Characterization of changes in the intestinal microbiome following combination therapy with zinc preparation and conventional treatment for children with rotavirus enteritis.

Background: Rotavirus (RV) is one of the most common pathogens causing diarrhea in infants and young children worldwide. Routinely, antiviral therapy, intestinal mucosa protection, and fluid supplementation are used in clinic, however this is not efficacious in some severe cases. Zinc supplementation has previously been shown to improve resolution of symptoms from infectious diarrhea. Methods: In this study differences in response rate, duration of hyperthermia, vomiting, and diarrhea, and the persistence time of cough and lung rales in groups were compared. 16SrDNA gene sequencing technology was used to analyze and compare changes in the intestinal microflora of children with RV enteritis who received the conventional treatment with or without the zinc preparation. In addition, the correlations between the differential bacterial species and the related inflammatory factors were determined. Results: Conventional therapy combined with the zinc preparation significantly shortened the duration of hyperthermia, vomiting, and diarrhea compared with the conventional treatment alone. In addition, the time to symptom relief showed that the absorption time of cough and lung rales was significantly shorter in the combination treatment group than that in the conventional treatment group in the children with pneumonia. Further, compared with the conventional treatment, the combined treatment significantly increased the diversity and abundances of florae as compared with the conventional treatment. This combination therapy containing zinc preparation markedly increased the abundances of Faecalibacterium, Bacteroidales, Ruminoccoccoccus, and Lachnospiraceae at the genus level. The LEfSe analysis suggested that Clostridiumbolteae were most significantly altered after the combination therapy. In addition, a correlation analysis revealed significantly negative correlations between the inflammatory factors especially IL-6, TNF-a, CRP and some intestinal florae such as Bacteroides, Faecalibacterium, Blautia, Parabacteroides, Subdoligranulum, and Flavonifractor. Conclusion: Compared with the conventional therapy alone, the combined therapy with the zinc preparation significantly improves symptoms caused by RV. The combination therapy containing the zinc preparation significantly increases the diversity and abundances of some beneficial groups of bacteria. Further, The presence of these groups was further negatively correlated with relevant inflammatory factors. More importantly, this combination therapy containing the zinc preparation provides a reference for the clinical management of children with RV enteritis.

Vitamin A deficiency and vitamin A supplementation affect innate and T cell immune responses to rotavirus A infection in a conventional sow model.

Rotavirus A (RVA) causes ~200,000 diarrheal deaths annually in children <5yrs, mostly in low- and middle-income countries. Risk factors include nutritional status, social factors, breastfeeding status, and immunodeficiency. We evaluated the effects of vitamin A (VA) deficiency/VA supplementation and RVA exposure (anamnestic) on innate and T cell immune responses in RVA seropositive pregnant and lactating sows and passive protection of their piglets post-RVA challenge. Sows were fed VA deficient (VAD) or sufficient (VAS) diets starting at gestation day (GD)30. A subset of VAD sows received VA supplementation from GD|76 (30,000IU/day, VAD+VA). Sows (6 groups) were inoculated with porcine RVA G5P[7] (OSU strain) or Minimal Essential Medium (mock) at GD~90: VAD+RVA; VAS+RVA; VAD+VA+RVA; VAD-mock; VAS-mock; and VAD+VA-mock. Blood, milk, and gut-associated tissues were collected from sows at several time points to examine innate [natural killer (NK), dendritic (DC) cells], T cell responses and changes in genes involved in the gut-mammary gland (MG)-immunological axis trafficking. Clinical signs of RVA were evaluated post inoculation of sows and post-challenge of piglets. We observed decreased frequencies of NK cells, total and MHCII+ plasmacytoid DCs, conventional DCs, CD103+ DCs and CD4+/CD8+ and T regulatory cells (Tregs) and NK cell activity in VAD+RVA sows. Polymeric Ig receptor and retinoic acid receptor alpha (RARα) genes were downregulated in mesenteric lymph nodes and ileum of VAD+RVA sows. Interestingly, RVA-specific IFN-γ producing CD4+/CD8+ T cells were increased in VAD-Mock sows, coinciding with increased IL-22 suggesting inflammation in these sows. VA supplementation to VAD+RVA sows restored frequencies of NK cells and pDCs, and NK activity, but not tissue cDCs and blood Tregs. In conclusion, similar to our recent observations of decreased B cell responses in VAD sows that led to decreased passive immune protection of their piglets, VAD impaired innate and T cell responses in sows, while VA supplementation to VAD sows restored some, but not all responses. Our data reiterate the importance of maintaining adequate VA levels and RVA immunization in pregnant and lactating mothers to achieve optimal immune responses, efficient function of the gut-MG-immune cell-axis and to improve passive protection of their piglets.

