ABSTRACT
In order to promote the innovative application of Sanjiao theory and Yingwei theory， this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases， integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body， and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi， and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion， which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis， which contributes to T cell exhaustion and is correlated with nutrient deprivation， lipid accumulation， and high lactate levels in the immunosuppressed tumor microenvironment， as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction， Shengming decoction， and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation， and hypoxia inducible factor-1α （HIF-1α） may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.
ABSTRACT
Lipid droplets (LD) are evolutionarily conserved lipid-enriched organelles with a diverse array of cell- and stimulus-regulated proteins. Accumulating evidence demonstrates that intracellular pathogens exploit LD as energy sources, replication sites, and part of the mechanisms of immune evasion. Nevertheless, LD can also favor the host as part of the immune and inflammatory response to pathogens. The functions of LD in the central nervous system have gained great interest due to their presence in various cell types in the brain and for their suggested involvement in neurodevelopment and neurodegenerative diseases. Only recently have the roles of LD in neuroinfections begun to be explored. Recent findings reveal that lipid remodelling and increased LD biogenesis play important roles for Zika virus (ZIKV) replication and pathogenesis in neural cells. Moreover, blocking LD formation by targeting DGAT-1 in vivo inhibited virus replication and inflammation in the brain. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development. Here, we review the progress in understanding LD functions in the central nervous system in the context of the host response to Zika infection.
ABSTRACT
Innate immune system, a non-specific defense system formed after birth, is body's first line of defense against pathogens. Innate immunity also plays a key role in the tumor immunosurveillance. With the clinical success of cancer immunotherapy, the regulatory mechanism of innate immune cells in antitumor response has begun to draw increasing attention. Recently, it has been recognized that metabolic regulation plays a vital role in innate immunity, in particular in the tumor microenvironment where the metabolic reprogramming in cancer increases the complexity of immunometabolism yet also provides therapeutic vulnerabilities. This review summarizes the recent progress in understanding the metabolic regulation of the innate immune response. We discuss how metabolites of glucose, amino acids, lipid and nucleotide metabolism regulate the function of innate immune cells. We pay the special attention to the metabolic crosstalk between immune cells or tumor-immune cells in the tumor microenvironment. With the review, we hope to get a better understanding of metabolic regulation of antitumor immunity and provide basis for metabolism-targeted immunotherapy.
ABSTRACT
The pathology of sepsis is extremely complex. Pathogen invasion, inflammatory factors secretion, coagulation disorder and microcirculation disturbance lead to metabolic disorder and organ dysfunction. In recent years, immunometabolism has aroused continuous attention in aspect of nutrition therapy and immune intervention for sepsis. Nutrition metabolites include amino acids, fatty acids, and glucose metabolites, which are not only the nutritional ingredients, but also the regulators of innate immune and adaptive immune. Fatty acids and glucose metabolites are involved in regulation of immune response mainly via free fatty acid receptors and AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Here, we summarized the research progress on the roles of nutrition metabolites in nutrition therapy and immune regulation during sepsis, which could provide a new direction for the development of metabolic therapy for sepsis.
ABSTRACT
Rheumatoid arthritis (RA), the most common inflammatory arthropathy word wild, is a systemic autoimmune disease that mainly affects the synovium of joints with a high disability rate. Metabolic mis-regulation has emerged as a fundamental pathogenesis of RA linked to immune cell dysfunction, while targeting immunometabolism provides a new and effective approach to regulate the immune responses and thus alleviate the symptom of RA. Recently, natural active compounds from traditional Chinese medicines (TCMs) have potential therapeutic effects on RA and regulating immunometabolism. In this review, in addition to updating the connection between cellular metabolism and cell function in immune cells of RA, we summarized that the anti-inflammatory mechanisms of the potential natural compounds from TCM by targeting metabolic reprogramming of immune cells, and discusses them as a rich resource for providing the new potential paradigm for the treatment of RA.
