sIgA Levels Research Articles

Mucosal humoral immune response of respiratory tract in medical workers during the post-COVID-19 period

Currently, the role of local respiratory tract immunoglobulins in COVID-19 and rearrangement of mucosal immune response in the post-COVID period have not been sufficiently studied. Our aim was to evaluate long-term effects of novel coronavirus infection on the mucosal immunity in healthcare workers over the post-infection period.
 A total of 180 healthcare workers, ranging in age from 18 to 65 years, were enrolled in a one-stage, cross-sectional study. The subjects with a history of COVID-19 were divided into three groups, depending on the severity of their disease. The control group consisted of 44 healthcare workers who had no history of novel coronavirus infection. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, naso- and oropharyngeal scrapings by ELISA technique. Specific anti-SARS-CoV-2 IgG antibodies were quantified in the serum by chemiluminescence immunoassay.
 Numerous shifts in adaptive immune response were detected for different mucosal compartments, i.e., in subjects who suffered from severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p 0.05 and p 0.005, respectively). An inverse correlation was demonstrated between the levels of total sIgA in all mucosal sites, and the number of days from the onset of disease to the start of study (r = 0.278, р 0.05). When compared to the control subjects, all the patients with prior COVID-19 had significantly higher levels of total IgG in the induced sputum samples. Total IgG in saliva was also higher in the group of patients who had severe infection (p 0.05). By contrast, IgG levels in nasopharyngeal samples were decreased in severe and moderately severe groups compared to the control group, thus, probably, indicating an immunodeficiency state in these cases. A direct significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum.
 Long-term changes in the humoral mucosal immune response were most pronounced in the healthcare workers with a history of severe or moderate-to-severe COVID-19.

Application of Intestinal Barrier Molecules in the Diagnosis of Acute Cellular Rejection After Intestinal Transplantation.

Diagnosing acute rejection after intestinal transplantation currently heavily relies on histopathological analysis of graft biopsies. However, the invasive risks associated with ileoscopic examination and the inaccessibility for biopsy after ileostomy closure hinder real-time detection of rejection responses. Molecules comprising the intestinal barrier have been identified as physiological and molecular biomarkers for various bowel conditions and systemic diseases. To investigate the potential of barrier function-related molecules in diagnosing rejection after intestinal transplantation, plasma samples were collected longitudinally from transplant recipients. The samples were categorized into "indeterminate for rejection (IND)" and "acute rejection (AR)" groups based on clinical diagnoses at each time point. The longitudinal association between plasma levels of these barrier function-related molecules and acute rejection was analyzed using the generalized estimating equations (GEE) method. Logistic GEE models revealed that plasma levels of claudin-3, occludin, sIgA, and zonulin were independent variables correlated with the clinical diagnosis of acute rejection. The subsequent prediction model demonstrated moderate ability in discriminating between IND and AR samples, with a sensitivity of 76.0%, specificity of 89.2%, and accuracy of 84.6%. In conclusion, monitoring plasma levels of claudin-3, occludin, sIgA, and zonulin shows great potential in aiding the diagnosis of acute rejection after intestinal transplantation.

