Japanese encephalitis virus E protein domain III immunization mediates cross-protection against Zika virus in mice via antibodies and CD8+T cells.

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are antigenically related flaviviruses that co-circulate in many countries/territories. The interaction between the two viruses needs to be determined. Recent findings by ourselves and other labs showed that JEV-elicited antibodies (Abs) and CD8+T cells exacerbate and protect against subsequent ZIKV infection, respectively. However, the impact of JEV envelope (E) protein domain III (EDIII)-induced immune responses on ZIKV infection is unclear. We show here that sera from JEV-EDIII-vaccinated mice cross-react with ZIKV-EDIII in vitro, and transfer of the same sera to mice significantly decreases death upon lethal ZIKV infection at a dose-dependent manner. Maternally acquired anti-JEV-EDIII Abs also significantly reduce the mortality of neonatal mice born to JEV-EDIII-immune mothers post ZIKV challenge. Similarly, transfer of ZIKV-EDIII-reactive IgG purified from JEV-vaccinated humans increases the survival of ZIKV-infected mice. Notably, transfer of an extremely low volume of JEV-EDIII-immune sera or ZIKV-EDIII-reactive IgG does not mediate the Ab-mediated enhancement (ADE) of ZIKV infection. Similarly, transfer of JEV-EDIII-elicited CD8+T cells protects recipient mice against ZIKV challenge. These results demonstrate that JEV-EDIII-induced immune components including Abs and T cells have protective roles in ZIKV infection, suggesting EDIII is a promising immunogen for developing effective and safety JEV vaccine.

Viral-mediated gene therapy in pediatric neurological disorders.

BACKGROUND: Due to the broad application of next-generation sequencing, the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable goal. However, treatments for neurological genetic disorders in children remain primarily symptomatic. On the other hand, with the continuous evolution of therapeutic viral vectors, gene therapy is becoming a clinical reality. From this perspective, we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological disorders. DATA SOURCES: We searched databases, including PubMed and Google Scholar, using the keywords "adenovirus vector," "lentivirus vector," and "AAV" for gene therapy, and "immunoreaction induced by gene therapy vectors," "administration routes of gene therapy vectors," and "gene therapy" with "NCL," "SMA," "DMD," "congenital myopathy," "MPS" "leukodystrophy," or "pediatric metabolic disorders". We also screened the database of ClinicalTrials.gov using the keywords "gene therapy for children" and then filtered the results with the ones aimed at neurological disorders. The time range of the search procedure was from the inception of the databases to the present. RESULTS: We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks, the administration routes of each vector, the research progress, and the clinical application status of viral-mediated gene therapy on pediatric neurological disorders. CONCLUSIONS: Viral-mediated gene therapy is on the brink of broad clinical application. Viral-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders, and many children with incurable diseases will meet the dawn of a cure. Nevertheless, the vectors must be optimized for better safety and efficacy.

Propofol induces rat embryonic neural stem cell apoptosis by activating both extrinsic and intrinsic pathways.

Propofol has previously been shown to have detrimental effects on the developing brain. Neural stem cells, identified in the embryonic brain as well as in the adult brain, are multipotent, self-renewing cells, which are capable of differentiating into different phenotypes of the nervous system. The present study was designed to investigate propofol-induced rat embryonic neural stem cell apoptosis and its potential mechanisms. Rat embryonic neural stem cells were isolated, cultured and characterized. Treatment of these cultured stem cells with different doses of propofol was carried out and cell proliferation was assessed by MTT assay and apoptosis by flow cytometric analysis. Cellular levels of active forms of caspase-3 and caspase-8, which regulate the extrinsic apoptotic pathway, and of caspase-9 and cytochrome C, which regulate the intrinsic apoptotic pathway, were detected by western blotting. Over 95% of isolated rat embryonic neural stem cells expressed the Nestin protein, as detected by immunofluorescence staining. Using an in vitro cell culture system, we showed that propofol inhibited cell growth and induced cell apoptosis in a dose-dependent manner. Furthermore, western blot analysis showed that propofol treatment significantly elevated levels of active forms of caspase-3, caspase-8, caspase-9 and cytochrome C in the embryonic neural stem cells. Propofol induced rat embryonic neural stem cell apoptosis and activated caspase-3, caspase-8, caspase-9 and cytochrome C, suggesting that propofol-induced stem cell apoptosis may be regulated through both the extrinsic and intrinsic apoptotic pathways.

[Clinical application of in vitro maturation of human immature oocytes for infertile women with polycystic ovary syndrome].

OBJECTIVE: To investigate clinical effect and safety of in vitro maturation (IVM) of human immature oocytes in infertile women with polycystic ovary syndrome by comparing with conventional in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI). METHODS: From Jan. 2003 to Dec. 2009, 157 infertile women with PCOS underwent 162 cycles IVM in Center for Reproductive Medicine, the First Affiliated Hospital of Anhui Medical University. In the mean time, 109 patients with PCOS underwent 114 IVF/ICSI cycles as control group 1 and 106 patients with other factors underwent 106 IVF/ICSI cycles as control group 2. Treatment and outcome of pregnancy and infant were compared among those 3 groups. RESULTS: No statistically significant difference were found in terms of the positive rate of hCG in urine [35.7% (56/157), 42.2% (46/109), 44.3% (47/106)], the rate of clinical pregnancy [29.3% (46/157), 37.6% (41/109), 41.5% (44/106)], the rate of entopic pregnancy [1.9% (3/157), 1.8% (2/109), 0.9% (1/106)], the rate of miscarriage [18.6% (8/43), 12.8% (5/39), 20.9% (9/43)] and the rate of live-birth [22.3% (35/157), 31.2% (34/109), 32.1% (34/106)] among three groups (IVM group, control group 1, control group 2, P > 0.05). The rate of preterm labor, low weight newborn, mean birth weight, ratio of male to female did not show significantly difference among 3 groups (P > 0.05). The average control ovarian stimulation was 6 days, the median dose of gonadotropin (Gn) was 675 IU, and the total hospital cost was (8392 ± 1328) RMB in IVM group, which were statistically lower than those in the other two control groups (P < 0.01). The rate of multiple pregnancy was 4.7% (2/43) and ovarian hyperstimulation syndrome (OHSS) 0 in IVM group, which were significantly lower than those in the other control group (P < 0.01). CONCLUSION: In vitro maturation is an effective treatment in infertile women with PCOS, it could obtain the similar pregnancy outcome and reduce total cost, the dosage of gonadotropin-releasing hormone and rate of OHSS compared with conventional IVF/ICSI.

[Characterization of vinflunine tartrate liposomes in vitro and in vivo].

Vinflunine tartrate-loaded liposomes (VT-L) with two drug-to-lipid ratios were prepared by pH gradient method. Vesicle size and zeta potential were determined by the Zetasizer Nano ZS. Entrapment efficiency was evaluated by cation exchange resin centrifugalization method. The toxicity and tumor inhibition to nude mouse administrated by VT-L with different drug-to-lipid ratios were investigated and compared with the vinflunine tartrate injection (VT-I). The results showed that the mean particle size, zeta potential and entrapment efficiency of the VT-L with drug-to-lipid ratios of 1 : 5 and 1 : 10 were 124.6 nm and 128.3 nm, -25.3 mV and -22.8 mV, 94.46% and 97.31%, respectively. The VT-L with two different drug-to-lipid ratios has significantly higher anti-tumor effect to nude mouse transplanted human non-small cell lung carcinoma A549 and lower toxicity than VT-I. While there were no significant differences in anti-tumor effect and toxicity between VT-L with two different drug-to-lipid ratios.