1.Role and mechanism of human umbilical cord mesenchymal stem cell exosomes in wounds with escharectomy and skin grafting in scalded rats
Di WANG ; Shuqian DOU ; Kongjia WU ; Gaofei ZHANG ; Hanxiao LOU ; Chenying ZHANG ; Guoxun YANG ; Chengbo JIN ; Ting QUE ; Wenjun LIU
Chinese Journal of Burns 2024;40(11):1075-1084
Objective:To investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (hUCMSC-ex) in wounds with escharectomy and skin grafting in scalded rats.Methods:The study was an experimental study. Twelve male Sprague-Dawley (SD) rats aged 6-8 weeks were divided into combined treatment group, fixed+allogeneic skin group, autologous skin+allogeneic skin group, and allogeneic skin group by random number table method (the same grouping method hereinafter), with 3 rats in each group. The four groups of rats were inflicted with scalded wounds on the back and performed with escharectomy, and then the wounds of rats in combined treatment group were fixed with a metal ring (the same fixing method hereinafter) and transplanted with autologous skin grafts and allogeneic skin grafts, and the other three groups of rats were fixed and/or transplanted with skin grafts corresponding to the group name. At 14, 21, and 28 d after surgery, the wound healing area in the four groups of rats was measured. Another 15 male SD rats aged 6-8 weeks were divided into normal group with no treatment, high exosome group, low exosome group, supernatant group, and phosphate buffer solution (PBS) group, with 3 rats in each group. The last 4 groups of rats were treated as that in the above-mentioned combined treatment group, and then were injected around the wounds with 200 μL of PBS containing 100 μg of hUCMSC-ex, 200 μL of PBS containing 50 μg of hUCMSC-ex, 200 μL of supernatant with no hUCMSC-ex, and 200 μL of PBS at 0 (immediately), 7, 14, and 21 d after surgery, respectively. At 14, 21, and 28 d after surgery, the wound healing area in the four groups of rats was measured. The wound neo-epithelial tissue of rats in high exosome group and PBS group at 28 d after surgery and the normal skin tissue of rats in normal group at the same time point were taken, and the differentially expressed proteins were screened by label-free quantitative proteomics method; the two up-regulated and differentially expressed proteins, the immunoglobulin G1 heavy chain constant region (IGHG1) and cystatin A (CSTA) with the largest and second largest fold changes in comparison between high exosome group and PBS group were selected, and their protein expressions were detected by Western blotting. The number of samples in all experiments was 3.Results:At 14, 21, and 28 d after surgery, the wound healing area in combined treatment group, autologous skin+allogeneic skin group, and allogeneic skin group of rats was significantly larger than that in fixed+allogeneic skin group ( P<0.05), the wound healing area in autologous skin+allogeneic skin group of rats at 21 d after surgery and that in allogeneic skin group of rats at 14 and 21 d after surgery was significantly larger than that in combined treatment group ( P<0.05), and the wound healing area in allogeneic skin group of rats at 14 d after surgery was significantly larger than that in autologous skin+allogeneic skin group ( P<0.05). The wound healing area of rats in high exosome group and low exosome group at 14, 21, and 28 d after surgery and in supernatant group at 14 and 28 d after surgery was significantly larger than that in PBS group ( P<0.05); the wound healing area in high exosome group of rats at 14 and 21 d after surgery was significantly larger than that in supernatant group ( P<0.05), and the wound healing area at 14 d after surgery was significantly larger than that in low exosome group ( P<0.05); the wound healing area in low exosome group of rats at 14 d after surgery was significantly larger than that in supernatant group ( P<0.05). Compared with that in PBS group, 332 proteins were differentially expressed in the neo-epithelial tissue of the wounds in high exosome group of rats at 28 d after surgery ( P<0.05), among which the protein expressions of IGHG1 and CSTA were significantly up-regulated (with fold change of 12.60 and 2.27, respectively, P<0.05). Compared with those of normal skin tissue in normal group, 1 400 and 1 057 proteins were differentially expressed in the neo-epithelial tissue of the wounds in high exosome group and PBS group of rats at 28 d after surgery, respectively. The protein expressions of IGHG1 and CSTA in the wound neo-epithelial tissue in high exosome group of rats at 28 d after surgery were significantly larger than those in normal skin tissue of rats in normal group ( P<0.05) and those in PBS group ( P<0.05). Conclusions:hUCMSC-ex may accelerate the repair process of wounds with escharectomy and skin grafting and improve the quality of wound healing in scalded rats by regulating the protein expressions of IGHG1 and CSTA.
2.Anticarin-β shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis.
