Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli

AIM: To investigate the effect of a new infant formula supplemented with a low level (0.24 g/100 mL) of galacto-oligosaccharide (GOS) on intestinal micro-flora (Bif idobacteria, Lactobacilli and E. coli) and fermentation characteristics in term infants, compared with human milk and a standard infant formula without GOS. METHODS: Term infants (n = 371) were approached in this study in three hospitals of China. All infants started breast-feeding. Those who changed to formula-feeding within 4 wk after birth were randomly assigned to one of the two formula groups. Growth and stool characteristics, and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period. Fecal samples were collected from a subpopulation of recruited infants for analysis of intestinal bacteria (culture technique), acetic acid (gas chromatography) and pH (indicator strip). RESULTS: After 3 mo, the intestinal Bifidobacteria, Lactobacilli , acetic acid and stool frequency were significantly increased, and fecal pH was decreased in infants fed with the GOS-formula or human milk, compared with those fed with the formula withoutGOS. No significant differences were observed between the GOS formula and human milk groups. Supplementation with GOS did not influence the incidence of crying, regurgitation and vomiting. CONCLUSION: A low level of GOS (0.24 g/100 mL) in infant formula can improve stool frequency, decrease fecal pH, and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk.

Liver immunity,autoimmunity,and inborn errors of immunity

The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.

Differential diagnosis in ulcerative colitis in an adolescent: Chronic granulomatous disease needs extra attention

Chronic granulomatous disease(CGD) is a primary immune deficiency that is commonly diagnosed under the age of 5 years(95%) and is rarely seen in adulthood. CGD may manifest as inflammatory bowel disease(IBD) in childhood. Without proper diagnosis, these patients may be monitored for years as IBD; some may even be regarded as steroid-resistant ulcerative colitis(UC) and end up having a colectomy. In this case report, we described a patient who had been followedup for years as UC and subsequently underwent colectomy, but was finally diagnosed in adulthood as primary immune deficiency.

Long-COVID-19: the persisting imprint of SARS-CoV-2 infections on the innate immune system

In a recent Cell publication,Cheong et al.uncover how COVID-19 causes IL-6 induced epigenetic reprogramming of human immune stem cells,which causes lasting alterations in the composition and response characteristics of circulating immune cells.1 The study provides important insights into the mechanisms by which SARSCoV-2 infections impact the human immune system and is an important hook into unraveling the mechanisms of post-acute sequelae of COVID-19(PASC)commonly referred to as longCOVID.

Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis

Background Overexpression of the components of the Janus kinase/signal transducer and activator of transcription(JAK/STAT)signalling pathway is the key factor of the pathogenic mechanisms underlying systemic juvenile idiopathic arthritis(sJIA).The study aims to investigate the association between miR-21 and the JAK/STAT signal pathway in JIA.Methods Total RNA was extracted from peripheral blood mononuclear cells(PBMCs)in active JIA patients.The relative expressions of miR-21,STAT3 and suppressor of cytokine signalling 3 in PBMCs were measured by real-time polymerase chain reaction and their expressions were measured by western blotting and dual-luciferase reported assay.Rheumatoid arthritis fibroblast-like synovial cell(RASF)was stimulated to become to osteoclasts using macrophage colony-stimulating factor(M-CSF)and factors that can impact on their differentiation ability were identified through the transfection of LV3-miR-21.The expression of STAT3/p-STAT3 was measured by western blot,and the levels of interleukin(IL)-17A,p65,matrix metalloproteinases(MMP)-3,MMP-4 and receptor activator of nuclear factor-κd3 after the LV3-miR-21 transfection were tested by enzyme-linked immunosorbent assay.Finally,the miR-21 targeted STAT3 gene was detected by the dualluciferase reported assay.Results The expression of miR-21 was significantly lower in JIA patients than in healthy control(P<0.05).The level of STAT3 was increased in PBMCs of JIA group compared with control group(P<0.05).Furthermore,the expression levels of miR-21 in sJIA and polyarticular JIA groups were negatively correlated with STAT3(r=-0.5854/r=-0.6134,P<0.05).The expression of STAT3 changed little in PBMCS after the stimulation of IL-6 and not in RASFs with transfection of LV3-miR-21.The expression of p-STAT3 decreased after the stimulation of IL-6 in RASFs transfected by LV3-miR-21(P<0.05).RASFs were induced into osteoclasts using M-CSF.The number of osteoclasts as determined by tartrate-resistant acid phosphatase staining was significantly lower in group miR-21 mimics as compared with the negative control group(P<0.05).Conclusions We showed that expression of miR-21 was significantly lower in JIA patients compared with healthy control.MiR-21 might affect the JAK/STAT signal pathway by suppressing the expression of STAT3 and phosphorylation of STAT3.MiR-21 could inhibit the production of osteoclasts induced from RASFs by M-CSF.

Effect of early atopic sensitization in children aged 0–2 years on the development of asthma symptoms at 9–11 years of age

Background Personal genetic predisposition and early life environmental factors are important for the development of childhood asthma.We aimed to search whether egg,milk and mite sensitizations at 0–2 years old are risk factors for asthma symptoms at 9–11 years old.Methods A total of 210 wheezer children who had specific immunoglobulin(Ig)E in 2010–2012 were included in the study(followed by pediatric allergy).Patients were divided into non-atopic(group 1,n=157)and atopic patients[groups 2–7,n=53(5 patients were in both group 4 and group 5)]based on sensitizations.Using the International Study of Asthma and Allergy in Childhood questionnaire,current wheeze(CW,2nd question),exercise wheezing(EW,7th question),and dry cough(DC,8th question)were surveyed.Also,parental allergies,eczema at 0–2 years,current eosinophil percentage and total IgE were recorded.Results Eczema was observed as an important risk factor[CW:odds ratio(OR)=2.83,95%confidence interval(CI)=1.54–5.23,P≤0.001;EW:OR=2.71,95%CI=1.33–5.54,P=0.006;DC:OR=3.03,95%CI=1.47–6.25,P=0.003],whereas having no atopic sensitization at 0–2-year-old(group 1)was found as a significant protective factor for asthma at 9–11 years old(CW:OR=0.32,95%CI=0.15–0.70,P=0.004;EW:OR=0.21,95%CI 0.10–0.44,P≤0.001;DC:OR=0.25,95%CI=0.10–0.59,P=0.002).Conclusion Early personal eczema is a significant risk factor for the development of asthma symptoms at 9–11 years old,whereas not having an allergic sensitization at 0–2 years old(group 1)is an important protective factor.

simplifyEnrichment:A Bioconductor Package for Clustering and Visualizing Functional Enrichment Results

Functional enrichment analysis or gene set enrichment analysis is a basic bioinformatics method that evaluates the biological importance of a list of genes of interest.However,it may produce a long list of significant terms with highly redundant information that is difficult to summarize.Current tools to simplify enrichment results by clustering them into groups either still produce redundancy between clusters or do not retain consistent term similarities within clusters.We propose a new method named binary cut for clustering similarity matrices of functional terms.Through comprehensive benchmarks on both simulated and real-world datasets,we demonstrated that binary cut could efficiently cluster functional terms into groups where terms showed consistent similarities within groups and were mutually exclusive between groups.We compared binary cut clustering on the similarity matrices obtained from different similarity measures and found that semantic similarity worked well with binary cut,while similarity matrices based on gene overlap showed less consistent patterns.We implemented the binary cut algorithm in the R package simplifyEnrichment,which additionally provides functionalities for visualizing,summarizing,and comparing the clustering.The simplifyEnrichment package and the documentation are available at https://bioconductor.org/packages/simplifyEnrichment/.