1.Reversal of trastuzumab resistance in gastric cancer cells by targeting GPRC5A with miR-195-5p
Xianjun ZHU ; Danni ZHANG ; Xijun LUO ; Junjie LIANG ; Tao LI ; Xingkui TANG ; Jialin HE ; Wei LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):929-934
AIM:To explore the role of miR-195-5p in mediating trastuzumab resistance in gastric cancer and to validate its potential as a therapeutic target along with its target gene GPRC5A.METH-ODS:Trastuzumab-resistant gastric cancer cell lines(NCI-N87 and MKN45)were established.Cell viabili-ty under trastuzumab treatment was assessed us-ing CCK-8 assays.Expression levels of miR-195-5p were determined by RT-qPCR.Transfection with miR-195-5p mimics was performed to evaluate changes in trastuzumab sensitivity and prolifera-tion.GPRC5A expression was also measured by RT-qPCR,and the targeting relationship between miR-195-5p and GPRC5A was confirmed using a dual-lu-ciferase reporter assay.RESULTS:Parental cells showed higher sensitivity to trastuzumab than re-sistant cells,with miR-195-5p expression signifi-cantly lower in the latter.Overexpression of miR-195-5p in resistant cells enhanced trastuzumab sen-sitivity and reduced proliferation.GPRC5A was found to be upregulated in resistant cells,and miR-195-5p directly targeted GPRC5A,affecting cell pro-liferation under trastuzumab treatment.CONCLU-SION:miR-195-5p may regulate trastuzumab sensi-tivity in gastric cancer by targeting GPRC5A,sug-gesting potential as a molecular marker for trastu-zumab therapy guidance.
2.Reversal of trastuzumab resistance in gastric cancer cells by targeting GPRC5A with miR-195-5p
Xianjun ZHU ; Danni ZHANG ; Xijun LUO ; Junjie LIANG ; Tao LI ; Xingkui TANG ; Jialin HE ; Wei LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(7):929-934
AIM:To explore the role of miR-195-5p in mediating trastuzumab resistance in gastric cancer and to validate its potential as a therapeutic target along with its target gene GPRC5A.METH-ODS:Trastuzumab-resistant gastric cancer cell lines(NCI-N87 and MKN45)were established.Cell viabili-ty under trastuzumab treatment was assessed us-ing CCK-8 assays.Expression levels of miR-195-5p were determined by RT-qPCR.Transfection with miR-195-5p mimics was performed to evaluate changes in trastuzumab sensitivity and prolifera-tion.GPRC5A expression was also measured by RT-qPCR,and the targeting relationship between miR-195-5p and GPRC5A was confirmed using a dual-lu-ciferase reporter assay.RESULTS:Parental cells showed higher sensitivity to trastuzumab than re-sistant cells,with miR-195-5p expression signifi-cantly lower in the latter.Overexpression of miR-195-5p in resistant cells enhanced trastuzumab sen-sitivity and reduced proliferation.GPRC5A was found to be upregulated in resistant cells,and miR-195-5p directly targeted GPRC5A,affecting cell pro-liferation under trastuzumab treatment.CONCLU-SION:miR-195-5p may regulate trastuzumab sensi-tivity in gastric cancer by targeting GPRC5A,sug-gesting potential as a molecular marker for trastu-zumab therapy guidance.
