Dietary polyphenols reduced the allergenicity ofβ-lactoglobulin via non-covalent interactions:a study on the structure-allergenicity relationship

Studies showed that complexation of polyphenols with milk allergens reduced their immunogenic potential.However,the relationship between structures of polyphenols and their hypoallergenic effects on milk allergens in association with physiological and conformational changes of the complexes remain unclear.In this study,polyphenols from eight botanical sources were extracted to prepare non-covalent complexes withβ-lactoglobulin(β-LG),a major allergen in milk.The dominant phenolic compounds bound toβ-LG with a diminished allergenicity were identified to investigate their respective role on the structural and allergenic properties ofβ-LG.Extracts from Vaccinium fruits and black soybeans were found to have great inhibitory effects on the IgE-and IgG-binding abilities ofβ-LG.Among the fourteen structure-related phenolic compounds,flavonoids and tannins with larger MWs and multi-hydroxyl substituents,notably rutin,EGCG,and ellagitannins were more potent to elicit changes on the conformational structures ofβ-LG to decrease the allergenicity of complexedβ-LG.Correlation analysis further demonstrated that a destabilized secondary structure and protein depolymerization caused by polyphenol-binding were closely related to the allergenicity property of formed complexes.This study provides insights into the understanding of structure-allergenicity relationship ofβ-LG-polyphenol interactions and would benefit the development of polyphenol-fortified matrices with hypoallergenic potential.

Association of Comorbid Asthma and the Efficacy of Bioabsorbable Steroid-eluting Sinus Stents Implanted After Endoscopic Sinus Surgery in Patients with Chronic Rhinosinusitis with Nasal Polyps

Objective To identify factors affecting the efficacy of steroid-eluting sinus stents implanted after endoscopic sinus surgery(ESS)in patients with chronic rhinosinusitis with nasal polyps(CRSwNP).Methods We performed a post-hoc analysis of a randomized self-controlled clinical trial on post-operative implantation of bioabsorbable steroid-eluting stents in patients with CRSwNP.Univariate logistic regression analysis was conducted to identify which of the following factors affect the response to post-operative stent implantation:sex,serum eosinophil levels,history of prior surgery,endoscopic scores,and comorbid conditions(asthma and allergic rhinitis).The primary outcome was the rate of post-operative intervention on day 30,and the secondary outcome was the rate of polypoid tissue formation(grades 2–3)on days 14,30,and 90.Results A total of 151 patients with CRSwNP were included in the post-hoc analysis.Asthma was identified as the only risk factor for a poor response to steroid-eluting sinus stents on post-operative day 30,with an odds ratio of 23.71(95%CI,2.81,200.16;P=0.004)for the need for post-operative intervention and 19(95%CI,2.20,164.16;P=0.003)for moderate-to-severe polypoid tissue formation.In addition,the asthmatic group showed higher rates of post-operative intervention and polypoid tissue formation than the non-asthmatic group on post-operative day 30.Blood eosinophil levels were not identified as a risk factor for poor outcomes after stent implantation.Conclusion Comorbid asthma,but not blood eosinophil level,impairs the efficacy of steroid-eluting sinus stents in the short term after ESS in patients with CRSwNP.

Cux1^(+)proliferative basal cells promote epidermal hyperplasia in chronic dry skin disease identified by single-cell RNA transcriptomics

Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hyperplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the transcriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.

α-突触核蛋白对小鼠星形胶质细胞的激活作用

目的研究外源性α-突触核蛋白(α-syn)及其A53T突变型对星形胶质细胞的激活作用。方法分离培养小鼠原代星形胶质细胞,经α-syn和A53T刺激后,用实时荧光定量聚合酶链反应和Western blot检测Toll样受体(TLRs)和核转录因子-κB(NF-κB)的表达变化。结果与对照组比较,2种α-syn提高TLRs1~4和NF-κB的表达水平(P<0.05),其中A53T作用更强;Western blot检测结果表明,A53T提高TLR2和NF-κB的蛋白水平。结论α-syn激活星形胶质细胞介导的固有免疫反应,为神经退行性疾病机制提供免疫学证据。

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China:A national multicenter survey of 35,566 individuals

