Zhihua Ren

Human brucellosis in the People's Republic of China during 2005–2010

Brucellosis is a worldwide re-emerging zoonotic disease. It remains a serious public health problem in many developing countries including China. This review summarizes the epidemiological characteristics, morbidity, and endemic distributions of human brucellosis in the Peoples Republic of China for the period 2005-2010. From 2005 to 2010, the incidence of human brucellosis rose substantially in China, especially in the provinces of Inner Mongolia, Shanxi3, Heilongjiang, Hebei, Jilin, and Shanxi1. Meanwhile human brucellosis increased gradually in some southern provinces, such as Henan, Guangdong, and Fujian. Due to the rapid expansion of human brucellosis in China, surveillance and prevention of this disease has been greatly challenged.

Individual and combined effects of deoxynivalenol and zearalenone on mouse kidney

This study was performed to investigate the individual and combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEA) on mouse kidney. A total of 360 female mice were divided into nine groups. Each group received intraperitoneal injection of solvent (control), DON, ZEA, or DON+ZEA four times for 12d. Results showed that ZEA and/or DON increased the apoptosis rate in the kidney, as well as the levels of serum creatinine and blood urea nitrogen. DON and/or ZEA also induced renal oxidative stress as indicated by increased malondialdehyde concentration and nitric oxide level and reduced superoxide dismutase enzyme activity and hydroxyl radical inhibiting capacity. The observed changes were dose and time dependent. This study reports that DON and/or ZEA induced apoptosis, dysfunction, and oxidative stress in mouse kidney. Furthermore, the combination of DON+ZEA exhibited a sub-additive nephrotoxic effect.

The Fusarium toxin zearalenone and deoxynivalenol affect murine splenic antioxidant functions, interferon levels, and T-cell subsets.

This study aimed to evaluate the effects of the Fusarium toxin zearalenone (ZEA) and deoxynivalenol (DON) on splenic antioxidant functions, IFN levels, and T-cell subsets in mice. Herein, 360 mice were assigned to nine groups for a 12-day study. Mice were administered an intraperitoneal injection for 4 consecutive days with different concentrations of ZEA alone, DON alone, or ZEA+DON. Spleen and blood samples were collected on days 0, 3, 5, 8, and 12. Mice in each of the experimental groups showed dysreglated splenic antioxidant functions, IFN levels, and T-cell subset frequencies, suggesting that the immune system had been affected. The ZEA+DON-treated groups, especially the group that received a higher concentration of ZEA+DON (Group D2Z2), showed more obvious effects on the dysregulation of splenic antioxidant functions, IFN levels, and T-cell subsets. This finding suggested that DON and ZEA exerted synergistic effects.

Deoxynivalenol-induced cytokines and related genes in concanavalin A-stimulated primary chicken splenic lymphocytes

Deoxynivalenol (DON) immunotoxicity and its induction of cytokines and related genes in the splenic lymphocytes of chickens have not been completely elucidated. In the present study, we aimed to evaluate the effects of 48 h of different DON treatments (0 μg/mL, 0.2 μg/mL, 0.8 μg/mL, 3.2 μg/mL, 12.5 μg/mL, and 50 μg/mL) on the secretion and the mRNA expressions of some cytokine genes, such as interleukin-1beta (IL-1β), IL-1RI, IL-2, IL-4, IL-6, IL-10, IL-12β, and IFN-γ in chicken splenic lymphocytes. The concentrations of IL-1RI, IL-6, IL-10, and IFN-γ were increased with the DON concentrations increasing (P<0.05 or P<0.01). However, the concentrations of IL-1β, IL-2, IL-4, and IL-12β were decreased with the DON concentrations increasing (P<0.05 or P<0.01). Except IL-1β, the mRNA expressions of the other cytokines were up-regulated by DON. The highest mRNA expressions values of IL-1RI, IL-4, IL-10, IL-12β, and IFN-γ were at 50 μg/mL DON treatment groups (P<0.05 or P<0.01), while the highest mRNA expressions values of IL-2 and IL-6 were at 12.5 μg/mL DON treatment groups (P<0.05 or P<0.01). Our data revealed that the potent effects of DON in affecting the secretion and the mRNA expression of the related cytokines in chicken splenic lymphocytes in vitro.

Effects of the Fusarium toxin zearalenone (ZEA) and/or deoxynivalenol (DON) on the serum IgA, IgG and IgM levels in mice

The aim of this study was to evaluate the effects of the Fusarium toxin zearalenone (ZEA) and/or deoxynivalenol (DON) on the serum IgA, IgG and IgM levels in mice. In our study, 360 healthy adult female mice were randomly assigned to nine groups for a 12-day study. Mice of all groups were given a 4-day continuous intraperitoneal injection with different concentrations of ZEA alone, DON alone and the mixture of ZEA and DON, individually. Blood samples were collected on days 0, 3, 5, 8 and 12 of the experiment. The experiment results showed that all the experimental groups could cause the dysregulation of the immunoglobulin, thus affecting the humoral immune of mice. The mixture groups, especially in the group with higher concentrations of ZEA and DON (Group D2Z2), showed more obvious effect on the dysregulation of the immunoglobulin.

Effect of the Fusarium toxins, zearalenone and deoxynivalenol, on the mouse brain

The aim of this study was to find effects of Fusarium toxins on brain injury in mice. We evaluated the individual and combined effect of the Fusarium toxins zearalenone and deoxynivalenol on the mouse brain. We examined brain weight, protein, antioxidant indicators, and apoptosis. After 3 and 5days of treatment, increased levels of nitric oxide, total nitric oxide synthase, hydroxyl radical scavenging, and malondialdehyde were observed in the treatment groups. This was accompanied by reduced levels of brain protein, superoxide dismutase (apart from the low-dose zearalenone groups), glutathione, glutathione peroxidase activity, and percentage of apoptotic cells. By day 12, most of these indicators had returned to control group levels. The effects of zearalenone and deoxynivalenol were dose-dependent, and were synergistic in combination. Our results suggest that brain function is affected by zearalenone and deoxynivalenol.