In Vitro Evaluation of Anti-Rotaviral Activity and Intestinal Toxicity of a Phytotherapeutic Prototype of Achyrocline bogotensis (Kunth) DC.

Viruses represent the primary etiologic agents (70-80%) of acute diarrheal disease (ADD), and rotavirus (RV) is the most relevant one. Currently, four rotavirus vaccines are available. However, these vaccines do not protect against emerging viral strains or are not available in low-income countries. To date, there are no approved drugs available against rotavirus infection. In this study, we evaluated the in vitro anti-rotaviral activity and intestinal toxicity of a phytotherapeutic prototype obtained from Achyrocline bogotensis (Kunth) DC. (PPAb); medicinal plant that contains compounds that inhibit the rotavirus replication cycle. Virucidal and viral yield reduction effects exerted by the PPAb were evaluated by immunocytochemistry and flow cytometry. Furthermore, the toxic impact of the PPAb was evaluated in polarized human intestinal epithelial C2BBe1 cells in terms of cytotoxicity, loss of cytoplasmic membrane asymmetry, and DNA fragmentation by MTT and fluorometry. PPAb concentrations under 0.49 mg/mL exerted significant virucidal and viral yield reduction activities, and concentrations under 16 mg/mL neither reduced cell viability, produced DNA fragmentation, nor compromised the C2BBe1cell membrane stability after 24-h incubation. Based on these results, the evaluated phytotherapeutic prototype of Achyrocline bogotensis might be considered as a promising alternative to treat ADD caused by rotavirus.

Rotavirus Vaccine Impact Within an Integrated Healthcare Delivery System in the United States.

We assessed rotavirus vaccine impact using data on acute gastroenteritis (AGE) encounters within an integrated healthcare delivery system during 2000-2018. Following rotavirus vaccine introduction, all-cause AGE rates among children <5 years declined by 36% (95% confidence interval [CI]: 32%-40%) for outpatient and 54% (95% CI: 46%-60%) for inpatient encounters.

The Combined Escherichia coli Nissle 1917 and Tryptophan Treatment Modulates Immune and Metabolome Responses to Human Rotavirus Infection in a Human Infant Fecal Microbiota-Transplanted Malnourished Gnotobiotic Pig Model.

Human rotavirus (HRV) is a major cause of childhood diarrhea in developing countries where widespread malnutrition contributes to the decreased oral vaccine efficacy and increased prevalence of other enteric infections, which are major concerns for global health. Neonatal gnotobiotic (Gn) piglets closely resemble human infants in their anatomy, physiology, and outbred status, providing a unique model to investigate malnutrition, supplementations, and HRV infection. To understand the molecular signatures associated with immune enhancement and reduced diarrheal severity by Escherichia coli Nissle 1917 (EcN) and tryptophan (TRP), immunological responses and global nontargeted metabolomics and lipidomics approaches were investigated on the plasma and fecal contents of malnourished pigs transplanted with human infant fecal microbiota and infected with virulent (Vir) HRV. Overall, EcN + TRP combined (rather than individual supplement action) promoted greater and balanced immunoregulatory/immunostimulatory responses associated with greater protection against HRV infection and disease in malnourished humanized piglets. Moreover, EcN + TRP treatment upregulated the production of several metabolites with immunoregulatory/immunostimulatory properties: amino acids (N-acetylserotonin, methylacetoacetyl-CoA), lipids (gamma-butyrobetaine, eicosanoids, cholesterol-sulfate, sphinganine/phytosphingosine, leukotriene), organic compound (biliverdin), benzenoids (gentisic acid, aminobenzoic acid), and nucleotides (hypoxathine/inosine/xanthine, cytidine-5'-monophosphate). Additionally, the levels of several proinflammatory metabolites of organic compounds (adenosylhomocysteine, phenylacetylglycine, urobilinogen/coproporphyrinogen) and amino acid (phenylalanine) were reduced following EcN + TRP treatment. These results suggest that the EcN + TRP effects on reducing HRV diarrhea in neonatal Gn pigs were at least in part due to altered metabolites, those involved in lipid, amino acid, benzenoids, organic compounds, and nucleotide metabolism. Identification of these important mechanisms of EcN/TRP prevention of HRV diarrhea provides novel targets for therapeutics development. IMPORTANCE Human rotavirus (HRV) is the most common cause of viral gastroenteritis in children, especially in developing countries, where the efficacy of oral HRV vaccines is reduced. Escherichia coli Nissle 1917 (EcN) is used to treat enteric infections and ulcerative colitis while tryptophan (TRP) is a biomarker of malnutrition, and its supplementation can alleviate intestinal inflammation and normalize intestinal microbiota in malnourished hosts. Supplementation of EcN + TRP to malnourished humanized gnotobiotic piglets enhanced immune responses and resulted in greater protection against HRV infection and diarrhea. Moreover, EcN + TRP supplementation increased the levels of immunoregulatory/immunostimulatory metabolites while decreasing the production of proinflammatory metabolites in plasma and fecal samples. Profiling of immunoregulatory and proinflammatory biomarkers associated with HRV perturbations will aid in the identification of treatments against HRV and other enteric diseases in malnourished children.