3.Layer-specific strain assessment of left ventricular systolic function in patients with bicuspid aortic valve
Xijun ZHANG ; Haohui ZHU ; Zhenhua WANG ; Changhua WEI ; Shuaiwei LUO ; Limin ZHU ; Jianjun YUAN
Chinese Journal of Ultrasonography 2019;28(1):21-26
Objective To quantitatively evaluate left ventricular ( LV ) systolic function in bicuspid aortic valve (BAV) using layer-specific strain ( LSS) . Methods Thirty BAV patients were divided into normal function (NF) group (10 cases) and non-normal function (N-NF) group (20 cases) based on aortic valvular lesion types ,and 20 healthy volunteers were taken as control group . Longitudinal strain( LS) and circumferential strain (CS) of three-layer myocardium and full thickness myocardium were assessed using layer-specific speckletracking imaging ,available by GE Vivid E9 and EchoPac workstation . Results There was no significant difference in left ventricular ejection fraction( LVEF) among the N-NF group ,NF group and control group ( P > 0 .05) ,all of them within the normal range[(63 .3 ± 7 .1)% ,(64 .6 ± 6 .2)% , ( 65 .3 ± 3 .9)% ] . It showed a gradient decrease from the endocardium to the epicardium in both control and BAV group . LS of endocardium ( LSendo) and LS of epicardium ( LSepi) in N-NF group and NF group were significantly reduced compared with those in control group ( P <0 .05) [ LSendo :( -21 .19 ± 3 .12)%vs ( -23 .06 ± 2 .07 )% vs ( -25 .53 ± 2 .51 )% ;LSepi:( -16 .08 ± 2 .68 )% vs ( -18 .85 ± 2 .12 )% vs ( -20 .72 ± 2 .28)% ] . Compared with control group ,there was no significant difference in NF group in CS of the three-layer myocardial and full-thickness myocardium as well as the LS of the whole medial myocardial layers and full-thickness ( P > 0 .05 ) . Compared with NF group [ CS :( -19 .57 ± 2 .9 )% vs ( -13 .43 ± 2 .19)% vs ( -20 .03 ± 3 .04)% ;LS :( -21 .38 ± 2 .05)% vs ( -18 .85 ± 2 .12)% vs ( -21 .09 ± 2 .03)% ] and control group[CS :( -21 .63 ± 3 .01)% vs ( -14 .34 ± 2 .55)% vs ( -21 .48 ± 2 .16)% ;LS :( -22 .18 ± 2 .30 )% vs ( -20 .72 ± 2 .28 )% vs ( -22 .89 ± 2 .30 )% ] , CS [ ( -16 .78 ± 3 .65 )% vs ( -11 .40 ± 3 .78 )% vs ( -15 .83 ± 2 .61 )% ] and LS [ ( -18 .34 ± 2 .85 )% vs ( -16 .08 ± 2 .68 )% vs ( -18 .51 ± 2 .86)% ] of middle myocardium ,epicardial myocardium and full-thickness myocardium in N-NF group were decreased significantly ( P < 0 .05) . Conclusions It is essential to maintain normal valvular function to prevent the progress of myocardial deterioration . LSendo and LSepi can be used to sensitively identify early left ventricular systolic dysfunction in BAV patients with normal LVEF .
4.The effect of 8-OH-DPAT and dapoxetine on gene expression in the brain of male rats during ejaculation.
Xijun QIN ; Xiaojun MA ; Dongping TU ; Zuliang LUO ; Jie HUANG ; Changming MO
Acta Pharmaceutica Sinica B 2017;7(3):381-389
The 5-HTreceptor agonist 8-hydroxy-2-[di--propylamino] tetralin (8-OH-DPAT) promotes ejaculation of male rats, whereas dapoxetine delays this process. However, the gene expression profile of the brain at ejaculation following administrationof these two compounds has not been fully elucidated. In the present study, a transcriptomic BodyMap was generated by conducting mRNA-Seq on brain samples of male Sprague-Dawley rats. The study included four groups: pre-copulatory control (CK) group, ejaculation (EJ) group, 0.5 mg/kg 8-OH-DPAT-ejaculation group (DPAT), and 60 mg/kg dapoxetine-ejaculation (DAP) group. The resulting analysis generated an average of approximately 47 million sequence reads. Significant differences in the gene expression profiles of the aforementioned groups were observed in the EJ (257 genes), DPAT (349 genes) and the DAP (207 genes) compared with the control rats. The results indicate that the expression ofandwas significantly different after treatment with 8-OH-DPAT, whereas the expression ofwas significantly different after treatment with dapoxetine. Other genes, such as,and, exhibited significant differences in expression after the two treatments and are related to bladder cancer, renal cell carcinoma and sexual addiction. The present study reveals the basic pattern of gene expression that was activated at ejaculation in the presence of 8-OH-DPAT or dapoxetine, providing preliminary gene expression information during rat ejaculation.
5.Cloning, expression and antiviral activity of arctic fox (Alopex lagopus) interferon-gamma gene.
