Correlation Between Granulomatous Mastitis and Autoimmune Function and the Immuneregulating Role of Traditional Chinese Medicine

Granulomatous mastitis(GM)is a benign granulomatous condition,and its pathogenesis may be related to autoimmune disorders.Cellular immunity,humoral immunity,immunoglobulins,and complement could all play a role in the disease process,showing certain clinical patterns.Corticosteroids can quickly control disease progression,and immunosuppressants can be used for complex and refractory GM cases.In traditional Chinese medicine(TCM),“healthy qi”is similar to immune system function.For GM with deficient healthy qi,TCM treatments such as internal and external herbal applications can help regulate immune function and shorten disease duration by staged and TCM treatment,regulating viscera,reinforcing healthy qi,and eliminating pathogenic factors.

Mesenchymal stem cell-derived exosomes regulate microglia phenotypes:a promising treatment for acute central nervous system injury

There is growing evidence that long-term central nervous system(CNS)inflammation exacerbates secondary deterioration of brain structures and functions and is one of the major determinants of disease outcome and progression.In acute CNS injury,brain microglia are among the first cells to respond and play a critical role in neural repair and regeneration.However,microglial activation can also impede CNS repair and amplify tissue damage,and phenotypic transformation may be responsible for this dual role.Mesenchymal stem cell(MSC)-derived exosomes(Exos)are promising therapeutic agents for the treatment of acute CNS injuries due to their immunomodulatory and regenerative properties.MSC-Exos are nanoscale membrane vesicles that are actively released by cells and are used clinically as circulating biomarkers for disease diagnosis and prognosis.MSC-Exos can be neuroprotective in several acute CNS models,including for stroke and traumatic brain injury,showing great clinical potential.This review summarized the classification of acute CNS injury disorders and discussed the prominent role of microglial activation in acute CNS inflammation and the specific role of MSC-Exos in regulating pro-inflammatory microglia in neuroinflammatory repair following acute CNS injury.Finally,this review explored the potential mechanisms and factors associated with MSCExos in modulating the phenotypic balance of microglia,focusing on the interplay between CNS inflammation,the brain,and injury aspects,with an emphasis on potential strategies and therapeutic interventions for improving functional recovery from early CNS inflammation caused by acute CNS injury.

Mannose metabolism and immune regulation:Insights into its therapeutic potential in immunology-related diseases

Mannose,a different isomer of the hydroxyl group at the C-2 position of glucose,shares the same transport carrier protein with glucose to enter cells and participate in the regulation of glucose metabolism.It affects cell growth,differentiation,and function and plays an active role in tumor immunity and inflammatory processes.This paper provides theoretical support for expanding the clinical applications of mannose by exploring its constitution,metabolic pathways,and role in regulating immune cell function and treating immunology-related diseases.

Cell polarization in ischemic stroke: molecular mechanisms and advances

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Microglia:a promising therapeutic target in spinal cord injury

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

Roles and application of exosomes in the development,diagnosis and treatment of gastric cancer

As important messengers of intercellular communication,exosomes can regulate local and distant cellular communication by transporting specific exosomal con-tents and can also promote or suppress the development and progression of gas-tric cancer(GC)by regulating the growth and proliferation of tumor cells,the tumor-related immune response and tumor angiogenesis.Exosomes transport bioactive molecules including DNA,proteins,and RNA(coding and noncoding)from donor cells to recipient cells,causing reprogramming of the target cells.In this review,we will describe how exosomes regulate the cellular immune respon-se,tumor angiogenesis,proliferation and metastasis of GC cells,and the role and mechanism of exosome-based therapy in human cancer.We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treat-ment of GC and their relationship with drug resistance.

