Multi-Omics Analysis Provides Insight into the Possible Molecular Mechanism of Hay Fever Based on Gut Microbiota

Due to the worldwide epidemic of allergic disease and a cure nowhere in sight,there is a crucial need to explore its pathophysiological mechanisms.As allergic disease has been associated with gut dysbiosis,we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis.Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen.This hyper reaction decreased the circulation of valine,isoleucine,aspartate,glutamate,glutamine,indole-propionate(IPA),and myo-inositol,and reduced short-chain fatty acids(SCFAs)in feces.Several beneficial genera belonging to Ruminococcaceae,Lachnospiraceae,and Clostridiales declined in the model group,whereas Helicobacter and Akkermansia were only expressed in the model group.Furthermore,the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria.Our results suggest that alterations in amino acids as well as their derivatives(especially valine,and IPA which is the reductive product of tryptophan),SCFAs,and the gut microbiome(specifically Akkermansia and Helicobacter)may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer,which further results in hay fever.

Advances in targeted drugs for allergic diseases

To the Editor:Since the first IgE monoclonal antibody was approved by the Food and Drug Administration in the USA in 2003,at least 14 kinds of targeted drugs are in the clinical application or pre-clinical trials.The two monoclonal antibodies targeting IgE are omalizumab and ligelizumab.Four drugs targeting interleukin 4(IL-4)or IL-4R are pascolizumab,pitrakinra,altrakincept,and dupilumab.Three monoclonal antibodies targeting IL-5/IL-5R are mepolizumab,reslizumab,and benralizumab.Two monoclonal antibodies targeting IL-13 are lebrikizumab and tralokinumab.The monoclonal antibody targeting thymic stromal lymphopoietin(TSLP)is tezepelumab.Th2 cytokine inhibitor is mesylate.These targeted drugs have achieved good results,but most of them are still in the pre-clinical stage.This article reviews the history,marketing situation,indications,contraindications,efficacy,and safety of these targeted drugs.

Clinicopathological features of atypical lipomatous tumors of the laryngopharynx

Atypical lipomatous tumor (ALT) of the laryngopharynx is rare.Here we report five cases to demonstrate their clinicopathological features.The patients were four males and one female,aged 41 to 69 years (median 53.6 years).All tumors (two in the hypopharynx and three in the larynx) presented as a slowly growing,painless mass.Symptoms included dysphagia (2/5),dysphonia (3/5),and the feeling of a foreign body in the throat (5/5).Tumors were well circumscribed or focally infiltrative,ranging from 2.0 to 5.0 cm (median,3.4 cm) in size,and microscopically showed the typical features of lipoma-like ALT.Immunohistochemically,tumor cells were stained with S-100,vimentin,murine double minute 2 (MDM-2),and cyclin-dependent kinase 4 (CDK4).Two patients had local tumor recurrences at 6 and 14 months after initial surgery during follow-up.ALT of laryngopharynx is an indolent tumor.Immunohistochemical staining for MDM-2 and CDK4 is helpful in pathological diagnosis.