1.Progress in the study of tubulin inhibitors.
Hai SHANG ; Li PAN ; Shu YANG ; Hong CHEN ; Maosheng CHENG
Acta Pharmaceutica Sinica 2010;45(9):1078-88
Microtubule is one of the key components of the cytoskeleton and plays an important role in the maintenance of cell shape and the process of signal transduction and mitosis. Due to the extreme importance of microtubule in the process of mitosis, tubulin becomes one of the most important targets for development of new anticancer drugs and tubulin inhibitors are used for the treatment of cancer nowadays. These inhibitors have antitumor activity by inhibiting or promoting the assembly of tubulin to microtubules and interfering the process of cell mitosis. This review summarized the research progress of the tubulin inhibitors, especially the introduction of the tubulin inhibitors of pharmacological activities and the progress of clinical research. Also, the development trend of these inhibitors is discussed.
2.Progress in the study of carbonic anhydrase inhibitors as potential anticancer drugs.
Jia GUO ; Fengran LI ; Yang LIU ; Maosheng CHENG
Acta Pharmaceutica Sinica 2013;48(11):1637-43
Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications.
3.Synthesis and immunosuppressive effects of novel phthalazine ketone derivatives.
Yali WANG ; Qinghe WANG ; Hongguang YANG ; Bojun HAO ; Guodong LIANG ; Chongguo JIANG ; Maosheng CHENG
Acta Pharmaceutica Sinica 2013;48(10):1579-84
A series of phthalazine ketone compounds were synthesized and the structures were confirmed by H NMR and HR-MS spectrum. All target compounds were obtained through 7 steps, including selective reduction, nitration, bromination, ring enlargement, reduction, Knoevenagel and acylated reaction. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and inhibitory activity of IMPDH type II in vitro, as well as their structure-activity relationship were assessed. Several compounds exhibited strong immunosuppressive properties, especially compounds 7f and 7h, with IC50 values of 0.093 micromol x L(-1) and 0.14 micromol x L(-1) respectively, which were superior to mycophenolic acid. The information obtained from the studies may be useful for further research on the immunosuppressive agents.
4.Bone marrow-derived mesenchymal stem cells improved prognosis in rats with extended liver resection
Weizheng REN ; Maosheng SU ; Xiaoxia DU ; Li ZHAO ; Yu CHENG ; Xiaozhong WU ; Wanqing GU
Chinese Journal of Hepatobiliary Surgery 2016;22(8):546-551
Objective To study the role of mesenchymal stem cells (MSC) in an animal model combining ischemia-reperfusion with 85% liver resection.Methods Eight-week-old male SD rats received BM-MSC by tail vein and then underwent 30-min ischemia followed by 85% liver resection.The survival rate was monitored for 7 days after surgery.Liver regeneration was assessed on day 2 after hepatectomy.Liver damage,liver cell apoptosis,and cytokine expression in the first 24 h after hepatectomy were also assessed.Results BM-MSC mostly homed to the spleen.Transplantation significantly inhibited myeloperoxidase [(19.9 ± 6.0) mg/g vs.(41.4 ± 10.2) mg/g] and downregulated proinflammatory cytokines.BM-MSC significantly reduced the ALT and AST levels [AST (1 475 ± 275) IU/L vs.(2 550 ± 441) IU/L,P < 0.05;ALT (738 ± 101) IU/L vs.(1 113 ± 268) IU/L,P < 0.05].The attenuation of liver injury was also verified histologically 24 h after surgery.Liver cell apoptosis was markedly reduced.Moreover,BM-MSC infusion significantly promoted remnant liver regeneration.As a result,the survival rate was improved by BM-MSC treatment in this model (95% vs 70%,P < 0.05).Conclusion In an animal model combining ischemia-reperfusion with 85% liver resection,BM-MSC infusion attenuated liver injury and promoted hepatocyte regeneration,resulting in improved survival rate.
