Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Orchestration between ILC2s and Th2 cells in shaping type 2 immune responses

The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.

Fungal mycobiome-mediated immune response:a non-negligible promoter in pancreatic oncogenesis and chemoresistance

Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal cancers in humans due to late diagnosis and poor response to treatments.The tumor microenvironment(TME)of PDAC is characterized by a distinctive,suppressive immune profile,which inhibits the protective functions of anti-tumor immunity and thereby contributes to PDAC progression.Recently,the study of Alam et al.discovered for the first time that the intratumoral fungal mycobiome could contribute to the recruitment and activation of type 2 immune cells in the TME of PDAC via enhancing the secretion of a chemoattractant,interleukin(IL-)33.In this article,we reviewed the important findings of this study.Together with our findings,we synthetically discussed the role of the fungal mycobiome in orchestrating the immune response and thereby modulating tumor progression.

Treatment of Integrated Traditional and Western Medicine in Recurrent Spontaneous Abortion of Immune Abnormality Type

Objective: Immune abnormality type of recurrent spontaneous abortion (RSA) is an important etiological type, major findings of that are the abnormal increases in auto and/or allo-antibodies of anti-zona pellucida, anti-phospholipid and anti-ABO blood group. The purpose of the present study is to assess the clinical values of integrated traditional and western medicine in treating the immune abnormality type of RSA.Methods: The aborters were treated by Zhibai Dihuang Pills for anti-zona pellucida antibodies, and clearing evil Heat, removing Dampness, replenishing blood and activating circulation by Chinese medicinal herbs recipe for anti-phospholipid and anti-ABO group antibodies.Results: After they had been treated by these recipes, 92.3% became pregnant with normal delivery. It was found in dynamic investigation that level of the antibodies turned to decrease gradually during the treatment, and that of anti-phospholipid and anti-ABO group antibodies increased again at beginning of pregnancy and then decreased gradually with continuing the treatment.Conclusion: Chinese herbs recipe could be used to treat RSA of immune abnormality-type by way of decreasing the elevated levels of auto and/or allo-antibodies.

A molecular arms race between host innate antiviral response and emerging human coronaviruses

Coronaviruses have been closely related with mankind for thousands of years. Communityacquired human coronaviruses have long been recognized to cause common cold. However,zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome(SARS) and Middle East respiratory syndrome(MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

STING-mediated DNA sensing in cancer immunotherapy

While STING(STimulator of INterferon Genes) has been shown to be essential for cytosolic DNA-triggered innate immune activation, accumulated evidence obtained from various studies suggested that an intrinsic relevance of STING-associated signaling in tumorigenesis can be observed. Also, several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for STING, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. However, cases have also been reported where the involvement of STING shows a protective role in tumor growth. Here we summarize recent findings that have pointed towards the STING pathway as an innate immune sensing mechanism driving type I interferon production in the tumor context. Better understanding of this pathway can guide further development of novel immunotherapeutic strategies in the treatment of cancer.

Type 2 immunity in the brain and brain borders

Recent research in neuroimmunology has revolutionized our understanding of the intricate interactions between the immune system and the central nervous system(CNS).The CNS,an“immune-privileged organ”,is now known to be intimately connected to the immune system through different cell types and cytokines.While type 2 immune responses have traditionally been associated with allergy and parasitic infections,emerging evidence suggests that these responses also play a crucial role in CNS homeostasis and disease pathogenesis.Type 2 immunity encompasses a delicate interplay among stroma,Th2 cells,innate lymphoid type 2 cells(ILC2s),mast cells,basophils,and the cytokines interleukin(IL)-4,IL-5,IL-13,IL-25,TSLP and IL-33.In this review,we discuss the beneficial and detrimental roles of type 2 immune cells and cytokines in CNS injury and homeostasis,cognition,and diseases such as tumors,Alzheimer’s disease and multiple sclerosis.