Hailing ZHANG ; Xiuli CHAI ; Guoliang LUO ; Fengxue WANG ; Li YI ; Xiqun SHAO ; Xijun YAN
Chinese Journal of Biotechnology 2008;24(9):1625-1630
In order to characterize the biological activity of fox (Vulpes vulpes) interferon gamma(VuIFN-gamma), We have isolated the cDNA encoding arctic fox (Alopex lagopus) VuIFN-gamma. This cDNA encodes a 23 amino acid signal peptide and a 144 amino acid mature protein, which shares 99.8% or 99.4% for nucleotide identity with silver fox and canine, respectively, and 100% for amino acid identity. Expression of recombinant mature arctic fox interferon gamma (mVuIFN-gamma) in bacterial system was confirmed by SDS-PAGE and Western blotting analysis. Recombinant VuIFN-gamma showed higher antiviral activity against vesicular stomatitis virus in cultured Vero and MDCK by inhibiting virus induced cytopathic effect, In view of the immunomodulatory and antiviral activities of VuIFN-gamma, it may provide a basis for further research on antiviral therapy of recombinant VuIFN-gamma in economic animal practice.
Animals
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Antiviral Agents
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pharmacology
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Base Sequence
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Cloning, Molecular
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Escherichia coli
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genetics
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metabolism
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Foxes
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genetics
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Interferon-gamma
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genetics
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pharmacology
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Molecular Sequence Data
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Recombinant Fusion Proteins
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genetics
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pharmacology
6.Effect of Kechuanning on Adjusting Cytokine in Children with Virus-induced Asthma
Mengqing WANG ; Yinghe LUO ; Xijun CHEN ; Ye ZHU ; Keli LIU ; Feijun MO ; Lan SHU ;
China Journal of Traditional Chinese Medicine and Pharmacy 2005;0(07):-
Objective:To observe the effect of Kechuanning on Th cytokine expression in pediatric virus-induced asthma.Methods:120 cases of pediatric virus-induced asthma were randomly divided into Kechuanning group(treatment group,n =60,treated with Kechuanning) and Western medicine group(control group,n=60,treated with virazole).The change of Th1 cytokine IL-12 and Th2 cytokine IL-4 in blood serum were detected and analyzed.Results:Kechuanning could increase IL-12 but decrease IL-4 level in the patient's blood,therefore regulate Th cell subset,and the effect was more obvious than in control group.Conclusion:The mechanism of Kechuanning in curing pediatrics asthma induced by virus was related with increasing IL-12 and decreasing IL-4 level.
7.Randomized Controlled Trial for the Effect of Amrinone and Aprotinin on Proinflammatory Cytokine Release in Patients with Prosthetic Valve Replacement during Perioperative Period
Xijun XIAO ; Chaozhi LUO ; Xiang ZHUANG ; Defu YIN ; Yongxiang CHEN ; Ge CAO ; Xuzhong HUANG ; Zipu TIAN ; Yingkang SHI
Journal of Sichuan University (Medical Sciences) 2001;32(2):291-293
Objective To explore the effect of amrinone and aprotinin on whole-body inflammatory response in the patients with prosthetic valve replacement during perioperative period. Methods 24 patients undergoing prosthetic valve replacment were randomized to control group (group A, n=8) , aprotinin group (group B, n=8) and amrinone combined with aprotinin group (group C, n=8). In the aprotinin group, 3×106 of aprotinin was added to the priming solution of the extracorporeal circulation (ECC). In the amrinone combined with aprotinin group 3×106 of aprotinin was added to the priming solution of the ECC and amrinone began with a bolus of 1mg/kg followed by a maintenance infusion of 8μg/(kg*min). The control group received an equivalent prime volume without aprotinin. Venous blood samples were drawn before the operation, at the end of ECC, 1 hour after the end of ECC, and one day after the operation respectively. Enzyme-linked immunosorbent assay techniques were used to measure each of the cytokines. Results Before ECC, there were no differences of the levels of IL-6 and IL-8 among groups (P>0.05). After ECC, the levels of IL-6 and IL-8 increased significantly in all groups (P<0.05). The levels on day one after the operation were still higher than those before the operation in all groups (except the level of IL-8 in group C), but no statistical significance was observed. (P>0.05). At 1 hour after the end of ECC, the level of IL-6 in group B was lower than that in group A, and the level of IL-6 in group C was lower than that in group B, but there was no statistically significant difference (P>0.05);At the end of ECC, the level of IL-8 in group B was lower than that in group A and the level of IL-8 in group C was lower than that in group B, but no significant difference was noted (P>0.05). It was also observed that the level of IL-8 was lower in group C than group A or B at 1 hour after the end of ECC. Conclusion Although amrinone and aprotinin have antiinflammatory activity, but pump prime only aprotinin or aprotinin combined with amrinone may fail in preventing proinflammatory cytokine release (IL-6, IL-8) completely in patients with prosthetic valve replacement during ECC perioperative period.

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