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.

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.

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.

Dynamic m6A-ncRNAs association and their impact on cancer pathogenesis, immune regulation and therapeutic response

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types,including non-coding RNAs(ncRNAs).N-6-methyladenosine(m6A)is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis,and serves as a crucial regulator for multiple cancer-associated signaling pathways.The ncRNAs usually regulate the epigenetic modification,mRNA transcription and other biological processes,displaying enormous roles in human cancers.In this review,we summarized the significant implications of m6A-ncRNA interaction in various types of cancers.In particular,the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely recognized.We also discussed the relevance of m6A-ncRNA interaction in immune regulation,followed by the interference on cancer immunotherapeutic procedures.In addition,we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among ncRNAs.In summary,this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

Regulation of fatty acid synthase on tumor and progress in the development of related therapies

Fatty acid synthase(FASN)is an essential molecule in lipid metabolic pathways,which are crucial for cancer-related studies.Recent studies have focused on a comprehensive understanding of the novel and important regulatory effects of FASN on malignant biological behavior and immune-cell infiltration,which are closely related to tumor occurrence and development,immune escape,and immune response.FASN-targeting antitumor treatment strategies are being developed.Therefore,in this review,we focused on the effects of FASN on tumor and immune-cell infiltration and reviewed the progress of related antitumor therapy development.

Functional diversity of long non-coding RNAs in immune regulation

Precise and dynamic regulation of gene expression is a key feature of immunity.In recent years,rapid advances in transcriptome profiling analysis have led to recognize long noncoding RNAs(lncRNAs)as an additional layer of gene regulation context.In the immune system,lncRNAs are found to be widely expressed in immune cells including monocytes,macrophages,dendritic cells(DC),neutrophils,T cells and B cells during their development,differentiation and activation.However,the functional importance of immune-related lncRNAs is just emerging to be characterized.In this review,we discuss the up-to-date knowledge of lncRNAs in immune regulation.

Germinal center kinases in immune regulation

Germinal center kinases （GCKs） participate in a variety of signaling pathways needed to regulate cellular functions including apoptosis, cell proliferation, polarity and migration. Recent studies have shown that GCKs are participants in both adaptive and innate immune regulation. However, the differential activation and regulatory mechanisms of GCKs, as well as upstream and downstream signaling molecules, remain to be fully defined. It remains unresolved whether and how GCKs may cross-talk with existing signaling pathways. This review stresses the progresses in research of GCKs relevant to the immune system.

Effect of Interstitial Chemotherapy with Ricin Temperature-Responsive Gel for Anti-Breast Cancer and Immune Regulation in Rats

Objective： To explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats. Methods： Ricin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally： the model group and three treated groups （blank gel, ricin, ricin-gel） were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate （FIR） by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor- oL （TNF- oL ） and interleukin-2 （IL-2）. The outcomes were compared between groups. Results： The TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down- regulated, bax expression was up-regulated, CD4＋ lymphocytes and CD4＋/CD8＋ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF- α and IL-2 were elevated （P〈0.05 or P〈0.01）. Conclusion： Intratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.

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.

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.

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.

Annual advances of traditional medicine on tumor immunity regulation in 2020

Tumor burden remains a global health problem that threatens human life worldwide.Over the past few years,the evolution of immune checkpoint inhibitors has represented one of the most successful approaches in the field of tumor therapy.Drugs regulating tumor immune microenvironment or enhancing body immunity have indicated a novel perspective to treat tumors.Therefore,an increased number of scientists have been shifting their research focus to explore the immunity regulation effects of anti-tumor traditional medicine or natural products.In this review,we summarize the research progress of traditional medicines on tumor immunity regulation in 2020.Our findings suggest that more herbal medicine-derived phytochemicals and formulas were derived from traditional Chinese medicine,and more papers were published in comprehensive journals.Traditional medicine can comprehensively regulate the tumor immune microenvironment,including natural killer cells,dendritic cells,CD4+/CD8+T lymphocytes,regulatory T cells,myeloid-derived suppressor cells,tumor-associated macrophages,immunosuppressive factors,and immune checkpoints.In 2020,a greater number of research papers focused on active ingredients and formulas that regulate tumor-associated macrophages and immune checkpoints.Active ingredients such as flavonoids became a global hotspot in 2020.Certain natural products were also found to exert synergistic anti-tumor activity with immune checkpoint inhibitors,such as curcumin.However,a distinct lack of high-quality experimental and clinical studies remains a prevalent and challenging issue that hinders the further development of traditional medicine.

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.