Objective:This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China.Methods:This study was conducted by 45 tertiary Grade-A hospitals in China.Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28,2022,and February 21,2023.The collected information included basic demographics,medical history,smoking and drinking history,vaccination history,changes in olfactory and gustatory functions before and after infection,and other postinfection symptoms,as well as the duration and improvement status of olfactory and gustatory disorders.Results:Complete questionnaires were obtained from 35,566 subjects.The overall incidence of olfactory and taste dysfunction was 67.75%.Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction.Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction.Before infection,the average olfactory and taste VAS scores were 8.41 and 8.51,respectively;after infection,they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey.The median duration of dysosmia and dysgeusia was 15 and 12 days,respectively,with 0.5%of patients having symptoms lasting for more than 28 days.The overall self-reported improvement rate was 59.16%.Recovery was higher in males,never smokers,those who received two or three vaccine doses,and those that had never experienced dental health issues,or chronic accompanying symptoms.Conclusions:The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China.Incidence and prognosis are influenced by several factors,including sex,SARS-CoV-2 vaccination,history of head-facial trauma,nasal and oral health status,smoking and drinking history,and the persistence of accompanying symptoms.

Pentoxifylline in hepatopulmonary syndrome

AIM： To determine the effects of pentoxifylline （PTX） on clinical manifestations and evaluate arterial blood gas data in hepatopulmonary syndrome （HPS） in chil- dren. METHODS： In a pilot study of 10 children with chronic liver disease, who had HPS, 20 mg/kg/d PTX was ad- ministered for 3 mo. Clinical data and arterial blood gas parameters were evaluated at baseline, the end of the treatment period, and 3 mo after drug discontinuation. RESULTS： Six patients could tolerate PTX, while four patients experienced complications, Among patients who could tolerate PTX, there was a significant increase in arterial oxygen pressure （PaO2） （P = 0,02） and oxy- gen saturation （Sa02） （P = 0.04） and alveolar-arterial oxygen gradient （P = 0.02） after 3 mo of treatment. Significant decreases in Pa02 （P = 0.02） and alveolararterial oxygen gradient （P = 0.02） were also seen after drug discontinuation. CONCLUSION： PTX may improve PaO2, Sa02 and alve- olar-arterial oxygen gradient in the early stage of HPS.

Rare large homozygous CFTR gene deletion in an Iranian patient with cystic fibrosis

Cystic fibrosis, a common autosomal recessive genetic disorder among Caucasians, is caused by defects in the transmembrane conductance regulatory(CFTR) gene. The analysis of CFTR gene mutations is useful to better characterize the disease, and for preconceptional screening, prenatal and preimplantation genetic diagnosis. Here we report the results of a genetic analysis in a 16-year-old boy from southwestern Iran diagnosed as having cystic fibrosis in infancy based on gastrointestinal and pulmonary manifestations, with positive sweat chloride tests. He lacked both normal and mutant forms of the fragment corresponding to the F508 allele in initial genetic studies. Multiplex ligationdependent probe amplification-based testing revealed a homozygous deletion spanning exons 4 to 10 of the CFTR gene. We predict an in-frame deletion removing 373 amino acids based on our sequencing results. Determining CFTR gene mutations in patients and their family members would be helpful to prevent the occurrence of new cases, especially in populations in which consanguinity is common.

Prunus genetics and applications after de novo genome sequencing:achievements and prospects

Prior to the availability of whole-genome sequences,our understanding of the structural and functional aspects of Prunus tree genomes was limited mostly to molecular genetic mapping of important traits and development of EST resources.With public release of the peach genome and others that followed,significant advances in our knowledge of Prunus genomes and the genetic underpinnings of important traits ensued.In this review,we highlight key achievements in Prunus genetics and breeding driven by the availability of these whole-genome sequences.Within the structural and evolutionary contexts,we summarize:(1)the current status of Prunus whole-genome sequences;(2)preliminary and ongoing work on the sequence structure and diversity of the genomes;(3)the analyses of Prunus genome evolution driven by natural and man-made selection;and(4)provide insight into haploblocking genomes as a means to define genome-scale patterns of evolution that can be leveraged for trait selection in pedigree-based Prunus tree breeding programs worldwide.Functionally,we summarize recent and ongoing work that leverages whole-genome sequences to identify and characterize genes controlling 22 agronomically important Prunus traits.These include phenology,fruit quality,allergens,disease resistance,tree architecture,and self-incompatibility.Translationally,we explore the application of sequence-based marker-assisted breeding technologies and other sequence-guided biotechnological approaches for Prunus crop improvement.Finally,we present the current status of publically available Prunus genomics and genetics data housed mainly in the Genome Database for Rosaceae(GDR)and its updated functionalities for future bioinformatics-based Prunus genetics and genomics inquiry.