THE CONTENT OF SECRETORY IMMUNOGLOBULIN A IN BREAST MILK OF PATIENTS WITH LACTATIONAL MASTITIS

Introduction. The protective function of breast milk is provided by a number of specific and non-specific anti-infective factors: secretory immunoglobulin A, immunoglobulins A, G, M, E, cellular elements (neutrophils, lymphocytes, macrophages), cytokines, lactoferrin, lysozyme, oligosaccharides, bifido- and lactobacteria, antioxidants and.
 The main class of human milk immunoglobulins is secretory immunoglobulin A (sIgA), which protects the surfaces of mucous membranes from the penetration of microorganisms, neutralizes toxins and localizes viruses, and stimulates phagocytosis. Currently, information on the local level of secretory immunoglobulin A in the development of the inflammatory process in the mammary gland is not numerous and requires research.
 The aim of the study. To assess the content of secretory IgA in breast milk of patients with lactational mastitis.
 Research metods. The study dealt with breast milk of 97 women aged 18 to 36 (average age: 26±5 years old). The standard indicators of the secretory immunoglobulin A contents in 30 practically healthy lactating women of the same age – the control group – were the issue of the analyses. The first group included 30 women with lactostasis, the second group consisted of 37 women with lactational mastitis. The content of secretory immunoglobulin A was determined by enzyme immunoassay using an automatic STAT FAX 303 plus analyzer.
 Results and discussion. The concentration of sIgA in breast milk with lactostasis is on average 0.72±0.04 mg/ml, which is 3 times higher than the control indicator (0.24±0.02 mg/ml; p<0.05). During the development of lactational mastitis, the level of sIgA is 0.75±0.05 mg/ml, which exceeds the control values by 3.1 times (р<0.05). The content of sIgA in the breast milk of women with lactostasis does not differ from the level of this immunoglobulin in patients with lactational mastitis. A high concentration of sIgA indicates the activation of immune protection on mucous membranes.
 Conclusions. Increased production of secretory immunoglobulin A in breast milk was found in experimental groups compared to practically healthy women, which indicates activation of local humoral immunity as a reaction to infection.

Prevalence and association of sIgA in saliva and Pseudomonas aeruginosa infection in TB patients: a cross-sectional study

Abstract Objectives Pseudomonas aeruginosa is pathogenic in immunocompromised individuals. It has several complex mechanisms for evading human immunity. The objective of the study was to examine the secretory immunoglobulin A (sIgA) mediated immune response in saliva to detect P. aeruginosa in pulmonary tuberculosis. Methods The infection with P. aeruginosa was categorized according to the Leeds criteria in the final 86 individuals who were proven to have pulmonary tuberculosis by polymerase chain reaction. Levels of serum immunoglobulin G (IgG) and sIgA which are specific to P. aeruginosa were measured using the method of ELISA. Results Patients in the “free of infection (patients who were infected with P. aeruginosa in the lower respiratory tract at the beginning of the study later became negative)” and “intermittent colonized (patients who were infected with P. aeruginosa throughout the study)” groups had substantially higher median baseline sIgA levels in saliva and a much greater proportion of sIgA positive than patients who were never colonized (patients who were found to be P. aeruginosa negative throughout the study) (p=0.038). Median baseline IgG level was 10.7 (1.7–145.0), 8.3 (2.5–22.9), and 6.7 (3.3–17.1) for the patients categorized as “intermittent colonization”, “free of infection” and “never colonized”, respectively. After 3 years of study, sIgA level was found in significant high level among the patients with infection of P. aeruginosa (p=0.003). Conclusions Secretory IgA may be readily collected from saliva and is a useful diagnostic technique for determining whether P. aeruginosa infection has occurred.

Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway.

Currently, the effect and molecular mechanism of calycosin, the main active ingredient of Qinshi Simiao San, which can alleviate chronic prostatitis (CP), on CP remain unclear. This study aimed to elucidate the potential mechanism of action of calycosin in CP in a rat CP model. The prostate tissue morphology was evaluated based on hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was conducted to evaluate inflammatory cytokine and immune factor levels (secretory immunoglobulin A [SIgA]; immunoglobulin G [IgG]) in prostate tissues and serum. Additionally, representative biomarkers of oxidative stress, including malondialdehyde, superoxide dismutase, and catalase were detected using detection kits, and reactive oxygen species release was evaluated using immunofluorescence staining. Furthermore, the p38 mitogen-activated protein kinase (p38MAPK)/NF-kappaB (NF-κB) signaling pathway was analyzed by western blotting. The results showed that calycosin substantially ameliorated the pathological damage to prostate tissues of the CP rats. Moreover, calycosin significantly downregulated interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha, IgG, and SIgA levels. Furthermore, we found that calycosin considerably suppressed oxidative stress and inhibited the activation of the p38MAPK/NF-κB signaling pathway in rats with CP. In summary, our findings revealed that calycosin protects against CP in rats by inhibiting the p38MAPK/NF-κB pathway.

