We used (H~3)-prazosin on rabbits to determine the changes of ?_1-adrenoceptor number (Bmax) and affinity (k_D) before and after ischemia, Within 15min of ischemia, we demonstrated that Bmax increased to twfold in ischeamic regions. The increase persisted for 30 min of ischemla and then began to fall at 45 min of ischemia. At the same time, in the nonischemic regions Bmax did not change. The results also showed that ischemia did not alter K_D markedly in both nonischeamic and ischeamic regions.

Two recombinant plasmids pVAX/Sj23 and pVAX/mIL-18 containing Schistosoma japonicum 23 000 membrane protein (Sj23) and murine IL-18 were evaluated for their ability to induce immune responses and to protect against S. japonicum challenge in mice. All animals vaccinated with pVAX/Sj23 alone or plus pVAX/mIL-18 developed specific anti-SWAP (soluble worm antigen preparation) ELISA antibody and splenocyte proliferation response,and co-injection of pVAX/mIL-18 significantly increased the production of IFN-γ and IL-2 compared with pVAX/Sj23 alone, indicating that IL-18 enhances the Th1-dominant immune response. The challenge experiment showed that worm reduction rates in pVAX/Sj23 group compared with control group (pVAX1) was 26.5% and in the pVAX/Sj23 plus pVAX/mIL-18 group was 41.9% ,and the hepatic egg reduction rates were 42.7 and 49.6%,respectively. These results indicated that co-injection of an IL-18 plasmid with Sj23 DNA vaccine efficiently improves the protective effect against S. japonicum infection.

Objective To explore the differences in immune responses between Cricetulus barabensis and their albino mutant infected with Trichinella spiralis.Methods The physiological parameters of blood , expression levels of IL-2 protein and IL-6 gene in the spleen were analyzed.Results The level of immune cells and cytokines of Cricetulus barabensis was higher than that in the albino mutant .Conclusions Cricetulus barabensis is a suitable model animal for research on long-term latent infection such as infection with Trichinella spiralis.

Patients with advanced hepatocellular carcinoma (HCC) often have poor prognosis, and early diagnosis and effective treatment measures can significantly improve the survival rate of patients. At present, alpha-fetoprotein (AFP) is the most widely used serum marker for the diagnosis of HCC in the world; however, no increase in AFP was found in some HCC patients. This article analyzes the application potential of AFP, hepatitis B core-related antigen, liquid biopsy technology, microRNA, long non-coding RNA, and exosomes in the early diagnosis of HCC and reviews related research advances, so as to provide a basis for exploring new methods for the early diagnosis of HCC.

The incurable chronic infection caused by hepatitis B virus (HBV) is the major health burden worldwide. Covalently closed circular DNA (cccDNA) exists in the nucleus of infected cells as a stable minichromosome, and when a new therapy realizes inactivation or eliminates persistent cccDNA in infected hepatocytes, the natural process of chronic infection and long-term antiviral therapy will no longer exist. This article introduces the methods targeting cccDNA, such as gene editing and epigenetic modification, so as to achieve the complete cure of HBV infection.

Osteosarcoma is the most common primary sarcoma of bone, and it is a leading cause of cancer death among adolescents and young adults. However, the molecular mechanism underlying osteosarcoma carcinogenesis remains poorly understood. Recently, cyclin-dependent kinase 6 (CDK6) was identified as an important oncogene. We found that CDK6 protein level, rather than CDK6 mRNA level, is much higher in osteosarcoma tissues than in normal adjacent tissues, which indicates a post-transcriptional mechanism involved in CDK6 regulation in osteosarcoma. MiRNAs are small non-coding RNAs that repress gene expression at the post-transcriptional level and have widely been shown to play important roles in many human cancers. In this study, we investigated the role of miR-29b as a novel regulator of CDK6 using bioinformatics methods. We demonstrated that CDK6 can be downregulated by miR-29b via binding to the 3'-UTR region in osteosarcoma cells. Furthermore, we identified an inverse correlation between miR-29b and CDK6 protein levels in osteosarcoma tissues. Finally, we examined the function of miR-29b-driven repression of CDK6 expression in osteosarcoma cells. The results revealed that miR-29b acts as a tumor suppressor of osteosarcoma by targeting CDK6 in the proliferation and migration processes. Taken together, our results highlight an important role for miR-29b in the regulation of CDK6 in osteosarcoma and may open new avenues for future osteosarcoma therapies.
3' Untranslated Regions ; Animals ; Base Sequence ; Bone Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cyclin-Dependent Kinase 6 ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Mice ; MicroRNAs ; metabolism ; Osteosarcoma ; metabolism ; pathology ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Rats ; Sequence Alignment ; Up-Regulation

3' Untranslated Regions ; Animals ; Antagomirs ; metabolism ; Base Sequence ; Binding Sites ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Mice ; MicroRNAs ; antagonists & inhibitors ; genetics ; metabolism ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Rats ; Sequence Alignment ; Snail Family Transcription Factors ; antagonists & inhibitors ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; pathology

MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.
A549 Cells ; Cell Movement ; Cell Proliferation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; MicroRNAs ; genetics ; metabolism ; RNA, Neoplasm ; genetics ; metabolism ; Tumor Suppressor Proteins ; biosynthesis ; genetics

The BCL6 (B-Cell Lymphoma 6) gene is a proto-oncogene that is often expressed in diffuse large B-cell lymphomas (DLBCLs). BCL6 loss of function can kill DLBCL cells, demonstrating that BCL6 is necessary for the survival of DLBCL cells and could be a therapeutic target. In this study, we found that BCL6 protein levels were consistently upregulated in DLBCL tissues, whereas its mRNA levels varied randomly in tissues, suggesting that a post-transcriptional mechanism was involved in BCL6 regulation. We used bioinformatics analysis to search for miRNAs, which potentially target BCL6, and identified specific targeting sites for miR-10a in the 3'-untranslated region (3'-UTR) of BCL6. We further identified an inverse correlation between miR-10a levels and BCL6 protein levels, but not mRNA levels, in DLBCL tumor tissue samples. By overexpressing or knocking down miR-10a in DLBCL cells, we experimentally validated that miR-10a directly recognizes the 3'-UTR of the BCL6 transcript and regulated BCL6 expression. Furthermore, we demonstrated that negatively regulating BCL6 by miR-10a suppressed the proliferation and promoted apoptosis of DLBCL cells.
3' Untranslated Regions ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Lymphoma, Large B-Cell, Diffuse ; genetics ; metabolism ; therapy ; MicroRNAs ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; biosynthesis ; genetics

Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.
Animals ; Apoptosis Regulatory Proteins ; genetics ; metabolism ; Caco-2 Cells ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Heterografts ; Humans ; Male ; Mice ; Mice, Nude ; Mice, SCID ; MicroRNAs ; genetics ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Transplantation ; RNA, Neoplasm ; genetics ; metabolism ; RNA-Binding Proteins ; genetics ; metabolism