Inhibition of G1P3 expression found in the differential display study on respiratory syncytial virus infection

<p>Abstract</p> <p>Background</p> <p>Respiratory syncytial virus (RSV) is the leading viral pathogen associated with bronchiolitis and lower respiratory tract disease in infants and young children worldwide. The respiratory epithelium is the primary initiator of pulmonary inflammation in RSV infections, which cause significant perturbations of global gene expression controlling multiple cellular processes. In this study, differential display reverse transcription polymerase chain reaction amplification was performed to examine mRNA expression in a human alveolar cell line (SPC-A1) infected with RSV.</p> <p>Results</p> <p>Of the 2,500 interpretable bands on denaturing polyacrylamide gels, 40 (1.6%) cDNA bands were differentially regulated by RSV, in which 28 (70%) appeared to be upregulated and another 12 (30%) appeared to be downregulated. Forty of the expressed sequence tags (EST) were isolated, and 20 matched homologs in GenBank. RSV infection upregulated the mRNA expression of chemokines CC and CXC and interfered with type α/β interferon-inducible gene expression by upregulation of MG11 and downregulation of G1P3.</p> <p>Conclusion</p> <p>RSV replication could induce widespread changes in gene expression including both positive and negative regulation and play a different role in the down-regulation of IFN-α and up-regulation of IFN-γ inducible gene expression, which suggests that RSV interferes with the innate antiviral response of epithelial cells by multiple mechanisms.</p

Coinfection with EBV/CMV and other respiratory agents in children with suspected infectious mononucleosis

<p>Abstract</p> <p>Background</p> <p>Numerous studies have shown that Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can infect immunocompetent patients simultaneously with other agents. Nonetheless, multiple infections with other agents in EBV/CMV-infected children have received little attention. We conducted a retrospective study of children with suspected infectious mononucleosis. Peripheral blood samples were analyzed by indirect immunofluorescence to detect EBV, CMV and other respiratory agents including respiratory syncytial virus; adenovirus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; <it>Chlamydia pneumonia</it>e and <it>Mycoplasma pneumoniae</it>. A medical history was collected for each child.</p> <p>Results</p> <p>The occurrence of multipathogen infections was 68.9%, 81.3% and 63.6% in the children with primary EBV, CMV or EBV/CMV, respectively, which was significantly higher than that in the past-infected group or the uninfected group (<it>p </it>< 0.001). Of the multipathogen-infected patients, the incidence of <it>C. pneumoniae </it>in children with primary infection was as high as 50%, significantly higher than in the other groups (<it>p </it>< 0.001). In the patients with multipathogen infection and EBV/CMV primary infection, fever, rash, lymphadenopathy, hepatomegaly, splenomegaly, atypical lymphocytes and abnormal liver function were more frequent and the length of hospital stay and duration of fever were longer than in other patients.</p> <p>Conclusion</p> <p>Our study suggests that there is a high incidence of multipathogen infections in children admitted with EBV/CMV primary infection and that the distribution of these pathogens is not random.</p

Multipathogen infections in hospitalized children with acute respiratory infections

<p>Abstract</p> <p>Background</p> <p>To explore the epidemiologic and clinical features of, and interactions among, multipathogen infections in hospitalized children with acute respiratory tract infection (ARTI). A prospective study of children admitted with ARTI was conducted. Peripheral blood samples were analyzed by indirect immunofluorescence to detect respiratory agents including respiratory syncytial virus; adenovirus; influenza virus (Flu) types A and B; parainfluenza virus (PIV) types 1, 2, and 3; chlamydia pneumonia; and mycoplasma pneumonia. A medical history of each child was taken.</p> <p>Results</p> <p>Respiratory agents were detected in 164 (51.9%) of 316 children with ARTI. A single agent was identified in 50 (15.8%) children, and multiple agents in 114 (36.1%). Flu A was the most frequently detected agent, followed by Flu B. Coinfection occurred predominantly in August and was more frequent in children between 3 and 6 years of age. A significantly higher proportion of Flu A, Flu B, and PIV 1 was detected in samples with two or more pathogens per sample than in samples with a single pathogen.</p> <p>Conclusion</p> <p>Our study suggests that there is a high occurrence of multipathogen infections in children admitted with ARTI and that coinfection is associated with certain pathogens.</p

RSV replication is attenuated by counteracting expression of the suppressor of cytokine signaling (SOCS) molecules

AbstractHuman RSV causes an annual epidemic of respiratory tract illness in infants and in elderly. Mechanisms by which RSV antagonizes IFN-mediated antiviral responses include inhibition of type I IFN mRNA transcription and blocking signal transduction of JAK/STAT family members. The suppressor of cytokines signaling (SOCS) gene family utilizes a feedback loop to inhibit cytokine responses and block the activation of the JAK/STAT signaling pathway. To evaluate the potential of SOCS molecules to subvert the innate immune response to RSV infection, eight SOCS family genes were examined. RSV infection up-regulated SOCS1, SOCS3, and CIS mRNA expression in HEp-2 cells. Suppression of SOCS1, SOCS3 and CIS by short interfering ribonucleic acid (siRNA) inhibited viral replication. Furthermore, inhibition of SOCS1, SOCS3, or CIS activated type I IFN signaling by inducing STAT1/2 phosphorylation. These results suggest that RSV infection escapes the innate antiviral response by inducing SOCS1, SOCS3 or CIS expression in epithelial cells