CATION COMPOSITION OF ORAL SECRETION IN PRIMARY SCHOOL-AGED CHILDREN

SUMMARY. Recurrent respiratory infections (RRIs) currently have the greatest medical and social burden among infectious diseases worldwide, with the highest prevalence and incidence rates of acute respiratory infections in children. Recent studies indicate the role of inadequate immune response and the development of recurrent acute respiratory infections (ARI) in children due to deficiencies in essential trace elements in the body, which are crucial for the proper functioning of physical barriers and the immune system. The hypothesis of our study assumed that, considering the recurrence of at least 6 episodes of ARI per year, children with RRIs may have changes in salivary ion levels, which could serve as a basis for local immune suppression of the upper respiratory mucosa. The aim – to investigate the levels of metals in the saliva of children of primary school age with recurrent respiratory infections in comparison with episodically ill peers and establish the relationship of these changes with the state of local immunity. Material and Methods. In the actual study, 40 children participated, with 30 of them (the main group) being children with recurrent respiratory infections and 10 other children who had episodic illnesses were assigned to the control group. The levels of metal cations in the saliva were examined using inductively coupled plasma atomic emission spectrometry, including essential metals such as copper, manganese, zinc, calcium, cobalt, potassium, magnesium, sodium, phosphorus, selenium, iron, chromium, and sulfur. Additionally, levels of conditionally essential metals like lithium, nickel, and boron were measured. The levels of secretory IgA and lysozyme in saliva were determined using the enzyme-linked immunosorbent assay method. Results. The main group was not homogeneous; therefore, we divided it into two clusters. Respondents in one cluster had significantly lower relative levels of essential ion content in saliva. Specifically, calcium was lower in 64 % (p=0.003), copper in 76.5 % (p=0.001), manganese in 41.1 % (p=0.008), magnesium in 64 % (p=0.02), and zinc in 58.8 % (p=0.027). This fact can be explained by their increased losses due to frequent inflammatory processes in the upper respiratory tract, resulting in higher daily replenishment needs compared to their peers. Correlation analysis revealed a connection between illness incidence and the levels of copper (p=0.008), sodium (p=0.00005), and phosphorus (p=0.028), indicating potential associations between saliva metal profiles and the frequency of ARI in children with RRIs. The presence of dental caries correlated with lithium (p=0.02), copper (p=0.032), and nickel levels (p=0.037). Integral indicators of local immunity, such as lysozyme and secretory IgA, exhibited correlations with metal levels in saliva (Li, Cu, Ni, Na, Co, P, Zn), confirming the hypothesis of their role in regulating immune reactions in the oral cavity. Conclusions. Cluster analysis of the metal profiles of the group of children with RRI shows its heterogeneity, 43 % of representatives of this cohort had significantly lower levels of calcium (p=0.003), copper (p=0.001), manganese (p=0.008), magnesium (p=0.02) and zinc (p=0.027) than the control group. Which may indicate the presence of deficient conditions in some children with PRI as a result of the increased need for their recovery. The presence of caries, the level of SIgA, lysozyme (clinical indicators of local immunity of the oral cavity) have certain relationships with the levels of essential and conditionally essential levels of salivary metals (Li, Cu, Ni, Na, Co, P, Zn), which indicates the benefit of the connection between the metal profile of saliva and the state of local immunity.

Bifidobacterium infantis and 2′-fucosyllactose supplementation in early life may have potential long-term benefits on gut microbiota, intestinal development, and immune function in mice

The health benefits of nutritional interventions targeting the gut microbiota in early life are transient, such as probiotics, prebiotics, and synbiotics. This study sought to determine whether supplementation with B. infantis 79 (B79), 2'-fucosyllactose (2'-FL), or both would lead to persistent health benefits in neonatal BALB/c mice. We found that at postnatal day (PND) 21, Ki67 and MUC2 expression increased while total serum IgE content decreased in the B79, 2'-FL, and B79+2'-FL groups. The gut microbiota's structure and composition altered as well. The levels of propionic acid, sIgA, and IL-10 increased in the 2'-FL group. Moreover, butyric acid content increased while IL-6, IL-12p40 and TNF-α decreased in the B79+2'-FL group. At PND 56, Ki67 and MUC2 expression increased while the gut microbiota remained altered in all 3 groups. The serum total IgG level increased only in the B79+2'-FL group. In conclusion, our study suggest that early life supplementation with B79, 2'-FL, or their combination persistently alters the gut microbiome and promotes intestinal development; the immunomodulatory capacity of B79 and 2'-FL occurs during weaning, and their combination may persist into adulthood.