Gan WANG ; Min ZHANG ; Ping MENG ; Chengbo LONG ; Xiaodong LUO ; Xingwei YANG ; Yunfei WANG ; Zhiye ZHANG ; James MWANGI ; Peter Muiruri KAMAU ; Zhi DAI ; Zunfu KE ; Yi ZHANG ; Wenlin CHEN ; Xudong ZHAO ; Fei GE ; Qiumin LV ; Mingqiang RONG ; Dongsheng LI ; Yang JIN ; Xia SHENG ; Ren LAI
Acta Pharmaceutica Sinica B 2022;12(5):2268-2279
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.
3.Study on the influencing factors of HIV testing awareness among Myanmar people in Dehong, Yunnan province
Wenkang ZHANG ; Fei DIAO ; Guowu LIU ; Mengjie HAN ; Yuecheng YANG ; Chengbo WANG ; Ximei XIE ; Xiaobin CAO
Chinese Journal of Experimental and Clinical Virology 2021;35(2):130-134
Objective:To analyze the influencing factors of HIV-testing awareness of Myanmar people in Dehong, and provide references for early discovery of HIV infection among Myanmar people.Methods:A cross-sectional study was conducted among 400 Myanmar people in Dehong through convenient sampling method in a form of face-to-face questionnaire interview. HIV-testing awareness and influencing factors were described and analyzed with χ2 and logistic regression method . Results:A total of 393 participants were included in the study, in whom 241 (61.3%) were males, 256(65.1%) were Myanmar people, 233(59.3%) received 1-7 years of education in Myanmar, 348 do not speak Chinese (88.5%), 226(57.5%) were married, 378(96.2%) were non-solitary, 257(65.4%) were workers, the main purpose of etering into China in 273(69.5%) was working in China, 273(69.5%) had stayed in China for more than 2 years, 573(95.4%) had a clear plan on whether to stay in China for a long time in the future. In these Myanmar people, the rate of AIDS-related knowledge awareness was 75.6%; 165(42.0%) had sexual behavior in the last 6 months. 221(56.2%) knew that they had been tested for HIV. Ninety (22.9%) were more likely to actively seek HIV-testing after they had unprotected behaviors such as homosexual sex, injecting drug use, and sex without using condom. Multivariate logistic regression analysis showed that the influencing factors of HIV-testing awareness included being women (compared with men, OR=2.155, 95% CI: 1.088-4.270), educational level of 8-10 years or more than 10 years (compared with education level 1-4 years, OR=5.207, 95% CI: 2.094-12.950; OR=19.780, 95% CI: 5.800-67.457), having sexual behavior in the last 6 months (compared with those who had not, OR=2.534, 95% CI: 1.343-4.779), having received AIDS-related education in the last 6 months (compared with those who had not, OR=2.462, 95% CI: 1.303-4.654), AIDS-related knowledge awareness (compared with those who had no awareness, OR=8.126, 95% CI: 2.936-22.491). Conclusions:Myanmar people have low awareness of HIV-testing in Dehong. Those who were women and high literacy levels, having received AIDS-related knowledge education in the past 6 months, and having AIDS-related knowledge have an active HIV-testing awareness, after they have high-risk behaviors. AIDS-related knowledge should be publicized to promote early discovery of high-risk behaviors.
4.Analysis of epidemiological characteristics of respiratory pathogens in children by multiple RT-PCR based on capillary electrophoresis
Wenyuan LIU ; Yizhi ZHANG ; Chengbo ZHOU ; Junhua WU ; Wenbo LU
Chinese Journal of Experimental and Clinical Virology 2021;35(4):467-471
Objective:To investigate the epidemiological characteristics of children respiratory pathogen infection in Ningbo city, and provide scientific reference for clinical prevention, control, diagnosis and treatment.Methods:A total of 3 103 specimens were collected from the children with acute respiratory infections in Ningbo Women and Children′s Hospital from July to October 2019. Thirteen common respiratory pathogens were detected by multiple reverse transcription-polymerase chain reaction (RT-PCR) based on capillary electrophoresis, and the result were analyzed.Results:Of the 3 103 specimens, 2 053 were positive for respiratory pathogens, with a total positive rate of 66.16%. The detection rates of Mycoplasma pneumoniae (Mp) 33.19% (1 030/3 103), human rhinovirus (HRV) 24.20% (751/3 103), and human adenovirus (HADV) 8.77% (272/3 103) were in the first three. The positive rates of pathogens in the male and female children were 65.70% (1 157/1 761) and 66.77% (896/1 342), respectively, and the difference was not statistically significant( χ2=0.386, P=0.535); the positive rates in the age groups of ≤1 year old, 1~≤3 years old, 3~≤6 years old and 6~≤16 years old were 58.02% (626/1 079), 74.37% (589/792), 73.78% (543/736) and 59.48% (295/496), respectively, and the difference among the groups was statistically significant( χ2=84.770, P=0.000); the positive rates in July to October were 71.64% (341/476), 68.81% (536/779), 67.01% (648/967) and 59.93% (528/881), respectively, the difference was statistically significant( χ2=24.395, P=0.000); the single infection rate was 52.30% (1 623/3 103), and the mixed infection rate of two or more pathogens was 13.86% (430/3 103), most of which were mixed infections of two pathogens. Conclusions:The main respiratory pathogens of children in Ningbo city were Mp and HRV, and the detection rates of respiratory pathogens varied among different ages and months.
