The Research Progress of Direct Thrombin Inhibitors.

Blood coagulation is the process of changing the blood from the flowing state to the gel state. It is an important part of the hemostatic function. Coagulation is a process by which a series of coagulation factors are sequentially activated, and finally thrombin is formed to form fibrin clot. Direct thrombin inhibitors are important anticoagulant drug. These drugs can selectively bind to the active site of thrombin, inhibit thrombin activity, have strong action and high specificity, and have important significance in the clinical treatment of thrombus diseases. Some of them come from natural products of animals or plants, and many of them have been applied in the clinic. The other part is derived from the design, synthesis and activity studies of small molecule inhibitors. This review discusses the progress of direct thrombin inhibitors in recent years.

Upregulated microRNA-15b alleviates ovarian cancer through inhitbition of the PI3K/Akt pathway by targeting LPAR3.

Ovarian cancer characterizes as the fourth leading consequence of death associated with cancer for women. Accumulating evidence underscores the vital roles of microRNAs (miRNAs) in preventing ovarian cancer development. Besides, induction of the phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/Akt) pathway associated with the ovarian cancer cell migration and invasion. The study aims to examine the effects of miR-15b on the proliferation, apoptosis, and senescence of human ovarian cancer cells by binding to lysophosphatidic acid receptor 3 (LPAR3) with the involvement of the PI3K/Akt pathway. The positive expression of LPAR3 protein was detected by immunohistochemistry. Then the interaction between miR-15b and LPAR3 was examined. The possible role of miR-15b in ovarian cancer was explored using gain- and loss-of-function experiments. Subsequently, the functions of miR-15b on PI3K/Akt pathway, proliferation, migration, invasion, senescence and apoptosis of ovarian cancer cells were assessed. Furthermore, in vivo tumorigenicity assay in nude mice was performed. LPAR3 was overexpressed, whereas miR-15b was poorly expressed in ovarian cancer tissues. LPAR3 is a direct target of miR-15b. Restored miR-15b promoted Bax expression, apoptosis, and senescence, inhibited expression of LPAR3 and Bcl-2, the extent of PI3K and Akt phosphorylation, as well as ovarian cancer cell proliferation, migration, and invasion. Further, tumor growth was observed to be prevented by miR-15b overexpression. Collectively, our study demonstrates that miR-15b represses the proliferation and drives the senescence and apoptosis of ovarian cancer cells through the suppression of LPAR3 and the PI3K/Akt pathway, highlighting an antitumorigenic role of miR-15b.

Effect of sex hormone-binding globulin polymorphisms on the outcome of in vitro fertilization-embryo transfer for polycystic ovary syndrome patients: A case-control study.

Polycystic ovary syndrome (PCOS), known as a common endocrine disorder among females, plagues many PCOS patients. The current study aimed to explore the correlations of sex hormone-binding globulin (SHBG) polymorphisms with the outcome of in vitro fertilization-embryo transfer (IVF-ET) in PCOS patients. PCOS patients who underwent IVF-ET and patients with non-PCOS-related infertility were selected in the study. Correlations of SHBG rs6259 and rs727428 with the risk factors in PCOS were analyzed, followed by the evaluation of the effect of SHBG polymorphisms on the outcome of IVF-ET in PCOS patients. At last, unconditional logistic regression analysis was performed to study the risk factors for IVF-ET treatment outcome. Compared with SHBG rs6259 GG carriers, the incidence of PCOS was found to be elevated in SHBG rs6259 GA+AA carriers which indicated that the A allele was a risk factor for PCOS. Compared with SHBG rs6259 TT carriers, the number of retrieved oocytes and embryo as well as the fertility rate in SHBG rs6259 GA+AA carriers was found to be decreased, while the abortion rate, incidence of ovarian hyperstimulation syndrome, transplant rejection rate, estradiol, and testosterone in serum, as well as testosterone in follicular fluid were elevated. The luteal hormone, serum testosterone, and progesterone and GA+AA genotype of rs6259 were the risk factors for IVF-ET treatment outcome. Taken together, the study showed that SHBG rs6259 polymorphisms might be correlated with the risk of PCOS and the outcome of IVF-ET treatment.

Identification of miRNA and mRNA expression profiles by PCR microarray in hepatitis B virus­associated hepatocellular carcinoma.