Prediction of the impact of air pollution on rates of hospitalization for asthma in Shiraz based on air pollution indices in 2007-2012

Objectives: This study was designed to determine the effects of air pollutants on emergency admissions for asthma, and to forecast the disease burden in Shiraz, Iran. Methods: The average daily concentrations of fine particles (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3) were calculated from data reported by two air quality monitoring stations in Shiraz from the beginning of 2007 to mid-2012. Results: The numbers of patients admitted with asthma attack during this period were collected from four main university-affiliated hospitals. Admissions correlated strongly with the levels of PM10, SO2, CO and O3 during warm seasons (P<0.001), and with NO2 level during cold seasons (P<0.001). We forecast increasing trends in air pollutants and patient admissions in the year 2015. Conclusion: Our findings are further evidence of the effects of air pollutants on asthma exacerbations.

Clarithromycin Attenuates the Bronchial Epithelial Damage Induced by <i>Mycoplasma pneumoniae</i>Infection

To analyze the bronchial epithelial cell damage induced by Mycoplasma pneumonia and the therapeutic effects of clarithromycin, we observed bronchial tissue damage by using a mouse model and performing immunostaining and scanning electron microscopy. The immunostaining study showed that M. pneumoniae-labeled fluorescence was found on the mucosal epithelium of mice, 6 days after inoculation. Clarithromycin treatment reduced the fluorescence. In this study, we demonstrated that the morphological alterations of bronchial mucosa, including the shortening and loss of ciliavisualized by scanning electron microscopy, and the inflammatory cell migration in the submucosal tissue visualized by differential interference contrast microscopy, were induced by mycoplasmal infection. We also showed that clarithromycin treatment, when administered from the first day of inoculation, attenuated both the bronchial epithelial damage and inflammatory cell migration in the submucosal tissue. These results suggest that the therapeutic effects of clarithromycin against mycoplasmal infection, may be due to its antibacterial and anti-inflammatory activities.

Exploring the potential and safety of quantum dots in allergy diagnostics

Biomedical investigations in nanotherapeutics and nanomedicine have recently intensified in pursuit of new therapies with improved efficacy.Quantum dots(QDs)are promising nanomaterials that possess a wide array of advantageous properties,including electronic properties,optical properties,and engineered biocompatibility under physiological conditions.Due to these characteristics,QDs are mainly used for biomedical labeling and theranostic(therapeutic-diagnostic)agents.QDs can be functionalized with ligands to facilitate their interaction with the immune system,specific IgE,and effector cell receptors.However,undesirable side effects such as hypersensitivity and toxicity may occur,requiring further assessment.This review systematically summarizes the potential uses of QDs in the allergy field.An overview of the definition and development of QDs is provided,along with the applications of QDs in allergy studies,including the detection of allergen-specific IgE(sIgE),food allergens,and sIgE in cellular tests.The potential treatment of allergies with QDs is also described,highlighting the toxicity and biocompatibility of these nanodevices.Finally,we discuss the current findings on the immunotoxicity of QDs.Several favorable points regarding the use of QDs for allergy diagnosis and treatment are noted.

Acquired von Willebrand Syndrome in a Male with Systemic Lupus Erythematosus Presented with Mucocutaneous Bleeding and Treated with rFVIIa

Background: Systemic lupus erythematosis (SLE) is a disorder with multiple organ involvement. Haematological abnormalities have been addressed in it, but acquired von Willebrand syndrome is a rarer phenomenon in current disease. The Case: We report acquired von Willebrand syndrome and SLE in a man with brown rash on face, gingival bleeding, easy bruising and epistaxis and laboratory finding of decreased complement, high level of anti-nuclear antibody and anti-DNA. These findings confirmed the diagnosis of SLE. He underwent kidney biopsy and experienced severe pain at the site of biopsy, but the ultra-sonography evaluation showed small sub capsular haematoma at the site of biopsy. During the next 48 hours, gradually APTT prolongation was continued and haematocrit dropped. In spite of FFP infusion and taking tranexamic acid every eight hours, there wasn’t any improvement in haemostatic condition. He received Methylprednisolone and Cyclophosphamid pulses. The patient underwent surgery to roll out vascular complication, but there wasn’t any vascular problem. On the third day, recombinant activated factor VII was infused every two hours until oozing was stopped.

