Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease.Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes.With the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune dysfunction.However,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological mechanism.In this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

miRNA-124 in immune system and immune disorders

In recent years,miR-124 has emerged as a critical modulator of immunity and inflammation.Here,we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases.They indicated that miR-124 exerts a crucial role in the development of immune system,regulation of immune responses,and inflammatory disorders.It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future.

TRADITIONAL CHINESE MEDICINE IN THE TREATMENT OF AUTOIMMUNE AND IMMUNE DISORDERS

It is well known that the treatment of Dampness-heat falling into the lowerburner(DHFLB) is very difficult to deal with by both traditional Chinese medicine(TCM) and western medicine.After TCM system of Epidemic Febril Disease(composed of three parts,Shanghan,exogenous febril disease;)

Gut microbiota in various childhood disorders:Implication and indications

Gut microbiota has a significant role in gut development,maturation,and immune system differentiation.It exerts considerable effects on the child's physical and mental development.The gut microbiota composition and structure depend on many host and microbial factors.The host factors include age,genetic pool,general health,dietary factors,medication use,the intestine's pH,peristalsis,and transit time,mucus secretions,mucous immunoglobulin,and tissue oxidation-reduction potentials.The microbial factors include nutrient availability,bacterial cooperation or antagonism,and bacterial adhesion.Each part of the gut has its microbiota due to its specific characteristics.The gut microbiota interacts with different body parts,affecting the pathogenesis of many local and systemic diseases.Dysbiosis is a common finding in many childhood disorders such as autism,failure to thrive,nutritional disorders,coeliac disease,Necrotizing Enterocolitis,helicobacter pylori infection,functional gastrointestinal disorders of childhood,inflammatory bowel diseases,and many other gastrointestinal disorders.Dysbiosis is also observed in allergic conditions like atopic dermatitis,allergic rhinitis,and asthma.Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders,including heart failure.Probiotic supplements could provide some help in managing these disorders.However,we are still in need of more studies.In this narrative review,we will shed some light on the role of microbiota in the development and management of common childhood disorders.

Research progress on the immune microenvironment of the gallbladder in patients with cholesterol gallstones

Cholesterol gallstones are very common in hepatobiliary surgery and have been studied to a certain extent by doctors worldwide for decades.However,the mechanism of cholesterol gallstone formation is not fully understood,so there is currently no completely effective drug for the treatment and prevention of cholesterol gallstones.The formation and development of cholesterol gallstones are caused by a variety of genetic and environmental factors,among which genetic susceptibility,intestinal microflora disorders,impaired gallbladder motility,and immune disorders are important in the pathogenesis of cholesterol gallstones.This review focuses on recent advances in these mechanisms.We also discuss some new targets that may be effective in the treatment and prevention of cholesterol gallstones,which may be hot areas in the future.

Anti-diabetics and antimicrobials:Harmony of mutual interplay

Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes.The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes,assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation.On a parallel basis,microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment,all of which can be reversed by antimicrobial treatment.Standing at the crossroads between diabetes,immunity and infection,we aim in this review at projecting the interplay between immunity and diabetes,shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents.Furthermore,we focused on the antidiabetic drugs that can confer antimicrobial or anti-virulence activities.

The Immune System,Cytokines,and Biomarkers in Autism Spectrum Disorder

Autism Spectrum Disorder（ASD） is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine pro？les and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may de？ne a subgroup of ASD,or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previouslyidenti？ed immune system abnormalities in ASD, speci？-cally addressing the role of cytokines in these aberrations.The roles and identi？cation of biomarkers are also addressed, particularly with respect to cytokine pro？les in ASD.

