Novel elucidation and treatment of pancreatic chronic graft-versus-host disease in mice

Chronic graft-versus-host disease (cGVHD) is a severe complication of allogeneic haematopoietic stem cell transplantation. There is a growing understanding of cGVHD, and several effective therapies for cGVHD have been reported. However, pancreatic cGVHD is a potentially untapped study field. Our thought-provoking study using a mouse model of cGVHD suggested that the pancreas could be impaired by cGVHD-induced inflammation and fibrosis and that endoplasmic reticulum (ER) stress was augmented in the pancreas affected by cGVHD. These findings urged us to treat pancreatic cGVHD through reduction of ER stress, and we used 4-phenylbutyric acid (PBA) as an ER stress reducer. A series of experiments have indicated that PBA can suppress cGVHD-elicited ER stress in the pancreas and accordingly alleviate pancreatic cGVHD. Furthermore, we focused on a correlation between epithelial to mesenchymal transition (EMT) and fibrosis in the cGVHD-affected pancreas, because EMT was conceivably implicated in various fibrosis-associated diseases. Our investigation has suggested that the expression of EMT markers was increased in the cGVHD-disordered pancreas and that it could be reduced by PBA. Taken together, we have provided a clue to elucidate the pathogenic process of pancreatic cGVHD and created a potentially effective treatment of this disease using the ER stress alleviator PBA

Therapeutic Approaches Targeting Cancer Stem Cells

Cancer stem cells (CSCs) have been identified in many types of cancer since their discovery in leukemia in the 1990s. CSCs have self-renewal and differentiation capacity, and are thought to be a key driver for the establishment and growth of tumours. Several intracellular signalling pathways are reported to play a significant role in the regulation of the biological activities of CSCs. Thus, many researchers have considered CSCs to be a compelling therapeutic target for cancer, and blockade of CSC-related signalling pathways can be efficacious for the treatment of multiple cancer types. This chapter succinctly summarises the recent progress in the development of treatments targeting signalling pathways related to the functions of CSCs

Graft-Versus-Host Disease: Pathogenesis and Treatment

Graft-versus-host disease (GVHD) is a disabling complication after allogeneic hematopoietic stem cell transplantation (HSCT) and negatively impacts patients’ quality of life. GVHD is classified into 2 forms according to clinical manifestations. Acute GVHD (aGVHD) typically affects the skin, gastrointestinal tract, and liver, whereas chronic GVHD occurs systemically and shows diverse manifestations similar to autoimmune diseases such as eosinophilic fasciitis, scleroderma-like skin disease. GVHD is induced by complicated pathological crosstalk between immune cells of the host and donor and involves various signaling pathways such as purinergic signaling. Although the past several decades have seen significant progress in the understanding of mechanisms of GVHD and several drugs have been approved by FDA for the prevention and treatment of GVHD, there is still vast scope for improvement in the therapy for GVHD. Thus, new drugs for GVHD will need to be developed. Towards this goal, this chapter succinctly summarises the pathogenic process of GVHD and emerging GVHD treatments in order to provide some insights into the mechanisms of GVHD and facilitate the development of novel drugs

Исследование влияния термической обработки на вид излома ударных образцов и трещиностойкость сталей типа 06Г2МБТ

В работе исследованы образцы Шарпи низкоуглеродистых трубных сталей типа 06Г2МБТ после контролируемой прокатки и ускоренного охлаждения и термической обработки по различным режимам. На основе литературных данных и результатов собственных экспериментов проведен анализ поверхностей разрушения, изучено влияние температуры нагрева на уровень ударной вязкости стали и вид поверхности излома

“Input/output cytokines” in epidermal keratinocytes and the involvement in inflammatory skin diseases

Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines

Photocatalytic Activity Enhancement of Anatase/Rutile-Mixed Phase TiO2 Nanoparticles Annealed with Low-Temperature O2 Plasma

Photodecomposition and photobactericidal activities of anatase/rutile-mixed phase TiO2 nanoparticles annealed with low-temperature O2 plasma were clarified by comparing them with those annealed in ambient air. The photocatalytic activities of plasma-assisted-annealed sample greatly enhanced as compared with the untreated sample, under not only ultraviolet irradiation but also visible-light irradiation. The photocatalytic activities of air-annealed samples did not enhance under ultraviolet irradiation but enhanced under visible-light irradiation. The enhanced photocatalytic activities due to the plasma-assisted annealing (PAA) originated from the increased photoexcited carrier concentration. This enhancement was discussed from PAA-induced characteristic factors. PAA facilitated the phase transformation to anatase, contributing directly to extending the photoexcited carrier lifetime. PAA introduced more oxygen vacancies, contributing to trapping more photogenerated electrons. PAA also introduced more bridging/terminal oxygen groups adsorbed on the surface, increasing the upward band-bending, the depletion layer width at the surface, and the charge transfer from rutile to anatase. These two introductions contributed to facilitating the separation of photoexcited carriers. Furthermore, PAA reduced the aggregate size of TiO2 nanoparticles formed on the surface, contributing to increasing optical absorptions. More reactive oxygen species produced from the bridging/terminal oxygen groups by the photoexcited carriers would also enhance the photocatalytic activities

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

This work is licensed under a Creative Commons Attribution 4.0 International License.Poly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fundamental posttranslational modification (PTM). PARP catalytic domains transfer the ADP-ribose moiety from NAD+ to amino acid residues of target proteins, leading to mono- or poly-ADP-ribosylation (MARylation or PARylation). This PTM regulates various key biological and pathological processes. In this review, we focus on the roles of the PARP family members in inflammation and host–pathogen interactions. Here we give an overview the current understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of macrophages, and various roles PARPs play in virus infections. We also demonstrate how innovative technologies, such as proteomics and systems biology, help to advance this research field and describe unanswered questions

Macroscopic Entanglement of a Bose Einstein Condensate on a Superconducting Atom Chip

We propose and analyse a practically implementable scheme to generate macroscopic entanglement of a Bose-Einstein condensate in a micro-magnetic trap magnetically coupled to a superconducting loop. We treat the superconducting loop in a quantum superposition of two different flux states coupled with the magnetic trap to generate macroscopic entanglement. Our scheme also provides a platform to realise interferometry of entangled atoms through the Bose-Einstein condensate and to explore physics at the quantum-classical interface.Comment: 4 Pages, Two figure