1.Transcriptomic Analysis of Wuzi Yanzongwan on Testicular Spermatogenic Function in Semi-castrated Male Mice
Dixin ZOU ; Yueyang ZHANG ; Xuedan MENG ; Wei LU ; Shuang LYU ; Fanjun ZENG ; Kun CHEN ; Chang LIU ; Zhongxiu ZHANG ; Yu DUAN ; Yihang DAI ; Zhaoyi WANG ; Zhimin WANG ; Ruichao LIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):61-69
ObjectiveTo screen out the transcriptomes related to the intervention of Wuzi Yanzongwan on the spermatogenic function of semi-castrated male mice, and to explore its potential mechanism in the intervention of the progress of low spermatogenic function. MethodBalb/c mice were randomly divided into sham-operated group, model group, testosterone propionate group(0.2 mg·kg-1·d-1, intramuscular injection) and Wuzi Yanzongwan group(1.56 g·kg-1·d-1, intragastric administration) according to body weight, with 12 mice in each group. The right testicle and epididymis were extracted from the model group and the drug administration group to construct the semi-castrated model of low spermatogenic function, while the fur and the right scrotum of the sham-operated group were only cut and immediately sterilized and sutured. At the end of the intervention, hematoxylin-eosin(HE) staining was used to observe the histopathology of testis, enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum testosterone(T), luteinizing hormone(LH) and follicle stimulating hormone(FSH). The sperm count and motility of epididymis were measured by automatic sperm detector of small animal. Transcriptomic microarray technology was used to detect the mRNA expression level of testicular tissue in each group, the transcriptome of genes related to the regulation of Wuzi Yanzongwan was screened, and three mRNAs were selected for Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) to verify the transcriptome data. Through the annotation analysis of Gene Ontology(GO) and the signaling pathway analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG), the related functions of drugs regulating transcriptome were analyzed. ResultCompared with the sham-operated group, the testicular tissue of mice in the model group showed spermatogenic injury, contraction and vacuolization of the seminiferous tubules, reduction of spermatogenic cells at all levels, widening of the interstitial space, obstruction of spermatogonial cell development and other morphological abnormalities, and serum T significantly decreased, LH significantly increased(P<0.01), and FSH elevated but no statistically significant difference, the count and vitality of epididymal sperm significantly decreased(P<0.01). There were 882 differentially expressed mRNAs in the testicular tissues, of which 565 were up-regulated and 317 were down-regulated. Cluster analysis showed that these differentially expressed mRNA could effectively distinguish between the sham-operated group and the model group. Compared with the model group, the damage to testicular tissue in the Wuzi Yanzongwan group was reduced, the structure of the seminiferous tubules was intact, vacuolization was reduced, and the number of spermatogenic cells at all levels was significantly increased and arranged tightly. The serum T significantly increased, LH significantly decreased(P<0.01), and FSH decreased but the difference was not statistically significant. The count and vitality of sperm in the epididymis were significantly increased(P<0.01). Moreover, Wuzi Yanzongwan could regulate 159 mRNA levels in the testes of semi-castrated mice, of which 32 were up-regulated and 127 were down-regulated, and the data of the transcriptome assay was verified to be reliable by Real-time PCR. GO and KEGG analysis showed that the transcriptome functions regulated by Wuzi Yanzongwan were involved in the whole cell cycle process of sperm development such as sex hormone production of interstitial cells in testis, renewal, differentiation, metabolism, apoptosis and signal transduction of spermatogenic cells, and were closely related to the biological behaviors of signaling pathways such as spermatogenic stem cell function, endoplasmic reticulum protein processing and metabolic program. ConclusionWuzi Yanzongwan can effectively improve the low spermatogenic function of semi-castrated male mice, and its mechanism may be related to the regulation of testicular transcriptional regulatory network, the synthesis of sex hormones in testicular interstitial cells, the function of spermatogenic stem cells, the whole cell cycle process of spermatogenesis, as well as the expression of endoplasmic reticulum protein processing and metabolic program related genes transcription.