Loss of stat3 function leads to spine malformation and immune disorder in zebrafish

STAT （Signal Transducers and Activators of Transcription） gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance, their functions are poorly studied at organ and systemic levels. In this study, we performed a genome-wide analysis using data from invertebrates to vertebrates to identify STAT genes and analyze their evolutionary history. Interestingly, the STAT gene family undergoes genome duplications during the evolutionary history with STAT3 homologues firstly appearing in the basal extant vertebrate, sea lamprey, suggesting its possible roles in spine formation. To investigate the functions of stat3 in fish species, TALEN technology was performed to generate mutant zebrafish lines, star3 mutant zebrafish showed no obvious defects at early developmental stage but displayed severe lateral and vertical curvature of the spine （scoliosis）, spine fracture and the incomplete bone joints with narrower junction between vertebrae at early juvenile stage, as indicated by Alizarin red and Alcian blue staining, radiography and micro-computed tomography （MicroCT） analysis. Transcriptome analysis reveals dramatic alterations in a number of genes involved in immune and infection response, skeletal development and somatic growth, especially downregulated expression of collagen gene family, in the juvenile stat3 mutant zebrafish. Moreover, most of the collagen genes were detected to have abnormal expression pattern during the formation of spine deformities in stat3 mutants. Our data reveal that stat3 is specially expressed in vertebrates and required for normal spine development and immune function in zebrafish.

Immunotherapy with Agonistic Anti-CD137:Two Sides of a Coin

CD137 (4-1BB),a member of the TNF receptor superfamily,is an inducible T cell costimulatory receptor primarily expressed on activated CD4^+ and CD8^+ T cells.Agonistic monoclonal antibodies (mAbs) against CD137 greatly enhance T cell-mediated immune responses against many types of tumors and viruses.Surprisingly,these agonists also showed therapeutic effects in several autoimmune diseases.These findings suggest that in different disease environments,CD137 engagement with agonist mAb in vivo can diametrically modulate immune response outcomes.Therefore,CD137 agonists represent a promising immunotherapeutic approach to a wide array of disparate immune disorders.However,CD137's potency in modulating immune response necessitates caution when targeting CD137 clinically.Cellular & Molecular Immunology.2004;1(1):31-36.

Case Report:Takayasu's arteritis associated with Crohn's disease

Takayasu's arteritis(TA),also known as the "pulseless disease," is a chronic vasculitis of the aorta and aortic branches.TA with Crohn's disease is rare and has not been documented in China before.In this paper we report on a case of Takayasu's arteritis associated with concurrent Crohn's disease.A 17-year-old Chinese male developed upper limb sourness and a sensation of fatigue,and his upper limb pulses were absent.He was diagnosed with TA and underwent an axillary artery bypass with autologous great saphenous vein on the left subclavian artery.After the surgery,he regained the normal blood pressure.This patient also had years of diarrhea and developed an anal canal ulcer,and was diagnosed with inflammatory bowel disease and ulcerative colitis before.Five months after the TA surgery,he was hospitalized for severe stomachache and diarrhea and was finally diagnosed with Crohn's disease.The possible pathophysiological mechanisms responsible for concurrent existence of TA and Crohn's disease may be associated with immune disorders,especially autoimmunity.

Alterations of peripheral CD4^(+)CD25^(+)Foxp3^(+)T regulatory cells in mice with STZ-induced diabetes