Synbiotic for Prevention of SARS-Cov2 Infection in High Risk Hospital Staffs: A Randomized Controlled Trial

Introduction: COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 increasingly involves people worldwide. Probiotics can improve immune system functions via different mechanisms. We proposed that Synbiotic Lactocare? may also reduce SARS-Cov2 infection in high-risk medical staff working in COVID-19 hospital wards. Method: In a randomized, controlled trial, 60 hospital staff without any history of clinical or laboratory evidence of SARS-Cov2 infection were received either once-daily oral synbiotic capsule (Lactocare?) that contains 1 billion CFU/Cap of L. (Lactobacillus) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium infantis, L. bulgaricus, and Fructooligosacharide (Zist Takhmir, Tehran, Iran) or placebo with the same appearance for 30 days. They were followed for two months. Result: During the two-month period of this study, SARS-COV-2 RT-PCR test results were positive in three participants (9.67%) in placebo group compared to zero positive tests in synbiotic group. The differences were not statistically significant (p = 0.238). During the study, two persons (7 %) of placebo group had respiratory complaints such as cough, rhinorrhea and/or dyspnea, compared with one in synbiotic group (p = 0.492). Conclusion: This study showed that overall frequency of SARS-COV2 infection in participants receiving synbiotic and those receiving placebo did not differ significantly. However, 3 hospital staff in placebo group compared to no one in synbiotic group had SARS-COV2 infection. Further studies with greater power and alternative probiotic strains and mixture are warranted to determine whether Synbiotic can prevent COVID-19 in at-risk hospital staff.

Two hits are better than one:rational dual strategy efficiently fights neuroblastoma

The recently published landmark paper by Bergaggio et al.from Roberto Chiarle’s group in Cancer Cell1 investigates an elegant double-hit strategy to improve anti-cancer immunotherapy.This important approach demonstrates in a preclinical model that chimeric antigen receptor(CAR)-T cell treatment can be rendered more efficient by increasing the cell surface expression of the CAR target structure via a small molecule.

Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity

Immune tolerance deletes or suppresses autoreactive lymphocytes and is established at multiple levels during the development,activation and effector phases of T and B cells.These mechanisms are cell-intrinsically programmed and critical in preventing autoimmune diseases.We have witnessed the existence of another type of immune tolerance mechanism that is shaped by lifestyle choices,such as diet,microbiome and microbial metabolites.Short-chain fatty acids(SCFAs)are the most abundant microbial metabolites in the colonic lumen and are mainly produced by the microbial fermentation of prebiotics,such as dietary fiber.This review focuses on the preventive and immunomodulatory effects of SCFAs on autoimmunity.The tissue-and disease-specific effects of dietary fiber,SCFAs and SCFA-producing microbes on major types of autoimmune diseases,including type I diabetes,multiple sclerosis,rheumatoid arthritis and lupus,are discussed.Additionally,their key regulatory mechanisms for lymphocyte development,tissue barrier function,host metabolism,immunity,autoantibody production,and inflammatory effector and regulatory lymphocytes are discussed.The shared and differential effects of SCFAs on different types and stages of autoimmune diseases are discussed.

Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids

A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses.Short-chain fatty acids(SCFAs),such as acetate,propionate,and butyrate,are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs.SCFAs act on many cell types to regulate a number of important biological processes,including host metabolism,intestinal functions,and immunity system.This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes.Current information regarding how SCFAs regulate innate lymphoid cells,T helper cells,cytotoxic T cells,and B cells and how these functions impact immunity,inflammation,and allergic responses are discussed.

Hepatitis B-specific T helper cell responses in uninfected infants born to HBsAg^(+)/HBeAg^(-) mothers

