1.Dihydromyricetin reverses Herceptin resistance by up-regulating miR-98-5p and inhibiting IGF1R/HER2 dimer formation in SKBR3 cells.
Ming Liang ZHANG ; Chen Xu GUO ; Yun Mian CHU ; Rui XU ; Fa Xiang YIN ; Jun QIAN
Journal of Southern Medical University 2022;42(2):207-214
OBJECTIVE:
To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells.
METHODS:
The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation.
RESULTS:
The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05).
CONCLUSION
Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.
Animals
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Cell Line, Tumor
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Flavonols/pharmacology*
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Humans
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Mice
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MicroRNAs/metabolism*
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Receptor, IGF Type 1
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Trastuzumab
2. The Adaptational Regulation Mechanism of the Apoptosis in Aged Rats’ Striatum in Response to Regular Aerobic Exercise Based on Carbonylation Proteomics
Shun-Ling YUAN ; Mei PENG ; Yi XIANG ; Qi-Ming YANG ; Yong LEI ; Wen-Feng LIU ; Xia LIU ; Chang-Fa TANG ; Wen-Feng LIU ; Da-Zhong YIN ; Da-Zhong YIN
Chinese Journal of Biochemistry and Molecular Biology 2021;37(11):1489-1501
This paper investigated the effects of regular aerobic exercise on protein oxidative stress and apoptosis in aging rat striatum, and further analyzed its target proteins and mechanism based on differential carbonylation proteomics. Totally 24 specific pathogen-free (SPF) 23-month-old male Sprague-Dawley (SD) rats were randomly divided into aged sedentary control group (Con-SED, n = 12) and aged regular aerobic exercise runner group (Aero-EXE, n = 12). The medium intensity of regular aerobic exercise model: The intensity of maximum oxygen consumption (VO
3.Analysis of the Detection Results of the Syphilis Specific Antibody in Blood Donors by Chemiluminescence Method and Enzyme Linked Immunosorbent Assay.
Shou-Shan MEN ; Fa-Kui SHANG ; Chun-Hua HAN ; Jin-Xiang SONG ; Jing-Yin HAN
Journal of Experimental Hematology 2017;25(1):226-230
OBJECTIVETo investigate the application value of chemiluminescence method (CMIA) detection of Treponema pallidum (TP) specific antibodies in the blood test.
METHODSOver the same period the de novo enzyme linked immunosorbent assay (ELISA) and Abbott chemical luminescence method were used to detect the specific antibody of syphilis in a total of 66298 samples; TP-ELISA negative and TP-CMIA positive unpaid blood donation blood samples for syphilis specific antibody were detected and confirmed by Western blot.
RESULTSBlood samples from 66298 blood donors were detected by TP-ELISA, the positive samples was 250 and the positive rate was 0.38%. The positive samples of TP-CMIA was 297, the positive rate was 0.45%, the difference was statistically significant (P<0.05). The blood samples of 47 unpaid blood donors were confirmed by TP-Western blot method, as a result, 32 samples were positive, 15 were negative, and result detected by TP-ELISA method was negative.
CONCLUSIONTP-CMIA sensitivity is higher than that of TP-ELISA, and possesses higher sensitivity and specificity, and quick detection, simple operation, easy automation, suggesting greater application value in blood detection of Treponema pallidum.