Bacteriocin-Producing Lactiplantibacillus plantarum YRL45 Enhances Intestinal Immunity and Regulates Gut Microbiota in Mice.

Bacteriocins production is one of important beneficial characteristics of probiotics, which has antibacterial property against intestinal pathogens and is helpful for regulating intestinal flora. To investigate the impact of bacteriocin-producing probiotics on gut microecology, bacteriocin-producing Lactiplantibacillus plantarum YRL45 was orally administered to mice. The results revealed that it promoted the release of cytokines and improved the phagocytic activity of peritoneal macrophages to activate the immune regulation system. L. plantarum YRL45 was conducive to maintaining the morphology of colon tissue without inflammation and increasing the ratio of villus height to crypt depth in the ileum. The gene expression levels of Muc2, ZO-1 and JAM-1 were significantly up-regulated in the ileum and colon, and the gene expression of Cramp presented an upward trend with L. plantarum YRL45 intervention. Moreover, L. plantarum YRL45 remarkably enhanced the levels of immunoglobulins sIgA, IgA and IgG in the intestine of mice. The 16S rRNA gene analysis suggested that L. plantarum YRL45 administration up-regulated the relative abundance of the beneficial bacteria Muribaculaceae and Akkermansia, down-regulated the abundance of the pathogenic bacteria Lachnoclostridium, and promoted the production of acetic acid, propionic acid and total short-chain fatty acids (SCFAs) in mice feces. Our findings indicated that L. plantarum YRL45 had the potential to be developed as a novel probiotic to regulate the intestinal barrier by altering gut microbiota to enhance intestinal immunity and ameliorate intestinal flora balance.

Ficolin A knockout alleviates sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit S100A4/STAT3 pathway.

Acute lung injury (ALI) is a life-threatening disease with high morbidity and mortality. Our previous results demonstrated that Ficolin A (FcnA) protected against lipopolysaccharide (LPS)-induced mild ALI via activating complement, however the mechanism of severe lung damage caused by sepsis remains unclear. This study aimed to investigate whether FcnA modulated gut microbiota to affect the progression of sepsis-induced severe ALI. Fcna-/- and Fcnb-/- C57BL/6 mice were applied to establish the ALI model by injection of LPS intraperitoneally. Mice were treated with antibiotics, fecal microbiota transplantation (FMT), and intratracheal administration of recombinant protein S100A4. Changes in body weight of mice were recorded, and lung injury were assessed. Then lung tissue wet/dry weight was calculated. We found knockout of FcnA, but not FcnB, alleviated sepsis-induced severe ALI evidenced by increased body weight change, decreased wet/dry weight of lung tissue, reduced inflammatory infiltration, decreased lung damage score, decreased Muc-2, TNF-α, IL-1β, IL-6, and Cr levels, and increased sIgA levels. Furthermore, knockout of FcnA restored gut microbiota homeostasis in mice. Correlation analysis showed that Akkermansia was significantly negatively associated with TNF-α, IL-1β, and IL-6 levels in serum and bronchoalveolar lavage fluid (BALF). Moreover, knockout of FcnA regulated gut microbiota to protect ALI through S100A4. Finally, we found knockout of FcnA alleviated ALI by inhibiting S100A4 via gut Akkermansia in mice, which may provide further insights and new targets into treating sepsis-induced severe lung injury.

Validation of secretory Immunoglobulin A (IgA) for early and efficient diagnosis of Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa is a gram-negative bacterium that is considered to be a major causal organism of nosocomial infection. This study brought data-specific evidence to reveal the efficacy of secretory Immunoglobulin A (IgA) measurement in diagnosing pulmonary P. aeruginosa infection and claims its validation as a diagnostic marker. This study has included controls and patients of Pseudomonas and grouped them into four, namely, controls, chronic cases, intermittent cases, and negative group. The last group, that is, the "Negative" group, is the ones who had a history of infection but currently showed negative blood culture. The level of sIgA was quantified in all the patients and the controls and then their status of pulmonary infection was determined by their blood culture. ANOVA and Pearson Chi-Square were employed for showing the association between sIgA and pulmonary infection. The mean value of salivary sIgA has been found the highest in chronic cases followed by Intermittent cases and Negative Infections. The boxplot diagram showed several parameters of sIgA quantification in each group and control. ANOVA and Pearson Chi-square (P<0.005) tests showed a significant association between sIgA level in saliva and pulmonary infection of P. aeruginosa. The ROC curve was plotted to determine the cut-off value of sIgA (sIgA≧13.09 U/ml) for efficient clinical diagnosis of pulmonary P. aeruginosa infection.The study has validated statistically that quantification of salivary sIgA can be used in clinical practice for early diagnosis of pulmonaryinfection of P. aeruginosa.

