1.Overexpression of multimerin-2 promotes cutaneous melanoma cell invasion and migration and is associated with poor prognosis.
Jinlong PANG ; Xinli ZHAO ; Zhen ZHANG ; Haojie WANG ; Xingqi ZHOU ; Yumei YANG ; Shanshan LI ; Xiaoqiang CHANG ; Feng LI ; Xian LI
Journal of Southern Medical University 2025;45(7):1479-1489
OBJECTIVES:
To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells.
METHODS:
Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed.
RESULTS:
MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment.
CONCLUSIONS
MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans
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Melanoma/metabolism*
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Animals
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Cell Movement
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Prognosis
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Skin Neoplasms/metabolism*
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Mice
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Cell Proliferation
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Neoplasm Invasiveness
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Cell Line, Tumor
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Protein Interaction Maps
2.Research progress on active mechanism and structure feature of polysaccharides from Zizyphus jujube in Rhamnaceae plants
Xiaoqiang DONG ; Chang WEN ; Jindan XU ; Lexue SHI ; Yulong HU ; Jieming LI ; Chunhong DONG ; Kan DING
Journal of China Pharmaceutical University 2024;55(4):443-453
The genus jujube(Ziziphus jujuba Mill.)within the Rhamnaceae family encompasses numerous varieties,such as Ziziphus jujuba Mill.var.jujuba,Ziziphus jujuba var.inermis,and var.spinosa,etc.Among these,the jujube fructus has the most abundant cultivated variants across the country,including Ziziphus jujuba cv.Hamidazao and Ziziphus jujuba cv.Huanghetanzao.Jujube plants are rich in variety and are used for both medicinal and food purposes.Polysaccharides,one of the main active ingredients of jujube,are important medicinal components that contribute to its efficacy.Jujube polysaccharides have been found to promote hematopoiesis,exhibit antioxidant and anti-tumor activities,repair liver damage,regulate the immune system,and provide anti-inflammatory effects.By comprehensively summarizing and analyzing the literature on jujube polysaccharides from different varieties and origins,this paper reviews the potential mechanisms of action of jujube polysaccharides in exerting biological activities.It also summarizes the primary structural features,such as relative molecular mass,monosaccharide composition,glycosidic linkage,and the substituent modifications of jujube polysaccharides by sulfation,phosphorylation,carboxymethylation,selenization,and acetylation.This review aims to provide a reference for the research and development of jujube in the fields of innovative polysaccharide drugs and functional foods.
3.Efficacy of Kunxian capsule in treating patients with lupus nephritis:A network Meta-analysis
Zifeng LI ; Yuling FAN ; Wen YI ; Xiaoqiang HOU ; Long YIN ; Caiyun CHANG
Chinese Journal of Immunology 2024;40(4):736-740
Objective:To systematically evaluate the effectiveness of Kunxian capsule related regimens for patients with lupus nephritis(LN)in order to provide a reference basis for treatment strategies for LN patients.Methods:The computer searched the rele-vant studies of Kunxian capsule in PubMed,Web of Science,Cochrane Library,CBM,CNKI,Wanfang and VIP databases on the treatment of LN,the limited time for the establishment of the database is April 6,2022,and used R 4.0.2 software and Revman 5.3 software for Meta-analysis.Results:Four RCTs with 1 cohort study including 310 patients were finally included.The results of the Me-ta-analysis showed that:In terms of 24 h urinary protein and SLEDAI score,Glucocorticoid+Cyclophosphamide+Kunxian capsule achieved the best result after treatment;in terms of Scr,IgE,and IgG,the levels of each index were significantly lower in Glucocorti-coid+Cyclophosphamide+Kunxian capsules than in Glucocorticoid+Cyclophosphamide(P<0.05).Conclusion:The 5 regimens may work best as Glucocorticoids+Cyclophosphamide+Kunxian capsules in terms of clinical efficacy in treating LN patients.Because of the quality and quantity limitations of the included studies,more high-quality studies are needed for validation.