ABSTRACT
Sepsis remains a major cause of morbidity and mortality worldwide, with increased burden in low- and middle-resource settings. The role of the inflammatory response in the pathogenesis of the syndrome has supported the modern concept of sepsis. Nevertheless, a definition of sepsis and the criteria for its recognition is a continuous process, which reflects the growing knowledge of its mechanisms and the success and failure of diagnostic and therapeutic interventions. Here we review the evolving concepts of sepsis, from the "systemic inflammatory response syndrome triggered by infection" (Sepsis-1) to "a severe, potentially fatal, organic dysfunction caused by an inadequate or dysregulated host response to infection" (Sepsis-3). We focused in the pathophysiology behind the concept and the criteria for recognition and diagnosis of sepsis. A major challenge in evaluating the host response in sepsis is to characterize what is protective and what is harmful, and we discuss that, at least in part, the apparent dysregulated host response may be an effort to adapt to a hostile environment. The new criteria for recognition and diagnosis of sepsis were derived from robust databases, restricted, however, to developed countries. Since then, the criteria have been supported in different clinical settings and in different economic and epidemiological contexts, but still raise discussion regarding their use for the identification versus the prognostication of the septic patient. Clinicians should not be restricted to definition criteria when evaluating patients with infection and should wisely use the broad array of information obtained by rigorous clinical observation.
Subject(s)
Humans , Sepsis/physiopathology , Sepsis/immunology , Sepsis/diagnosis , Sepsis/metabolism , Lactic Acid/blood , Organ Dysfunction Scores , Medical IllustrationABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disease characterized by excessive activation of autoreactive T cells and B cells, abundant production of autoantibodies and multiple joint involvement. Under the influence of heredity and environment, the disorder of innate immunity and adaptive immunity is the fundamental cause of the disease. In recent years, with rapid development of immunometabolism, milestone has been made in regulating the differentiation and function of immune cells through different energy metabolism pathways and related molecules. Many studies have shown that Trp-IDO1,2/TDO2-Kyn metabolic pathway mediates the pathogenesis and development of autoimmune diseases such as RA. This review summarizes the role of tryptophan (Trp), kynurenine (Kyn) and other metabolites in this metabolic pathway, as well as the role of rate-limiting enzymes indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2) and tryptophan-2,3-dioxygenase 2 (TDO2) in mediating RA inflammatory immune response and synovitis inflammation. This provides an important basis for elucidating the new pathological mechanism of RA and discovering new drug targets.
ABSTRACT
Immunometabolism, focusing on the changes in intracellular metabolic pathways in immune cells that alter their function, is one of the most important research fields in recent years. Researches on the metabolism of carbohydrates, lipids,and proteins of immune cells shed important light on a better understanding of the physiological and pathological mechanisms of several diseases. For example, innate and adaptive immunity have been recently confirmed to be involved in obesity, further increasing risk of type 2 diabetes, cardiovascular disease, cancer and neurodegenerative disease. Interactions between metabolic aberrations and chronic kidney diseases always lead to a vicious spiral in disease etiology and progression. Up to date, emerging evidence has also indicated a therapeutic role of immune-metabolism. In this perspective,we aim to discuss some of these novel findings, with a special focus on how protein metabolism shaping immune system and gut microbiome in kidney disease. We hope the readers find our account understandable, interesting and thought-provoking for their own research.
ABSTRACT
Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.
Subject(s)
Biosynthetic Pathways , Carcinogenesis , Glucose , Glycolysis , Homeostasis , Kynurenine , Lactic Acid , Metabolism , Oncogenes , Oxidation-Reduction , Oxygen , Proto-Oncogenes , Protons , Quality Control , T-Lymphocytes , Tumor Microenvironment , YeastsABSTRACT
Recent studies have shown that immune cells play an important role in the development of non-immune diseases.Regulatory T cells (Treg) are a group of T cell subsets which have immunoregulatory and immunosuppressive functions.Abnormalities in the number and function of Treg cells may cause immune imbalance, which leads to the development of diseases.Immunometabolic disorders may in turn affect the generation, proliferation and function of Treg cells.Clarification of the relationship and interaction between immunometabolism and Treg cells will make it possible to treat metabolic diseases with cellular immunotherapy.
ABSTRACT
The rates of type 2 diabetes (T2D) in children and adolescents are rising globally, and this is closely linked to the obesity epidemic that is affecting millions of youth around the world. In this review, we examine the differences between type 1 diabetes and T2D, and highlight the mechanisms involved in T2D development including genetic, epigenetic and environmental factors. We also highlight the role of inflammation in causing insulin resistance, one of the main drivers of T2D genesis.