1.MMP10 promotes the proliferation,migration,invasion and lymph node metastasis of oral squamous cell carcinoma cells
Jing QU ; Xiaoting WU ; Ting LAN ; Dali ZHENG ; Youguang LU ; Ruihuan GAN ; Lincan DING
Tumor 2024;44(4):380-392
Objective:To investigate the effects of matrix metalloproteinase 10(MMP10)on the proliferation,migration,invasion,and lymph node metastasis of oral squamous cell carcinoma(OSCC)cells,and to explore the underlying mechanisms.Methods:Gene expression profile data and survival data of head and neck squamous cell carcinoma(HNSCC)tissues and adjacent non-cancerous tissues were downloaded from The Cancer Genome Atlas(TCGA).Protein expression profile data of HNSCC tissues and adjacent non-cancerous tissues were downloaded from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)database,and select the data of OSCC from HNSCC.The data from public database were used to analyze the differences in MMP10 expression at the mRNA and protein level between HNSCC/OSCC tissues and adjacent non-cancerous tissues,and to analyze the impact of MMP10 expression level on the survival rate of HNSCC patients,as well as the impact of human papillomavirus(HPV)on MMP10 gene expression in HNSCC patients.MMP10 expression level in 52 pairs of OSCC tissue samples and adjacent non-cancerous tissue samples(from the First Affiliated Hospital of Fujian Medical University)was measured by real-time quantitative PCR.After silencing MMP10 expression using siRNA(siMMP10-1291 and siMMP10-1336),the effect of MMP10 on the proliferation ability of OSCC cells was detected by CCK-8 assay and colony formation assay.The effects of MMP10 on the migration and invasion abilities of OSCC cells was assessed by wound-healing assay and transwell assay,respectively.To verify the effect of MMP10 knocking down on lymph node metastasis of OSCC cells in vivo,we constructed a nude mouse tongue cancer orthotopic model by shRNA(shMMP10-1291 and shMMP10-1336).Differential expression genes associated with MMP10 were screened from the gene expression profile data of OSCC patients in the TCGA database,and pathway enrichment analysis was performed using the GSEA software to further analyze the correlation between MMP10 and genes from the significantly enriched pathway.Results:Compared with adjacent non-cancerous tissues,the expression level of MMP10 in HNSCC and OSCC tissues was significantly increased(P<0.000 1),and HNSCC patients with high MMP10 expression had a lower survival rate(HR=1.32,P=0.04).HNSCC patients in the HPV-group had higher MMP10 gene expression levels(P<0.000 1),but their survival rate was significantly lower than that of HNSCC patients in the HPV+group(HR=0.48,P=0.004).Downregulating MMP10 expression could inhibit the migration,invasion and lymph node metastasis in vivo of OSCC cells.In OSCC patients,differentially expressed genes associated with MMP10 were significantly enriched in the Wnt signaling pathway(NES=1.505,P=0.029),and multiple genes in the Wnt signaling pathway,including WNT3,WNT3A,WNT5A,and WNT5B,were positively correlated with the expression level of MMP10.Conclusion:MMP10 promotes the invasion,metastasis and lymph node metastasis in vivo of OSCC cells by regulating the Wnt signaling pathway.