5.Association between low body mass indeX and flag-raising syncope in children and adolescents
Shuo WANG ; Chuanmei TAN ; Maosheng YANG ; Yiyi DING ; Runmei ZOU ; Cheng WANG
Chinese Journal of Applied Clinical Pediatrics 2019;34(5):355-358
Objective To discuss the relationship between body mass index(BMI)and flag_raising syncope ( PS)and micturition syncope(MS)in children and adolescents. Methods One hundred and six children and adoles_cents with PS or MS diagnosed at the Department of Dediatric Cardiovasology,Childrenˊs Medical Center,the Second Xiangya Hospital,Central South University from January 2003 to September 2017 were studied,including 51 males and 55 females,and their ages ranged from 5 to 18 years. There were 63 cases in the PS group(21 males and 42 females) and 43 cases in the MS group(30 males and 13 females). One hundred healthy children and adolescents including 50 males and 50 females who had routine healthy examinations at the hospital in the same period were selected as control subjects(healthy control group). Body length and body mass were measured,and BMI was calculated. Statistical inves_tigations were conducted with SDSS 22. 0 software. Results (1)The body mass and BMI in the PS group were lower than those in the MS group[(36. 33 ± 9. 85)kg vs.(42. 85 ± 12. 44)kg;(16. 56 ± 2. 41)kg∕m2 vs.(18. 48 ± 3. 04) kg∕m2],and the differences were statistically significant(F﹦7. 529,12. 411,all P〈0. 05). There was no difference in body length among the PS group,the MS group and the healthy control group[(146. 62 ± 12. 89)cm vs.(150. 79 ± 12. 78)cm vs.( 149. 75 ± 16. 02 )cm,F ﹦1. 314,P 〉0. 05 ]. No differences were found in age,frequency,body length,body mass and BMI between the PS syncope group and the MS group with different genders(all P〉0. 05).(2) The number of BMI_underweight children increased in the PS group(82. 53%,52∕63 cases)compared with that of the MS group(58. 14%,25∕43 cases)and that of the healthy control group( 52. 00%,52∕100 cases),and the difference was statistically significant(χ2 ﹦14. 556,P〈0. 01).(3)The positive rate by head_up tilt test(HUTT)was 72. 64%(77∕104 cases),and HUTT of the PS group was higher than that of the MS group[82. 53%(52∕63 cases)vs. 58. 14%(25∕43 cases)],and there was a significant difference statistically(χ2 ﹦7. 656,P〈0. 01). Conclusions Low BMI is prone to PS in children and adolescents.
6.Practice of "ideological and political education" in online nursing teaching under the COVID-19 epidemic
Ting CHU ; Xuemei LUO ; Qunli WANG ; Cheng ZHANG ; Maosheng YANG
Chinese Journal of Medical Education Research 2020;19(6):687-690
Jishou University School of Medicine has actively explored the application and effect of online teaching of "ideological and political education" in nursing courses under the COVID-19 epidemic. Taking 135 undergraduates majoring in nursing in batch 2017 as research objects, this study introduces the implementation scheme of online teaching of "ideological and political education". The results show that the online teaching of "ideological and political education" can help nursing undergraduates to establish the professional identity and cultivate medical ethics during the epidemic, to enhance the awareness of the prevention and control of the epidemic, to strengthen the understanding of relevant nursing professional knowledge, and improve students' learning attitude, worthy of reference and promotion.
7.Optimization of chromosome flaking technique for mesenchymal stem cells.
Maosheng CHEN ; Chuang LI ; Dehua CHENG ; Yueqiu TAN ; Hua MEI ; Siqi WANG ; Xiang LI ; Lamei CHENG
Chinese Journal of Medical Genetics 2019;36(2):143-146
OBJECTIVE:
To optimize the condition for chromosome flaking of mesenchymal stem cells to ensure the cytogenetic quality control of expanding production and clinical application.
