This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female

OBJECTIVES: To investigate the effect of interleukin-17 (IL-17) gene polymorphism on the susceptibility to cow's milk protein allergy (CMPA) in infants and its association with gut microbiota. METHODS: A prospective study was conducted involving 100 infants diagnosed with CMPA at the Women and Children's Hospital of Ningbo University from January 2022 to October 2024. A total of 100 healthy infants undergoing routine check-ups at the same hospital during the same period was enrolled as the control group. Medical information was obtained through the electronic medical record system. IL-17A (rs2275913) and IL-17F (rs1889570) polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism method. Serum IL-17 levels were measured using enzyme-linked immunosorbent assay, and high-throughput sequencing was employed to analyze the relative abundance of Lactobacillus and Bifidobacterium. Multivariate logistic regression analysis was used to explore the influencing factors of CMPA occurrence in infants. RESULTS: The proportions of infants with a family history of allergy and those with vitamin D deficiency or insufficiency were significantly higher in the CMPA group compared to those in the control group (P<0.05). The distribution of IL-17F (rs1889570) genotypes showed significant differences between the CMPA and control groups (P<0.05), with the frequency of the A allele being significantly higher in the CMPA group (P<0.05). Multivariate logistic regression analysis revealed that a family history of allergy, vitamin D deficiency or insufficiency, and carrying the IL-17F (rs1889570) AA genotype were independent influencing factors for CMPA in infants (P<0.05). Infants in the CMPA group with the IL-17F (rs1889570) AA genotype had significantly higher serum IL-17 levels compared to those with AG/GG genotypes (P<0.05), while the relative abundance of Lactobacillus and Bifidobacterium was significantly lower (P<0.05). CONCLUSIONS IL-17F (rs1889570) gene polymorphism influences susceptibility to CMPA in infants, potentially through mechanisms involving IL-17 expression and the relative abundance of gut probiotics.
Humans ; Interleukin-17/genetics* ; Milk Hypersensitivity/microbiology* ; Female ; Infant ; Male ; Prospective Studies ; Genetic Predisposition to Disease ; Gastrointestinal Microbiome ; Polymorphism, Genetic ; Milk Proteins/immunology*

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult

OBJECTIVE: To study the association between maternal Th1/Th2 immune level at different pregnancy stages and cow's milk protein allergy (CMPA) in infants. METHODS: The healthy women with a singleton pregnancy, as well as their offspring, who attended Yidu Central Hospital of Weifang and Qingzhou Traditional Chinese Medicine Hospital from July 2016 to December 2018 were enrolled. The maternal levels of interleukin-2 (IL-2), interferon gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10) at the second and third trimesters of pregnancy were measured. A CMPA questionnaire survey was conducted within one year after birth. Food avoidance and cow's milk oral challenge tests were performed in infants suspected of CMPA. The 48 infants who met the diagnostic criteria for CMPA were included in the observation group, and the remaining 977 normal infants were included in the control group. A univariate analysis was performed on the infants with CMPA. A Poisson regression analysis was used to determine the association between maternal Th1/Th2 immune factors at different pregnancy stages and CMPA. RESULTS: The detection rate of CMPA was 4.68%. The clinical manifestations included the symptoms of the digestive system, skin, and respiratory system and other symptoms. The univariate analysis showed that compared with the control group, the observation group had significantly higher incidence rates of maternal food allergy and maternal history of allergic diseases (P<0.05) and a significantly lower breastfeeding rate (P<0.05). The observation group had significantly lower maternal levels of IL-2 (second and third trimesters) and IFN-γ (third trimester) than the control group (P<0.05). Maternal low IFN-γ at the third trimester and maternal low IL-2 at the second and third trimesters were significantly associated with CMPA in infants (P<0.05). After correction of the factors of breastfeeding, maternal food allergy, and maternal history of allergic diseases, it was found that maternal low IL-2 and IFN-γ at the third trimester were still significantly associated with CMPA in infants (P<0.05). CONCLUSIONS The maternal decrease in Th1 level at the third trimester of pregnancy may lead to the change in fetal immunity and thus increase the risk of CMPA in offspring.
Allergens ; Animals ; Breast Feeding ; Cattle ; Female ; Humans ; Infant ; Milk Hypersensitivity ; Milk Proteins/immunology* ; Pregnancy

Recent studies have shown that diet can affect the body's immunity. Roughage of dairy cows consists of a variety of plant materials which make different contributions to health. This study investigated the effect of different roughages on the immunity of dairy cows. Serum, peripheral blood mononuclear cells (PBMCs), and milk samples were collected from 20 multiparous mid-lactation cows fed mixed forage (MF)- or corn straw (CS)-based diets. Expression profile analysis was used to detect the differentially expressed genes (DEGs) from PBMCs. The results showed that milk protein in the MF group increased to 3.22 g/100 ml, while that of the CS group milk was 2.96 g/100 ml; by RNA sequencing, it was found that 1615 genes were differentially expressed between the CS group and the MF group among the 24 027 analyzed probes. Gene ontology (GO) and pathway analysis of DEGs suggested that these genes (especially genes coding cytokines, chemokine and its receptors) are involved in the immune response. Results were confirmed at the protein level via detecting the levels of interleukin-2 (IL-2), IL-6, IL-10, IL-12, leptin (LEP), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) in peripheral blood by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay analysis. Our data supported the conclusions that the protein content in milk of the MF group was higher than that of the CS group, the CS-based diets induced more release of cytokines than the MF-based diets in dairy cows' PBMCs, and milk protein content may be affected by cytokines.
Animals ; Cattle/immunology* ; Cytokines/physiology* ; Diet ; Female ; Gene Ontology ; Leukocytes, Mononuclear/immunology* ; Milk/chemistry* ; Transforming Growth Factor beta/physiology* ; Zea mays

Female ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Milk Hypersensitivity ; diagnosis ; Milk Proteins ; immunology

OBJECTIVETo understand the clinical features of gastrointestinal cow's milk allergy in children, and to assess the importance of cow's milk challenge.

