Prognostic, Immunological, and Mutational Analysis of MTA2 in Pan-Cancer and Drug Screening for Hepatocellular Carcinoma.

BACKGROUND: Metastasis-associated protein 2 (MTA2) is a member of the metastasis-associated transcriptional regulator family and is a core component of the nucleosome remodeling and histone deacetylation complex. Despite growing evidence that MTA2 plays a crucial role in the tumorigenesis of certain cancers, no systematic pan-cancer analysis of MTA2 is available to date. Therefore, the aim of our study is to explore the prognostic value of MTA2 in 33 cancer types and to investigate its potential immune function. METHODS: by comprehensive use of databases from TCGA, GTEx, GEO, UCSC xena, cBioPortal, comPPI, GeneMANIA, TCIA, MSigDB, and PDB, we applied various bioinformatics approaches to investigate the potential role of MTA2, including analyzing the association of MTA2 with MSI, prognosis, gene mutation, and immune cell infiltration in different tumors. We constructed a nomogram in TCGA-LIHC, performed single-cell sequencing (scRNA-seq) analysis of MTA2 in hepatocellular carcinoma (HCC), and screened drugs for the treatment of HCC. Finally, immunohistochemical experiments were performed to verify the expression and prognostic value of MTA2 in HCC. In vitro experiments were employed to observe the growth inhibition effects of MK-886 on the HCC cell line HepG2. RESULTS: The results suggested that MTA2 was highly expressed in most cancers, and MTA2 expression was associated with the prognosis of different cancers. In addition, MTA2 expression was associated with Tumor Mutation Burden (TMB) in 12 cancer types and MSI in 8 cancer types. Immunoassays indicated that MTA2 positively correlated with activated memory CD4 T cells and M0 macrophage infiltration levels in HCC. ScRNA-seq analysis based on the GEO dataset discovered that MTA2 was significantly expressed in T cells in HCC. Finally, the eXtreme Sum (Xsum) algorithm was used to screen the antitumor drug MK-886, and the molecular docking technique was utilized to reveal the binding capacity between MK-886 and the MTA2 protein. The results demonstrated excellent binding sites between them, which bind to each other through Π-alkyl and alkyl interaction forces. An immunohistochemistry experiment showed that MTA2 protein was highly expressed in HCC, and high MTA2 expression was associated with poor survival in HCC patients. MK-886 significantly inhibited the proliferation and induced cell death of HepG2 cells in a dose-dependent manner. CONCLUSIONS: Our study demonstrated that MTA2 plays crucial roles in tumor progression and tumor immunity, and it could be used as a prognostic marker for various malignancies. MK-886 might be a powerful drug for HCC.

[Effect of berberin hydrochloride on blood concentration of cyclosporine A in cardiac transplanted recipients].

OBJECTIVE: To observe the clinic effect of combined use of berberin hydrochloride (Ber) with cyclosporine A (CsA) on the blood concentration of CsA in heart transplanted recipients. METHODS: The blood concentration of CsA, liver-renal function and blood lipids in 22 heart transplanted recipients, who received Ber-CsA combined therapy, were measured. RESULTS: The whole blood steady state concentration of CsA, C0 and C2, in recipients after being treated with Ber-CsA significantly increased than those before applying Ber-CsA (P < 0.01), with the mean increment of 26% and 18% respectively; the dosage of CsA used decreased in 21 patients by 25-100 mg/d; and the Ber-CsA showed no significant effect on liver-renal function or blood lipids (P > 0.05). CONCLUSION: Combined use of CsA with Ber could markedly increase the blood concentration of CsA in heart transplanted recipients and reduce the dosage of CsA required, save the fee for medical service, and shows no obvious adverse reaction.

[Effect of Ginkgo biloba extract preconditioning on discordant cardiac xenografts].

OBJECTIVE: To investigate the effect of ginkgo biloba extract (ginaton) preconditioning on discordant cardiac xenografts from guinea pig to rat, and explore its mechanism. METHODS: Cervical cardiac transplantation model was established in the rats,which were divided into 4 groups Group 1 (cobra venom factor ( CVF) pretreatment, n = 10]; Group 2 (CVF + ginaton, n = 5) ; Group 3 Ccyclosporine (CsA); Group 4 (CVF + CsA + ginaton, n = 8]. The survival time and histopathology after xenograft were observed and expressions of intercellular adhesion molecule-1 (ICAM-1) heme oxygenase-1 (HO-1) CD68 and CD57 were detected. RESULTS: Pathologic manifestion of grafts showed changes of acute vascular rejection (AVR) in all groups. The mean survival time after car diac xenograft was 41 hrs in Group 1, 68 hrs in Group 2, 55 hrs in Group 3 and 74 hrs in Group 4. Expression of intercellular adhesion molecule-1 (ICAM-1 ) decreased after ginaton preconditioning (P < 0. 05). CD68 and CD57 expressions were down-regulated, HO-1 expression was up-regulated, as well as the apoptotic index (Al) reduced significantly after ginaton with cyclosporine A preconditioning. CONCLUSION: Ginaton preconditioning can prolong the survival time after discordant xenograft, and significantly alleviate pathological lesion from acute xenograft vascular rejection combined with cyclosporine A.