Discovery of ZFD-10 of a pyridazino[4,5-b]indol-4(5H)-one derivative as an anti-ZIKV agent and a ZIKV NS5 RdRp inhibitor.

Zika virus (ZIKV) infection is associated with the birth defect microcephaly and Guillain-Barré syndrome in adults. There is no approved vaccine or specific antiviral agent against ZIKV. ZFD-10, a novel structural skeleton of 1H-pyridazino[4,5-b]indol-4(5H)-one, was firstly synthesized and discovered to be a potent anti-ZIKV inhibitor with very low cytotoxicity.

Antiviral effects of the fused tricyclic derivatives of indoline and imidazolidinone on ZIKV infection and RdRp activities of ZIKV and DENV.

The prevalence and ravages of Zika virus (ZIKV) seriously endanger human health, especially causing significant neurological defects in both neonates as pediatric microcephaly and adults as Guillain-Barré syndrome. In this work, we studied anti-ZIKV effects of the fused tricyclic derivatives of indoline and imidazolidinone and discovered that some of them are valuable leads for drug discovery of anti-ZIKV agents. The current results show that certain compounds are broad-spectrum inhibitors of ZIKV- and dengue virus (DENV)-infection while distinctive compounds are selective ZIKV inhibitors or selective DENV inhibitors.

Discovery of dehydroandrographolide derivatives with C19 hindered ether as potent anti-ZIKV agents with inhibitory activities to MTase of ZIKV NS5.

Infection by Zika virus (ZIKV), a mosquito-transmitted arbovirus and a member of Flavivirus, could make pediatric microcephaly and Guillain-Barré syndrome, which remains an ongoing global threat. The efficient antivirals to ZIKV infection are of great medical need. Andrographolide and its analogues were discovered to be active against flaviviral infection.

Consistency of spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users in China.

Background: As the transmission routes of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are similar, previous studies based on separate research on HIV-1 and HCV assumed a similar transmission pattern. However, few studies have focused on the possible correlation of the spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected patients.

Methods: A total of 310 HIV-1/HCV coinfected drug users were recruited in Yingjiang and Kaiyuan prefectures, Yunnan Province, China.

Non-volatile acylphloroglucinol components from Eucalyptus robusta inhibit Zika virus by impairing RdRp activity of NS5.

Eucalyptus is a large genus of the Myrtaceae family with high value in various fields of industry. Recently, attention has been focused on the functional properties of Eucalyptus extracts. These extracts have been traditionally used to combat various infectious diseases, and volatile oils are usually considered to play a major role.

Scaffold attachment factor B suppresses HIV-1 infection of CD4 T cells by preventing binding of RNA polymerase II to HIV-1's long terminal repeat.

The 5' end of the HIV, type 1 (HIV-1) long terminal repeat (LTR) promoter plays an essential role in driving viral transcription and productive infection. Multiple host and viral factors regulate LTR activity and modulate HIV-1 latency. Manipulation of the HIV-1 LTR provides a potential therapeutic strategy for combating HIV-1 persistence.

HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA.

HIV-1 depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy. The cellular protein Naf1 (HIV-1 Nef-associated factor 1) is a CRM1-dependent nucleo-cytoplasmic shuttling protein, and has been identified to regulate multiple receptor-mediated signal pathways in inflammation.

Antibodies to P-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death.

P-selectin glycoprotein ligand-1 (PSGL-1) has been proved to serve as the functional receptor for enterovirus 71 (EV71). We found the abundant expression of PSGL-1 on monocyte-derived dendritic cells (MDDCs). However, we have previously demonstrated that MDDCs did not support efficient replication of EV71.

Inhibition of CDK2 promotes inducible regulatory T-cell differentiation through TGFβ-Smad3 signaling pathway.