2.Comparison of the risk of gastroesophageal reflux between the lithotomy position and the supine position under SaCoVLM laryngeal mask ventilation
Kun LIU ; Xiao ZHAO ; Chao GONG ; Shuang WU ; Shi-Tong LI ; Lian-Hua CHEN
Fudan University Journal of Medical Sciences 2024;51(3):385-391
Objective To observe whether SaCoVLM laryngeal mask can cause gastroesophageal reflux when the body position changes(lithotomy position and supine position).Methods A total of 70 patients were selected for elective surgery in Shanghai General Hospital from Dec 1st,2021 to Sep 30th,2022.There were 35 patients with ureteroscopy in urology and 35 patients with ankle surgery in trauma orthopedics selected as lithotomy position group and supine position group,respectively.Under SaCoVLM laryngeal mask anesthesia,a dual probe pH electrode was placed in the esophagus to continuously monitor the pH value in the esophagus.The pH values and their changing trends in the lithotomy position and supine position of the esophagus were compared under general anesthesia with SaCoVLM laryngeal mask ventilation,and the possibility of gastroesophageal reflux occurring in both positions was explored.Results The peak airway pressure at each time point(5 min,10 min,15 min,20 min and 30 min)after body position was determined in the two groups,and it in lithotomy position group was significantly higher than that in supine position group,and the difference was statistically significant(P<0.05).The middle and upper esophageal pH values of the two groups were compared 10 min after laryngeal mask insertion,and it in lithotomy position group(6.045±0.490)was significantly lower than the supine group(6.532±0.366),and the difference was statistically significant(P<0.05).The middle and upper esophageal pH values of the two groups were compared 10 min and 15 min after laryngeal mask insertion.They in lithotomy position group were significantly lower than those in supine position group,and the differences were statistically significant(10 min:6.045±0.490 vs.6.532±0.366,P=0.031;15 min:5.828±0.487 vs.6.474±0.411,P=0.048).There was no significant difference in the pH of the middle and upper esophagus between the two groups at 1,5,20 and 30 minutes of laryngeal mask insertion.There was no significant difference in the pH value of the esophageal opening between the two groups at each time point after laryngeal mask insertion.Conclusion Under SaCoVLM laryngeal mask ventilation,the risk of gastroesophageal reflux during lithotomy surgery may be higher than during supine surgery.
3.A retrospective study on the efficacy of Roxadustat in peritoneal dialysis patients with erythropoietin hyporesponsiveness
Jie LIU ; Shuang LI ; Fan YANG ; Tianyu LI ; Rui LI ; Yousuf WAHEED ; Chen MENG ; Shulin LI ; Kun LIU ; Yanshan TONG ; Haisheng XU ; Chuankuo TIAN ; Xinglei ZHOU
The Korean Journal of Internal Medicine 2024;39(3):488-500
Background/Aims:
Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness.
Methods:
Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks.
Results:
The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group.
Conclusions
For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.
4.Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism.
Hao LUAN ; Shuang XING ; Jing-Kun YANG ; Ye-Mei WANG ; Xue-Wen ZHANG ; Zi-Zhi QIAO ; Xing SHEN ; Zu-Yin YU
Journal of Experimental Hematology 2023;31(2):546-552
OBJECTIVE:
To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness.
METHODS:
Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected.
RESULTS:
Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01).
CONCLUSION
The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.
Humans
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Mice
;
Animals
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Thrombopoietin/metabolism*
;
Hematopoietic Stem Cells
;
Blood Platelets
;
Recombinant Proteins/therapeutic use*
;
Radiation Injuries
;
RNA, Messenger/metabolism*
5.Signal transducer and activator of transcription 3 and cancer associated fibroblasts jointly generate chemo-resistance and affect prognosis in epithelial ovarian cancer.
Ya Nan ZHANG ; Bin LI ; Yu Qing LI ; Shuang Huan LIU ; Hong Yi HOU ; Kun Yu WANG ; Miao AO ; Yan SONG
Chinese Journal of Obstetrics and Gynecology 2023;58(5):368-377
Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.
Female
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Humans
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Cancer-Associated Fibroblasts/pathology*
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Carcinoma, Ovarian Epithelial
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Ovarian Neoplasms/pathology*
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Prognosis
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STAT3 Transcription Factor/metabolism*
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Drug Resistance, Neoplasm
6.Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis.
Cheng Yuan LI ; Shuang CHEN ; Wei Lu QIAN ; Liu YANG ; Qiu ZHENG ; Ai Jun CHEN ; Jin CHEN ; Kun HUANG ; Sheng FANG ; Ping WANG ; Li HU ; Xin Ran LIU ; Xiao Qin ZHAO ; Na TAN ; Tao CAI
Chinese Journal of Preventive Medicine 2023;57(10):1590-1595
To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans
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Dermatitis, Atopic/drug therapy*
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Quality of Life
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Retrospective Studies
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Severity of Illness Index
;
Treatment Outcome
7.Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis.
