Notes

Improved upon contiguity with the threespine stickleback genome making use of long-read sequencing.
Biologic drugs, especially anti-TNF, are considered as the gold standard therapy in rheumatoid arthritis. However, non-uniform efficacy, incidence of infections, and high costs are major concerns. Novel tissue-specific agents may overcome the current limitations of systemic administration, providing improved potency, and safety. We developed a bispecific antibody (BsAb), combining human arthritic joint targeting, via the synovial-specific single-chain variable fragment (scFv)-A7 antibody, and TNFα neutralization, via the scFv-anti-TNFα of adalimumab, with the binding/blocking capacity comparable to adalimumab -immunoglobulin G (IgG). Tissue-targeting capacity of the BsAb was confirmed on the human arthritic synovium in vitro and in a synovium xenograft Severe combined immune deficient (SCID) mouse model. Peak graft accumulation occurred at 48 h after injection with sustained levels over adalimumab-IgG for 7 days and increased therapeutic effect, efficiently decreasing tissue cellularity, and markers of inflammation with higher potency compared to the standard treatment. This study provides the first description of a BsAb capable of drug delivery, specifically to the disease tissue, and a strong evidence of improved therapeutic effect on the human arthritic synovium, with applications to other existing biologics.Emerging evidence accumulated over the past several years has uncovered intestinal CD4+ T cells as an essential mediator in modulating intestinal immunity in health and diseases. It has also been increasingly recognized that dietary and microbiota-derived factors play key roles in shaping the intestinal CD4+ T-cell compartment. This review aims to discuss the current understanding on how the intestinal T cell immune responses are disturbed by obesity and metabolic stress. In addition, we review how these changes influence systemic metabolic homeostasis and the T-cell-mediated crosstalk between gut and liver or brain in the progression of obesity and its related diseases. Lastly, we highlight the potential roles of some drugs that target intestinal T cells as a therapeutic treatment for metabolic diseases. this website A better understanding of the interaction among metabolites, bacterial signals, and T cell immune responses in the gut and their roles in systemic inflammation in metabolic tissues should shed new light on the development of effective treatment of obesity and related disorders.Neurodegenerative diseases are closely related to inflammatory and autoimmune events, suggesting that the dysregulation of the immune system is a key pathological factor. Both multiple sclerosis (MS) and Alzheimer's disease (AD) are characterized by infiltrating immune cells, activated microglia, astrocyte proliferation, and neuronal damage. Moreover, MS and AD share a common pro-inflammatory signature, characterized by peripheral leukocyte activation and transmigration to the central nervous system (CNS). MS and AD are both characterized by the accumulation of activated neutrophils in the blood, leading to progressive impairment of the blood-brain barrier. Having migrated to the CNS during the early phases of MS and AD, neutrophils promote local inflammation that contributes to pathogenesis and clinical progression. The role of circulating T cells in MS is well-established, whereas the contribution of adaptive immunity to AD pathogenesis and progression is a more recent discovery. Even so, blocking the transmigration of T cells to the CNS can benefit both MS and AD patients, suggesting that common adaptive immunity mechanisms play a detrimental role in each disease. There is also growing evidence that regulatory T cells are beneficial during the initial stages of MS and AD, supporting the link between the modulatory immune compartments and these neurodegenerative disorders. The number of resting regulatory T cells declines in both diseases, indicating a common pathogenic mechanism involving the dysregulation of these cells, although their precise role in the control of neuroinflammation remains unclear. The modulation of leukocyte functions can benefit MS patients, so more insight into the role of peripheral immune cells may reveal new targets for pharmacological intervention in other neuroinflammatory and neurodegenerative diseases, including AD.Myeloid derived suppressor cells (MDSC) are heterogeneous populations that through the release of soluble factors and/or by cell-to-cell interactions suppress both innate and adaptive immune effector cells. In pathological conditions, characterized by the presence of inflammation, a partial block in the differentiation potential of myeloid precursors causes an accumulation of these immunosuppressive cell subsets both in peripheral blood and in tissues. On the contrary, NK cells represent a major player of innate immunity able to counteract tumor growth. The anti-tumor activity of NK cells is primarily related to their cytolytic potential and to the secretion of soluble factors or cytokines that may act on tumors either directly or indirectly upon the recruitment of other cell types. NK cells have been shown to play a fundamental role in haploidentical hemopoietic stem cell transplantation (HSCT), for the therapy of high-risk leukemias. A deeper analysis of MDSC functional effects demonstrated that these cells are capable, through several mechanisms, to reduce the potent GvL activity exerted by NK cells. It is conceivable that, in this transplantation setting, the MDSC-removal or -inactivation may represent a promising strategy to restore the anti-leukemia effect mediated by NK cells. Thus, a better knowledge of the cellular interactions occurring in the tumor microenvironment could promote the development of novel therapeutic strategies for the treatment of solid and hematological malignances.Viral hepatitis particularly Hepatitis B Virus (HBV) is still an ongoing health issue worldwide. Despite the vast technological advancements in research and development, only HBV vaccines, typically given during early years, are currently available as a preventive measure against acquiring the disease from a secondary source. In general, HBV can be cleared naturally by the human immune system if detected at low levels early. However, long term circulation of HBV in the peripheral blood may be detrimental to the human liver, specifically targeting human hepatocytes for cccDNA integration which inevitably supports HBV life cycle for the purpose of reinfection in healthy cells. Although there is some success in using nucleoside analogs or polyclonal antibodies targeting HBV surface antigens (HBsAg) in patients with acute or chronic HBV+ (CHB), majority of them would either respond only partially or succumb to the disease entirely unless they undergo liver transplants from a fully matched healthy donor and even so may not necessarily guarantee a 100% chance of survival.
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