Characteristics of intussusception in the period of arbitrary Rotavirus vaccination.

BACKGROUND: In November 2011, rotavirus (RV) vaccine was launched in Japan as a voluntary vaccination to prevent RV-associated gastroenterocolitis. We examined the characteristics of intussusception following RV vaccination in our two centers. METHODS: We investigated intussusception patients <16 years old from January 2006 to September 2020. Patients were categorized according to the period (before [Group A] or after the introduction of arbitrary RV vaccination [Group B]). The patient characteristics and treatment of intussusception were retrospectively investigated. RESULTS: During the study period, 560 patients (group A, n = 233; group B, n = 327) were identified. The distribution of patients who were 0-6 months old was not significantly different between the groups (group A, n = 12, 5.2%; group B, n = 18, 5.5%). Among these 18 patients in Group B, 7 were vaccinated against RV, and 10 were not. One patient was excluded due to incomplete data. On comparing patients with and without RV vaccination, the mean age at the onset of intussusception was 3.3 ± 0.4 versus 4.0 ± 0.3 months (P = 0.19), the mean interval from the onset to treatment was 7.5 ± 2.4 versus 16.0 ± 2.2 h (P = 0.03), the time of the contrast enema for treatment was 9.1 ± 3.3 versus 7.7 ± 2.8 min (P = 0.76), and the final pressure of the contrast enema was 92.5 ± 4.4 versus 92.2 ± 4.4 cmH2 O (P = 0.97). CONCLUSIONS: Arbitrary RV vaccination did not influence the age distribution of intussusception, and the interval from the onset to treatment was significantly shorter in the patients with RV vaccination than in those without it. Recognizing the presence of intussusception following RV vaccination enables accurate treatment.

Establishment of a rotavirus-infected zebrafish model and its application in drug screening.

Rotavirus (RV) is one of the main pathogens that induce infantile diarrhea and by now no effective drugs are available for RV-induced infantile diarrhea. Thus the development of novel models is of vital importance for the pathological research of RV-induced infantile diarrhea, as well as the progress of the associated treatment strategy. Here we introduced for the first time that RV-Wa strain and RV-SA-11 strain could infect 5 dpf(day post fertilization) and 28 dpf larvae, to induce infantile diarrhea model that was highly consistent with the clinical infection of infants. RV infection significantly changed the signs, survival rate and inflammation of larvae. Some important indicators, including the levels of RV antigen VP4 and VP6, the in vivo RV tracking, and the RV particles were also analyzed, which collectively demonstrated that the model was successfully established. More importantly, we also determined the potentials of the proposed RV-infected zebrafish model for anti-viral drug assessment. In conclusion, we established a RV-infected zebrafish model with formulated relevant indicators both larvae and adult fish, which might be served as a high throughput platform for antiviral drug screening.

Norovirus and Other Viral Causes of Medically Attended Acute Gastroenteritis Across the Age Spectrum: Results from the Medically Attended Acute Gastroenteritis Study in the United States.

BACKGROUND: Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. METHODS: Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014-June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into 1 episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting-specific incidence estimates were calculated using age-stratified bootstrapping. RESULTS: The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged < 5 years (20.4 episodes per 1000 PY), followed by adults aged ≥ 65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY; astrovirus: 1.3 per 1000 PY; rotavirus: 0.5 per 1000 PY). CONCLUSIONS: Viral enteropathogens, particularly norovirus, are important contributors to MAAGE, especially among children < 5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE.