Inducible regulatory T-cells (iTReg) can be generated from CD4(+)Foxp3(-) naïve conventional T-cells by a combination of TGF-β and T-cell receptor (TCR) signaling. It is of enormous clinical importance to identify agents that can promote the generation and differentiation of functional iTreg cells. We have established a phenotypic screening platform to identify new compounds that can promote the TGFβ-mediated iTreg differentiation.

miRNA-1236 inhibits HIV-1 infection of monocytes by repressing translation of cellular factor VprBP.

Primary monocytes are refractory to HIV-1 infection and become permissive upon differentiation into monocyte-derived dendritic cells (MDDCs) or macrophages. Multiple mechanisms have been proposed to interpret HIV-1 restriction in monocytes. Human cellular miRNAs can modulate HIV-1 infection by targeting either conserved regions of the HIV-1 genome or host gene transcripts.

Disease association and arthritogenic potential of circulating antibodies against the α1,4-polygalacturonic acid moiety.

Much progress has been made in recent years on the diagnostic value, Ag specificity, and pathogenic roles of autoantibodies correlated to the development of rheumatoid arthritis (RA) in humans. However, carbohydrate Ag-specific autoantibodies that may also play important roles in RA have largely been ignored. In this article, we report that serum levels of Abs capable of recognizing α1,4-polygalacturonic acid [(PGA); major structural component of pectin] strongly correlate with RA in humans.

The molecule of DC-SIGN captures enterovirus 71 and confers dendritic cell-mediated viral trans-infection.

Background: Enterovirus 71 (EV71) is the main causative agent of hand, foot and mouth disease that occurs in young children. Neither antiviral agents nor vaccines are available for efficiently combating viral infection. Study of EV71-host interplay is important for understanding viral infection and developing strategies for prevention and therapy.

The (1->6)-β-glucan moiety represents a cross-reactive epitope of infection-induced malignancy surveillance.

Exposure to pathogen-associated molecular patterns (PAMPs) by vaccination or infection is known to have beneficial effects on neoplastic diseases, although the underlying molecular mechanisms are so far unclear. In this article, we report that Abs against (1→6)-β-d-glucan, a typical microbial PAMP and a major target for high titer circulating natural Abs in healthy human subjects, cross-recognize a novel tumor-associated carbohydrate Ag on cancer cells. The (1→6)-β-glucan cross-reactive moiety is immunologically dominant in tumor cells, as C57BL/6 mice harboring EL-4 solid tumors produced anti-(1→6)-β-glucan Abs and the titer of which significantly correlated with enhanced survival and smaller tumor burden.

Self-oligomerization is essential for enhanced immunological activities of soluble recombinant calreticulin.

We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities. We herein further demonstrate that rCRT fragments 18-412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50-100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. We narrowed down the active site of CRT to residues 150-230, the activity of which also depends on dimerization.

Coxsackievirus B3 infection induced viral myocarditis by regulating the expression pattern of chemokines in cardiac myocytes.

Viral myocarditis is a common cardiovascular disease, which has greatly threatened human health. However, up to now, the pathogenesis of viral myocarditis has been unclear, which leads to the lack of its effective treatments. To investigate the role of chemokines in pathogenesis of viral myocarditis, mRNA expression for a panel of 19 chemokines detected by RT-PCR in myocardial tissue of BALB/c mice that were inoculated intraperitoneally with coxsackievirus B3.

Does chemotherapy augment anti-tumor immunotherapy by preferential impairment of regulatory T cells?

Chemotherapy, the treatment modality of choice for advanced cancers, is considered immunosuppressive due to its depletion of immune cells. Hence, chemotherapy is traditionally thought to adversely affect anti-tumor immune responses and antagonistic to tumor immunotherapy. Contrary to conventional belief, recent studies have shown that combining chemotherapy with immunotherapy resulted in enhanced anti-tumor immunity and improved therapeutic outcome.

[Complete sequence determination and phylogenetic analysis of FKN among seven higher primates including homonids and Old World Monkeys].