Vertically transmitted hepatitis B virus(HBV)usually causes chronic infection.While combined active–passive immunoprophylaxis in neonates of hepatitis B surface antigen-positive(HBsAg1)mothers at birth prevents vertical transmission,it is not yet clear whether neonates encounter the virus or its products in the absence of hepatitis B e antigen(HBeAg).This study was undertaken to investigate HBV antigen-specific T-cell responses in vaccinated neonates of HBsAg1/HBeAg2 mothers.Blood was collected from 46 HBsAg1 mothers and their neonates(subjects)as well as 24 age-matched controls.All neonates of HBsAg1 mothers received appropriate immunoprophylaxis,and HBsAg and hepatitis B surface antibody(anti-HBs)antibody titers were determined after completion of the vaccination course.Peripheral blood mononuclear cells(PBMCs)from infants at birth,1 and 6 months of age were stimulated with recombinant HBsAg,hepatitis B core antigen(HBcAg)and mitogen,and interferon(IFN)-c concentrations were determined by ELISA.HBsAg-induced production of IL-2,IL-5,IL-6 and IL-10 was assessed using a cytometric bead array kit on cells from 6-month-old neonates post-vaccination.All neonates were HBsAg2 and responded to vaccination.Increased IFN-c production following HBcAg stimulation was seen in 30.4%of neonates born to HBsAg1/HBeAg2 mothers.Subjects demonstrated significantly higher IL-2 production post-HBsAg stimulation,whereas IL-5,IL-6 and IL-10 cytokine responses were not significantly different.Almost one-third of uninfected neonates developed viral antigen-induced IFN-c production,suggesting that they had been exposed to virions or viral derivatives.This encounter,however,did not impair their T-cell responses to vaccination.

Anaphylaxis and generalized urticaria from eating Chinese bayberry fruit

Chinese bayberry Myrica rubra is a very popular fruit in southeastern China.In spite of its wide consumption,no allergies to this fruit have been reported previously.Here we report on a 40-year-old woman suffering from anaphylaxis to Chinese bayberry fruit.Prick-prick skin tests revealed strong reactions to fresh Chinese bayberry fruits as well as to peach,and weaker reactions to some other fruits including apple,melon,and banana.ImmunoCAP analysis revealed identical titers of specific IgE(4.3 kU A /L) to peach extract and its lipid transfer protein(LTP,rPru p 3),which was confirmed by detection of a 9 kD band following immunoblotting.Immunoblot analysis with Chinese bayberry extract gave bands of 22,45,and 90 kD,but no 9 kD band was recognized.There was also no evidence of LTP recognition for loquat(36 kD) or melon(24 kD).This first report of a severe allergic reaction to Chinese bayberry fruit in a patient with LTP-mediated peach allergy indicates that other as yet unidentified non-pollen related fruit allergens are involved in this new severe fruit allergy.

A demonstration project of Global Alliance against Chronic Respiratory Diseases:Prediction of interactions between air pollution and allergen exposure—the Mobile Airways Sentinel NetworK-Impact of air POLLution on Asthma and Rhinitis approach

This review analyzes the state and recent progress in the field of information support for pollen allergy sufferers.For decades,information available for the patients and allergologists consisted of pollen counts,which are vital but insufficient.New technology paves the way to substantial increase in amount and diversity of the data.This paper reviews old and newly suggested methods to predict pollen and air pollutant concentrations in the air and proposes an allergy risk concept,which combines the pollen and pollution information and transforms it into a qualitative risk index.This new index is available in an app(Mobile Airways Sentinel NetworK-air)that was developed in the frame of the European Union grant Impact of Air POLLution on sleep,Asthma and Rhinitis(a project of European Institute of Innovation and Technology-Health).On-going transformation of the pollen allergy information support is based on new technological solutions for pollen and air quality monitoring and predictions.The new information-technology and artificial-intelligence-based solutions help to convert this information into easy-to-use services for both medical practitioners and allergy sufferers.

心脏外科手术中的过敏反应：对临床医生的启示

手术过程中，患者与麻醉药物、抗生素、血液制品、肝素、多肽（如抑肽酶、乳胶、鱼精蛋白）以及血容量扩充剂等多种外源性物质相接触，这些药物可能引发致命的“过敏”性变态反应。围手术期过敏反应主要表现为急性心肺功能障碍。心脏手术的患者由于有全面的监测，过敏反应一旦发生，能够被快速识别并加以治疗。由于使用治疗剂量之前，先给予患者小剂量药物（常称为试验量）即可能引发过敏反应，因此，临床医生必须随时准备应对可能发生的过敏反应。对于血流动力学不稳定的患者，建立心肺转流不失为一种拯救生命的策略，尤其适用于顽固性心血管功能失代偿的患者。对于血管扩张性休克者，还应考虑使用精氨酸加压素。本篇综述着重围绕心脏手术患者，针对手术室内具有过敏危险的患者，探讨过敏发生率和过敏处理措施的新理念。