METHODS:
Chromosomal flaking methods were optimized from current chromosome preparation techniques from the aspects of MSCs cell culture concentration, colchicine treatment time and low permeability time.
RESULTS:
By repeated pre-experiments, the optimal MSCS chromosome flaking condition of MSCs was determined as cell culture concentration of (1-2)× 10 cells per T25 cell culture bottle, and the colchicines processing time was determined as 2 hours and 10 minutes, and the low permeability was 1 hour.
CONCLUSION
The optimized chromosome flaking condition can fulfill the requirement of cytogenetic quality control for MSCs.
Cell Culture Techniques
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Cell Differentiation
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Cells, Cultured
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Chromosome Disorders
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Chromosomes, Human
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Cytogenetics
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Humans
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Mesenchymal Stem Cells
8.The value analysis of shear wave velocity combined with thyroid stimulating hormone in diagnosis of hyperthyroidism
Xinping LIU ; Kaicheng DUAN ; Maosheng SUN ; Yanyan WANG ; Siyu CHENG
Chinese Journal of Postgraduates of Medicine 2020;43(6):527-531
Objective:To analyze the value of shear wave velocity (SWV) combined with thyroid stimulating hormone (TSH) in the diagnosis of hyperthyroidism.Methods:Thirty-five patients with hyperthyroidism who were treated and confirmed in the Fuyang Affiliated Hospital of Anhui Medical University from December 2017 to September 2019 were selected as hyperthyroidism group, and 30 cases of normal health check-up patients in the outpatient department were selected as control group. All of the patients and medical persons were checked by conventional two-dimensional ultrasound and SWV, and the SWV and serum TSH, thyrotrophin receptor antibody(TRAb), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) expression levels of two groups were tested and compared. The correlation relationship in SWV value and serum TSH, TRAb, TGAb, TPOAb levels of hyperthyroidism patients was analyzed by Pearson methods. The receiver operating characteristic curve (ROC curve) method was used to analyze the value of SWV, serum TSH and SWV combined with serum in diagnosis of hyperthyroidism.Results:The SWV values of upper pole, middle pole and lower pole in the hyperthyroidism group had no significant differences ( P>0.05). The SWV values of upper hole, middle pole and lower pole of the left and right lobe of thyroid in the hyperthyroidism group were significantly higher than those in the control group [left lobe: (2.41 ± 0.34) m/s vs. (2.07 ± 0.28) m/s, (2.44 ± 0.39) m/s vs. (2.08 ± 0.25) m/s, (2.46 ± 0.43) m/s vs. (2.04 ± 0.30) m/s; right lobe: (2.47 ± 0.42) m/s vs.(2.01 ± 0.25) m/s, (2.41 ± 0.40) m/s vs. (1.95 ± 0.23) m/s, (2.43 ± 0.35) m/s vs. (2.06 ± 0.24) m/s] ( P<0.01). The serum TSH level in the hyperthyroidism group were significantly lower than that in the control group [(0.05 ± 0.03) kU/L vs. (2.74 ± 1.17) kU/L], while serum TRAb, TGAb and TPOAb levels were significantly higher than those in the control group [(15.82 ± 5.54) U/L vs. (0.55 ± 0.13) U/L, (290.63 ± 145.03) kU/L vs. (25.63 ± 7.12) kU/L, (627.17 ± 250.33) kU/L vs. (34.32 ± 5.95) kU/L], and the differences were statistically significant ( P<0.01). In the hyperthyroidism group, the SWV was negatively correlated with serum TSH ( r=- 0.862, P<0.05), but positively correlated with serum TRAb, TGAb and TPOAb ( r=0.763, 0.837, 0.804, P<0.05). The area under curve(AUC), sensitivity and specificity of combined diagnosis of hyperthyroidism with SWV value and serum TSH were 0.936, 94.29% and 91.43%, which was better than that of SWV (0.803, 80.00%, 74.29%) and serum TSH (0.842, 82.86%, 77.14%). Conclusions:SWV combined with TSH has a high clinical value in the diagnosis of hyperthyroidism.
