Rheumatoid arthritis (RA) is an autoimmune disease that starts with decreased tolerance to modified self-antigens and eventually leads to synovitis and destruction of bone and cartilage. Age is a risk factor for developing RA. Major changes in the immune system come with age due to chronic oxidative stress on the deoxyribonucleic acid (DNA) damage pathway, somatic mutation, modifications of auto-antigens, T cell tolerance and activation of fibroblast-like synoviocytes (FLS). Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2) suppress T cell receptor signaling. Sirtuin 1 (SIRT1) is a critical immune suppressor of T cell activation and a key regulator of oxidative stress. When oxidative stress reduces activity of SIRT1, the breakdown of tolerance to modified self-antigens is expected. Generation of ROS can be perpetuated by enhanced DNA damage and dysfunctional mitochondria in a feedback loop during the development of RA. Through major T cell loss and selective proliferation of peripheral T cells, pro-inflammatory T cell pools with abnormal features are established in the T cell compartment. Hypoxic and inflammatory condition in synovium perpetuates ROS generation, which leads to the activation of FLS. In both T cell and synovium compartment, oxidative stress reshapes the immune system into the development of pre-clinical RA.
Arthritis, Rheumatoid* ; Autoantigens ; Autoimmune Diseases ; Cartilage ; DNA ; DNA Damage ; Immune System ; Mitochondria ; NADP ; NADPH Oxidase ; Oxidative Stress ; Oxidoreductases ; Reactive Oxygen Species* ; Receptors, Antigen, T-Cell ; Risk Factors ; Sirtuin 1 ; Synovial Membrane ; Synovitis ; T-Lymphocytes

Restoring the microbiota via fecal microbiota transplantation (FMT) can be an effective treatment for steroid-refractory acute graft-versus-host disease (GVHD) of the gut. Here, we report two adult patients who underwent FMT to treat steroid-refractory acute GVHD of the gut. The first patient was a 43-year-old man who underwent allogeneic hematopoietic stem cell transplantation (HSCT) with cells from a matched sibling donor. The second patient was a 70-year-old woman who underwent haplo-identical HSCT with cells from her son. Gut GVHD developed at 7 and 4 weeks after HSCT, respectively. After undergoing FMT, the clinical symptoms improved; the first patient had a complete response and the second patient had a partial response. Microbial analyses using RNA gene sequencing showed that a diverse fecal microbiome was recovered by 4 weeks after FMT. FMT should be considered an effective therapeutic option for managing steroid-refractory acute GVHD of the gut.

Restoring the microbiota via fecal microbiota transplantation (FMT) can be an effective treatment for steroid-refractory acute graft-versus-host disease (GVHD) of the gut. Here, we report two adult patients who underwent FMT to treat steroid-refractory acute GVHD of the gut. The first patient was a 43-year-old man who underwent allogeneic hematopoietic stem cell transplantation (HSCT) with cells from a matched sibling donor. The second patient was a 70-year-old woman who underwent haplo-identical HSCT with cells from her son. Gut GVHD developed at 7 and 4 weeks after HSCT, respectively. After undergoing FMT, the clinical symptoms improved; the first patient had a complete response and the second patient had a partial response. Microbial analyses using RNA gene sequencing showed that a diverse fecal microbiome was recovered by 4 weeks after FMT. FMT should be considered an effective therapeutic option for managing steroid-refractory acute GVHD of the gut.

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.
Acetylcysteine ; Ascorbic Acid ; Humans ; Mitochondria ; Parasites ; Reactive Oxygen Species ; Retinaldehyde ; Superoxides ; Toxoplasma ; Toxoplasmosis