Nedaplatin and oxaliplatin are widely used in clinic as new antineoplastic agents against a broad spectrum of solid tumors, which are characterized by broader anticancer spectrum, higher activity and less toxicity, especially no cross resistance with cisplatin. In addition, the lipophilic platinum compound, the muhinuclear platinum compound and others are being still clinically tested, which also show the advantages of high efficacy and low toxicity. Current researches are mainly focus on reforming the structure of cisplatin and carboplatin, and exploring platinum compounds with totally new structure to improve quality of life and prolon-ging survival time of patients. Platinum compounds still have exceedingly vital position and satisfactory applica-tion perspective in cytotoxic drugs.
Key words:
Antineoplastic agents; Platinum compounds; Neoplasms
The application of cardiac resynchronization therapy in the treatment of chronic heart failure is growing widely, the risks of arrhythmia post-CRT has been receiving much attention.The mechanical and electrical reverse remodeling of the heart after CRT had reduced the valvular regurgitation, diminished of cardiac chamber and decreased of sympathetic nervous system activity that thought to be relevant to lower ventricular arrhythmia risk after CRT.Left ventricular ejection fraction, fragmented QRS complex, transmural dispersion of repolarization, the heart failure etiology and the comorbidity etc., were concerned to association with the occurrence of ventricular arrhythmia post-CRT.Systematic and comprehensive acknowledge needed to help to assess or quantify the arrhythmia risk after such device implantation.This article reviewed research advances in ventricular arrhythmia after CRT.
Key words:
Chronic heart failure; Cardiac resynchronization therapy; Ventricular arrhythmia
Background: Liver fibrosis is characterized by extensive deposition of extracellular matrix (ECM) components in the liver. RCAN1 (regulator of calcineurin 1), an endogenous inhibitor of calcineurin (CaN), is required for ECM synthesis during hypertrophy of various organs. However, the functional role of RCAN1 in liver fibrogenesis has not yet been addressed. Methods: We induced experimental liver fibrosis in mice by intraperitoneal injection of 10 % CCl4 twice a week. To investigate the functional role of RCAN1.4 in the progression of liver fibrosis, we specifically over-expressed RCAN1.4 in mice liver using rAAV8-packaged RCAN1.4 over-expression plasmid. Following the establishment of the fibrotic mouse model, primary hepatic stellate cells were isolated. Subsequently, we evaluated the effect of RCAN1.4 on hepatic fibrogenesis, hepatic stellate cell activation, and cell survival. The biological role and signaling events for RCAN1 were analyzed by protein-protein interaction (PPI) network. Bisulfite sequencing PCR (BSP) was used to predict the methylated CpG islands in the RCAN1.4 gene promoter. We used the chromatin immunoprecipitation (ChIP assay) to investigate DNA methyltransferases which induced decreased expression of RCAN1.4 in liver fibrosis. Results: Two isoforms of RCAN1 protein were expressed in CCl4-induced liver fibrosis mouse model and HSC-T6 cells cultured with transforming growth factor-beta 1 (TGF-β1). RCAN1 isoform 4 (RCAN1.4) was selectively down-regulated in vivo and in vitro. The BSP analysis indicated the presence of two methylated sites in RCAN1.4 promoter and the downregulated RCAN1.4 expression levels could be restored by 5-aza-2'-deoxycytidine (5-azadC) and DNMTs-RNAi transfection in vitro. ChIP assay was used to demonstrate that the decreased RCAN1.4 expression was associated with DNMT1 and DNMT3b. Furthermore, we established a CCl4-induced liver fibrosis mouse model by injecting the recombinant adeno-associated virus-packaged RCAN1.4 (rAAV8-RCAN1.4) over-expression plasmid through the tail vein. Liver- specific-over-expression of RAN1.4 led to liver function recovery and alleviated ECM deposition. The key protein (a member of the NFAT family of proteins) identified on PPI network data was analyzed in vivo and in vitro. Our results demonstrated that RCAN1.4 over-expression alleviates, whereas its knockdown exacerbates, TGF-β1-induced liver fibrosis in vitro in a CaN/NFAT3 signaling-dependent manner. Conclusions: RCAN1.4 could alleviate liver fibrosis through inhibition of CaN/NFAT3 signaling, and the anti-fibrosis function of RCAN1.4 could be blocked by DNA methylation mediated by DNMT1 and DNMT3b. Thus, RCAN1.4 may serve as a potential therapeutic target in the treatment of liver fibrosis.
The incidence of cancer is increasing at an alarming rate despite recent advances in prevention strategies, diagnostics and therapeutics for various types of cancer. The identification of novel biomarkers to aid in prognosis and treatment for cancer is urgently required. Uncontrolled proliferation and dysregulated apoptosis are characteristics exhibited by cancer cells in the initiation of various types of cancer. Notably, aberrant expression of crucial oncogenes or cancer suppressors is a defining event in cancer occurrence. Research has demonstrated that SAD1/UNC84 domain protein-2 (SUN2) serves a suppressive role in breast cancer, atypical teratoid/rhabdoid tumors and lung cancer progression. Furthermore, SUN2 inhibits cancer cell proliferation, migration and promotes apoptosis. Recent reports have also shown that SUN2 serves prominent roles in resistance to the excessive DNA damage that destabilizes the genome and promotes cancer development, and these functions of SUN2 are critical for evading initiation of cancer. Additionally, increasing evidence has demonstrated that SUN2 is involved in maintaining cell nuclear structure and appears to be a central component for organizing the natural nuclear architecture in cancer cells. The focus of the present review is to provide an overview on the pharmacological functions of SUN2 in cancers. These findings suggest that SUN2 may serve as a promising therapeutic target and novel predictive marker in various types of cancer.
To explore the relationship between the changes of ECG indexes and the prognosis after PCI in patients with acute ST-elevation myocardial infarction (STEMI), and to develop the evaluation method and analyze the advantages and characteristics. 420 patients with acute myocardial infarction (AMI) were admitted to our hospital from March 2017 to April 2020. They were divided into the observation group (ST segment elevation type) with 220 patients and control group (non-ST segment elevation type) with 200 patients according to whether ST segment elevation was or not. ECG was detected before and 1 hour after operation, evaluation of thrombolytic effect, 6-minute walking test and echocardiography were performed 3 months after operation. Compared with the control group, the ECG of the observation group showed St Compared with the control group, the thrombolytic effect of the observation group was significantly improved, and the difference was statistically significant (P < 0.05); compared with the control group, the thrombolysis effect of the observation group was significantly improved, the difference was statistically significant (P < 0.05); ECG index can effectively reflect the recovery of cardiac function after PCI in patients with acute STEMI, and can effectively indicate the improvement of symptoms in patients with AMI, which is worthy of clinical application.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)