2.MMP10 promotes the proliferation,migration,invasion and lymph node metastasis of oral squamous cell carcinoma cells
Jing QU ; Xiaoting WU ; Ting LAN ; Dali ZHENG ; Youguang LU ; Ruihuan GAN ; Lincan DING
Tumor 2024;44(4):380-392
Objective:To investigate the effects of matrix metalloproteinase 10(MMP10)on the proliferation,migration,invasion,and lymph node metastasis of oral squamous cell carcinoma(OSCC)cells,and to explore the underlying mechanisms.Methods:Gene expression profile data and survival data of head and neck squamous cell carcinoma(HNSCC)tissues and adjacent non-cancerous tissues were downloaded from The Cancer Genome Atlas(TCGA).Protein expression profile data of HNSCC tissues and adjacent non-cancerous tissues were downloaded from the Clinical Proteomic Tumor Analysis Consortium(CPTAC)database,and select the data of OSCC from HNSCC.The data from public database were used to analyze the differences in MMP10 expression at the mRNA and protein level between HNSCC/OSCC tissues and adjacent non-cancerous tissues,and to analyze the impact of MMP10 expression level on the survival rate of HNSCC patients,as well as the impact of human papillomavirus(HPV)on MMP10 gene expression in HNSCC patients.MMP10 expression level in 52 pairs of OSCC tissue samples and adjacent non-cancerous tissue samples(from the First Affiliated Hospital of Fujian Medical University)was measured by real-time quantitative PCR.After silencing MMP10 expression using siRNA(siMMP10-1291 and siMMP10-1336),the effect of MMP10 on the proliferation ability of OSCC cells was detected by CCK-8 assay and colony formation assay.The effects of MMP10 on the migration and invasion abilities of OSCC cells was assessed by wound-healing assay and transwell assay,respectively.To verify the effect of MMP10 knocking down on lymph node metastasis of OSCC cells in vivo,we constructed a nude mouse tongue cancer orthotopic model by shRNA(shMMP10-1291 and shMMP10-1336).Differential expression genes associated with MMP10 were screened from the gene expression profile data of OSCC patients in the TCGA database,and pathway enrichment analysis was performed using the GSEA software to further analyze the correlation between MMP10 and genes from the significantly enriched pathway.Results:Compared with adjacent non-cancerous tissues,the expression level of MMP10 in HNSCC and OSCC tissues was significantly increased(P<0.000 1),and HNSCC patients with high MMP10 expression had a lower survival rate(HR=1.32,P=0.04).HNSCC patients in the HPV-group had higher MMP10 gene expression levels(P<0.000 1),but their survival rate was significantly lower than that of HNSCC patients in the HPV+group(HR=0.48,P=0.004).Downregulating MMP10 expression could inhibit the migration,invasion and lymph node metastasis in vivo of OSCC cells.In OSCC patients,differentially expressed genes associated with MMP10 were significantly enriched in the Wnt signaling pathway(NES=1.505,P=0.029),and multiple genes in the Wnt signaling pathway,including WNT3,WNT3A,WNT5A,and WNT5B,were positively correlated with the expression level of MMP10.Conclusion:MMP10 promotes the invasion,metastasis and lymph node metastasis in vivo of OSCC cells by regulating the Wnt signaling pathway.
3.Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities.
Dong GAN ; Chenzhe LI ; Yan SHU ; Jiapeng WANG ; Chengyao WANG ; Li ZHU ; Yujun YANG ; Jiaqi LIU ; Bijian HE ; Le CAI ; Zhongtao DING
Chinese Journal of Natural Medicines (English Ed.) 2023;21(2):154-160
The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C28-steroid with an unusual β- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61 ± 0.05 μmol·L-1. The β-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 μg·mL-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 μg·mL-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2 ± 0.03 and 13.3 ± 0.01 μmol·L-1, respectively.
Humans
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Acetylcholinesterase
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Molecular Docking Simulation
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Anti-Bacterial Agents
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Glycosides
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Lactones
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Pain
4.Low-dose rituximab combined with dexamethasone in the treatment of refractory ITP in children: Clinical analysis of 31 cases
Gaoyuan SUN ; Xin TIAN ; Chunlian FANG ; Jiaxin GAN ; Yuhong WU ; Xiaoyan MAO ; Runxiu YIN ; Yiling GUO ; Jingjing QIN
Chinese Journal of Blood Transfusion 2021;34(6):616-619
【Objective】 To investigate the clinical efficacy and safety of low-dose rituximab combined with dexamethasone in the treatment of refractory ITP (RITP) in children. 【Methods】 A total of 31 RITP children, admitted to the Hematology Department of Kunming Children′s Hospital from January 2016 to December 2019 and agreed to receive low-dose rituximab (100 mg/ time, once a week, for 4 successive weeks) combined with dexamethasone (0.6 mg/kg, once a day, for 4 successive days) were enrolled and studied. Blood routine was monitored every other day during treatment, and adverse drug reactions were recorded. The influence of gender, disease course and age on prognosis was compared by χ2 test. 【Results】 1) Among the 31 cases, 11 (35.5%) had platelets >100×109/L after 4 weeks and had no recurrence in 6 months; 9 (29%) had platelets >30×109/L but <100×109/L and had no recurrence in 6 months; 11 (35.5%) showed no recovery of platelets, which were consistently lower than 30×109/L. 2) Rituximab was used in 4 cases (12.9%), 1 case (3.2%) presented with severe drug-induced rashes; Headache, vomiting and elevated blood pressure occurred in 2 cases (6.4%). 1 case (3.2%) presented with laryngeal edema. 3) There was no difference in the total effective rate among different gender, age and disease course (P >0.05). 【Conclusion】 The total effective rate of low-dose rituximab combined with dexamethasone for children with refractory ITP in 6 months is 64.5%, and the adverse reactions are tolerable, so it can be used as a treatment option for children with refractory ITP.