4.Clinical monitoring of chromosome karyotype and fusion gene expression after allogeneic hematopoietic stem cell transplantation in chronic myelocytic leukemia
Zheng-Fa LI ; Wei LIU ; Yun-Yun DU ; Tong-Hua YANG ; Jie ZHAO ; Ke-Qian SHI ; Xin-Hua TANG ; Yan-Mei YANG ; Yin-Hong ZHANG ; Xun LAI ; Yan WEN ; Zhi-Xiang LU
Chinese Journal of Tissue Engineering Research 2017;21(29):4691-4696
BACKGROUND:It has been reported that 70% of patients with chronic myeloid leukemia (CML) are negative for cytogenetic and genetic markers within 1-5 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT),but there are still some patients who have repeatedly varied outcomes in cytogenetic and genetic marker detection.Overall,the negative rate is up to 89.5% at 3-12 months after allo-HSCT.OBJECTIVE:To monitor the changes in cytogenetic and genetic marker expression and to explore the prognostic significance in CML patients undergoing allo-HSCT.METHODS:Seventeen CML patients who had undergone allo-HSCT were enrolled.Chromosome G banding pattern of the bone marrow from these patients were analyzed using short-term culture method and direct method at 30 days,2,3,4,6,12,24,36,48,60,72 months after allo-HSCT.Dual-color fluorescence in situ hybridization was used to detect bcr-abl fusion gene;bcr-abl expressions in primary bone marrow ceils from CML patients were detected using RQ-PCR.Results and conclusion:There were 8/17 cases of male patient/male donor and 7/17cases of male patient/female donor (compatriots).46XX karyotype (women) was detected by multiple reexaminations after transplantation,and there was no Y chromosome or other aberration of chromosome karyotype in their karyotype.Among the 17 cases,1 case of female patient/female donor (compatriots) and 1 case of female patient/male donor (unrelated) manifested 46 XY chromosome karyotype and bcr-abl positive at 1 month after transplantation;after 4 months,these two cases still maintained 46 XY chromosome karyotype but bcr-abl negative;after 4-96 months,the karyotype continued to remain as 46 XY,and bcr-abl (-).Among the 17 cases,1 case of male patient/male donor of full-matched compatriot (brother) manifested that Ph chromosomal bcr-abl gene continuously expressed within 1-12 months after allo-HSCT;then the cases was given donor lymphocyte infusion,and the bcr-abl expression returned to be negative at 48 months after transplantation.To conclude,chromosomal karyotype analysis and bcr-abl fusion gene monitoring provide important reference value for subsequent treatment options and prognosis judgment for CML patients with allo-HSCT.
5.Gene chip technology for detecting mycobacteria and Mycobacterium tuberculosis resistance of isoniazid and rifampin in the application of tuberculous empyema
Xiu-Hua LIN ; Guo-Xiang LAI ; Yu-Yan CHEN ; Dan ZHENG ; Yin-Fa ZHOU ; Xiao-Hong CHEN
Chinese Journal of Zoonoses 2017;33(8):720-723,729
To evaluate the clinical value of gene chip technology (GCT) in detecting the mycoba-cteria,isoniazid and rifampin resistance of patients diagnosed tuberculous empyema.The 182 patients who met the inclusion criteria were enrolled to this study from January 2011 to December 2015,whose pus mycobacterial species were detected by GCT and MGIT,the simultaneous and sensitivity of them were compared.Meanwhile,36 patients diagnosed tuberculous empyema were selected to detect isoniazid and rifampin resistance.The simultaneous and sensitivity of GCT were evaluated base on the standard of MGIT.The 135 patients were diagnosed by tuberculous empyema.The specificity of GCT was same to MGIT (95.7%),the the sensitivity was 48.9% (66/135)in GCT,26.7% in MGIT,there was significant difference between them (x2=80.5,P< 0.05).The sensitivity,specificity and coincidence rate of GCT in rifampin resistance were 100%,the sensitivity,specificityand coincidence rate in INH were 50.0%(1/2),97.1%(33/34) and 94.4%.Gene chip technology for detection of mycobacteria has high sensitivity and specificity,which can identify non-tuberculous mycobacteria quickly.And it can also effectively detect the resistance of Mycobacterium tuberculosis to isoniazid and rifampicin.It has important significance in early diagnosis and treatment of tuberculous empyema.
6. ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients
Bin WANG ; Li-Hua HUANG ; Man WEI ; Hua FANG ; Dan-Yang WANG ; Mei XIANG ; Ji-Xue ZHAO ; Hong-Fa WANG ; Ji-Gang YIN
Asian Pacific Journal of Tropical Biomedicine 2015;5(11):909-914
Objective: To investigate the azole susceptibility of Candida albicans ( C. albicans) from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance. Methods: Three hundred and two clinical isolates of Candida species were collected. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans (2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced. Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and 4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total, 27 missense mutations were detected in ERG11 genes from resistant/susceptible dose-dependent isolates. Among them, Y132H, A114S, and Y257H substitutions were most prevalent and were known to cause fluconazole resistance. G464S and F72S also have been proved to cause fluconazole resistance. Two novel substitutions (T285A, S457P) in hotspot regions were identified. Conclusions: Twenty seven mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions (T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis.
7.Treatment of varicocele infertility men patients of different Chinese medical syndrome types by integrative medicine treatment selection: a primary research.
Kai NI ; Bin CHEN ; He LI ; Hong-Xiang WANG ; Hao YANG ; Kai HU ; Yin-Fa HAN ; Yi-Xin WANG ; Yi-Ran HUANG
Chinese Journal of Integrated Traditional and Western Medicine 2013;33(3):326-331
OBJECTIVETo explore the optimal treatment selection for treating varicocele (VC) male infertility patients accompanied with oligozoospermia or azoospermia of different Chinese medical syndrome types by comparing the efficacies of integrative medicine.