Activation of GABA receptor attenuates intestinal inflammation by modulating enteric glial cells function through inhibiting NF-κB pathway

AimsEmerging research indicates that γ-aminobutyric acid (GABA) provides substantial benefits during enteritis. Nevertheless, GABA signaling roles on enteric glial cells (EGCs) remain unknown. The study's objective was to evaluate the underlying mechanisms of GABA signaling on EGCs in vitro and in vivo. Main methodsWe established LPS-induced mouse models and stimulated EGCs with LPS to mimic intestinal inflammation, and combined GABA, GABAA receptor (GABAAR) or GABAB receptor (GABABR) agonists to explore the exact mechanisms of GABA signaling. Key findingsEGCs were immunopositive for GAD65, GAD67, GAT1, GABAARα1, GABAARα3, and GABABR1, indicating GABAergic and GABAceptive properties. GABA receptor activation significantly inhibited the high secretions of proinflammatory factors in EGCs upon LPS stimulation. Interestingly, we found that EGCs express immune-related molecules such as CD16, CD32, CD80, CD86, MHC II, iNOS, Arg1, and CD206, thus establishing their characterization of E1 and E2 phenotype. EGCs exposed to LPS mainly acted as E1 phenotype, whereas GABABR activation strongly promoted EGCs polarization into E2 phenotype. Transcriptome analysis of EGCs indicated that GABA, GABAAR or GABABR agonists treatment participated in various biological processes, however all of these treatments exhibit inhibitory effects on NF-κB pathway. Notably, in LPS-induced mice, activation of GABABR mitigated intestinal damage through modulating inflammatory factors expressions, strengthening sIgA and IgG levels, inhibiting NF-κB pathway and facilitating EGCs to transform into E2 phenotype. SignificanceThese data demonstrate that the anti-inflammatory actions of GABA signaling system offer in enteritis via regulating EGCs-polarized function through impeding NF-κB pathway, thus providing potential targets for intestinal inflammatory diseases.

Salivary secretory immunoglobulin A as a potential biomarker of psychosocial stress response during the first stages of life: A systematic review

Mucosal secretory immunoglobulin A (s-IgA) has been recognized as a key component of human first line defense against infection. However, its reactivity to psychosocial stressors is poorly understood. This systematic review aimed to explore whether s-IgA levels changed after psychosocial stress in subjects under the age of 18. Fifteen articles were included. s-IgA basal levels are increased in children older than 9 years old exposed to stress. Furthermore, s-IgA seems to follow a circadian rhythm, which is altered under stress conditions. Finally, the collective evidence suggests that salivary s-IgA rapidly increases under acute stress after puberty. Overall, our review indicates that s-IgA could be considered a potential psychosocial stress biomarker of interest for pediatric and child-juvenile psychiatric population. Further studies are needed to validate the role of s-IgA circadian rhythm and basal levels as psychosocial stress biomarkers and disentangle the role of age and type of stressor.

Microbiota and Mitochondrial Sex-Dependent Imbalance in Fibromyalgia: A Pilot Descriptive Study.

Fibromyalgia is a widespread chronic condition characterized by pain and fatigue. Among the long list of physiological disturbances linked to this syndrome, mitochondrial imbalance and oxidative stress stand out. Recently, the crosstalk between mitochondria and intestinal microbiota has caught the attention of biomedical researchers, who have found connections between this axis and several inflammatory and pain-related conditions. Hence, this pilot descriptive study focused on characterizing the mitochondrial mass/mitophagy ratio and total antioxidant capacity in PBMCs, as well as some microbiota components in feces, from a Peruvian cohort of 19 females and 7 males with FM. Through Western blotting, electrochemical oxidation, ELISA, and real-time qPCR, we determined VDAC1 and MALPLC3B protein levels; total antioxidant capacity; secretory immunoglobulin A (sIgA) levels; and Firmicutes/Bacteroidetes, Bacteroides/Prevotella, and Roseburia/Eubacterium ratios; as well as Ruminococcus spp., Pseudomonas spp., and Akkermansia muciniphila levels, respectively. We found statistically significant differences in Ruminococcus spp. and Pseudomonas spp. levels between females and males, as well as a marked polarization in mitochondrial mass in both groups. Taken together, our results point to a mitochondrial imbalance in FM patients, as well as a sex-dependent difference in intestinal microbiota composition.