5.Pharmacological mechanism of Qingfei Dayuan Granules for the treatment of pneumonia by network pharmacology
Dali GAN ; Junfeng SHI ; Suqin YANG ; Meixian XIANG
Journal of China Pharmaceutical University 2020;51(5):568-576
To explore the potential mechanism of Qinfei Dayuan Granules for the treatment of pneumonia by the network pharmacology, the potential active ingredients and drug targets of Qinfei Dayuan Granules were obtained through the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP). The "component-target-disease" network and PPI network were constructed by Cytoscape 3.7.2 software, and GO functional enrichment analysis and KEGG pathway enrichment analysis were performed on the TCMIP platform to obtain a multi-dimensional network analysis of the "Chinese medicinal materials-chemical components-key targets-action pathways" and to explore the mechanism of its multi-component multi-target multi-action pathways of Qinfei Dayuan Granules for the treatment of pneumonia. A total of 474 active ingredients and 865 drug targets were identified from Qinfei Dayuan Granules; the key core targets of drugs include NF-κB, TNF-α, MAPK3, IL-1β, PTGS and CASP3, etc.. The results of GO functional enrichment analysis showed that drugs may interfere with inflammation through biological pathways such as immune regulation and apoptosis. KEGG signal pathway enrichment analysis showed that it was mainly related to the diabetic complications AGE-RAGE signaling pathway, IL-17 signaling pathway, T cell receptor signaling pathway and tumor necrosis factor signaling pathway, etc.. Qinfei Dayuan Granules can exert its effect on the treatment of pneumonia through inflammatory response and immune system with multi-ingredient, multi-target and multi-pathway pharmacological characteristics.
6.Effect of Field Inoculation with Arbuscular Mycorrhizal Fungi on Rhizosphere Soil Structure of Paris polyphylla var. yunnanensis
Yan-ping HUANG ; Qiu-xia GAN ; Min YANG ; Jun-sheng QI ; Xing-jiao PAN ; Jie ZHANG ; Nong ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(22):110-115
Objective:To investigate the effects of arbuscular mycorrhiza(AM) fungi inoculation on the rhizosphere soil of
7.The effects of anti-inflammatory on activation of nuclear factor-kappaB and expression of cell adhesion molecules in patients with ulcerative colitis.
Youqin CHEN ; Huatian GAN ; Qin OUYANG ; Dan XU ; Yun PAN ; Zhoucun A
Journal of Biomedical Engineering 2004;21(5):732-736
The purpose of this study is to assess the effects of anti-inflammatory on activation of nuclear factor-kappaB and mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative colitis (UC). A total of 27 cases with UC were investigated. 15 cases received sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did not receive any medication related with UC. Normal mucosa from 9 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were determined by reversal transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA binding activity was evaluated by electrophoretic mobility shift assay (EMSA). The results showed that NF-kappaB DNA binding activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased significantly in patients with UC, compared with normal control (P<0.05). Glucocorticoids and SASP markedly inhibited NF-kappaB activation and significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1 (P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant positive correlation with the NF-kappaB DNA binding activity (r=0.8652 P<0.05, r=0.7902, P<0.05, respectively). We concluded that NF-kappaB is a major and essential factor in regulating the expression of adhesion molecules, it plays an important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC via inhibition of NF-kappaB activation and reduction of adhesion molecules expression.
Adult
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Anti-Inflammatory Agents
;
therapeutic use
;
Colitis, Ulcerative
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drug therapy
;
metabolism
;
Female
;
Humans
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Intercellular Adhesion Molecule-1
;
biosynthesis
;
genetics
;
Intestinal Mucosa
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metabolism
;
Male
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NF-kappa B
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metabolism
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Prednisone
;
therapeutic use
;
RNA, Messenger
;
biosynthesis
;
genetics
;
Sulfasalazine
;
therapeutic use
;
Vascular Cell Adhesion Molecule-1
;
biosynthesis
;
genetics

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