METHODSOne hundred and twenty male infertility patients with VC accompanied with oligozoospermia or azoospermia were assigned to Chinese medical treatment group (A) and the surgical group (B), each consisting of three Chinese medical syndrome types, i.e., damp-heat stagnation syndrome (DHSS), Shen-deficiency blood stasis syndrome (SDBSS), and blood stasis stagnation syndrome (BSSS), 20 in each group. Corresponding Chinese medical treatment was administered to those in Group A, C, and E, while microscopic ligation of internal vena spermatic was administered to those in Group B, D, and F. The routine analysis of semen, biochemical analysis of seminal plasma, and serum sex hormones (prolactin, testosterone, follicle stimulating hormone, luteinizing hormone, and estradiol) were performed before treatment and by the end of the 24th week after treatment.
RESULTSTotally 18 patients' spouses were pregnant. Of them, 1 in Group A of DHSS (abbreviated as Group A), 3 in Group B of DHSS (abbreviated as Group B), 4 in Group A of SDB-SS (abbreviated as Group C), 5 in Group A of SDBSS (abbreviated as Group D), 1 in Group A of BSSS (abbreviated as Group E), and 4 in Group B of BSSS (abbreviated as Group F). After 24-week treatment, the sperm concentration, class a sperm percentage, class a + b sperm percentage, the motility rate, the seminal plasma of fructose density, and the seminal plasma neutral alpha-glucosidase were more significantly improved in Group B, C, D and F, when compared with the same group before treatment (P <0. 01, P <0. 05). There was no statistical difference in the aforesaid indices between before and after treatment in Group A and Group E (P >0.05). As for the improvement percentage of seminal routine indices, the difference of the seminal plasma of fructose density, and the difference of seminal plasma neutral alpha-glucosidase between before and after treatment in the same Chinese medical syndrome types, better effects were obtained in Group B than in Group A (P <0.01), and better effects were obtained in Group F than in Group E (P <0.01). There was no statistical difference between Group C and D (P >0.05). There was no statistical difference in the 5 items of sex hormones in each group between before and after treatment (P >0.05).
CONCLUSIONSSurgical treatment could effectively improve the semen quality for male infertility VC patients accompanied with oligozoospermia or azoospermia. Of them, Chinese medical treatment could be recommended to those of SDBSS who would not receive surgical treatment.
Adult ; Humans ; Infertility, Male ; diagnosis ; etiology ; therapy ; Integrative Medicine ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Varicocele ; complications ; diagnosis ; therapy
8.Sexual function inspection room for special penile insertion disorder.
Hong-Xiang WANG ; Bin CHEN ; Chen HUANG ; Yin-Fa HAN ; Yi-Xin WANG ; Yi-Ran HUANG
National Journal of Andrology 2012;18(3):284-287
OBJECTIVETo determine the role of the sexual function inspection room in the treatment of patients with special penile insertion disorder.
METHODSThis study included 6 couples received at the Andrology Clinic of Shanghai Renji Hospital from September, 2010 to February, 2011, who complained of being unable to accomplish sexual intercourse, all due to the husbands' abnormal penile erection. The couples had tried to make love 3 to 6 times after getting married, but never succeeded. Consequently the wives were planning to divorce, unwilling to attempt sexual activity again. We performed examinations and sexual education for the patients in the sexual function inspection room of Shanghai Institute of Andrology. The inspection room consisted of an inner and an outer section separated by a one-way transparent glass, through which what happened in the outer section could be observed from the inner section. The husband was given 20 mg of tadalafil to induce penile erection, followed by Doppler ultrasonographic determination of penile hemodynamics. Meanwhile, the wife was allowed to observe her husband's penile erection through the glass to get sensory stimuli and relieve the mental burden. In the end, the doctor advised the couple to try sexual intercourse.
RESULTSIn nature, the 6 wives were all impatient, while their husbands were all introverted. Doppler ultrasonography displayed normal penile hemodynamics. After sensory stimulation, the wives gained confidence in their husbands' erectile function. A one month follow-up visit showed that all the 6 couples could perform sexual intercourse normally.
CONCLUSIONThis sexual function inspection room can help doctors and wives to observe the status of the patient's penile erection, and meanwhile disburden the mind of the wives by giving them sensory stimuli, which contributes much to successful attempt at sexual intercourse.
Coitus ; physiology ; Erectile Dysfunction ; diagnosis ; Health Facilities ; Humans ; Male
9.Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China.