5.Progress in treatment of PD-1/PD-L1 inhibitors for bladder cancer
Fan ZHANG ; Yanyou LI ; Zhengqi SHI ; Chengbo WANG ; Zhilong DONG
Chinese Journal of Surgery 2021;59(11):952-955
Because of the limited effect of traditional treatment methods such as surgical treatment, radiotherapy and chemotherapy,the emergence of immunotherapy has brought new hope for the treatment of patients with bladder cancer. As an immune checkpoint inhibitor, programmed death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) inhibitor has shown good anti-tumor activity and safety in the treatment of advanced bladder cancer, and has been recommended for advanced bladder cancer as second-line treatment by NCCN guidelines. PD-1/PD-L1 inhibitor for the treatment of bladder cancer has covered the first-line and second-line treatment, as well as maintenance therapy after first-line chemotherapy of locally advanced or metastatic bladder cancer, adjuvant and neoadjuvant therapy of muscle-invasive bladder cancer, treatment of high-risk non-muscle invasive bladder cancer failed by Bacille Calmette-Guérin vaccine perfusion, and bladder preservation therapy of muscle-invasive bladder cancer. Some of related studies have achieved certain results, and some are in progress, both of which need to be further examined. Maybe it can provide new guidance and ideas for clinical treatment of bladder cancer.
6.Progress in treatment of PD-1/PD-L1 inhibitors for bladder cancer
Fan ZHANG ; Yanyou LI ; Zhengqi SHI ; Chengbo WANG ; Zhilong DONG
Chinese Journal of Surgery 2021;59(11):952-955
Because of the limited effect of traditional treatment methods such as surgical treatment, radiotherapy and chemotherapy,the emergence of immunotherapy has brought new hope for the treatment of patients with bladder cancer. As an immune checkpoint inhibitor, programmed death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) inhibitor has shown good anti-tumor activity and safety in the treatment of advanced bladder cancer, and has been recommended for advanced bladder cancer as second-line treatment by NCCN guidelines. PD-1/PD-L1 inhibitor for the treatment of bladder cancer has covered the first-line and second-line treatment, as well as maintenance therapy after first-line chemotherapy of locally advanced or metastatic bladder cancer, adjuvant and neoadjuvant therapy of muscle-invasive bladder cancer, treatment of high-risk non-muscle invasive bladder cancer failed by Bacille Calmette-Guérin vaccine perfusion, and bladder preservation therapy of muscle-invasive bladder cancer. Some of related studies have achieved certain results, and some are in progress, both of which need to be further examined. Maybe it can provide new guidance and ideas for clinical treatment of bladder cancer.
7.Regulation of aerobic glycolysis to decelerate tumor proliferation by small molecule inhibitors targeting glucose transporters.