Investigating barriers to the protective efficacy provided by rotavirus vaccines in African infants.

Julie Bines discusses an accompanying study by Sheila Isanaka and colleagues on nutrient supplementation and immune responses to rotavirus vaccination.

Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

BACKGROUND: Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS: We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS: This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccination.

BACKGROUND: Recent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. METHODS: Over a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. RESULTS: Among 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19-2.65). CONCLUSIONS: Data from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.

Study on the effectiveness and safety of Xingpi Yanger granule combined with Saccharomyces boulardii for rotavirus enteritis in children: A protocol for systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the effectiveness and safety of traditional Chinese medicine preparation XPYEG combined with SBI and SBI alone in the treatment of REC, and to provide the reference in drugs for the clinical treatment of children with rotavirus enteritis. METHODS: Retrieving the English databases: PubMed, Cochrane Library and Embase; Chinese databases: CNKI, CBM and WANFANG Data. Retrieving a randomized controlled trial of XPYEG and SBI in the treatment of REC. The retrieval time is from the above database until September 2020. The retrieval strategy of combining free words and subject words is adopted, and the references included in the literature are searched manually in accordance with the literature studied in this paper and not included in the above database. Two researchers screen the literature according to the literature inclusion and exclusion criteria, extract valid data and evaluate the quality of the literature, and cross-check it. Using the RevMan 5.3 software to conduct the meta-analysis on the main outcome and secondary outcome indicators of the included literature, while assessing the evidence quality of included study. RESULTS: The effectiveness and safety of XPYEG and SBI in the treatment of REC are presented through the main and secondary outcome indicators. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/3QSZG. CONCLUSION: This study will conclude whether the combination of XPYEG and SBI is more effective than SBI alone in the treatment of REC, and whether the medication increases the risk of adverse reactions compared with single medication. ETHICS AND DISSEMINATION: This study does not involve the specific patients, and all research data comes from publicly available professional literature, so an ethics committee is not required to conduct an ethical review and approval of the study.

Escherichia coli Nissle 1917 Enhances Innate and Adaptive Immune Responses in a Ciprofloxacin-Treated Defined-Microbiota Piglet Model of Human Rotavirus Infection.

Human rotavirus (HRV) infection is a major cause of gastroenteritis in children worldwide. Broad-spectrum antibiotic-induced intestinal microbial imbalance and the ensuing immune-metabolic dysregulation contribute to the persistence of HRV diarrhea. Escherichia coli Nissle 1917 (EcN), a Gram-negative probiotic, was shown to be a potent immunostimulant and alleviated HRV-induced diarrhea in monocolonized gnotobiotic (Gn) piglets. Our goal was to determine how EcN modulates immune responses in ciprofloxacin (Cipro)-treated Gn piglets colonized with a defined commensal microbiota (DM) and challenged with virulent HRV (VirHRV). Cipro given in therapeutic doses for a short term reduced serum and intestinal total and HRV-specific antibody titers, while EcN treatment alleviated this effect. Similarly, EcN treatment increased the numbers of total immunoglobulin-secreting cells, HRV-specific antibody-secreting cells, activated antibody-forming cells, resting/memory antibody-forming B cells, and naive antibody-forming B cells in systemic and/or intestinal tissues. Decreased levels of proinflammatory but increased levels of immunoregulatory cytokines and increased frequencies of Toll-like receptor-expressing cells were evident in the EcN-treated VirHRV-challenged group. Moreover, EcN treatment increased the frequencies of T helper and T cytotoxic cells in systemic and/or intestinal tissues pre-VirHRV challenge and the frequencies of T helper cells, T cytotoxic cells, effector T cells, and T regulatory cells in systemic and/or intestinal tissues postchallenge. Moreover, EcN treatment increased the frequencies of systemic and mucosal conventional and plasmacytoid dendritic cells, respectively, and the frequencies of systemic natural killer cells. Our findings demonstrated that Cipro use altered immune responses of DM-colonized neonatal Gn pigs, while EcN supplementation rescued these immune parameters partially or completely.IMPORTANCE Rotavirus (RV) is a primary cause of malabsorptive diarrhea in children and is associated with significant morbidity and mortality, especially in developing countries. The use of antibiotics exacerbates intestinal microbial imbalance and results in the persistence of RV-induced diarrhea. Probiotics are now being used to treat enteric infections and ulcerative colitis. We showed previously that probiotics partially protected gnotobiotic (Gn) piglets against human RV (HRV) infection and decreased the severity of diarrhea by modulating immune responses. However, the interactions between antibiotic and probiotic treatments and HRV infection in the context of an established gut microbiota are poorly understood. In this study, we developed a Gn pig model to study antibiotic-probiotic-HRV interactions in the context of a defined commensal microbiota (DM) that mimics aspects of the infant gut microbiota. Our results provide valuable information that will contribute to the treatment of antibiotic- and/or HRV-induced diarrhea and may be applicable to other enteric infections in children.

