1.Changes of visual development in critical period produced by monocular chronic atropinization in rats
Ya-Zhen, WU ; Yong-Xin, XING ; Hong, YAN
International Eye Science 2015;(4):592-595
AIM:To investigate the changes of visual development produced by monocular atropinization in rats.
METHODS: Twenty normal SD rats were randomly divided into two groups: control group ( n = 10 ) and atropinization ( experimental) group ( n=10 ) . All the left eyes were selected as the experimental eyes, and the right eyes served as the normal eyes. The left eyes in atropinization group was produced by 1% atropine, 3 times a day and the right eyes in control group was treated with normal saline, 3 times a day. The flash visual evoked potentials ( F-VEP ) and retinoscopy refraction of the rats'both eyes were detected at five time points:0, 7, 14, 21, and 28d after atropinization, respectively. After 28d, six rats were randomly selected from both groups and each group had three rats. The expression of the c- fos mRNA was observed in both visual cortexes. Another six rats were chosen for the same test after 2d dark environment with 2h light later. The expression of c-fos mRNA was detected again.
RESULTS: After 14d anisometropia was observed in experimental group, the difference was 3. 9D ( P<
0.0 5 ) , F-VEP P1 wave of the rats left in experimental group was reached to 88. 9±1. 889ms at 21d, there was statistical difference compared with the right eye ( P<0.05). After 28d, c-fos mRNA expression in the left visual cortex of rats in the experimental group was higher than that of the right side, but there was no significant difference. But when underwent 2h light stimulation after in the darkroom 2d, the c-fos mRNA expression in in the left visual cortex of rats in the experimental group was 5 times higher than that of the right side, there was a statistically significant difference (P<0. 05).
CONCLUSION: In the critical period of visual development, monocular chronic atropine in rats can form anisometropia, may delay the transmission of the optic nerve, hinder the normal development of the visual cortex. Monocular atropinization in rats can be used as the model of anisometropia.
2.Research progress of anti-acute marrow leukemia drugs by targeting FLT3
Hui-ya JIA ; Bo YANG ; Xiao-meng ZHANG ; Jian-hong GONG ; Ya WU ; Yan-le ZHI
Acta Pharmaceutica Sinica 2023;58(3):605-615
Acute myeloid leukemia (AML) is a genetic heterogeneous disease in which primordial and juvenile myeloid cells proliferate or accumulate abnormally in bone marrow, peripheral blood and other tissues, resulting in damage to normal hematopoietic function. Studies have shown that about 30% of AML patients have FMS-like tyrosine kinase 3 (FLT3), FLT3 abnormal regulation is closely related to the occurrence and development of AML. At present, FLT3 has become an important target for developing small molecular targeted drugs. Currently, a variety of FLT3 inhibitors and FLT3 degraders have been developed targeting FLT3, and some compounds have exhibited good anti-AML activity. This article summarizes and sorts out the current mainstream drugs for AML therapeutic targeting FLT3, in order to provide a reference for the development and design of AML drugs.
3.Influence of arsenic exposure on menstruation
Wei-hong, YANG ; Zhi-wei, GUO ; Xiao-hong, HAN ; Ya-juan, XIA ; Ke-gong, WU ; Yan-hong, LI
Chinese Journal of Endemiology 2013;(1):27-29
Objective To study the influence of arsenic exposure on menstruation.Methods A cluster sampling method was applied to select the subjects of women aged 10 to 65 from Linhe,Hangjinhouqi and Wuyuan counties in Inner Mongolia in 2004.Drinking water samples were collected to detect arsenic levels,and menstrual related situation was surveyed.The subjects were divided into four groups according to drinking water arsenic concentration:control(≤0.01 mg/L),low(> 0.01-0.10 mg/L),moderate(> 0.10-0.20 mg/L) and high(> 0.20mag/L).Results A total of 602 women were surveyed.There were 83 subjects exposed to arsenic before menarche and their menarche age was (14.37 ± 1.54) years old.There were 90 people exposed to arsenic before menopause and the menopause age was (48.13-0.41) years old.The age of menarche and menopause were positively related to the years of arsenic exposure,and correlation coefficients were 0.268 and 0.278 (all P < 0.05).Compared to control group(14.0%,16/112),menstrual abnormality rate decreased in low(12.1%,21/173) and high dose groups(10.2%,19/186),while increased in the moderate dose group(18.2%,16/88),but the differences were not statistically significant(x2 =3.664,P > 0.05).Conclusions Long-term arsenic exposure delays the menarche and menopause age,suggesting that arsenic has certain endocrine disruption or estrogen-like effects.
6.Reversal effect of 5-Aza-dc on cisplatin-resistance in human NSCLC cells in vitro.
Chinese Journal of Oncology 2011;33(5):349-353
OBJECTIVEThe aim of this study was to investigate the effect of 5-aza-2'-deoxycytidine (5-Aza-dc), a methylation inhibitor, on cisplatin-resistance in non-small cell lung cancer cell line A549/DDP and to explore its possible mechanism.
METHODSMTT assay was used to test the cytotoxicity of 5-Aza-dc on A549/DDP cells, and the IC(50) and cisplatin resistance index of A540/DDP cells at 48 hours after 5-Aza-dc (0 µmol/L, 20 µmol/L, 40 µmol/L) treatment at different concentrations. MSP, fluorescence quantitative RT-PCR (real-time RT-PCR) and Western blot were used to detect the hMLH1 methylation status, mRNA and protein expressions, respectively.