Yue-Yun LAI ; Xiao-Jun HUANG ; Zhen CAI ; Xiang-Shan CAO ; Fang-Ping CHEN ; Xie-Qun CHEN ; Bao-An CHEN ; Mei-Yun FANG ; Jia-Fu FENG ; Wei-Ling FU ; Hai-Ying GUO ; Ming HOU ; Jian HOU ; Yu HU ; Xiao-Tong HU ; Xiao-Mei HU ; Li-Qiang HUANG ; Jie JIN ; Jian-Yong LI ; Juan LI ; Wei LI ; Ying-Min LIANG ; Ting LIU ; Qi-Fa LIU ; Yan-Hui LIU ; Ping MAO ; Jian OUYANG ; Lu-Gui QIU ; Lin QIU ; Chun-Kui SHAO ; Bin SHI ; Yong-Ping SONG ; Zi-Min SUN ; Qi-Shan WANG ; Chun WANG ; Jian-Ming WANG ; Yun-Shan WANG ; Zhao WANG ; Jian-Bo WU ; Yin-Xia WU ; Rui-Xiang XIA ; Yong-Quan XUE ; Bao-Zhen YANG ; Guang YANG ; Zheng-Lin YANG ; Li YU ; Zhong YUAN ; Sheng ZHANG ; Yin ZHANG ; Hong-Guo ZHAO ; Li ZHAO ; Dao-Bin ZHOU ; Shan-Hua ZOU ; Yun-Feng ZHU
Chinese Medical Journal 2012;125(15):2663-2670
BACKGROUNDChromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.
METHODSAll 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.
RESULTSThe analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.
CONCLUSIONSChinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.
Adult ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; genetics ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; pathology
10.Epidemiologic analysis on severe fever with thrombocytopenia syndrome in Hubei province, 2010
Li LIU ; Xu-Hua GUAN ; Xue-Sen XING ; Xing-Fu SHEN ; Jun-Qiang XU ; Jin-Liang YUE ; Xi-Xiang HUO ; Sha SHA ; Hai-Xiang WU ; Jing HUANG ; Wei JIANG ; Fan DING ; Hang ZHOU ; Wen-Wu YIN ; Qun LI ; Mi-Fang LIANG ; Fa-Xian ZHAN
Chinese Journal of Epidemiology 2012;33(2):168-172
Objective To identify the epidemic characteristics and risk factors of an emerging infectious disease-severe fever with thrombocytopenia syndrome (SFTS) in Hubei province.Methods Active surveillance program on SFTS was set up in monitoring sites-hospitals,at the township level or above,in Suizhou,Huanggang and Wuhan from January to December,2010.Specific surveillance program on SFTS was launched across the province in hospitals above the county level.Cases that matched the definition of surveillance case were identified and reported to Centers for Disease Control and Prevention (CDCs).Cases were interviewed and their blood samples collected and detected using PCR and virus isolation.We also conducted serum antibody surveys among healthy population and livestock and surveillance on vector ticks in those high-epidemic areas.Results 188 cases that matched the definition of surveillance case and 21 deaths were reported in 11 cities,32 countries and 100 towns in 2010,with an incidence rate of 0.33/106.The fatality rate was 11.2%.Data showed that the patients were from hilly areas at the altitude elevated between 28-940 meters.The epidemic period was between April and December with the peak from May to September.The youngest case was an 11-year old,while the eldest was 81 with median age as 56-year old.95.3 % of the patients were farmers.All Patients did not have the history of traveling,two weeks before the onset of SFTS.93.6% of the patients engaged in different kind of work which was associated with agriculture.52.8% of the patients had been exposed to ticks.22.0% of the patients had been bitten by ticks.Skin injury was found in 64.2% of the patients.Samples from 129 cases (68.6%) were collected and detected,with 67.4% of them (87 cases) showed positive by Real time-PCR for SFTS virus.An elevation in antibody titer by a factor of four or evidence of sero-conversion was observed in 11 patients; SFTS virus was isolated from 2 patients.The total antibody positive rates were 3.8%,55.0% (6/11 ),36.7% (2/3) and 80.0% (4/5) respectively in healthy population,dogs,sheep and cows.Ticks from grass,cattle and sheep were detected positive by Real time-PCR.Conclusion Most cases of SFTS in Hubei were infected by SFTS virus,and cases of livestock were infected by SFTS virus.Ticks might serve as an important vector.Skin injury,exposure to tick bites seemed to be the risk factors.

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