The present study aimed to identify differentially expressed microRNAs (miRNAs) and mRNAs in hepatitis B virus­associated hepatocellular carcinoma (HCC). A total of five HCC tissues and paired adjacent non­tumor tissues were screened to identify the differentially expressed miRNAs and target mRNAs using polymerase chain reaction microarrays. The interaction between differential miRNA and mRNA expression was concurrently analyzed using bioinformatics methods. A total of 32 differentially expressed miRNAs (four upregulated miRNAs and 28 downregulated miRNAs) and 16 differentially expressed mRNAs (11 upregulated mRNAs and five downregulated mRNAs) were identified. Among these, upregulated hsa­miRNA (miR)­96­5p and hsa­miR­18b­5p suppressed their target mRNAs forkhead box O1 and MET transcriptional regulator MACC1 (MACC1). Downregulation of hsa­miR­199a­5p led to upregulation of its target mRNAs, cyclin dependent kinase 4 and insulin like growth factor 2 (IGF2). The high­level expression of IGF2 mRNA and cyclin E1 mRNA was due to the low­level expression of hsa­miR­145­5p, hsa­miR­181a­5p, hsa­miR­199a­5p and hsa­miR­223a­3p, and hsa­miR­26a­5p and hsa­miR­26b­5p, respectively. The low­level expression of coronin 1A mRNA and MACC1 mRNA was due to overexpression of hsa­miR­517a­3p and hsa­miR­18a­5p, and hsa­miR­18b­5p, respectively. Numerous gene ontology terms were associated with oncogenesis. The most enriched pathways targeted by the dysregulated miRNAs and mRNAs were associated with cancer and oncogenesis pathways. The present data suggested that differential miRNA and mRNA expression is present in HCC. Thus, interactions between certain miRNAs and mRNAs may be involved in the pathogenesis of HCC.

C-arm Lipiodol CT in transcatheter arterial chemoembolization for small hepatocellular carcinoma.

AIM: To investigate the value of C-arm Lipiodol computed tomography (CT) for intra-procedural hepatocellular carcinoma (HCC) lesion detection during transcatheter arterial chemoembolization (TACE). METHODS: Forty patients (37 male, 3 female; mean age, 52.6 ± 12.5 years, age range: 25-82 years) diagnosed with HCC were enrolled in this study. All patients underwent 64-slice CT 1-2 wk before TACE. During the procedure, hepatic angiography was performed first. Following diagnostic embolization with Lipiodol injected into the hepatic artery, a C-arm CT scan was immediately conducted (C-arm Lipiodol CT). If new HCC lesions were confirmed, gelfoam particles were super-selectively injected into the tumor-nourishing blood vessel. A Lipiodol CT scan was performed 7-14 d after TACE. All images acquired from 64-slice CT, digital subtraction angiography (DSA), C-arm Lipiodol CT and Lipiodol CT were retrospectively reviewed by four radiologists and the number of detected lesions in each examination was counted, respectively. The results of Lipiodol CT were taken as the diagnostic reference. Alpha-fetoprotein values were examined both before and after TACE. This study only takes into account the lesions that were not found or were considered suspicious on 64-slice CT before TACE. RESULTS: Preprocedural 64-slice CT detected a total of 13 suspicious lesions in the 40 patients. DSA detected ten definite and four suspicious lesions. C-arm Lipiodol CT detected 71 lesions in total and Lipiodol CT confirmed 67 lesions with a diameter range of 3-12 mm. Four false-positive lesions, which were detected by C-arm Lipiodol CT, were considered to be hepatic artery-portal vein fistulas. The average alpha-fetoprotein values before and after TACE were significantly different (452.3 ± 192.6 ng/mL vs 223.8 ± 93.2 ng/mL; P = 0.039). CONCLUSION: C-arm Lipiodol CT has a higher diagnostic sensitivity for small HCC lesions. This technique may help physicians make intraprocedural decisions to provide patients with earlier treatment.

Randomized trial of [131I] metuximab in treatment of hepatocellular carcinoma after percutaneous radiofrequency ablation.

To assess the efficacy of combining radioimmunoconjugate [(131)I] metuximab with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) treatment compared with RFA alone, a single-center randomized controlled trial was conducted on 127 patients with Barcelona Clinic Liver Cancer staging system (BCLC) classifications of 0-B stage. Patients received either RFA followed by [(131)I] metuximab (n = 62) or RFA alone (n = 65). The primary outcome was overall tumor recurrence. Statistical tests were two-sided. The one- and two-year recurrence rates in the combination group were 31.8% and 58.5%, whereas those in the RFA group were 56.3% and 70.9%, respectively. The median time to overall tumor recurrence was 17 months in the combination group and 10 months in the RFA group (P = .03). The RFA-[(131)I] metuximab treatment showed a greater antirecurrence benefit than RFA in the metuximab target (ie, CD147)-positive subpopulation (P = .007). [(131)I] metuximab may yield prevention of tumor recurrence after RFA.