Induction of humoral and cell-mediated immunity in mice by chitosan-curdlan composite nanoparticles administered intranasally and subcutaneously

Infectious diseases seriously threaten human life. The need for novel delivery systems and adjuvants suitable to be used in clinic for antigens remains a challenge. Among various attempts that have been made to provide optimum immune responses for protein antigens with poor immunogenicity, polymeric nanoparticles offer great opportunities. In this study, carboxymethyl curdlan (CMC) as a polyanionic polymer and chitosan chloride (CC) and N-trimethyl chitosan (TMC) as polycationic polymers were synthesised in-house and composite nanoparticles (CC-CMC-BSA and TMC-CMC-BSA) loaded with bovine serum albumin (BSA) as a model antigen were prepared via polyelectrolyte complexation and reported here for the first time. Nanoparticles with an average size ranging from 153 nm to 615 nm, positive surface charge (from +24 mV to +55 mV) and encapsulation efficiency as high as 90% were obtained depending on the concentration of polymers in the formulation. The nanoparticles showed good physical stability for three months and low toxicity in Calu-3 and A549 cells. Furthermore, SDS integrity of antigen was maintained. In vivo studies in mice indicated that nasal and subcutaneous administration of composite nanoparticles could provide long-term humoral and cellular immunity as determined by serum antibody titres (IgG, IgG1, IgG2a) and cytokine (IL-2, IL-4, IL-6, IL-10 and IFN-γ) levels. Elevated sIgA levels after nasal administration of the nanoparticles showed that mucosal immunity was successfully stimulated. These findings suggest that chitosan-curdlan composite nanoparticles show optimum properties to be used as nanovaccine for nasal immunisation of protein antigens.

Immune Response and Nutritional Status of Infants’ Birth after Supplementation with Dadih and Zinc during Pregnancy: A Prospective Intervention Study

BACKGROUND: Dadih is an Indonesian traditional fermented buffalo milk produced and consumed by the secretory immunoglobulin A (sIgA) level and nutritional status of infants aged 4–10 months. AIM: This study aims to assess the effect of dadih and zinc supplementation given to pregnant mothers for 6 months on fecal. MATERIALS AND METHODS: A prospective randomized controlled trial was conducted in two districts on 138 pregnant mothers for 6 months, randomly assigned into three groups, namely, control, dadih, combination of dadih and zinc groups. Then, the combination of groups was supplemented to expecting mothers, respectively, 6 times a week during 6 months. Anthropometric measurement and fecal sIgA of infants were assessed. RESULTS: The prevalence of nutritional status of infants who mothers were supplemented during pregnancy with dadih, dadih and zinc, and, normal diet, respectively, are 10% stunting, 5.0% underweight, and 5.0% wasting infants; and 22.5% stunted, 20.0% underweight, and 5.0% wasting infants were found in expecting mothers supplemented with it and without any supplementation (control group). The percentage of stunting in 8 months and older infants tended to reduce: 28.57%, 31.25%, and 11.76%. Their mothers were supplemented with all groups. CONCLUSION: Dadih and zinc are potential for improving nutritional status of the newborn. In addition, the two types of supplementation are recommended to pregnant mothers, to reduce the prevalence of stunting. Potential probiotic contained in Dadih which consumed in adequate amounts can help the absorption of nutrients and increase immunity of mothers and infants amounts confer a health benefit. Acceleration and growth of infants to achieve optimal growth and development should be carried out before they are under two years old.

Protein and Immune Component Content of Donor Human Milk in Japan: Variation with Gestational and Postpartum Age.