Cheng Yuan LI ; Shuang CHEN ; Wei Lu QIAN ; Liu YANG ; Qiu ZHENG ; Ai Jun CHEN ; Jin CHEN ; Kun HUANG ; Sheng FANG ; Ping WANG ; Li HU ; Xin Ran LIU ; Xiao Qin ZHAO ; Na TAN ; Tao CAI
Chinese Journal of Preventive Medicine 2023;57(10):1590-1595
To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans
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Dermatitis, Atopic/drug therapy*
;
Quality of Life
;
Retrospective Studies
;
Severity of Illness Index
;
Treatment Outcome
8.Logistic regression analysis of risk factors related to severe imported falciparum malaria
Shuang WU ; Dan-ning WEN ; Shu-kun YU ; Shu PAN ; Dan XIE ; Ke-jiao LONG ; Chong FU ; Han-dan ZHENG ; Dan LUO ; Hua-dong LI
Journal of Public Health and Preventive Medicine 2022;33(6):72-75
Objective To explore and analyze the risk factors of severe falciparum malaria cases,and to provide evidence for early clinical prevention and intervention measures. Methods A total of 114 imported cases of falciparum malaria in Wuhan from March 2012 to November 2019 were selected,divided into mild group(n=87)and severe group(n=27),and logistic regression analysis was performed on the risk factors of severe disease. Results There were significant differences in length of stay, erythrocyte, hemoglobin, platelet, urea, creatinine, albumin, creatine kinase isoenzyme, lactate dehydrogenase, urine occulting blood and urine protein between mild group and severe group (P<0.05).Multivariate Logistic regression analysis showed that alanine aminotransferase (OR=0.167, 95%CI: 0.042-0.668), albumin (OR=24.843, 95% CI: 5.170-119.383), urea (OR=0.240,95%CI: 0.074-0.779) and occulted blood in urine (OR=0.204, 95%CI: 0.062-0.672) were independent influencing factors for the occurrence of severe falciparum malaria. Conclusion Patients with liver function damage and alanine aminotransferase increased by more than 2 times(≥80U/L),albumin decreased(<30g/L),renal function damage,increased urea nitrogen,hematuria and other abnormal results, the possibility of severe falsiparum malaria development should be highly suspected.
9.Dihydromyricetin mediates epithelial mesenchymal transformation and regulates the proliferation and apoptosis of esophageal squamous cell carcinoma cells.
Ya Ping TIAN ; Yi Shuang CUI ; Xuan ZHENG ; Bao Lin LIU ; Yong Pan ZHANG ; Kun Peng WEI ; Zhi ZHANG ; Wan Ning HU ; Xue Mei ZHANG ; Guo Gui SUN
Chinese Journal of Oncology 2022;44(4):326-333
Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 μmol/L) for 24 hours. The median inhibition concentration (IC50) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-β1 (DMY+ TGF-β1), transforming growth factor-β1 (TGF-β1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC50 values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 μmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-β1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-β1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-β1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-β1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-β1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-β1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-β1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-β1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-β1 group were lower than those in DMY+ TGF-β1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-β1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-β1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-β1 group were higher than those in DMY+ TGF-β1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-β1 and promote cell apoptosis.
Apoptosis
;
Caspase 3/metabolism*
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Caspase 9/metabolism*
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Cell Line, Tumor
;
Cell Movement
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Cell Proliferation
;
Dimethyl Sulfoxide/pharmacology*
;
Epithelial-Mesenchymal Transition
;
Esophageal Neoplasms/metabolism*
;
Esophageal Squamous Cell Carcinoma
;
Flavonols
;
Humans
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Signal Transduction
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Transforming Growth Factor beta1/pharmacology*
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Vimentin/metabolism*
;
bcl-2-Associated X Protein/pharmacology*
10.Overview of research and development of polypeptide drugs and traditional Chinese medicine-peptides.
Xiao-Nan YANG ; Li-Jun RUAN ; Xing JIANG ; Zhi-Jun SONG ; Kun-Hua WEI ; Shuang-Shuang QIN ; Ying LIANG ; Xiao-Li HOU ; Xi-Jun WANG ; Jian-Hua MIAO
China Journal of Chinese Materia Medica 2022;47(22):5978-5990
Peptide is a compound consisting of 2-50 amino acids, which is intermediate between small molecule and protein. It is characterized by a variety of biological activities, easy absorption, strong specific targeting, and few side effects and has become one of the hotspots in biomedical research in recent years. Chinese medicine contains a large number of peptides. The traditional processing methods such as decocting and boiling can effectively boost peptides to exert their due biological activities. At present, however, the research on Chinese medicinal components in laboratory generally employs high-concentration alcohol extraction method, which may cause the peptides to be ignored in many natural Chinese medicines. Substantial studies have revealed that the peptides in Chinese medicine are important material basis responsible for the traditional efficacy. Based on years of research and literature retrieval, this study put forward the concept of "traditional Chinese medicine(TCM)-peptides", referring to the components consisting of two or more amino acids with molecular weight between small molecules and proteins that can express the efficacy of Chinese medicine. Furthermore, this study also summarized the extraction and separation of TCM-peptides, and structure determination methods and routes, predicted the research prospect of modern research methods of TCM-peptides based on "holistic view" and big data. The artificial intelligence prediction was combined with high-throughput screening technology to improve the discovery efficiency and accuracy of TCM-peptides, and holographic images between TCM-peptides and biological targets were established to provide references for the innovative drug design and related health product development of TCM-peptides based on TCM theories.
Medicine, Chinese Traditional
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Artificial Intelligence
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Drugs, Chinese Herbal/chemistry*
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Research Design
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Peptides
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Proteins
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Amino Acids


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