4.Effect of oxytocin on empathy in male adolescents with conduct disorder
Qingsen MING ; Jing ZHANG ; Chang CHENG ; Daifeng DONG ; Xiaoqiang SUN ; Wen CHEN ; Shuqiao YAO
Chinese Journal of Behavioral Medicine and Brain Science 2021;30(10):887-891
Objective:To investigate the effect of intranasal oxytocin administration on empathy in male adolescents with conduct disorder.Methods:The male adolescents with conduct disorder in the Psychological Counseling Clinic of the Second Xiangya Hospital of Central South University from September 2015 to August 2016 were selected.And they were randomly assigned to oxytocin group ( n=46) and placebo group ( n=51) by random number table. Subjects in oxytocin group were given nasal spray of 24 IU oxytocin twice per day for two weeks, while those in placebo group were given nasal spray of 0.9% sodium chloride solution for two weeks. The empathy of patients was assessed with a pain-related empathy task and interpersonal reactivity index (IRI) before and after two weeks′ administration. SPSS 20.0 software was used for statistical analysis, and repeated measurement analysis of variance was used to compare the empathy ability of the two groups before and after intervention. Results:Repeated measurement analysis of variance showed that there were significant time×group interaction effects in the scores of painful expressions during the pain-related empathy task ( F=13.86, P<0.001), IRI ( F=5.59, P=0.020) and empathic concern subscale ( F=4.99, P=0.028). There was significant between-group effect in the score of perspective-taking subscale of IRI( F=4.22, P=0.043). Simple effect analysis revealed that after two weeks of intervention, the score of needle-pain expression in oxytocin group was significantly higher than that at baseline ( t=-2.08, P=0.040). And the score of needle-pain expression in oxytocin group was significantly higher than that in placebo group ( t=2.33, P=0.022). After two weeks of intervention, the total IRI score ( t=-2.58, P=0.011) and empathy factor score ( t=-3.15, P=0.002) of oxytocin group were both higher than those at baseline. After intervention, the total IRI score ( t=2.30, P=0.024) and perspective-taking factor score ( t=2.57, P=0.012) in oxytocin group were higher than those in placebo group, and the differences were statistically significant. Conclusions:Oxytocin may improve the cognitive and emotional empathy in male adolescents with conduct disorder.
5.Effect of lentivirus vector-mediated RNA interference dbpA gene silencing on the biological behavior of colorectal cancer cells
Ruiting LIU ; Yali HOU ; Xiangtian WU ; Guorong WANG ; Chang LIU ; Jirong BAI ; Jian QIU ; Likun YAN ; Xiaojun LI ; Xiaoqiang WANG
Chinese Journal of General Surgery 2019;34(7):613-617
Objective To investigate the effects of lentivirus-mediated RNA interference (RNAi) targeting DNA binding protein A (dbpA) on the proliferation and the biological behavior of colorectal cancer cell line SW620.Methods The experiment was divided into 3 groups:KD group (siRNA-dbpA,lentivirus interference group),CON group (non-specific sequence group) and NC group (blank control group).The lentiviral vector siRNA-dbpA was constructed and verified by PCR and DNA sequencing.SW620 cells were transfected with siRNA-dbpA plasmid,nontargeting siRNA plasmid,or empty plasmid.After 48 h the transfection,the cells were examined for dbpA expression using Western blot.After 72 hrs transfection,flow cytometry was used to detect the cell apoptosis and cell cycle changes.The cell growth inhibition rate was detected by MTT (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay,and then clone formation was detected,and the ability of SW620 cells to form tumors in vivo after dbpA was silenced was studied in nude mice.Results PCR analysis and DNA sequencing demonstrated that the RNAi sequence targeting dbpA gene was successfully inserted into the lentiviral vector.siRNA-dbpA transfection resulted in reduced expression of dbpA in SW620 cells.After transfection,the apoptosis rate of siRNA-dbpA-transfected cells increased to 26.60% ± 0.38%,significantly higher than that in cells transfected with the nontargeting plasmid or the empty plasmid 12.54% ± 0.25% and 4.46% ± 0.19%,respectively (F =28.159,P <0.01).The growth inhibition test indicate that the OD value of the fifth day in siRNA-dbpA group was 0.194 ±0.037,significantly lower than that in the other two groups 0.814 ±0.043 and 1.625 ±0.061,respectively(F =23.214,P < 0.01).The colony formation number is 37 ± 3,64 ± 5and 175 ± 10 respectively,siRNA-dbpA is significantly higher than that in the other two groups(F =40.254,P < 0.01).After the completion of nude mouse transplantation tumor model,through the detection of tumor volume,KD group (group siRNA-dbpA) tumor volume after 14 d and CON and NC group had obvious difference (F =38.256,P < 0.05),and after 21d is more significant difference in tumor size (F =40.241,P < 0.01),can be clearly observed after 35 d KD group (group siRNA-dbpA) growing tumors had differences with the control group (F =30.257,P < 0.05).Conclusion Lentivirus-mediated RNAi targeting dbpA can effectively suppress the expression of dbpA in colorectal tumor in nude mice,it is proved that dbpA silencing has a significant inhibitory effect on the growth of living tumor cells and decrease the proliferation of the colorectal cells.