Donor human milk (DHM) is the second-best nutrition for preterm infants when their own mother's milk is unavailable. The nutrient content of human milk is influenced by various factors, including gestational and postpartum age, but there are no data regarding DHM composition in Japan. The aim of this study was to determine the protein and immune component content of DHM in Japan and to elucidate the effects of gestational and postpartum age on nutrient composition. From September 2021 to May 2022, 134 DHM samples were collected from 92 mothers of preterm and term infants. Protein concentrations in preterm DHM (n = 41) and term DHM (n = 93) were analyzed using a Miris Human Milk Analyzer. The concentrations of secretory immunoglobulin A (sIgA) and lactoferrin, major immune components, were measured using enzyme-linked immunosorbent assays. Preterm DHM exhibited higher protein content than term DHM (1.2 g/dL and 1.0 g/dL, respectively, p < 0.001), whereas sIgA content was higher in term DHM than in preterm DHM (110 μg/mL and 68.4 μg/mL, respectively, p < 0.001). Gestational age was negatively correlated with protein levels and positively correlated with sIgA and lactoferrin levels. Furthermore, a negative correlation was found between postpartum week and protein, sIgA, and lactoferrin concentrations. Our data suggest that gestational and postpartum age affects protein, sIgA, and lactoferrin concentrations in DHM. These results indicate the importance of nutritional analysis for the appropriate use of DHM in preterm infants.

Correlation between salivary immunoglobulin A and interleukin-1beta in smokers with dental caries.

Introduction. Dental caries is one of the most common infectious diseases of the oral cavity, and is an inflammatory disease caused by several factors. Interleukin-1β (IL-1β) is a major mediator of acute inflammation and essential for the development of specific immune responses. The objective of this study was to assess the levels of secretory IgA (s-IgA) and IL-1β in the saliva of smokers with dental caries, and to discover the correlation between these parameters and dental caries. Methods. Saliva samples were collected from 30 smokers, age range 21-70 years, with dental caries, in addition to 18 healthy non-smoker volunteers, age range 21-65 years. s-IgA and IL-1β levels in the saliva samples were estimated by enzyme-linked immunosorbent assay (ELISA). Results. The mean saliva IgA levels between smokers with dental caries group and healthy subjects were not significantly different (p=0.077), while the saliva levels of IL-1β were higher in the smokers in dental caries group, with a significant difference of p<0.05. No significant associations were found between s-IgA and IL-1β levels, and other parameters such as age, sex, body mass index (BMI) and C-reactive protein (CRP) (p>0.05). There were highly positive associations and significant differences between IL-1β and CRP levels in the two groups under the study (p=0.006). Conclusions. Our study revealed a significant increase in IL-1β levels in saliva of smokers with dental caries, and a positive association between IL-1β levels and caries disease. There is no significant relationship between elevated IL-1β levels and s-IgA in smokers with dental caries.

Mucosal immunity in health care workers’ respiratory tracts in the post-COVID-19 period

Coronavirus disease (COVID-19) has generated interest in the assessment of systemic immune status, but existing knowledge about mucosal immunity is clearly insufficient to understand the full pathogenetic mechanisms of the disease. The aim of this study was to evaluate the long-term effects of novel coronavirus infection on mucosal immunity in the postinfection period among health care workers (HCWs). A total of 180 health care workers with and without a history of COVID-19 who ranged in age from 18 to 65 years were enrolled in this one-stage, cross-sectional study. The study subjects completed the 36-Item Short Form (36) Health Survey (SF-36) and the Fatigue Assessment Scale. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, and nasopharyngeal and oropharyngeal scrapings by an enzyme-linked immunosorbent assay. Specific anti-SARS-CoV-2 IgG antibodies were quantified in serum samples by chemiluminescence immunoassay. Analysis of the questionnaire data showed that all HCWs with a history of COVID-19 reported health problems that limited their daily activities and negative changes in their emotional health three months after the disease, regardless of its severity. The following shifts were detected in the adaptive arm of the immune response in different mucosal compartments. Among subjects who had severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p < 0.05 and p < 0.005, respectively). Compared to the subjects in the control group, all subjects with prior COVID-19 had significantly higher levels of total IgG in induced sputum. In the group of patients who had had severe infection, total IgG in saliva was also higher (p < 0.05). A direct statistically significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum. A significant correlation was observed between total IgG levels and the parameters of physical and social activities, mental health, and fatigue levels. Our study demonstrated long-term changes in the humoral mucosal immune response, which were most pronounced in health care workers with a history of severe or moderate-to-severe COVID-19, and an association of these changes with certain clinical signs of post-COVID-19 syndrome.

