Circ-AGTPBP1 promotes white matter injury through miR-140-3p/Pcdh17 axis role of Circ-AGTPBP1 in white matter injury.

White matter injury (WMI) resulting from intracerebral hemorrhage (ICH) is closely associated with adverse prognoses in ICH patients. Although Circ-AGTPBP1 has been reported to exhibit high expression in the serum of premature infants with WMI, its effects and mechanisms in ICH-induced WMI remain unclear. This study aimed to investigate the role of circ-AGTPBP1 in white matter injury after intracerebral hemorrhage. An intracerebral hemorrhage rat model was established by injecting autologous blood into rat left ventricles and circ-AGTPBP1 was knocked down at the ICH site using recombinant adeno-associated virus, AAV2/9. Magnetic resonance imaging (MRI) and gait analysis were conducted to assess long-term neurobehavioral effects. Primary oligodendrocyte progenitor cells (OPCs) were isolated from rats and overexpressed with circ-AGTPBP1. Downstream targets of circ-AGTPBP1 in OPCs were investigated using CircInteractome, qPCR, FISH analysis, and miRDB network. Luciferase gene assay was utilized to explore the relationship between miR-140-3p and Pcdh17 in OPCs and HEK-293T cells. Finally, CCK-8 assay, EdU staining, and flow cytometry were employed to evaluate the effects of mi-RNA-140-3p inhibitor or silencing of sh-pcd17 on the viability, proliferation, and apoptosis of OPCs. Low expression of circ-AGTPBP1 alleviates white matter injury and improves neurological functions in rats after intracerebral hemorrhage. Conversely, overexpression of circ-AGTPBP1 reduces the proliferative and migrative potential of oligodendrocyte progenitor cells and promotes apoptosis. CircInteractome web tool and qPCR confirmed that circ-AGTPBP1 binds with miR-140-3p in OPCs. Additionally, miRDB network predicted Pcdh17 as a downstream target of miR-140-3p. Moreover, pcdh17 expression was increased in the brain tissue of rats with intracerebral-induced white matter injury. Furthermore, inhibiting miR-140-3p suppressed the proliferation and migration of OPCs and facilitated apoptosis through Pcdh17. Circ-AGTPBP1 promotes white matter injury through modulating the miR-140-3p/Pcdh17 axis. The study provides a new direction for developing therapeutic strategies for white matter injury.

High human bocavirus viral load is associated with disease severity in children under five years of age.

Human bocavirus (HBoV) is a parvovirus and detected worldwide in lower respiratory tract infections (LRTIs), but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses. To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity, we performed a 3-year prospective study of HBoV in healthy controls, outpatients and inpatients under five years of age with X-ray diagnosed LRTIs. Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1-4. Nasopharyngeal swabs from healthy controls and serum samples and stools from inpatients were also tested for HBoV1-4 by real time PCR. Viral loads were determined by quantitative real time PCR in all HBoV positive samples. HBoV1 was detected in 7.0% of inpatients, with annual rates of 5.1%, 8.0% and 4.8% in 2010, 2011 and 2012, respectively. Respiratory syncytial virus (RSV) subtype A was the most frequent co-infection detected; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations. High HBoV viral loads (>10(6) copies/ml) were significantly more frequent in inpatients and outpatients than in healthy controls. There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus. In summary, our data suggest that HBoV1 can cause LRTIs, but symptomatic HBoV infection is only observed in the context of high viral load.

Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

BACKGROUND: The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. METHODS AND PRINCIPAL FINDINGS: We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. CONCLUSION AND SIGNIFICANCE: A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations.