between sFKN and NT-proBNP was studied. 
 Results: Compared with Control group, CHF group had increased sFKN level, P=0.004, and the patients with NYHY III, IV were more than NYHY II, and CHF group also had the higher CX3CR1 expression (14.7 ± 8.1), P<0.05. The CX3CR1 level increased accordingly with NYHY classiifcation, as the patients with NYHY II, CX3CR1 was at (25.1 ± 12.4), P=0.03 compare with Control group;with NYHY III, CX3CR1 was at (37.3 ± 11.0) , P=0.04 compared with NYHY II;with NYHY IV, CX3CR1 was at (41.7 ± 11.1), P=0.009 compared with NYHY II. The circulating sFKN level was positively related to pro-BNP level (r=0.364, P<0.01). 
 Conclusion: The circulating FKN l and its receptor CX3CR1 might be involved in pathogenesis of immune-inlfammatory pathogenesis in CHF patients.
		                        		
		                        		
		                        		
		                        	
10.Effects of apolipoproteinA1 on reverse cholesterol transport and expression of ATP-binding cassette transporter A1 in human acute monocytic leukemia cell line macrophage-derived foam cells
Xiaochun CHEN ; Meili ZHAO ; Yunzeng ZOU ; Junbo GE
Chinese Journal of Geriatrics 2010;29(3):241-245
		                        		
		                        			
		                        			Objective To investigate the effects of apolipoproteinA1 (apoA1) on levels of cholesterol, cholesteryl ester (CE), and expression of ATP-bindiag cassette transporter A1 (ABCA1) in human acute monocytie leukemia cell line (THP-1) macrophage-derived foam cells.Methods The cultured THP-1 cells were induced into foam cells by exposing first to phorbol myristate acetate (PMA, 50 ng/ml) for 48 h, and then to oxidized-low density lipoprotein (ox-LDL, 50μg/ml) for 48 h.Under treatment of apoA1 in different doses (5, 10, 15 and 20 μg/ml) and one simple dose (10 μg/ml) for different time (6, 12 and 24 h), THP-1 macrophage-derived foam cells were incubated to observe the expression of cholesterol and ABCA1.The concentrations of cellular total cholesterol (TC), free cholesterol (FC) and CE were determined by oxidization enzymatic methods.Oil red O dyeing experiment was used to show the cellular lipid droplets in the cells.The expression of ABCA1 was tested by immunofluorescence method.Reverse transcription-polymerase chain reaction was applied to investigate mRNA expression of ABCA1.Results The THP-1 cells turned into typical foam cells after treated with PMA (50 ng/ml) for 48 h, and ox-LDL (50 μg/ml) for 48 h.apoA1 could lower the levels of TC, FC and CE in THP-1 macrophage-derived foam cells in a dose-dependent and a time-dependant manner, apoA1 could increase the expression of ABCA1 protein in THP-1maerophage-derived foam cells without up-regulation of mRNA.Antibody of ABCA1 could up- regulate the expression of ABCA1.Conclusions apoA1 may decrease the levels of cholesterols in THP-1 macrophage-derived foam cells, by promoting the expression of ABCA1 and the reverse cholesterol transport of high density lipoprotein.
		                        		
		                        		
		                        		
		                        	
            

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