Research Progress on the Immunomodulatory Effect of Mesenchymal Stem Cells on Chronic Periodontitis

Periodontal disease is an inflammatory and destructive disease of periodontal support tissue caused by microorganisms in dental plaque. During the development of periodontal disease, host immune regulation plays an important role, and unnecessary excessive immune regulation often exacerbates the course of chronic periodontal disease. Mesenchymal stem cells (MSCs) are adult stem cells with self replication ability and multi-directional differentiation potential. Many studies have found that MSCs have strong immunosuppressive effects on both adaptive and innate immunity. In recent years, literature has reported that MSCs are involved in the immune regulatory effect of chronic periodontal disease, inhibiting its inflammatory response and alveolar bone resorption, but the specific regulatory mechanism has not been elucidated. This article reviews the current research status of the immune regulatory effects of MSCs on chronic periodontitis.

Research Progress on the Association Between Gut Microbiota and Respiratory System Diseases

This paper aims to review the association between gut microbiota and respiratory system diseases, and explore their potential mechanisms and clinical significance. Gut microbiota, as an important microbial ecosystem in the human body, has profound effects on host health. Recent studies have shown that the imbalance of gut microbiota is closely related to the occurrence and development of respiratory system diseases, including asthma, chronic obstructive pulmonary disease (COPD), and pneumonia. We comprehensively analyzed the current research progress and found that gut microbiota may affect respiratory system diseases through various pathways, including immune regulation, inflammatory responses, and airway mucus secretion. Additionally, environmental factors, lifestyle, and dietary habits are also closely related to gut microbiota and respiratory system health. Understanding the relationship between gut microbiota and respiratory system diseases not only helps to reveal the mechanisms of disease occurrence but also provides a theoretical basis for the development of new treatment strategies. Future research should focus on exploring the types and functions of gut microbiota, conducting clinical trials based on this, investigating the effects of gut microbiota modulation on the treatment and prevention of respiratory system diseases, and providing new directions for personalized medicine.

Chinese medicine in the treatment of autoimmune hepatitis:Progress and future opportunities

Autoimmune hepatitis(AIH)is a chronic inflammatory liver disease occurring in indi-viduals of all ages with a higher incidence in females and characterized by hypergam-maglobulinemia,elevated serum autoantibodies and histological features of interface hepatitis.AIH pathogenesis remains obscure and still needs in-depth study,which is likely associated with genetic susceptibility and the loss of immune homeostasis.Steroids alone and in combination with other immunosuppressant agents are the pri-mary choices of AIH treatment in the clinic,whereas,in some cases,severe adverse effects and disease relapse may occur.Chinese medicine used for the treatment of AIH has proven its merits over many years and is well tolerated.To better under-stand the pathogenesis of AIH and to evaluate the efficacy of novel therapies,several animal models have been generated to recapitulate the immune microenvironment of patients with AIH.In the current review,we summarize recent advances in the study of animal models for AIH and their application in pharmacological research of Chinese medicine-based therapies and also discuss current limitations.This review aims to provide novel insights into the discovery of Chinese medicine-originated therapies for AIH using cutting-edge animal models.

Role of myeloid-derived suppressor cells in autoimmune disease

Myeloid-derived suppressor cells(MDSCs) represent an important class of immunoregulatory cells that can be activated to suppress T cell functions. These MDSCs can inhibit T cell functions through cell surface interactions and the release of soluble mediators. MDSCs accumulate in the inflamed tissues and lymphoid organs of patients with autoimmune diseases. Much of our knowledge of MDSC function has come from studies involving cancer models, however many recent studies have helped to characterize MDSC involvement in autoimmune diseases. MDSCs are a heterogeneous group of immature myeloid cells with a number of different functions for the suppression of T cell responses. However, we have yet to fully understand their contributions to the development and regulation of autoimmune diseases. A number of studies have described beneficial functions of MDSCs during autoimmune diseases, and thus there appears to be a potential role for MDSCs in the treatment of these diseases. Nevertheless, many questions remain as to the activation, differentiation, and inhibitory functions of MDSCs. This review aims to summarize our current knowledge of MDSC subsets and suppressive functions in tissue-specific autoimmune disorders. We also describe the potential of MDSC-basedcell therapy for the treatment of autoimmune diseases and note some of hurdles facing the implementation of this therapy.