Meng GAO ; Jian HUANG ; Xin JIANG ; Yafei YUAN ; Huanhuan PANG ; Shuchen LUO ; Nan WANG ; Chengbo YAO ; Zuwan LIN ; Debing PU ; Shuo ZHANG ; Pengcheng SUN ; Zhuoyi LIU ; Yu XIAO ; Qian WANG ; Zeping HU ; Hang YIN
Protein & Cell 2020;11(6):446-451
8.Prescription Rules for the Prescriptions Containing Coptis chinensis-Zingber ojjicinale Couplet Medicine Based on TCM Inheritance Support Platform
Guangzhi LUO ; Xuming JI ; Ting MA ; Cheng’en HAN ; Wanchen YU ; Shijun WANG ; Chengbo ZHANG
China Pharmacy 2019;30(1):99-103
OBJECTIVE: To provide a theoretical basis for the development of the following products of Coptis chinensis- Zingiber ojjicinale couplet medicine (“Coptis chinensis-Zingiber ojjicinale” for short) prescription. METHODS: The prescriptions containing Coptis chinensis-Zingiber ojjicinale were collected from the Dictionary of TCM Prescription and input into TCM inheritance support platform software (V2.5) to establish the database. The frequency of major diseases and compatibility medicinal materials were analyzed statistically. The core combination of medicinal materials in the prescriptions containing Coptis chinensis-Zingiber ojjicinale were analyzed statistically with association rule Apriori algorithm (support degrees were 15%, 20%, 25%, confidence was 0.90). Top 2 main diseases in the list of frequency, compatibility medicinal materials for dispelling internal cold and medicine for clearing heat with highest compatibility frequency were selected and analyzed in respect of prescription rules. RESULTS: A total of 492 prescriptions containing Coptis chinensis-Zingiber ojjicinale were screened, 9 kinds of major diseases (frequency≥15), such as dysentery, diarrhea, accumulation, fullness. There were 21 commonly used compatibility medicinal materials (frequency≥55), including Angelica sinensis-Panax ginseng, Magnolia officinalis, Aconitum carmichaelii, Scutellaria baicalensis, etc. There were 19 commonly used medicinal materials combinations, including Coptis chinensis-Zingiber ojjicinale-Panax ginseng, Coptis chinensis-Zingiber ojjicinale- Magnolia officinalis, Coptis chinensis-Zingiber ojjicinale-Angelica sinensis. There are 5 kinds of core medicinal materials commonly used in treating dysentery with Coptis chinensis-Zingiber ojjicinale,and 9 kinds of core medicinal materials for treating dysentery. There are 8 kinds of core medicinal materials in Coptis chinensis-Zingiber ojjicinale compatible with medicine for dispelling internal cold Aconitum carmichaelii prescription.and 7 core medicinal materials in compatible with medicine for clearing heat Scutellaria baicalensis prescription. CONCLUSIONS: The major diseases treated with prescriptions containing Coptis chinensis-Zingiber ojjicinale are mainly digestive tract diseases. It can treat different diseases being compatible with different medicinal materials, this study aslo can provide theoretical basis for the development of subsequent products.
9.Efficacy and safety of endostar intracavitary infusion in treatment of malignant serous cavity effusion: A case control study
ZHANG Shuling ; MA Jietao ; ZHAO Jianzhu ; SUN Li ; JING Wei ; ZHOU Yang ; HUANG Letian ; HAN Chengbo
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2018;25(2):138-142
Objective To analyze the clinical efficacy and safety of endostar or carboplatin combined with endostar intracavitary perfusion in the treatment of malignant serous cavity effusion. Methods We retrospectively reviewed the clinical data of 78 cancer patients with malignant serous cavity effusion who received paracentesis and intracavitary endostar, or carboplatin combined with endostar in Shengjing Hospital of China Medical University between November 2011 and November 2016. There were 42 males and 36 females at a median age of 62 years ranging from 17 to 78 years. According to treatment methods, 78 patients were divided into two groups, in which 33 patients received intracavitary endostar combined with carboplatin (a combination group, 15 males and 18 females at a median age of 56 years ranging from 17 to 66 years), and 45 patients received intracavitary endostar (an endostar group, 27 males and 18 females at a median age of 63 years ranging from 38 to 78 years). The efficacy and safety of two methods were analyzed and compared. Results The response rate in the combination group was 75.8%, which was higher than that in the endostar group (60.0%, P=0.035). In quality of life improvement, there was no statistical difference between the two groups (P=0.113). The incidence of fatigue, myelosuppression and gastrointestinal reactions in the endostar group was significantly lower than that of the combination group (P=0.006, 0.000 and 0.017, respectively). Analysis of long-term efficacy revealed that the median time to progress (TTP) in the combination group and endostar group was 171 days and 143 days, respectively (P=0.030). Conclusion Intracavitary infusion of endostar alone, or carboplatin combined with endostar is effective and tolerable for controlling malignant serous cavity effusion. But for the patients with poor physical state who can not tolerant platinum perfusion, intracavitary infusion of endostar alone can be adopted to control malignant serous cavity effusion.
10.C-Diterpenoid alkaloid arabinosides from an aqueous extract of the lateral root of and their analgesic activities.
Qinglan GUO ; Huan XIA ; Xianhua MENG ; Gaona SHI ; Chengbo XU ; Chenggen ZHU ; Tiantai ZHANG ; Jiangong SHI
Acta Pharmaceutica Sinica B 2018;8(3):409-419
Eight new C-diterpenoid alkaloid arabinosides, named aconicarmichosides E-L (-), were isolated from an aqueous extract of the lateral roots of (Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds -, together with the previously reported four neoline 14--arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0 mg/kg (i.p.), as compared with the black control, compounds , , and - exhibited analgesic effects with >65.6% inhibitions against acetic acid-induced writhing of mice. Structure-activity relationship was also discussed.

Result Analysis
Print
Save
E-mail