Complications arising from abnormal immune responses are the major causes of mortality and morbidity in diabetic patients.CD4^(+)CD25^(+)T regulatory cells(Tregs)play pivotal roles in controlling immune homeostasis,immunity and tolerance.The effect of hyperglycemia on CD4^(+)CD25^(+)Tregs has not yet been addressed.Here we used streptozotocin(STZ)-induced diabetic mice to study the effects of long-term hyperglycemia on CD4^(+)CD25^(+)Tregs in vivo.Four months after the onset of diabetes,the frequency of CD4^(+)CD25^(+)Foxp3^(+)T regulatory cells was significantly elevated in the spleen,peripheral blood lymphocytes(PBLs),peripheral lymph nodes(pLNs)and mesenteric LNs(mLNs).CD4^(+)CD25^(+)Tregs obtained from mice with diabetes displayed defective immunosuppressive functions and an activated/memory phenotype.Insulin administration rescued these changes in the CD4^(+)CD25^(+)Tregs of diabetic mice.The percentage of thymic CD4^(+)CD25^(+)naturally occurring Tregs(nTregs)and peripheral CD41Helios1Foxp31 nTregs were markedly enhanced in diabetic mice,indicating that thymic output contributed to the increased frequency of peripheral CD4^(+)CD25^(+)Tregs in diabetic mice.In an in vitro assay in which Tregs were induced fromCD4^(+)CD25^(+)T cells by transforming growth factor(TGF)-b,high glucose enhanced the efficiency of CD4^(+)CD25^(+)Foxp3^(+)T inducible Tregs(iTregs)induction.In addition,CD4^(+)CD25^(+)T cells from diabetic mice were more susceptible to CD4^(+)CD25^(+)Foxp3^(+)TiTreg differentiation than those cells from control mice.These data,together with the enhanced frequency of CD4^(+)CD25^(+)Foxp3^(+)T iTregs in the periphery of mice with diabetes,indicate that enhanced CD4^(+)CD25^(+)Foxp3^(+)T iTreg induction also contributes to a peripheral increase in CD4^(+)CD25^(+)Tregs in diabetic mice.Our data show that hyperglycemia may alter the frequency of CD4^(+)CD25^(+)Foxp3^(+)T Tregs in mice,which may result in late-state immune dysfunction in patients with diabetes.

Mesenchymal stem cells in tissue repairing and regeneration: Progress and future

The presence of mesenchymal progenitor cells within bone marrow has been known since the late nineteenth century. To date, mesenchymal stem cells (MSCs) have been isolated from several different connective tissues, such as adipose tissue, muscle, placenta, umbilical cord matrix, blood, liver, and dental pulp. Bone marrow, however, is still one of the major sources of MSCs for preclinical and clinical research. MSCs were first evaluated for regenerative applications and have since been shown to directly influence the immune system and to promote neovascularization of ischemic tissues. These observations have prompted a new era of MSC transplantation as a treatment for various diseases. In this review, we summarize the important studies that have investigated the use of MSCs as a therapeutic agent for regenerative medicine, immune disorders, cancer, and gene therapy. Furthermore, we discuss the mechanisms involved in MSC-based therapies and clinical-grade MSC manufacturing.

Mechanism of Traditional Chinese Medicine on Intestinal Mucosal Immunity in Chronic Intestinal Diseases

Although irritable bowel syndrome(IBS) and inflammatory bowel disease(IBD) are clinically common diseases with unclear pathogenesis, both of them are related to the immune system. With progress in studies on their pathogenesis, the two diseases are currently believed to be associated with the presence of intestinal inflammation and intestinal mucosal immune disorder. In recent years, a new approach for the prevention and treatment of chronic intestinal disease is to protect the complete structure and normal immunity of the intestinal mucosal barrier during the treatment of intestinal diseases. However, traditional Chinese medicine(TCM) may have more advantages in regulating the imbalance of the intestinal immune microenvironment, as various single herbs and compounds of TCM have been investigated from the perspective of immune regulation. The use of TCM is prevalent in China. The effectiveness of these therapies appears to be supported by preliminary evidence and clinical experience, although the mechanisms that underlie these effects will require further research. In this paper, with common chronic bowel diseases including IBS, ulcerative colitis and Crohn's disease as the research objects, the relationship between TCM and immunity was explored from the perspectives of the pathogenesis of intestinal mucosal immune injury, the correlation between TCM syndromes and immune disorders, and TCM immune regulation. Moreover, the problems and limitations of the present study were pointed out, and several suggestions were proposed. The purpose of this article is to explore the potential mechanism of TCM on intestinal mucosal immunity in chronic intestinal diseases.