1.Relationship between serum levels of vascular endothelial growth factor and matrix metalloproteinase-9 and Suzuki' s grading in adult moyamoya disease
Wenhua LIU ; Wusheng ZHU ; Xianjun HUANG ; Wen SUN ; Guanzhong NI ; Minmin MA ; Gelin XU ; Xinfeng LIU
Chinese Journal of Neurology 2012;45(6):404-408
Objective To investigate the relationship between serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and Suzuki' s grading system in adult moyamoya disease (MMD).Methods Fifty-two adult patients with MMD,who were diagnosed in Jinling hospital between April 2009 and January 2010,were retrieved from the Nanjing Stroke Registry Program (NSRP).Sixteen sex- and age-matched healthy individuals with MMD patients consisted of the control group.Using enzyme-linked immunosorbent assay,serum concentrations of VEGF and MMP-9 were compared between adult MMD patients and healthy individuals.By Suzuki' s six-grading system,patients were divided into different subgroups,and the correlation of serum levels of VEGF and MMP-9 corresponding to different subgroup and Suzuki's grading was respectively analyzed.In addition,the correlation of serum levels of VEGF and MMP-9 was also evaluated.Results Serum VEGF concentrations in ischemic and hemorrhagic MMD patients was respectively ( 289.4 + 69.2 ) pg/ml and ( 324.3 ± 95.6 ) pg/ml and were significantly higher compared to those in healthy controls ( ( 63.5 ± 7.6 ) pg/ml; F =69.43,P < 0.01 ).Similar findings were observed for MMP-9 ( ( 499.4 ± 76.2 ) ng/ml and ( 531.2 + 100.2 ) ng/ml versus (257.1 ±30.7) ng/ml; F =66.023,P <0.01 ).With the increase of Suzuki' s grading,serum levels of VEGF and MMP-9 respectively showed a high trend ( r =0.879,P < 0.01:r =0.838,P < 0.01 ).In addition,a positive correlation between serum levels of VEGF and MMP-9 was found in the MMD group( r =0.590,P <0.01 ).Conclusion The results show that serum levels of VEGF and MMP-9 in adult MMD are higher than those in healthy controls,which may play a role in neovascularization in MMD,and moreover,serum levels of VEGF and MMP-9 show a high trend with the progression of MMD,which suggest that serum levels of VEGF and MMP-9 can reflect the severity of MMD.
2.Effects of PNU 282987 on Improving Cardiac Remodeling and JAK 2/STAT3 Signaling Pathway
Huanle FANG ; Xiaoming LI ; Minmin NI ; Yuwen ZHAO ; Yonghua YANG
China Pharmacy 2021;32(10):1246-1251
OBJECTIVE:To st udy the effects of α7 nicotinic acetylcholine receptor agonists (PNU282987)on improving cardiac remodeling of mice and Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway. METHODS:Male Kunming mice were randomly divided into normal control group ,model group ,propranolol group (positive control,i.g. 40 mg/kg)and PNU 282987 low-dose,medium-close and high-dose groups (intraperitoneal injection of 0.5,1.0,3.0 mg/kg),with 10 mice in each group. Except for the normal control group ,mice in the other groups were given isoproterenol (ISO,30 mg/kg) subcutaneously for 7 days to induce the cardiac remodeling model. After 30 minutes of ISO injection , administration groups were given relevant liquid ,once a day ,for 7 consecutive days. Twelve hours after last administration ,the left ventricular ejection fraction (EF)and left ventricular short axis shortening rate (FS)of mice in each group were measured ,and the whole heart mass index (HMI)was calculated ;the pathological changes of myocardium were observed. The serum contents of lactate dehydrogenase (LDH),creatine kinase (CK),tumor necrosis factor α(TNF-α),interleukin 6(IL-6),the protein expression of intercellular adhesion molecule 1(ICAM-1)and adhesion molecule 1(VCAM-1)were also determined. The ratios of p-JAK2/JAK2,p-STAT3/STAT3 in myocardial tissue were detected. RESULTS :Compared with normal control group ,EF and FS of model group were significantly reduced ,HMI,the contents of LDH,CK,TNF-α and IL-6,the protein expression of ICAM- 1 and VCAM- 1,the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were increased significantly (P<0.05 or P<0.01); blue collagen deposition in the interstitium of myocardium was obvious,and the degree of fibrosis was severe. Compared with model group , the EF and FS of the mice in the medium-dose and high-dose groups were increased significantly , HMI (except for PNU 282987 medium-dose group ),the contents of LDH (except for PNU 282987 medium-dose group ),CK,TNF-α and IL-6,the protein expression of ICAM- 1 and VCAM- 1,the ratio of p-JAK 2/JAK2 and p-STAT 3/STAT3 were decreased significantly (P<0.05 or P< 0.01);blue collagen deposition in the myocardial interstitium was significantly reduced ,and the degree of myocardial fibrosis was significantly reduced. There was no significant difference in the comparison of the above indicators in PNU 282987 low-dose group (P>0.05). CONCLUSIONS :PNU282987 can improve cardiac remodeling of mice ,the mechanism of which may be associated with inhibiting JAK 2/STAT3 signaling pathway.