To obtain full-length FKN nucleotide sequences of homonids including human, chimpanzee, gorilla, orangutan and gibbon, and Old World Monkeys including macaque and leaf monkey and make phylogenetic analysis, three exons of FKN were amplified by degenerated PCR using obtained peripheral blood cells DNA as template which was extracted from homonids and Old World Monkeys. After extracting and purifying from agarose gels, PCR products were sequenced and then spliced by using BioEdit. All the FKN sequences were aligned and compared the percent identity by using DNAStar.

The distinct effects of three tandem repeats of C3d in the immune responses against tumor-associated antigen hCGbeta by DNA immunization.

Several examples have shown that C3d3, when fused to a corresponding antigen, had a strong adjuvant effect on certain specific antibody production. In a previous study, we attempted to prove that this was the case of the human chorionic gonadotrophin beta chain (hCGbeta)-induced immunity following DNA vaccination. However, we found that C3d3 when fused to hCGbeta inhibited rather than enhanced the antigen-specific immune response.

[Inoculation of the cells transfected with IP10 inhibited experimental tumor metastases in vivo].

Objective: To explore the inhibitory effects of IP10 on the experimental tumor metastases of a mammary carcinoma cell line 4T1 in vivo.

Methods: 4T1 cells were transfected with pcDNA3-IP10 plasmid and the positive clones (IP10-4T1) were screened in the presence of G418. The parental 4T1 cells and 4T1 cells transfected with pcDNA3 (pcDNA3-4T1) were used as controls.

CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

Aim: To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism of T lymphocyte infiltration regulated by CXCL16.

Methods: Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis.

[The role of CXCR4 in lung cancer metastasis and its possible mechanism].

Objective: To investigate the role of CXCR4 in the metastasis of human lung cancer and its possible mechanism.

Methods: Lung cancer cells of the lines 95C and 95D with high or low metastatic potential were transfeted with CXCR4 antisense plasmid pcDNA-ASX4, whole length eukaryotic expression plasmid pcDNA-CXCR4 (95D-ASX4 and 95C-X4 cell lines), and corresponding plasmid pcDNA3 (95C-pC and 95D-pC cell lines). 95C, 95C-pC, 95C-X4, 95D, and 95D-pC cells were injected subcutaneously into Balb/c nu/nu mice, 4 approximately 5 mice in a group.

[Relations between the expression of cyclin E, p16ink4, ki67 and HPV16/18 infection in cervical exfoliated cells].

Objective: To confirm the relations between the expression of cyclin E, p16ink4, ki67 and HPV16/18 infection using cervical exfoliated cells, and evaluate the usefulness of cyclin E, p16ink4 and ki67 as biomarkers for screening of cervical carcinomas.

Methods: The expression of cyclin E, p16ink4 oncoproteins and ki67 proliferative activity was evaluated immunohistochemically in 78 cervical exfoliated epithelial specimens. Human papillomavirus type16 and 18 (HPV16/18) infection was assessed by polymerase chain reaction (PCR) using type specific primers.

[Expression of target gene in eukaryotic cells driven by prokaryotic T7 promoter and its RNA polymerase].

To enhance the efficiency of the expression of target gene in eukaryotic cells, one of the strongest prokaryotic expression systems, the T7 RNA polymerase and T7 promoter, was introduced into eukaryotic cells. A duel-plasmid gene expression system of T7 bacteriophage components was developed; one containing the T7 phage RNA polymerase gene under the control of eukaryotic promoter CMV (pCMV-T7pol) and the other (pT7IRES) containing the T7 promoter and T7 terminator as well as EMCV IRES. To test the feasibility of this plasmid system for eukaryotic expression, hepatitis B virus envelop HBV preS2/S was used to construct pT7IRES-HBs.

[Anti-tumor effect of anti-dsDNA autoantibodies].

Objective: To investigate effects of anti-dsDNA autoantibodies on growth of tumor in vitro and in vivo.

Methods: BALB/c mice were inoculated with inactivated tumor cells and challenged s.c.