Anticancer effect of sodium metavanadate on murine breast cancer both in vitro and in vivo.

Sodium metavanadate (NaVO3) exhibits important physiological effects including insulin-like, chemoprevention and anticancer activity. However, the effects of NaVO3 on breast cancer and underlying mechanisms are still unclear. In this study, our results revealed that NaVO3 was able to inhibit proliferation of murine breast cancer cells 4T1 with IC50 value of 8.19 µM and 1.92 µM at 24 h and 48 h, respectively. The mechanisms underlying the inhibition activity were that NaVO3 could increase reactive oxygen species (ROS) level in a concentration-dependent way, arrest cells at G2/M phase, diminish the mitochondrial membrane potential (MMP), finally promote the progress of apoptosis. Furthermore, NaVO3 also exhibited a dose-dependent anticancer activity in breast cancer-bearing mice that led to the shrinkage of tumor volume (about 50%), lower microvessel density, less propagating cells and more apoptotic cells in vivo, as compared to the saline group. Therefore, NaVO3 may act as a potential chemotherapeutic agent in breast cancer treatment.

Comparative liver transcriptome analysis in ducklings infected with duck hepatitis A virus 3 (DHAV-3) at 12 and 48 hours post-infection through RNA-seq.

Duck hepatitis A virus 3 (DHAV-3), the only member of the novel genus Avihepatovirus, in the family Picornaviridae, can cause significant economic losses for duck farms in China. Reports on the pathogenicity and the antiviral molecular mechanisms of the lethal DHAV-3 strain in ducklings are inadequate and remain poorly understood. We conducted global gene expression profiling and screened differentially expressed genes (DEG) of duckling liver tissues infected with lethal DHAV-3. There were 1643 DEG and 8979 DEG when compared with mock ducklings at 12 hours post-infection (hpi) and at 48 hpi, respectively. Gene pathway analysis of DEG highlighted mainly biological processes involved in metabolic pathways, host immune responses, and viral invasion. The results may provide valuable information for us to explore the pathogenicity of the virulent DHAV-3 strain and to improve our understanding of host-virus interactions.

Molecular cloning and mRNA expression of IFIT5 in tissues of ducklings infected with virulent duck hepatitis A virus type 3.

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are a family of proteins strongly induced downstream of type I interferon signaling. The function of IFITs has been investigated extensively in mammals. IFIT5 is the sole protein in this family found in birds and little information is available about the function of avian IFIT5. In this study, duck IFIT5 was cloned from peripheral blood mononuclear cells. Multiple amino acid sequence alignment and phylogenetic analysis showed that duck IFIT5 is highly homologous to chicken IFIT5. Tissue specificity analysis demonstrated that duck IFIT5 was ubiquitously expressed in all examined tissues of five-day-old ducklings, with the highest expression levels in heart, followed by thymus, cerebrum, liver, and lung; kidney expressed the lowest. Quantitative real-time PCR (qRT-PCR) analysis revealed that duck IFIT5 expression rapidly increased both in vitro and in vivo after stimulation with polyinosinic:polycytidylic acid [poly (I:C)] and infection with virulent duck hepatitis A virus type 3 (DHAV-3), respectively. Altogether, these results indicate that the expression of duck IFIT5 is positively correlated with viral load and may play an important role in the immune response to DHAV-3 infection. This study lays a foundation for further research into the innate antiviral immune responses of ducklings.

Behavioral and neurophysiological abnormalities during cued continuous performance tasks in patients with mild traumatic brain injury.

Objective: This study's aim was to investigate the features and neural mechanisms of sustained attention in patients with mild traumatic brain injury (mTBI) by comparing and analyzing neuropsychological, behavioral, event-related potentials, and event-related desynchronization and synchronization between mTBI patients and healthy controls. Methods: Twenty mTBI patients with mTBI and 20 healthy controls underwent the Mini-Mental State Examination (MMSE) and a cued continuous performance task (AX-CPT). Neuropsychological, behavioral, and electroencephalogram (EEG) data were collected and analyzed. Results: There were significant differences between the mTBI group and the control group in their MMSE total scores, attention, and calculation, but there were no significant differences in orientation, memory, recall, and verbal scores. There were significant differences between the mTBI group and the control group in hitting the number, reaction time, and the number of errors of omission, but there were no significant differences in the number of false errors. The amplitude of Go-N2 and Nogo-N2 was significantly smaller for the mTBI group than that for the control group. The amplitude of Go-P3 was significantly smaller for the mTBI group than that for the control group, but not for the amplitude of Nogo-P3. The Go-αERS were significantly less for the mTBI group than for the control group during the 0-200 ms after the stimulus onset. The Go-αERD and Nogo-αERD were significantly less for the mTBI group than for the control group during the 600-1,000 ms after the stimulus onset. The Go-ßERS were significantly less for the mTBI group than for the control group during the 200-400 ms after the stimulus onset. There were no significant differences in the Nogo-αERS and Nogo-ßERD/ERS between the mTBI group and the control group. Conclusion: Patients with mTBI exhibited impairments in sustained attention and conflict monitoring, while response inhibition may have been spared.

Pathogenicity of duck hepatitis A virus type 3 and innate immune responses of the ducklings to virulent DHAV-3.

Duck virus hepatitis caused by duck hepatitis A virus (DHAV) is an acute and contagious disease. To better understand the pathogenic mechanism of DHAV-3 in ducklings, an infection experiment was performed. Our results showed that typical symptoms were observed in the infected ducklings. DHAV-3 could infect many tissues, leading to pathological lesions, especially on the livers and spleen, and the host immune responses are activated in infection. Real-time quantitative PCR demonstrated that expression of many innate immune-related genes was mostly up-regulated in the livers and spleen, and antiviral innate immune response was established, but not sufficient to restrict the virus replication of lethal dose. Many major pattern recognition receptors (PRRs) (RIG-1, MDA5, and TLR7) are involved in the host immune response to DHAV-3, and the expression of interferon (IFNα, IFNß and IFNγ) and antiviral proteins (MX, OAS and PKR) are also up-regulated in the liver and spleen. The expression of most cytokines (IL-1ß, IL-2 and IL-6) was also up-regulated to different degrees and was various; the expression of IL-2 increased most significantly in liver. Our data provide a foundation for further study of the pathogenicity of duck virus hepatitis and extend our understanding of the immune responses of ducklings to DHAV-3 infection.