Large-scale identification of small noncoding RNA with strand-specific deep sequencing and characterization of a novel virulence-related sRNA in Brucella melitensis

Brucella is the causative agent of brucellosis, a worldwide epidemic zoonosis. Small noncoding RNAs (sRNAs) are important modulators of gene expression and involved in pathogenesis and stress adaptation of Brucella. In this study, using a strand-specific RNA deep-sequencing approach, we identified a global set of sRNAs expressed by B. melitensis 16M. In total, 1321 sRNAs were identified, ranging from 100 to 600 nucleotides. These sRNAs differ in their expression levels and strand and chromosomal distributions. The role of BSR0441, one of these sRNAs, in the virulence of B. melitensis 16M was further characterized. BSR0441 was highly induced during the infection of macrophages and mice. The deletion mutant of BSR0441 showed significantly reduced spleen colonization in the middle and late phases of infection. The expression of the BSR0441 target mRNA genes was also altered in the BSR0441 mutant strain during macrophage and mice infection, which is consistent with its reduced intracellular survival capacity. In summary, Brucella encodes a large number of sRNAs, which may be involved in the stress adaptation and virulence of Brucella. Further investigation of these regulators will extend our understanding of the Brucella pathogenesis mechanism and the interactions between Brucella and its hosts.

Protective role of selenium in the activities of antioxidant enzymes in piglet splenic lymphocytes exposed to deoxynivalenol

We evaluated the effects of selenium (Se) on antioxidant enzymes of piglet splenic lymphocytes exposed to deoxynivalenol (DON). We measured cell viability, the activities of several antioxidant enzymes, and lactate dehydrogenase (LDH), as well as total antioxidant capacity (T-AOC) and the levels of malonaldehyde (MDA) and hydrogen peroxide (H2O2). We found that DON exposure increased the concentrations of LDH, MDA, and H2O2 in all experimental groups in a dose-dependent manner, while the concentrations of other antioxidant enzymes were decreased. In Se-pretreated DON-exposed cells, damage to antioxidant enzymes was reduced, especially in the lower-dose DON groups over longer exposure times. These results may indicate that in piglet splenic lymphocytes, Se can alleviate DON-induced damage to antioxidant enzymes by improving glutathione peroxidase activity. Se may function as a potential antioxidative agent to alleviate DON-induced oxidative stress.

E. adenophorum Induces Cell Cycle and Apoptosis of Renal Cells through Mitochondrial Pathway and Caspase Activation in Saanen Goat.

The cytotoxicity effects of E. adenophorum on cell cycle and apoptosis of renal cells in Saanen goat was evaluated by TUNEL, DAPI, AO/EB staining, DNA fragmentation assay, Caspase activity, Western-blot, qRT-PCR and flow cytometry analysis. 16 saanen goats randomly divided into four groups were fed on 0%, 40%, 60% and 80% E. adenophorum diets. The Results showed that E. adenophorum induced typical apoptotic features of renal cells. E. adenophorum significantly suppressed renal cells viability, caused cell cycle activity arrest and induced typical apoptotic features in a dose-dependent manner. However, the protein levels of Fas/FasL, Bid and caspase-8 did not appear significant changes in the process of E. adenophorum-induced apoptosis. Moreover, E. adenophorum administration slightly decreased Bcl-2 expression, promoted Bax translocation to mitochondria, triggered the release of Cyt c from mitochondria into cytosol and activated caspase-9, -3, and cleaved PARP. The mitochondrial p53 translocation was significantly activated, accompanied by a significant increase in the loss of ΔΨm, Cyt c release and caspase-9 activation. Above all, these data suggest that E. adenophorum induces renal cells apoptosis via the activation of mitochondria-mediated apoptosis pathway in renal cells. These findings may provide new insights to understand the mechanisms involved in E. adenophorum-caused cytotoxicity of renal cells.

First isolation of new canine parvovirus 2a from Tibetan mastiff and global analysis of the full-length VP2 gene of canine parvoviruses 2 in China.

Canine parvovirus 2 (CPV-2) was first identified in 1978, and is responsible for classic parvoviral enteritis. Despite the widespread vaccination of domestic carnivores, CPVs have remained important pathogens of domestic and wild carnivores. In this study, we isolated CPV-2 from Tibetan mastiffs and performed a global analysis of the complete VP2 gene sequences of CPV-2 strains in China. Six isolates were typed as new CPV-2a, according to key amino acid positions. On a phylogenetic tree, these six sequences formed a distinct clade. Five isolates occurred on the same branch as KF785794 from China and GQ379049 from Thailand; CPV-LS-ZA1 formed a separate subgroup with FJ435347 from China. One hundred ninety-eight sequences from various parts of China and the six sequences isolated here formed seven distinct clusters, indicating the high diversity of CPVs in China. Of 204 VP2 sequences, 183 (91.04%) encoded the mutation Ser297Ala, regardless of the antigenic type, implying that most Chinese CPV-2 strains contain the VP2 mutation Ser297Ala. However, the biological significance of this change from prototype CPV-2a/2b to new CPV-2a/2b types remains unclear. This study is the first to isolate new CPV-2a from the Tibetan mastiff. Our data show that new CPV-2a/2b variants are now circulating in China.