3.Effect of Shenbai Jiedu Prescription on Fecal Metabolomics and Intestinal Flora Distribution in Patients with Colorectal Adenoma
Ye ZHANG ; Mingxin NI ; Meng SHEN ; Yuquan TAO ; Liu LI ; Minmin FAN ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):55-63
ObjectiveTo observe the effects of Shenbai Jiedu prescription on fecal metabolomics and intestinal flora diversity distribution in patients with colorectal adenoma and explore its potential targets. MethodA total of 21 patients diagnosed with colorectal adenoma were enrolled in this study. Following a four-week administration of Shenbai Jiedu prescription, their clinical symptoms were observed, and fecal samples of patients before and after treatment were collected. Untargeted metabolomics and metagenomic analysis based on liquid chromatography-mass spectrometry (LC-MS) were employed to investigate the possible metabolic pathway of Shenbai Jiedu prescription and its influence on the distribution of intestinal flora in patients. ResultThe total scores of traditional Chinese medicine (TCM) syndromes of patients after drug administration decreased significantly (P<0.01). The results of untargeted metabolomics showed that the distribution of metabolites exhibited aggregation before and after drug administration, and a total of 106 differential metabolites were screened out (P<0.05). The Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed that arginine-proline metabolism, ferroptosis, glycine, and serine and threonine metabolism were significantly enriched metabolic pathways (P<0.05). Notably, L-4-hydroxyglutamate semialdehyde, glutathione, isopentenyl pyrophosphate, creatinine, 4-acetamido-2-aminobutanoic acid, and guanidoacetic acid were found to be involved in these aforementioned metabolic pathways. Furthermore, the association between these metabolites and different intestinal flora was analyzed, and the results showed that Shenbai Jiedu prescription could interfere with metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma by regulating intestinal flora such as Lachnoclostridium, Eggerthella, and Dialister (P<0.05). ConclusionShenbai Jiedu prescription may improve the clinical symptoms of patients by increasing the abundance of intestinal beneficial bacteria, reducing the abundance of harmful bacteria, and regulating metabolic pathways such as amino acid and ferroptosis in patients with colorectal adenoma. This study may provide some research ideas and directions for Shenbai Jiedu prescription to interfere with colorectal adenoma recurrence and carcinogenesis.
4.Biological Foundation of Colorectal Adenoma Carcinogenesis in Damp-heat Accumulation Syndrome Based on Transcriptome Sequencing and Mechanism of Shenbai Jiedu Prescription
Yuquan TAO ; Haibo CHENG ; Minmin FAN ; Chengtao YU ; Liu LI ; Ye ZHANG ; Mingxin NI ; Meng SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):48-54
ObjectiveTo explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription. MethodEight patients with colorectal adenoma in damp-heat accumulation syndrome, 11 patients with non-damp-heat accumulation syndrome, and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained, and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases. The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome, damp-heat accumulation syndrome, and colorectal cancer, and functional enrichment analysis and signaling pathway enrichment analysis were carried out. Real-time polymerase chain reaction (Real-time PCR) was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes. ResultBy comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome, a total of 384 differentially expressed genes were screened, of which 203 were up-regulated genes, and 181 were down-regulated genes. By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome, a total of 2 965 differentially expressed genes were screened, of which 2 460 were up-regulated genes, and 505 were down-regulated genes. The intersection of differentially expressed genes of the two groups was taken, and a total of 58 differentially expressed genes with the same changes were screened. The gene ontology functions were mainly enriched in UDP-galactose: β-N-acetylglucosamine beta-1,3-galactosyltransferase activity, N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase activity, and poly-N-acetyllactosamine biosynthetic process. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways were mainly enriched in glycosphingolipid biosynthesis-globo and isoglobo series, glycosphingolipid biosynthesis-lacto and neolacto series, and IL-17 signaling pathway. Shenbai Jiedu prescription significantly inhibited the expression of key genes involved in the enrichment, such as FOSB and B3GALT5, in a dose-dependent manner (P<0.05). ConclusionGlycolipid metabolism may be the biological foundation of colorectal adenoma in damp-heat accumulation syndrome, and Shenbai Jiedu prescription may inhibit colorectal adenoma carcinogenesis by down-regulating the expression of FOSB and B3GALT5.
5.Research Progress of Traditional Chinese Medicine Compounds in Prevention and Treatment of Colorectal Adenoma: A Review
Meng SHEN ; Ye ZHANG ; Kai CHEN ; Yuquan TAO ; Minmin FAN ; Mingxin NI ; Liu LI ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):64-72
Colorectal adenoma is a benign tumor originating from the mucosal glandular epithelium of the colorectum and belongs to the category of intraepithelial neoplasia. Its etiology and pathogenesis are not completely clear, and some patients have genetic factors. In recent years, with the improvement in living standards, the incidence of colorectal adenoma has gradually increased due to high-fat diets, intestinal flora disorder, and emotional disturbance. As one of the precancerous lesions of colorectal cancer, colorectal adenoma is increasingly threatening human health. Surgical resection is the most direct and effective method for the treatment of colorectal adenoma, but some patients with colorectal adenoma have the possibility of recurrence after resection. At present, there is still a lack of effective prevention and treatment measures for the recurrence of colorectal adenoma. Traditional Chinese medicine (TCM) plays a unique advantage in improving the clinical symptoms of patients with colorectal adenoma and preventing postoperative recurrence and carcinogenesis. Therefore, this review summarized the clinical research and mechanism of TCM compounds in the prevention and treatment of colorectal adenoma in recent years. The clinical study on the prevention and treatment of colorectal adenoma by TCM compounds can be divided into internal treatment, external treatment, and internal and external combined treatment. The internal treatment mainly focuses on strengthening the spleen, and the external treatment includes retention enema, acupoint application, and other methods. The internal and external combined treatment is mainly based on the internal administration of TCM compounds combined with acupuncture, retention enema, and acupoint stimulation. The study on the mechanism of TCM compounds in preventing and treating colorectal adenoma was mainly explored from the aspects of regulating intestinal flora, regulating cell proliferation immune function, and achieving anti-inflammation. This review summarized the research progress of TCM compounds in the prevention and treatment of colorectal adenoma in recent years and provided a reference for future treatment with TCM.