1.BRD4 regulates m6A of ESPL1 mRNA via interaction with ALKBH5 to modulate breast cancer progression.
Haisheng ZHANG ; Linlin LU ; Cheng YI ; Tao JIANG ; Yunqing LU ; Xianyuan YANG ; Ke ZHONG ; Jiawang ZHOU ; Jiexin LI ; Guoyou XIE ; Zhuojia CHEN ; Zongpei JIANG ; Gholamreza ASADIKARAM ; Yanxi PENG ; Dan ZHOU ; Hongsheng WANG
Acta Pharmaceutica Sinica B 2025;15(3):1552-1570
The interaction between m6A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m6A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m6A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.
2.Correlation study of rights & interests maintenance and occupational stress in nurses
Wenyuan XU ; Xianyuan JIANG ; Xinhong YIN
Chinese Journal of Modern Nursing 2016;22(31):4522-4525
Objective To investigate the current situation of clinical nurses′ rights & interests maintenance and occupational stress in Hengyang, and explore the relationship between nurses′rights&interests maintenance and occupational stress.Methods Totally 690 nurses from ten secondary and tertiary hospitals in Hengyang were surveyed during August and September 2015 by general information questionnaires, nurses′rights & interests maintenance questionnaire and nurses occupational stress scale.Results The scores of nurses′rights & interests maintenance and nurses′occupational stress were (3.47±0.67), (3.21±0.95). The score and dimension scores of nurses′rights&interests maintenance were negative correlated with the total score and factor scores of nurses′occupational stress (r=-0.263- -0.425,P< 0.01). Job stress, one child or not, age, role adaptation, monthly income were indicated as predictive factors of rights & interests maintenance of nurses. Conclusions Rights & interests maintenance and occupational stress of nurses has a significant correlation, therefore, the medical and health institutions should further implement relevant laws and regulations; protect rights and interests of nurses from different aspects to reduce occupational stress;and stabilize the nursing team and promote development of nursing career.
3.The effects of selected decontamination of the digestive tract on endotoxemia and inflammation mediator of patients undergoing cardiopulmonary bypass
Jiang YU ; Yingbin XIAO ; Xianyuan WANG
Journal of Chinese Physician 2001;0(02):-
Objective To evaluate the effects of selected decontamination of the digestive tract(SDD) on intestinal derived endotoxmia,inflammation mediator and clinical outcome in patients of rheumatic heart disease undergoing valve replacement operation with cardiopulmonary bypass(CPB).Methods Thirty patients with CPB were randomly divided into control group(n=15) and treatment group(SDD group,n=15).The patients in control group routinely took preoperative preparation while those in treatment group orally administrated Tobramycin 100 mg,garlicin 40 mg and Lactulose 10ml three times per day in addition to routinely preoperative bowel preparation.The levels of endotoxin,D-lactate,TNF-? and complement 3 were measured at four time points of anesthetic induction,CPB end,2 h and 24 h after CPB.Results The level of D-lactate in the patients of SDD group was significantly lower than that of the control group at time points of anesthetic induction and 2 h after CPB(P0.05).Conclusion The endotoxemia can be induced by CPB.The regime of SDD is an effective way of preventing endotoxemia,but it may not have effect on inflammation medium and clinical outcome.
4.The antagonistic effect of zinc on hepatic ischemia-reperfusion injury and the mechanism
Yugang JIANG ; Xianyuan WANG ; Changjiang GUO ; Jingyu WEI ; Lanxing GAO
Chinese Journal of Pathophysiology 1986;0(02):-
AIM: To investigate the antagonistic effect of zinc on hepatic ischemia- reperfusion (HIR) injury and the effect of zinc on the expression of adhesion molecules in rat liver to clarify the mechanisms involved. METHODS: After zinc supplementation (5 ?mol/kg bw,po) , the changes in hepatocellular morphology,ALT and AST activities in serum,MDA levels in serum,and expression of ICAM-1,VCAM-1 in liver of the animals subjected to HIR were examined. RESULTS: The results showed that HIR (30 minutes of ischemia followed by 90 minutes of reperfusion) significantly increased ALT, AST activities and MDA levels in serum. The destruction of hepatic structure was observed in HIR rats. In the mean time, the expression of adhesion molecule was enhanced.After zinc administration, ALT and AST activities in serum and MDA levels in serum were all decreased. The structure of hepatocyte was nearly normal.The further experiment showed that adhesion molecule expression was suppressed.CONCLUSION: These results indicate that zinc may protect liver against ischemia-reperfusion injury by inhibiting the production of free radicals and the expression of adhesion molecule.

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