Direct evidence of the preventive effect of milk replacer-based probiotic feeding in calves against severe diarrhea.

Diarrhea is a major cause of death in calves and this is linked directly to economic loss in the cattle industry. Fermented milk replacer (FMR) has been used widely in clinical settings for calf feeding to improve its health and growth. However, the protective efficacy of FMR on calf diarrhea remains unclear. In this study, we verified the preventive effects of FMR feeding on calf diarrhea using an experimental infection model of bovine rotavirus (BRV) in newborn calves and a field study in dairy farms with calf diarrhea. In addition, we evaluated the protective efficacy of lactic acid bacteria-supplemented milk replacer (LAB-MR) in an experimental infection model. In the experimental infection, calves fed FMR or high-concentrated LAB-MR had diarrhea, but the water content of feces was lower and more stable than that of calves fed normal milk replacer. The amount of milk intake also decreased temporarily, but recovered immediately in the FMR- and LAB-MR-fed calves. As compared with the control calves, FMR- or LAB-MR-fed calves showed less severe or reduced histopathological lesions of enteritis in the intestinal mucosa. In a field study using dairy calves, FMR feeding significantly reduced the incidence of enteritis, mortality from enteritis, duration of a series of treatment for enteritis, number of consultations, and cost of medical care for the disease. These results suggest that feeding milk replacer-based probiotics to calves reduces the severity of diarrhea and tissue damage to the intestinal tract caused by BRV infection and provides significant clinical benefits to the prevention and treatment of calf diarrhea.

Influence of individual or group housing of newborn calves on rotavirus and coronavirus infection during the first 2 months of life.

Bovine rotavirus A (RVA) and bovine coronavirus (CoV) are the two main viral enteropathogens associated with neonatal calf diarrhea. The aim of the present work was to study the impact of group and individual housing systems in the epidemiology of RVA and CoV infection. Eleven calves reared in individual housing (FA) and nine calves in group housing (FB) were monitored during the first 7 weeks of life. Stool and serum samples were screened for RVA and CoV antigens by ELISA. IgG1 antibodies (Ab) to both antigens were also measured. From the 160 fecal samples collected, the proportion of positive samples to RVA and CoV was significantly higher in FB (23.6%) than in FA (9%) (p = 0.03). The geometric mean of colostral IgG1 Ab titers to CoV and RVA in FA (IgG1 anti-CoV 1024 and anti-RVA 1782.9) was lower than in FB (IgG1 anti-CoV 10,321.2 and anti-RVA 4096) at birth. Calves less than 2 weeks of life from FB had a higher risk of being infected by RVA (OR = 4.9; p = 0.01) and CoV (OR = 17.15; p = 0.01) than calves from FA. The obtained results showed that there was higher RVA and CoV shedding in group-housed calves than in individual-housed animals.

Valeriana jatamansi Jones Inhibits Rotavirus-Induced Diarrhea via Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway.

Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1ß (IL-1ß), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.

Generation of recombinant rotaviruses encoding a split NanoLuc peptide tag.

Recombinant viruses expressing fluorescent or luminescent reporter proteins are used to quantitate and visualize viral replication and transmission. Here, we used a split NanoLuc luciferase (NLuc) system comprising large LgBiT and small HiBiT peptide fragments to generate stable reporter rotaviruses (RVs). Reporter RVs expressing NSP1-HiBiT fusion protein were generated by placing an 11 amino acid HiBiT peptide tag at the C-terminus of the intact simian RV NSP1 open reading frame or truncated human RV NSP1 open reading frame. Virus-infected cell lysates exhibited NLuc activity that paralleled virus replication. The antiviral activity of neutralizing antibodies and antiviral reagents against the recombinant HiBiT reporter viruses were monitored by measuring reductions in NLuc expression. These findings demonstrate that the HiBiT reporter RV systems are powerful tools for studying the viral life cycle and pathogenesis, and a robust platform for developing novel antiviral drugs.

