Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.

Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury.

Comparative analysis of the envelope glycoproteins of foamy viruses.

One of the most fascinating findings in retrovirology is the construction of viral vectors based on foamy viruses (FVs) for gene therapy. The envelope glycoprotein (Env), one of the structural proteins of FV, is an important antigen in the immunoassays, as it is highly specific. To compare the characteristics of all 15 available FV Envs, the phylogenesis, hydrophobicity, modifications, and conserved motifs were analyzed based on the Env sequences. Meanwhile, the secondary structures of transmembrane (TM) domains of FV Envs were predicted. The results of phylogenetic analyses based on Envs indicated that the foamy viruses from different hosts could form three groups. The hydrophobicity analysis revealed that FV Envs had two prominent hydrophobic regions, which was similar to other retroviruses. Though the glycosylation, ubiquitination, and the secondary structures of TM domains of FV Envs were in line with other retroviruses, the roles were distinctly different. Interestingly, the analyses of conserved motifs suggested that FV Envs possessed several specific functional motifs.

[The research progress of foamy virus Bet protein].

Foamy virus can establish lifelong persistent infection in mammal hosts without inducing diseases. Such special characteristic stimulates the interests of researchers. As reported, the accessory protein Bet of foamy virus could regulate the gene expression and infection cycle of foamy virus and take part in the generation of chronic viral infection. And also, Bet might prevent the host cellular defense factor APO-BEC3 from interfering the replication of virus and play a role in maintaining viral persistent infection. In order to elucidate the roles of Bet in the foamy virus replication and infection, this review summarized the research progress of Bet protein reported in recent years.

Selective inhibition of CCR7(-) effector memory T cell activation by a novel peptide targeting Kv1.3 channel in a rat experimental autoimmune encephalomyelitis model.

The voltage-gated Kv1.3 K(+) channel in effector memory T cells serves as a new therapeutic target for multiple sclerosis. In our previous studies, the novel peptide ADWX-1 was designed and synthesized as a specific Kv1.3 blocker. However, it is unclear if and how ADWX-1 alleviates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. In this study, the administration of ADWX-1 significantly ameliorated the rat experimental autoimmune encephalomyelitis model by selectively inhibiting CD4(+)CCR7(-) phenotype effector memory T cell activation. In contrast, the Kv1.3-specific peptide had little effect on CD4(+)CCR7(+) cells, thereby limiting side effects. Furthermore, we determined that ADWX-1 is involved in the regulation of NF-κB signaling through upstream protein kinase C-θ (PKCθ) in the IL-2 pathway of CD4(+)CCR7(-) cells. The elevated expression of Kv1.3 mRNA and protein in activated CD4(+)CCR7(-) cells was reduced by ADWX-1 engagement; however, an apparent alteration in CD4(+)CCR7(+) cells was not observed. Moreover, the selective regulation of the Kv1.3 channel gene expression pattern by ADWX-1 provided a further and sustained inhibition of the CD4(+)CCR7(-) phenotype, which depends on the activity of Kv1.3 to modulate its activation signal. In addition, ADWX-1 mediated the activation of differentiated Th17 cells through the CCR7(-) phenotype. The efficacy of ADWX-1 is supported by multiple functions, which are based on a Kv1.3(high) CD4(+)CCR7(-) T cell selectivity through two different pathways, including the classic channel activity-associated IL-2 pathway and the new Kv1.3 channel gene expression pathway.

[Inhibitive effect of human foamy virus induced IL-24 on cancer cells].

AIM: To construct replication-defective HFV-IL24 virus vector and to investigate its inhibitive effect on cancer cells after infected or transfected by this vector. METHODS: pDeltaphi-IL24 was constructed and was co-transfected with helper-plasmids into HEK 293T cells. Recombinant HFV-IL24 vector was extracted to infect HeLa cells and the inhibitive effect of IL-24 on cancer cells was examined by RT-PCR, MTT, cell counting and FCM methods. RESULTS: pDeltaphi-IL24 plasmid and HFV-IL24 particles were successfully constructed. HeLa cells exhibited obvious growth inhibition, cell cycle variation and visible apoptosis (mortality) after infected or transfected by HFV-IL24 or pDeltaphi-IL24. CONCLUSION: The results of the study provide some evidence for human foamy virus used as an effective gene transfer tool and for cancer gene therapy with HFV-IL24.