1.VIRMA-mediated SHQ1 m6A modification enhances liver regeneration through an HNRNPA2B1-dependent mechanism.
Hao CHEN ; Haichuan WANG ; Jiwei HUANG ; Guoteng QIU ; Zheng ZHANG ; Lin XU ; Xiao MA ; Zhen WANG ; Xiangzheng CHEN ; Yong ZENG
Acta Pharmaceutica Sinica B 2025;15(10):5212-5230
N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl4) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.
2.Effects of non-invasive bi-level pressure triggering on oxygenation index, partial pressure of oxygen and utilization rate of mechanical ventilation in premature infants with respiratory distress syndrome
Haichuan HUANG ; Dier HUANG ; Pingxuan MA
Chinese Journal of Postgraduates of Medicine 2021;44(3):269-273
Objective:To compare the effects of non-invasive bi-level pressure triggering (BiPhasic tr) on oxygenation index (OI), partial pressure of oxygen and utilization rate of mechanical ventilation in premature infants with respiratory distress syndrome (RDS).Methods:The clinical data of 100 premature infants with RDS in Shantou Dafeng Hospital of Guangdong Province from March 2018 to May 2019 were retrospectively analyzed. Among them, 56 cases treated with nasal continuous positive airway pressure (nCPAP) were enrolled as control group, and 44 cases treated with BiPhasic tr were as observation group. The OI, arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) before and after respiratory support, duration of auxiliary ventilation, utilization rate of mechanical ventilation and incidence of complication were compared between 2 groups. Results:There were no statistical difference in PaO 2, PaCO 2 and OI before respiratory support between 2 groups ( P>0.05); the PaO 2, PaCO 2 and OI 1, 6, 12 and 24 h after respiratory support in 2 groups were significantly improved compared with those before respiratory support, and the improvement degree in observation group were significantly better than those in control group, and there were statistical differences ( P<0.05). The duration of auxiliary ventilation, utilization rate of mechanical ventilation, incidence of complication in observation group were significantly lower than those in control group: (52.41 ± 16.53) h vs. (57.42 ± 17.82) h, 11.36% (5/44) vs. 19.64% (11/56) and 15.91% (7/44) vs. 33.93% (19/56), and there were statistical differences ( P<0.05). Conclusions:BiPhasic tr can effectively improve the oxygenation state, reduce the use rate of mechanical ventilation and carbon dioxide retention, reduce the incidence of complications such as intraventricular hemorrhage and so on in the treatment of RDS premature infants.
3.Comparison of the value of MRS and MRI in diagnosis of primary epilepsy with hippocampal lesions
Xuejun LIU ; Haichuan MA ; Guang LI
Chinese Journal of Primary Medicine and Pharmacy 2015;(14):2111-2114
Objective To discuss Magnetic Resonance Spectroscopy(MRS) on the localization diagnosis of primary epilepsy patients with hippocampal lesions before operation.Methods 50 patients with idiopathic epilepsy (epilepsy group) and 32 healthy volunteers (healthy control group) were underwent Magnetic Resonance Imaging ( MRI) and MRS examination.Results ( 1 ) MRI showed that results of examination in the healthy control group were all normal.Epilepsy group of 38 cases were found abnormal in hippocampal area,and all patients were unilateral. 27 cases of them reduced with hippocampal volume, while signal abnormality was in 7 cases, 4 cases occurred simultaneously reduced with hippocampal volume,and therer was no obvious abnormal signals in 12 cases of patients with epilepsy of hippocampus volume and signal.( 2 ) MRS examination results:the healthy control group MRS were normal.50 epileptic patients in group MRS showed that hippocampal abnormalities.The epilepsy group NAA/( Cho+Cr) ,NAA/Cho,NAA/Cr were significantly lower than those of the healthy control group;epilepsy group disease side hippocampus NAA/(Cho+Cr),NAA/Cho,NAA/Cr values have different degrees of reduction,compared with the contralateral side,the value of t were 12.716,9.155,17.476,all P<0.01.(3)50 cases of epilepsy patients in the epilepsy group disease side compared with the contralateral side,the side of hippocampus NAA/disease ( Cho+Cr) , NAA/Cho,NAA/Cr values were decreased,the test values of t were 7.295,6.303,2.761,all P<0.01.(4)50 cases of operation patients underwent postoperative pathological examination of resected tissue,resection of neurons,tissue showed different degrees of reduction,microglia proliferation and neuronophagia phenomenon.Comparison of the posi-tive rate of MRS and MRI examination,χ2 =13.636,P<0.01.Conclusion Magnetic resonance spectroscopy analy-sis can play the important role in the evaluation of epilepsy surgery preoperative epilepsy,MRS examination for preop-erative diagnosis positive rate is high,the localization diagnosis with high reliability.

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