METHODAn analysis was performed on the clinical manifestations and the challenge results of 50 children who received cow's milk challenges after admission to the department of gastroenterology, Children' s Hospital of Zhejiang University School of Medicine from January,2009 to December, 2012. The value of immunoglobulin E antibody was also analyzed among the 50 children, 25 cases were male and the other 25 were female. The youngest subject was 1. 6 months old, and the oldest was 20 months, most of the cases were younger than 6 months (36 cases).

RESULT(1) Diarrhea (27 cases, 54%) and hematochezia (25 cases, 50%) were the most common clinical features, vomiting, hematemesis and abdominal distention were rare. (2) Cow's milk challenges failed in 58% of the cases, 90% of whom showed delayed allergy. Diarrhea (19 cases, 73%) was the major later presentation, whereas the immediate hypersensitivity showed angio-edema, gastrointestinal symptom and rash. (3) The neutrophil count ((3.8 ± 2.8) x 10(9)/L vs. (2.5 ± 1.3) x 10(9)/L) was higher after challenge among children who failed the challenge. The change in the count of blood cell, neutrophil and platelet was studied, however, there were no statistical differences between the challenge-failed children and the passed ones. (4) Forty-seven cases had milk specific immunoglobulin E antibody test, and 5 showed positive results, 4 of whom were seen among the challenge-failed children.

CONCLUSIONDiarrhea and hematochezia was the most common clinical manifestation, and cow's milk protein induced proctocolitis was the most common disease in practice. It is important and necessary to perform cow's milk challenge.

Animals ; Female ; Gastrointestinal Diseases ; etiology ; Gastrointestinal Hemorrhage ; etiology ; Hematemesis ; etiology ; Humans ; Hypersensitivity, Immediate ; immunology ; Infant ; Infant, Newborn ; Male ; Milk ; Milk Hypersensitivity ; immunology ; Vomiting ; etiology

OBJECTIVETo determine the clinical significance of milk protein-specific IgE (sIgE) for infants with cow's milk protein allergy (CMPA).

METHODSNinety-six infants with CMPA were divided into IgE+ group (n=26) and IgE- group (n=70) and clinical characteristics were compared between the two groups. Infants were denied allergy-inducing food and fed instead extensively hydrolyzed formulas or amino-acid formulas for 16 weeks before the two groups were compared.

RESULTSTwenty-seven percent of the infants were sIgE-seropositive. The first onset age of CMPA was significantly younger in the IgE+ group than in the IgE- group (P<0.05), and the family history of allergy and respiratory symptoms were significantly less common in the IgE- group than in the IgE+ group (P<0.05). Severe CMPA, gastrointestinal symptoms, underweight, growth retardation, anemia, and hypoproteinemia were significantly more common in the IgE- group than in the IgE+ group (P<0.05). Erythema, urticaria, vomiting, nasal discharge, cough, wheezing, and paroxysms of crying were major clinical symptoms of the IgE+ group, and their incidences were significantly higher in the IgE+ group than in the IgE- group (P<0.05); eczema, constipation, and diarrhea were major symptoms of the IgE- group, and their incidences were significantly higher in the IgE- group than in the IgE+ group (P<0.05). The remission rate of each symptom was as high as over 80% in the two groups after 16 weeks of intervention and there was no significant difference in the remission rates between the two groups (P>0.05).

CONCLUSIONSIgE seropositive rate is not high in infants with CMPA. Atypical signs instead of allergic symptoms are more common in the IgE seronegative infants with CMPA. Avoiding allergy-inducing food and eating extensively hydrolyzed formulas or amino-acid formulas in early age benefit infants with IgE-mediated or non-IgE-mediated CMPA.

Female ; Follow-Up Studies ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Milk Hypersensitivity ; immunology

Presented are guidelines for the prevention, diagnosis, and treatment of cow's milk protein allergy (CMPA) which is the most common food allergy in infants. It manifests through a variety of symptoms that place a burden on both the infant and their caregivers. The guidelines were formulated by evaluation of existing evidence-based guidelines, literature evidence and expert clinical experience. The guidelines set out practical recommendations and include algorithms for the prevention and treatment of CMPA. For infants at risk of allergy, appropriate prevention diets are suggested. Breastfeeding is the best method for prevention; however, a partially hydrolyzed formula should be used in infants unable to be breastfed. In infants with suspected CMPA, guidelines are presented for the appropriate diagnostic workup and subsequent appropriate elimination diet for treatment. Exclusive breastfeeding and maternal dietary allergen avoidance are the best treatment. In infants not exclusively breastfed, an extensively hydrolyzed formula should be used with amino acid formula recommended if the symptoms are life-threatening or do not resolve after extensively hydrolyzed formula. Adherence to these guidelines should assist healthcare practitioners in optimizing their approach to the management of CMPA and decrease the burden on infants and their caregivers.
Allergy and Immunology ; Breast Feeding ; Caregivers ; Consensus* ; Delivery of Health Care ; Diagnosis* ; Diet ; Food Hypersensitivity ; Humans ; Hypersensitivity* ; Infant ; Infant Formula ; Middle East* ; Milk Hypersensitivity ; Milk Proteins*

Animals ; China ; epidemiology ; Clinical Trials as Topic ; Evidence-Based Medicine ; Humans ; Infant ; Infant, Newborn ; Milk Hypersensitivity ; diagnosis ; epidemiology ; therapy ; Milk Proteins ; adverse effects ; immunology ; Practice Guidelines as Topic ; standards ; Skin Tests ; methods