Antitumor and immune regulation activities of the extracts of some Chinese marine invertebrates

Extracts of 21 marine invertebrates belonging to Coelenterata, Mollusca, Annelida, Bryozoa, Echiura, Arthropoda, Echinodermata and Urochordata were screened for the studies on their antitumor and immune regulation activities. Antitumor activity was determined by MTT method and immune regulation activity was studied using T- and B-lymphocytes in mice spleen in vitro. It was found that the n-butanol part of Asterina pectinifera, the acetic ether part of Tubuaria marina,95% ethanol extract of Acanthochiton rubrolineatus have a high inhibition rate of 96.7%,63.9% and 50.5% respectively on tumor cell line HL-60 at the concentration of 0.063 mg/ml. The inhibition rate of the acetic ether part of Tubuaria marina on the tumor cell line A-549 is 65.4 % at concentration of 0.063 mg/mL. The 95% ethanol extract of Meretrix meretrix has so outstanding promoting effect on T-lymphocytes that their multiplication increases 25% when the sample concentration is only 1 μg/ml. On B-lymphocytes, the 95% extract of Rapana venosa, at concentration of 100 μg/ml, has a promotion percent- age of 60%. On the other hand, under the condition of no cytotoxic effect, the 95% ethanol extracts of Acantho- chiton rubrolineatus and Cellana toreum can reach 92% inhibition rate on T lymphocyte at concentration of 100 μg/ml, while the inhibition rate on B lymphocyte of the 95% extract of Acanthochiton rubrolineatus reaches 92% at the same concentration.

Expression and prognosis analyses of Dectin-1 cluster genes in patients with lung adenocarcinoma (LUAD) and the association with immune checkpoint molecules

Reviews The Dectin-1 cluster comprises seven members:CLEC-12A,CLEC-12B,CLEC-1A,CLEC-7A,CLEC-2,CLEC-9A and OLR1.These members have been demonstrated to be involved in the tumorigenesis,progression,and metastasis of several cancers.However,little is known about their roles in human lung adenocarcinoma(LUAD).The expression patterns of the Dectin-1 cluster were analyzed via the ONCOMINE and GEPIA databases.We evaluated the prognostic value of the Dectin-1 cluster in patients with LUAD using the Kaplan-Meier plotter and GEPIA.Differential expression was validated with the EMBL-EBI database,and protein expression was analyzed with the HPA database.In addition,protein-protein interaction network,GO,and KEGG analyses were conducted.Finally,the correlations between CLEC-12A and immune molecules(immune inhibitors and MHC molecules)were investigated via TISIDB and GEPIA.The expression levels of Dectin-1 cluster genes were downregulated in LUAD tissues compared to those in normal lung tissues.The expression levels of CLEC-12A,CLEC-12B,CLEC-2,and CLEC-9A correlated with tumor stage,and CLEC-12A and CLEC-12B were significantly associated with survival in patients with LUAD.The seven genes mostly participated in immune regulation processes and were involved in autoimmune disorders and hematological malignancies.Finally,correlation analyses revealed CLEC-12A expression was associated with most immune inhibitors and MHCs.CLEC-12A was positively related to PD-1,PD-L1,PD-L2,CTLA4,TIM3,and LAG3.In conclusion,our findings suggest that CLEC-12A and CLEC-12B can be used as prognostic biomarkers in LUAD.CLEC-12A expression was associated with immune checkpoint molecules,and CLEC-12A may be a potential assistant target to improve the efficacy of immune checkpoint inhibitors immunotherapy.