Treatment Options for Complications of Sickle-cell Disease in Children

Prospecting clinical comprehensive and approach paradigms of therapeutic management in pediatric age groups with sickle-cell disease is the mainstay indigence. Data over the last two decades was gathered to perform this review through multiple databases such Pubmed, Medline (OvidSP), Embase, Cochrane library, CINAHL (EBSCOHost), Web of science CPCI-S and from manual search in google scholar. The search terms included anemia, sickle cell, sickle cell disease, acute pain, complication, treatment, and management with highlight on pediatric age. Those have full text recoverable with English language where involved for this review. Sickle-cell disease is an umbrella term of hereditary illness, the most common of hemoglobinopathy worldwide with epidemiological importance and challenge in public health. The disease is encompassing the mutations in the gene of hemoglobin subunit β, and manifesting via the acute vaso-occlusive crisis. It is highlighted with a troika of pain syndromes, anemia and its corollaries, and end-organ dysfunction, involving infection states whence its classification into a multisystem illness. Acute pain crisis, therefore, is the hallmark of the condition and tyrannizes its clinical presentation during the whole life of the patients. In some children, the remedy has been accomplished by practicing cord blood transplantation or allogeneic bone marrow transplantation. A thorough management of the disease on approach supportive, symptomatic, preventive, acute, and curative based, enhances in timely the quality of life of patients, except the cost burden of healthcare system which is higher

Profile and clinical characterization of seizures in hospitalized children

Introduction: seizure is the commonest pediatric neurological disorder, which is frightening to caretakers. The current study aims to determine profile, clinical spectrum and analyze the commonest etiology of seizures in children admitted to a tertiary hospital in Central China. Methods: this was a hospital based retrospective study carried out in Zhongnan Hospital of Wuhan University, China. Computerized data was collected from January 2012 to May 2015. Variables collected were demographics, clinical presentations and laboratory tests; brain imaging studies, electroencephalography, diagnosis, prognosis, outcome and duration of hospitalization. Results: a total of 200 patients were admitted with seizures. There were 109 (54.5%) males and 91 (45.5%) females. Among these patients, 193 (96.5%) were aged 1 month to 5 years and 182 (91.0%) presented with seizures and fever. Generalized tonic-clonic seizure was the most common seizure type in 196 (98.0%) children. Febrile seizure was the leading etiology of seizure in 175 (87.5%) children followed by epilepsy in 11 (5.5%) children. There were only 3 (2%) children with central nervous system infections. Abnormal brain images were noted in 10 (20%) out of 50 patients. Among 193 children tested for different infections, 49 (25.4%) had positive results. Viral infections were commonest infections by 49.0%, atypical bacterial 34.7% and 16.3% coinfections. Conclusion: seizure was the commonest neurological condition of children admitted in our hospital, febrile seizures being the commonest etiology. The prognosis and outcomes were good but there were prolonged days of hospitalization. Children with unprovoked seizures require brain-imaging studies for better understanding of seizure etiology.The Pan African Medical Journal 2016;2

Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling

Respiratory syncytial virus (RSV) infection upregulates genes of the suppressor of cytokine signaling (SOCS) family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS) protein expression plasmids (pNS1, pNS2, and pNS1/2) and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN-) α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling

High-dose of intravenous immunoglobulin modulates immune tolerance in premature infants

Abstract Background Intravenous immunoglobulin (IVIG) is commonly used to improve the immunomodulatory effects, although its regulatory effect on premature Treg cells is unclear. The purpose of this study is to study the effect of high dose of IVIG (HD-IVIG) on Treg cells expression and cytokine profile in premature birth. Methods Fifty-two premature infants were enrolled in this study and thirty-one premature infants who were suspected to have intrauterine infection received HD-IVIG (1–2 g/kg) at the first day of birth; the remaining 21 premature infants were assigned as the control group. The peripheral blood CD4 + T and foxp3+ Treg cells were checked by flow cytometry, and cytokine concentrations were detected by cytometric bead array. Results With the gestational age growth, peripheral blood CD4 + T and foxp3+ Treg cells of prematurity gradually declined from 50% to 35% and from 8% to 6%, respectively. Meanwhile, HD-IVIG increased the percentage of CD4 + T and foxp3+ Treg cells compared with their baseline levels (p < 0.001). HD-IVIG demonstrated different regulating effects on cytokines secretion, increased IL-17 and TGF-β, and inhibited IL-6 secretion. Conclusion Our results demonstrated that HD-IVIG not only enhanced the premature immune tolerance, but also suppressed the excessive inflammation response mediated by IL-6. Trial registration This study was under the clinical study registration (ChiCTR-ORC-16008872, date of registration, 2016–07-21)

A SARS-CoV-2 familial cluster infection reveals asymptomatic transmission to children

Information on SARS-CoV-2 asymptomatic infection and infectivity in children is limited. In this study, we aimed to report the epidemiological and clinical characteristics of a familial cluster infection including children with SARS-CoV-2. On February 1, 2020, two children(case 1 and case 2), an 8-year-old girl and a 9-year-old boy, were admitted to the isolation ward in Xiangyang Central Hospital, Hubei province, China, with the diagnosis of COVID-19. Before admission, they had been staying at home with their father and never contacted with any confirmed patients except their mother (case 3) who returned from Wuhan on January 22. Both case 1 and case 2 got mild symptoms. Case 3 did not develop any symptoms until February 6, 2020, with an asymptomatic period of 15 days. She was transferred to ICU and administered multiple treatment according to the disease progression and chest CT manifestations. Her nucleic acid test turned positive until Feb 21, 2020, 15 days after symptoms onset, 30 days after her return from Wuhan. Our data showed that patients with SARS-CoV-2 may have the ability to transmit during their asymptomatic period even with the negative of viral nucleic acid in pharyngeal swabs