6.Bioremediation of oil-contaminated field by two Pseudomonas aeruginosa strains.
Lei HUANG ; Tingting ZHAO ; Yun HE ; Yilin LIU ; Chang LIU ; Dayao JIN ; Xiaoqiang JIA
Chinese Journal of Biotechnology 2017;33(6):957-967
We studied the remediation of petroleum-contaminated soils. Two Pseudomonas aeruginosa strains were screened from soil samples in the mine environment. The degradation rate of crude oil was 95.67% after 10 days by mixed culture of the two strains, which was 32% higher than that of single bacterium. It means that the two bacteria had synergistic effect on degrading crude oil. Based on the result, bacterial agent was prepared, and the oil pollution sites were artificially constructed to simulate the degradation of crude oil under different operating conditions. During the experiment, the petroleum hydrocarbon content of the sites after treating with the bacterial agent, decreased obviously in 60 days. The content decreased to among 0.1% and 0.3% from the initial 0.8% per gram of soil. Then, the site with organic manure as supplemental source of carbon and nitrogen had the highest degradation rate of 85.28%, compared to that without adding bacterial agent of only 25.85%.
7.Expression of DNA binding protein A in colorectal carcinoma tissues and cells and its clinical significance
Ruiting LIU ; Guorong WANG ; Jian QIU ; Xiaoqiang WANG ; Likun YAN ; Xiaojun LI ; Chang LIU
Cancer Research and Clinic 2015;27(8):505-509,514
Objective To investigate the expression of DNA binding protein A (dbpA) in patients with colorectal carcinoma of different stages and its significance.Methods Expression of dbpA protein and mRNA in specimens of normal tissues and colorectal cancer were detected by immunohistochemistry,expression of dbpA mRNA and protein of colorectal cancer cell lines SW480,RKO,SW620,DLD-1,HT-29,SW1463 and tissues were detected by immunohistochemistry,RT-PCR and Western blot.Results There was no positive staining dbpA protein and mRNA in normal colorectal tissues.However,dbpA was expressed in epithelial cells of colorectal mucosa [dbpA mRNA:80.0 % (48/60),10.0 % (6/60);dbpA protein:83.3 % (50/60),10.0 % (6/60),P < 0.01].And there was no expression in normal colorectal cell,but its expression was high in 6 colorectal cancer cells (P < 0.05).The high expression of dbpA was correlation with the infiltration depth,lymph node metastasis and type of histology (P < 0.05),and had effect in prognosis of colorectal cancer (P < 0.05).Conclusion Elevated dbpA may be related to the pathogenesis and development of colorectal carcinoma,and dbpA may be a prognostic factor of colorectal carcinoma.
8.Biliary nut-craker syndrome caused by hilar biliary stricture due to portal vein variation
Bin LIANG ; Xiaoqiang HUANG ; Jiahong DONG ; Jing WANG ; Ruiping CHANG ; Zhilei CHENG ; Zhiqiang HUANG
Chinese Journal of Digestive Surgery 2011;10(1):74-76
Benign biliary stricture is a challenging problem in hepatobiliary surgery. Benign biliary stricture is associated with major portal vein variation, which is not be found in literatures. A male patient with benign biliary stricture was admitted to the Chinese PLA General Hospital in March, 2010.The stricture was located in the hilar confluence with intrahepatic biliary dilation and hepatolithiasis. The result of computed tomography showed that the hilar biliary confluence was compressed by the left portal vein and right anterior portal vein. The patient was cured after receiving gallbladder interposition, choledocholithotomy and T tube drainage. We suggested that the benign hilar biliary stricture due to portal vein variation may be named as biliary nut-craker syndrome.
9.Effects of lipopolysaccharide on mice iron metabolism related genes mRNA expression
Xiaoqiang GUO ; Yajuan MA ; Sha TIAN ; Hui DING ; Guoqing REN ; Yanzhong CHANG ; Xianglin DUAN
Acta Anatomica Sinica 2010;41(2):224-227
ObjectiveTo investigate the effects of lipopolysaccharide (LPS) on mRNA expression of iron metabolism related genes. Methods Ten male mice (2 months) were injected intraperitoneally with lipopolysaccharide(0.5 μg/g). After 6 hours, mice were sacrificed and then sera, liver and spleen were collected. The mice blood routine was measured. The serum iron and total iron binding capacity (TIBC) were determined with reagent kit. The quasi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed for mRNA of hepatic hepcidin(HP), ferroportin1(Fpn1), transferrin receptor 1(TfR1) and spleenic HP, Fpn1 and interleukin-6(IL-6). Results The serum iron and TIBC were reduced in mice injected LPS, which exhibited mild anemia(P<0.05) . LPS can increase the expression of hepatic hepcidin and decrease Fpn1 and TfR1 in liver after LPS administration 6 hours(P<0.05). In spleen, IL-6 was upregulated and Fpn1 downregulated(P<0.05). Conclusion LPS can influence serum iron through regulating the mRNA expression of hepatic and spleenic iron metabolism related genes, such as HP, Fpn1 and TfR1.
10.Fibroblast growth factor receptor 3 and p53 gene mutation in recurrent bladder cancer
Yi WANG ; Guang SUN ; Xiaoqiang LIU ; Zhanjun GUO ; Baomin QIAO ; Jiwu CHANG ; Shumin ZHANG ; Jin WANG ; Haitao NIU
Chinese Journal of Urology 2009;30(12):820-823
Objective To study the gene mutation of fibroblast growth factor receptor 3 (FGFR3) and p53 in bladder cancer tissue and to explore their relationship with tumor recurrence. Methods DHPLC and PCR direct sequence were used to detect the mutation of FGFR3 and p53 in BTCC (n=98) and normal bladder mucosa (n=10). Genomic DNA of 98 BTCC was extracted. The exon 5-8 of P53 and the exon 7, 10, 15 were amplification by PCR. The products of PCR was screened by DHPLC to detect the mutation of the production. The results of the FGFR3 and p53 mutation were analyzed by Kaplan-Meier method and no recurrence survival rate was tested by log rank test. All the analysis were aim to explore the clinical biological value of the mutation of FGFR3 and p53. Results Mutation of FGFR3 in BTCC (44. 9%) was higher than normal bladder mucosa(0, P<0.01). Mutation in T_a-T_1 was 75. 6%(33/45) ,T_2 -T_4 was 26. 6%C10/53). Mutation in G_1 was84. 6%(11/13),inG_2 was 61. 4% (27/44), in G_3 was 14. 6% (6/41), (P<0. 05). The mutation rate was lower with the higher of stage and grade. Mutation of p53 in BTCC (34. 6%) was higher than normal bladder mucosa (0%) (P<0. 01). Mutation in T_a - T_1 was 20. 0% (9/45), T_2 - T_4 was 47. 2%(25/53). Mutation in G_1 was G_1 7. 7%(1/13), in G_2 18. 2%(8/44),in G_3 58. 1%(25/41) , (P<0. 05). The mutation rate was higher in the higher stage and grade. Kaplan-Meier method results revealed that mutation of FGFR3 indicating a favorable prognosis while mutation of p53 indicating a poor prognosis. As to the analysis of genotype, the type of FGFR3mut/p53wt had a relative longer recurrent interval (P<0. 01). Conclusions Mutation of FGFR3 indicated a relative longer recurrent interval, which revealed a favorable prognosis of BTCC. Mutation of p53 indicated a relative shorter recurrent interval, which revealed a poor prognosis.

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