Gegen huangqin huanglian decoction for children rotavirus enteritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rotavirus infection is the main cause of severe dehydration enteritis in children under 5 years old. It gives rise to malnutrition and even death in children even though there were rotavirus vaccines. However, there is no effective anti-virus drugs for rotavirus, supporting treatments are used in the clinics. Traditional Chinese medicine (TCM) has been treating diarrhea for many years. Gegen Huangqin Huanglian Decoction (GHHD)is a classic prescription for diarrhea in TCM. With the development of clinical trials and basic studies, GHHD has been proved that a good curative effect on diarrhea. Therefore, a systematic review is necessary to improve available evidence for GHHD in therapy of children under 5 years old with rotavirus enteritis. METHODS: Different studies from various databases will be involved in this study. Only randomized controlled trials of rotavirus enteritis patients diagnosed with Guidelines for the Treatment of Acute Gastroenteritis in Outpatient Pediatrics, which released by the Washington International Children's Medical Center, Zhu Futang's Practical Pediatrics (7 th Edition), and the 2016 clinical practice guidelines for children with acute infectious diarrhea in China. We will search the literature in the databases from China Conference Paper Database, manual searching. Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, CNKI (China National Knowledge Internet), WanFang, VIP (Chongqing VIP), and CBM (China Biomedical Literature CDROM Database). The primary outcomes include the total effective rate, the time of stopping diarrhea, the level of IL-6 serum concentration, fecal microflora ratio, the conversion of fecal rotavirus antigen. The secondary outcomes include clinical efficacy and the quantitative integral of TCM symptom, recovery time of stool character, treatment period. Besides, incidence of adverse events (such as irritation and toxicity) and costs will be also considered. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3 and Stata V.12.0. RESULTS: This study will synthesize and provide high-quality evidence based on the data of the currently published GHHD for the treatment of children rotavirus enteritis, in terms of the total effective rate, the time of stopping diarrhea, the level of IL-6 serum concentration, fecal microflora ratio, stool rotavirus antigen, clinical efficacy and the quantitative integral of TCM symptom, recovery time of stool character, treatment period, and safety. CONCLUSION: This systematic review aims to evaluated the benefits and harms of GHHD for the treatment of children rotavirus enteritis reported in randomized controlled trials, and provide more options for clinicians and patients to treat children rotavirus enteritis. REGISTRATION NUMBER: INPLASY2020100023.

Acupoint application for rotavirus diarrhea in infants and children: A protocol for systematic review and meta analysis.

BACKGROUND: Diarrheal disease currently claims the lives of approximately 500,000 children each year. Rotaviruses are the pathogens primarily responsible for more severe cases and more than one-third of diarrhea-associated deaths in children under 5 years old globally. At present, commonly used drug therapies for rotavirus diarrhea in Western medicine, such as oral rehydration salts, montmorillonite, probiotics, and nitazoxanide, often cannot achieve satisfactory curative effects. Moreover, infants' and children's compliance with drugs and injections is often lower than their compliance with acupoint application therapy. A large number of studies have shown that acupoint application can increase the clinical cure rate and shorten the duration of diarrhea. However, there is a lack of systematic reviews on the safety and efficacy of acupoint application in the treatment of rotavirus diarrhea. Therefore, we will conduct a study to evaluate the safety and efficacy of acupoint application for rotavirus diarrhea in infants and children. METHODS: We will search the relevant medical literature using PubMed, EMBASE, Web of Science, Cochrane CENTRAL, China National Knowledge Infrastructure, the Wanfang Database, the Chinese Biomedical Literature Database, and the Chinese Scientific Journal Database from inception to August 2020. Both MeSH and free text terms will be utilized to obtain the maximum numbers of papers. No language restrictions will be applied, and the publication type will be limited to randomized controlled trials. Two teams will independently review and assess the studies for inclusion in the review. RevMan V 5.0 software will be applied for data extraction. The methodological quality of the included studies will be evaluated according to the Cochrane Handbook. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: The conclusion of this systematic review will provide evidence regarding whether acupoint application is an effective intervention for infants and children with rotavirus diarrhea. INPLASY REGISTRATION NUMBER: INPLASY202070123.