Regulatory roles of extracellular vesicles in immune responses against Mycobacterium tuberculosis infection

Extracellular vesicles(EVs)are cystic vesicles naturally released by most mammalian cells and bacteria.EV contents include proteins,lipids,and nucleic acids.EVs can act as messengers to transmit a variety of molecules to recipient cells and thus play important regulatory roles in intercellular signal transduction.EVs,released by either a host cell or a pathogen,can carry pathogen-associated antigens and thus act as modulators of immune responses.EVs derived from Mycobacterium tuberculosis(Mtb)-infected cells can regulate the innate immune response through various pathways,such as regulating the release of inflammatory cytokines.In addition,EVs can mediate antigen presentation and regulate the adaptive immune response by transmitting immunoregulatory molecules to T helper cells.In this review,we summarize the regulatory roles of EVs in the immune response against Mtb.

Role of traditional Chinese medicine in incomplete immune reconstitution of HIV/AIDS:a review

Despite continuous progress,the prevention and treatment of human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(AIDS)remain the world’s most serious public health challenges.A key problem is the degree of immune function reconstruction after antiretroviral therapy.Antiretroviral therapy has enriched the treatment of HIV/AIDS and improved the present conditions and the life quality of HIV/AIDS patients.However,some patients still fail to achieve normalization of CD4+T lymphocyte counts although persistent virological suppression.These patients are referred to as immunological non-responders,and usually present with severe immunological dysfunction.To date,since the underlying mechanism of incomplete immune reconstitution in HIV/AIDS has not been fully elucidated,remaining to be the focus and difficulties of current research.It is still a challenge to explore a safe,effective,and reliable therapeutic method for immunological non-responders.Due to fewer side effects and lower drug resistance,traditional Chinese medicine is often sought to provide alternative pharmacotherapy for regulating the immunity of immunological non-responders in China.In this review,we aimed at summarizing the latest and most comprehensive information on traditional Chinese medicine therapeutic methods for promoting immune reconstruction.In addition,outlooks and perspectives for possible future research that related are also discussed.

Effect of FasL High Expression on Immune Regulative Function of Sertoli Cell in Transgenic Mouse

Objective To study the immune regulative function of Sertoli cell on testis local infection Methods Ureaplasma urealyticum （UU） was directly injected into bladders of FasL transgenic mice and wild-type mice, which mimicked an ascending infectious way. At week 1, 2 and 3 after injection respectively, the mice were killed to observe the pathological alterations in testis section. And at the same time cytokines was tested by immunohistochemistry. Comparison of levels of FasL, TGF-β, IL-1α and IL-6 between UU-infected and control groups of wild mice and FasL transgenic mice was made respectively. Then the capability of Sertoli cell （FasL^＋） to mediate apoptosis of Fas^＋ cells between wild control and wild UU-infected groups was analyzed. Results The pathological changes of testis in FasL transgenic mice were more seriously compared with wild counterpart and the changing mode of cytokines secreted by Sertoli cells were different between the two kinds of mice. The UU-infected Sertoli cells increased Fas^＋ Jurkat cell apoptosis. Conclusions High expression of FasL in FasL transgenic mice can influence the cytokines secretion during anti-infection, thus affecting the testis immune response to infection and immune balance. The high expression of FasL is not beneficial for body＇s anti-inflection immune response.

Research Progress of Vitamin D and Autoimmune Diseases

As a fat-soluble vitamin,Vitamin D is a necessary hormone to maintain normal physiological activities of the body.In recent years,vitamin D has been considered as a new neuroendocrine-immunomodulatory hormone,and researchers have paid more attention to the study of immune regulatory mechanism.It is not only related to calcium and phosphorus metabolism,bone metabolism and other important metabolic mechanisms of the body,but also closely related to the immune regulation mechanism of the body.Vitamin D deficiency caused by many factors can play a certain role in the development of autoimmune diseases.In this paper,the related mechanisms of vitamin D affecting autoimmune diseases were reviewed,with a view to expound the close correlation between vitamin D and autoimmune diseases,so as to find new diagnosis and treatment approaches for clinical autoimmune diseases and improve the quality of life of patients with autoimmune diseases.