RESULTSThe IC(50) value of cisplatin in A549/DDP cells was 30.15 ± 0.76 µmol/L. The MTT assay results demonstrated that during the 5-Aza-dc treatment for 48 hours, the dose of 20 µmol/L was non-toxic and 40 µmol/L was low-toxic. 5-Aza-dc at those two doses reduced IC(50) value of cisplatin to 16.54 ± 0.35 µmol/L (RI = 1.82) and 6.82 ± 0.16 µmol/L (RI = 4.42), respectively. MSP, real-time RT-PCR and Western blot showed that 5-Aza-dc at non-toxic and low-toxic doses removed the partial hMLH1-hypermethylation, and up-regulated hMLH1 mRNA and protein expressions.
CONCLUSIONSLow dose 5-Aza-dc can partially reverse the cisplatin-resistance in A549/DDP cells, which may be achieved through removal of hMLH1 hypermethylation and increased expression of hMLH1 gene. 5-Aza-dc may have a role in increasing the efficacy of chemotherapy for patients whose tumors are lack of hMLH1 expression because of hMLH1 promoter hypermethylation.
Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; Azacitidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; DNA Methylation ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Lung Neoplasms ; metabolism ; pathology ; MutL Protein Homolog 1 ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; metabolism
7.Effect of simulated microgravity on proliferation and differentiation of the human megakaryocyte cell
Chunyan YUE ; Xinru MAO ; Lei ZHENG ; Ya GAO ; Yangmin ZHU ; Bin WU ; Jiaqiong HONG ; Baohong PING
The Journal of Practical Medicine 2014;(12):1867-1870
Objective To investigate the effect of simulated microgravity on the proliferation and differentiation of the human megakaryocyte cells in vitro. Methods The fourth generation rotating cell culture system (RCCS-4) was used to generate the simulated microgravity environment. The cell viability was assessed by trypan blue staining method. The proliferation of cells was assessed by cell counting method and CCK8 method. The CD41+/CD61+ cells rate and the cells cycle were detected by flow cytometry. The expression levels of thrombopoietin receptor (c-mpl) and transcription factors were detected with RT-PCR. Results After 24, 48, 72 h, culture under simulated microgravity resulted in a significant decrease in the cell number , proliferative activity, cells in the G2/M phase and levels of c-mpl mRNA expression in comparison with that under the normal gravity (P < 0.05). After 48 h and 72 h culture, CD41+/CD61+ cells ratio decreased and RUNX-1 mRNA expression was down-regulated in cells of the group SMG compared with that of the group NG (P < 0.05). Conclusion Microgravity can inhibit the proliferation and differentiation of human megakaryocyte cells in vitro. The mechanism may be that TPO/c-mpl pathway was inhibited by down regulating the expression of c-mpl which transcriptional inhibition lead to.
8.Analysis of risk factors of skin lesion of population exposed to arsenic via drinking water in Inner Mongolia
Zhi-wei, GUO ; Ya-juan, XIA ; Ke-gong, WU ; Yan-hong, LI
Chinese Journal of Endemiology 2011;30(6):638-641
Objective To study the risk factors of skin lesion (keratosis and abnormal skin pigmentation) of population exposed to arsenic via drinking water in Inner Mongolia.Methods A cluster sampling method was used to select 902 cases from Linhe district,Hanghou and Wuyuan county in Inner Mongolia and physical examination was done.They were interviewed for information by questionnaire.The sample of fingernails and drinking water were collected.Water arsenic (As) was analyzed by inductively coupled plasma mass spectrometry (ICPMS); fingernail As and Se content were analyzed by instrumental neutron activation analysis(INAA).Data were analyzed by univariate and multivariate non-conditional Logistic regression.Results Single factor analysis showed that risk factors of keratosis were age,pesticide,arsenic in nails,smoking,years of smoking,drinking of alcohol,arsenic content in drinking water,fluorosis and duration of drinking arsenic-containing water,while occupation,nail selenium content and vitamin were protective factors.There were 10 risk factors for pigment abnormalities,which were age,pesticide,arsenic in nails,smoking,years of smoking,numbers of cigarette smoked daily,drinking of alcohol,fluorosis,the arsenic content in drinking water and duration of drinking arseniccontaining water,while sex,occupation and nails with selenium were protective factors.The multivariate factor analysis showed that the risk factors of keratosis were age,pesticide and arsenic content in drinking water(OR =1.387,1.583,1.321,all P < 0.05),while occupation and vitamin were protective factors(OR =0.307,0.260,all P < 0.05).The risk factors of abnormal skin pigmentation were age,pesticide,arsenic in nails,fluorosis and arsenic content in drinking water(OR =1.724,2.636,2.741,3.699,1.863,all P < 0.05),while sex was protective factor(OR =0.255,P < 0.01 ).Conclusions Many factors have influence on endemic arsenism and a composite measure should be implemented to prevent it such as excluding arsenic from drinking water,health education,and a reasonably intake of nutrients.
9.Effect of Simvastatin on Severe Complications of Subarachnoid Heamorrhage
Shi-wen WU ; Wei-ya MA ; Hong BIAN ; Guang YANG ; Wenbin ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2006;12(4):326-328
ObjectiveTo investigate the effect of simvastatin on severe complications and prognosis of subarachnoid heamorrhage (SAH).Methods98 cases with SAH were randomly divided into the treatment groups and control group (finally, there were 32 cases in treatment group, 48 cases in control group). Patients in treatment group were given simvastatin 20 mg/day, and those in control group were treated with routine therapy. The incidences of cerebral vasospasm, hydrocephalus, rebleeding and mortality between the two groups were compared.ResultsThe incidence of hydrocephalus of treatment group was 3.13%; that of control group was 18.7%, there was a significantly difference between two groups (P<0.05). There were no significant differences for incidences of cerebral vasospasm, rebleeding and mortality between two groups (P>0.05).ConclusionSimvastatin can reduce the occurrence of hydrocephalus after SAH.