9.Prognostic value of rate-pressure product in children with postural tachycardia syndrome
Shuo WANG ; Hong CAI ; Yiyi DING ; Chuanmei TAN ; Maosheng YANG ; Yuwen WANG ; Runmei ZOU ; Yi XU ; Cheng WANG
Chinese Journal of Applied Clinical Pediatrics 2020;35(13):969-973
Objective:To investigate the value of rate-pressure product (RPP) in predicating the prognosis of postural tachycardia syndrome (POTS) in children.Methods:Fifty-three children (26 males and 27 females) aged 5 to 15 who had syncope of unknown reasons or presyncope and were diagnosed with POTS by head-up tilt test (HUTT) at the Children′s Syncope Specialist Clinic, the Second Xiangya Hospital, Central South University from April 2012 to May 2019 were selected as the POTS group.Thirty-eight children aged 5 to 16 (19 males and 19 females) who underwent medical examinations at the Children′s Health Specialist Clinic of the Second Xiangya Hospital, Central South University over the same period were enrolled as controls (control group). POTS children were followed up after intervention and they were divided into the response group ( n=40) and the non-response group ( n=13) according to the follow-up results.The products (RPP0, RPP5, RPP10) of the heart rate (HR0, HR5, HR10) and systolic blood pressure (SBP0, SBP5, SBP10) at baseline (HUTT 0 min), HUTT 5 min and HUTT 10 min were calculated.Statistical analysis was performed using SPSS 22.0 software and EmpowerStats software. Results:(1) There was no statistical difference in age and gender between the POTS group and the control group (all P> 0.05). (2) HR5 [(115.45±14.50) times/min vs.(95.79±13.89) times/min], HR10 [(120.57±16.13) times/min vs.(96.05±12.43) times/min], RPP5 (12 814.55±2 304.56 vs.10 371.42±1 910.20), and RPP10 (13 449.17±2 360.40 vs.10 523.18±1 771.48) in the POTS group were significantly higher than those in the control group( t=0.799, 7.842, 5.747, 6.446, all P<0.01). No statistical difference of HR0 and RPP0 was observed between the 2 groups (all P>0.05). (3) In the POTS group: HR5 [(98.73±12.43) times/min vs.(113.77±17.65) times/min], HR10 [(96.90±13.96) times/min vs.(119.08±13.52) times/min], RPP5 (11 125.45±1 952.35 vs.12 914.69±3 192.12) and RPP10 (10 819.58± 2 144.26 vs.13 375.46±2 807.01) in the response group were significantly lower than those in the non-response group( t=3.406, 5.012, 2.432, 3.455, all P<0.01). HR0 and RPP0 were no significantly different between the 2 groups(all P>0.05). (4) When SBP10<114 mmHg(1 mmHg= 0.133 kPa), the probability of response after POTS intervention increased by 10% with every 1 mmHg increase in SBP10, and there was a non-linear relationship between the 2 group ( P<0.05). (5) The receiver operating characteristic curve suggested that when RPP5 was 11 548.50, the sensitivity and specificity to predict the response after POTS intervention were 81.82% and 61.70%, respectively.When RPP10 was 10 988.00, the sensitivity and specificity were 77.78% and 86.21%, respectively. Conclusions:RPP is closely related to the intervention effect of POTS in children.RPP5 and RPP10 can predict the prognosis of POTS in children.There is a non-linear relationship between SBP10 and the intervention effect of POTS in children.
10.Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors.
Mengchi SUN ; Hailun JIANG ; Tian LIU ; Xiao TAN ; Qikun JIANG ; Bingjun SUN ; Yulong ZHENG ; Gang WANG ; Yang WANG ; Maosheng CHENG ; Zhonggui HE ; Jin SUN
Acta Pharmaceutica Sinica B 2022;12(2):952-966
Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.