The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection. Here, we verified the diagnostic value of serum Adenosine Triphosphate (ATP) as a potential marker for differential HBV infection progress by detecting the level of ATP in the serum from a wide spectrum of HBV-infected populations, and confirmed the role of ATP in the deterioration of HBV infection-related diseases through HBV-infected cells and mouse models. The results showed that there were significantly lower serum ATP levels in HBeAg-positive CHB patients compared with healthy controls. And during the progression of CHB to liver cirrhosis and hepatocellular carcinoma, the ATP level was increased but not higher than healthy controls. The area under the curve (AUC) of serum ATP was 0.9063 to distinguish HBeAg-positive CHB from healthy, and another AUC was 0.8328 in the CHB against the HCC group. Preliminary exploration of the mechanism indicated that the decline of serum ATP was due to impaired mitochondria in CHB patients. Our data provide evidence that serum ATP distinguishes the various progress of HBV infection-related diseases and expands diagnostic biomarkers for HBeAg-positive CHB patients with healthy controls.

The concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.

As important effector cells in inflammation, macrophages can be functionally polarized into either inflammatory M1 or alternatively activated anti-inflammatory M2 phenotype depending on surroundings. The key roles of glycolysis in M1 macrophage polarization have been well defined. However, the relationship between glycolysis and M2 polarized macrophages is still poorly understood. Here, we report that 2-deoxy-d-glucose (2-DG), an inhibitor of the glycolytic pathway, markedly inhibited the expressions of Arg, Ym-1, Fizz1, and CD206 molecules, the hall-markers for M2 macrophages, during macrophages were stimulated with interleukin 4. The impacted M2 macrophage polarization by 2-DG is not due to cell death but caused by the impaired cellular glycolysis. Molecular mechanism studies indicate that the effect of 2-DG on M2 polarized macrophages relies on AMPK-Hif-1α-dependent pathways. Importantly, 2-DG treatment significantly decreases anti-inflammatory M2 macrophage polarization and prevents disease progression in a series of mouse models with chitin administration, tumor, and allergic airway inflammation. Thus, the identification of the master role of glycolysis in M2 macrophage polarization offers potential molecular targets for M2 macrophages-mediated diseases. 2-DG therapy may have beneficial effects in patients with tumors or allergic airway inflammation by its negative regulation on M2 macrophage polarization.

Accumulated reactive oxygen species (ROS) directly contribute to biomacromolecule damage and influence various inflammatory responses. Reactive oxygen species act as mediator between innate and adaptive immune cells, thereby influencing the antigen-presenting process that results in T cell activation. Evidence from patients with chronic granulomatous disease and mouse models support the function of ROS in preventing abnormal autoimmunity; for example, by supporting maintenance of macrophage efferocytosis and T helper 1/T helper 2 and T helper 17/ regulatory T cell balance. The failure of many anti-oxidation treatments indicates that ROS cannot be considered entirely harmful. Indeed, enhancement of ROS may sometimes be required. In a mouse model of rheumatoid arthritis (RA), absence of NOX2-derived ROS led to higher prevalence and more severe symptoms. In patients with RA, naïve CD4+ T cells exhibit inhibited glycolysis and enhanced pentose phosphate pathway (PPP) activity, leading to ROS exhaustion. In this "reductive" state, CD4+ T cell immune homeostasis is disrupted, triggering joint destruction, together with oxidative stress in the synovium.

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.

Alloreactive donor T cells undergo extensive metabolic reprogramming to become activated and induce graft-versus-host disease (GVHD) upon alloantigen encounter. It is generally thought that glycolysis, which promotes T cell growth and clonal expansion, is employed in this process. However, conflicting data have been reported regarding the requirement of glycolysis to induce T cell-mediated GVHD due to the lack of T cell-specific treatments using glycolysis inhibitors. Importantly, previous studies have not evaluated whether graft-versus-leukemia (GVL) activity is preserved in donor T cells deficient for glycolysis. As a critical component affecting the clinical outcome, it is necessary to assess the anti-tumor activity following treatment with metabolic modulators in preclinical models. In the present study, we utilized T cells selectively deficient for glucose transporter 1 (Glut1T-KO), to examine the role of glycolysis exclusively in alloreactive T cells without off-targeting effects from antigen presenting cells and other cell types that are dependent on glycolysis. We demonstrated that transfer of Glut1T-KO T cells significantly improved acute GVHD outcomes through increased apoptotic rates, impaired expansion, and decreased proinflammatory cytokine production. In addition to impaired GVHD development, donor Glut1T-KO T cells mediated sufficient GVL activity to protect recipients from tumor development. A clinically relevant approach using donor T cells treated with a small molecule inhibitor of glycolysis, 2-Deoxy-D-glucose ex vivo, further demonstrated protection from tumor development. These findings indicate that treatment with glycolysis inhibitors prior to transplantation selectively eliminates alloreactive T cells, but spares non-alloreactive T cells including those that protect against tumor growth. The present study has established a definitive role for glycolysis in acute GVHD and demonstrated that acute GVHD can be selectively prevented through targeting glycolysis.