Research Progress of Anti-tumor Effects of Curcuma zedoaria and its Active Ingredients Through Immune Regulation Mechanism

The continuous increase in the incidence rate of various fatal malignant tumors in the recent years warrants an imperative search for medications or drugs with obvious anti-tumor eflects and reliable curative effects.Previous studies have found that Curcuma zedoaria and its active ingredients,such as turmeric oil,curcumol,and P-elemene,have obvious antitumor effects,and they do not have the adverse reactions and side effects seen in the anti-tumor drugs of Western medicine.Based on the review and inductive analysis of related literature,we summarize in the present article the results of some researchers who investigated the anti-tumor effects of Curcuma zedoaria and its active ingredients through the immune regulation mechanism.

Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells

BACKGROUND Mesenchymal stem cells(MSCs)have great potential for the treatment of various immune diseases due to their unique immunomodulatory properties.However,MSCs exposed to the harsh inflammatory environment of damaged tissue after intravenous transplantation cannot exert their biological effects,and therefore,their therapeutic efficacy is reduced.In this challenging context,an in vitro preconditioning method is necessary for the development of MSC-based therapies with increased immunomodulatory capacity and transplantation efficacy.AIM To determine whether hypoxia and inflammatory factor preconditioning increases the immunosuppressive properties of MSCs without affecting their biological characteristics.METHODS Umbilical cord MSCs(UC-MSCs)were pretreated with hypoxia(2%O_(2))exposure and inflammatory factors(interleukin-1β,tumor necrosis factor-α,interferon-γ)for 24 h.Flow cytometry,polymerase chain reaction,enzyme-linked immunosorbent assay and other experimental methods were used to evaluate the biological characteristics of pretreated UC-MSCs and to determine whether pretreatment affected the immunosuppressive ability of UC-MSCs in coculture with immune cells.RESULTS Pretreatment with hypoxia and inflammatory factors caused UC-MSCs to be elongated but did not affect their viability,proliferation or size.In addition,pretreatment significantly decreased the expression of coagulationrelated tissue factors but did not affect the expression of other surface markers.Similarly,mitochondrial function and integrity were retained.Although pretreatment promoted UC-MSC apoptosis and senescence,it increased the expression of genes and proteins related to immune regulation.Pretreatment increased peripheral blood mononuclear cell and natural killer(NK)cell proliferation rates and inhibited NK cell-induced toxicity to varying degrees.CONCLUSION In summary,hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics.

A Review on the Biological Characteristics and Secretory Functions of Adipose-derived Mesenchymal Stem Cells

Adipose-derived mesenchymal stem cells （ADSCs） can be largely and easily obtained from a wide range of sources. Moreover, they have self-renewal ability, multi-differentiation potential, and an important role in immune regulation. They can secrete a variety of cytokines to regulate the in vivo micro-environment. Therefore, ADSCs are the ideal seed ceils for stem ceils application. This paper reviews the location, isolation, surface markers, proliferation, differentiation and other biological characteristics of ADSCs, as well as their secretory function and relative researches. ADSCs are expected to become excellent seed cells for cell therapy and tissue engineering through in-depth studies.

Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation

Human placenta-derived mononuclear cells （MNC） were isolated by a Percoll density gradient and cultured in mesenchymal stem cell （MSC） maintenance medium. The homogenous layer of adherent cells exhibited a typical fibroblastlike morphology, a large expansive potential, and cell cycle characteristics including a subset of quiescent cells. In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic, osteogenic and chondrogenic lineages. Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells, which uniformly expressed CD29, CD44, CD73, CD105, CD166, laminin, fibronectin and vimentin while being negative for expression of CD31, CD34, CD45 and m-smooth muscle actin. Most importantly, immuno-phenotypic analyses demonstrated that these cells expressed class Ⅰ major histocompatibility complex （MHC-I）, but they did not express MHC-Ⅱ molecules. Additionally these cells could suppress umbilical cord blood （UCB） lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli. This strongly implies that they may have potential application in allograft transplantation. Since placenta and UCB are homogeneous, the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells （HSC） from UCB to reduce the potential graft-versus-host disease （GVHD） in recipients.