Dachaihu decoction ameliorates septic intestinal injury via modulating the gut microbiota and glutathione metabolism as revealed by multi-omics

Ethnopharmacological relevanceDachaihu decoction (DCH), a classic formula for Yangming and Shaoyang Syndrome Complex recorded in “Treatise on Cold Damage”, has been widely used in treating intestinal disorders and inflammatory diseases with few side effects in China. However, the mechanism of DCH on septic intestinal injury (SII) remains to be explored. Aim of the studyThis study aimed to clarify the mechanism of DCH on SII. Materials and methodsSII model of rat, established by cecal ligation and puncture (CLP), was used to study the effect of DCH on SII. 24 h mortality was recorded. Histological changes were observed by H&E staining. The expression of tight junction protein ZO-1 (ZO-1) and mucin2 (MUC2) was determined by immunohistochemical analysis. Secretory IgA (sIgA), diamine oxidase (DAO) and intestinal fatty acid binding protein (iFABP) were determined by enzyme-linked immunosorbent assay (ELISA). IL-1β, IL-6 and TNF-α were measured by ELISA and quantitative Real-time PCR (RT-qPCR). The gut microbiota was analyzed by 16S rRNA sequencing. The potential targets and pathways of DCH in treating SII were analyzed by integrative analysis of transcriptomic and metabolomic methods. Total glutathione (T-GSH), GSH, GSSG (reduced form of GSH), GSH peroxidase (GPX), superoxide dismutase (SOD), malonaldehyde (MDA) and indicators of hepatic and renal function were measured by biochemical kits. ResultsMedium dose of DCH improved 24 h mortality of SII rats, reduced the pathological changes of ileum, and increased the expression levels of ZO-1, MUC2 and sIgA. DCH decreased DAO, iFABP of serum and IL-1β, IL-6, TNF-α of ileum. DCH improved α- and β-diversity and modulated the structure of gut microbiota, with Escherichia_Shigella decreased and Bacteroides and Ruminococcus increased. GSH metabolism was identified as the key pathway of DCH on SII by integrative analysis of transcriptome and metabolome. GSH/GSSG and the most common indicators of oxidative stress, were validated. Antioxidative T-GSH, GSH, GPX and SOD were increased, while MDA, the mark of lipid peroxidation was downregulated by DCH. Eventually, DCH was proved to be safe and hepato- and nephro-protective. ConclusionDCH ameliorated septic intestinal injury possibly by modulating the gut microbiota and enhancing glutathione metabolism of SII rats, without hepatotoxicity and nephrotoxicity.

Ameliorating role of Tetrastigma hemsleyanum polysaccharides in antibiotic-induced intestinal mucosal barrier dysfunction in mice based on microbiome and metabolome analyses

The intestinal mucosal barrier is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. This study investigated the reparative effect and possible mechanism of Tetrastigma hemsleyanum polysaccharides (THP) on ceftriaxone-induced intestinal mucosal damage. Our results suggested that THP repaired the mechanical barrier damage of intestinal mucosa by enhancing the expression of intestinal tight junction proteins, reducing intestinal mucosal permeability and improving the pathological state of intestinal epithelial cells. Intestinal immune and chemical barrier was further restored by THP via the increment of the body's cytokine levels, intestinal SIgA levels, intestinal goblet cell number, intestinal mucin-2 levels, and short-chain fatty acid levels. In addition, THP increased the abundance of probiotic bacteria (such as Lactobacillus), reduced the abundance of harmful bacteria (such as Enterococcus) to repair the intestinal biological barrier, restored intestinal mucosal barrier function, and maintains intestinal homeostasis. The possible mechanisms were related to sphingolipid metabolism, linoleic acid metabolism, and D-glutamine and D-glutamate metabolism. Our results demonstrated the potential therapeutic effect of THP against intestinal flora disorders and intestinal barrier function impairment caused by antibiotics.