CGRP overexpression does not alter depression-like behavior in mice

Background The calcitonin gene-related peptide (CGRP) is a neuropeptide that is released from capsaicin-sensitive nerves as a potent vasodilator involved in nociceptive transmission. While CGRP has been rigorously studied for its role in migraines owing to its vasodilation and inflammation activities, the effects of CGRP overexpression on depressive-like behaviors remain insufficiently understood. Methods In the present study, we performed a battery of behavioral tests, including the social interaction test, open field test, and sucrose preference test, to evaluate social defeat stress using male C57BL6J or CGRP overexpression in transgenic (Tg) mice (CGRP Tg). We performed mRNA and protein analyses on the brain-derived neurotrophic factor (BDNF), phosphorylated Akt, mTOR, and p70S6K in the hippocampi. Results CGRP Tg mice showed increased levels of Bdnf mRNAs, low locomotor activity, and no deficits in social interaction, which indicate that CGRP Tg mice exhibit stress resistance and not depression. However, the open field test significantly decreased after 15-day social defeat stress exposure. We also evaluated depressive-like behavior using the sucrose preference and social interaction tests. Our data indicate that defeated CGRP Tg mice exhibited a depressive-like phenotype, which was inferred from increased social avoidance and reduced sucrose preference compared with non-defeated controls. Although stress exposure did not change the BDNF levels in CGRP Tg mice, it significantly decreased the expression levels of p-Akt, p-mTOR and p-p70S6K in the mice hippocampi. We conclude that CGRP-overexpressing Tg mice have normal sensitivity to stress and down-regulated hippocampal Akt/mTOR/p70S6K pathways

RNA Modification in Inflammatory Bowel Diseases

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by damage to the intestinal mucosa, which is caused by a combination of factors. These include genetic and epigenetic alterations, environmental influence, microorganism interactions, and immune conditions. Some populations with IBD show a cancer-prone phenotype. Recent studies have provided insight into the involvement of RNA modifications in the specific pathogenesis of IBD through regulation of RNA biology in epithelial and immune cells. Studies of several RNA modification-targeting reagents have shown preferable outcomes in patients with colitis. Here, we note a new awareness of RNA modification in the targeting of IBD and related diseases, which will contribute to early diagnosis, disease monitoring, and possible control by innovative therapeutic approaches

Pancreatic Cancer Research beyond DNA Mutations

Pancreatic ductal adenocarcinoma (PDAC) is caused by genetic mutations in four genes: KRAS proto-oncogene and GTPase (KRAS), tumor protein P53 (TP53), cyclin-dependent kinase inhibitor 2A (CDKN2A), and mothers against decapentaplegic homolog 4 (SMAD4), also called the big 4. The changes in tumors are very complex, making their characterization in the early stages challenging. Therefore, the development of innovative therapeutic approaches is desirable. The key to overcoming PDAC is diagnosing it in the early stages. Therefore, recent studies have investigated the multifaced characteristics of PDAC, which includes cancer cell metabolism, mesenchymal cells including cancer-associated fibroblasts and immune cells, and metagenomics, which extend to characterize various biomolecules including RNAs and volatile organic compounds. Various alterations in the KRAS-dependent as well as KRAS-independent pathways are involved in the refractoriness of PDAC. The optimal combination of these new technologies is expected to help treat intractable pancreatic cancer

Remaking an institution and community : the Vancouver Japanese Language School after the war

This present thesis is a study of the re-establishment of the Vancouver Japanese Language School (first established in 1906), and the Japanese Canadian community in Vancouver after World War II. Focusing on the reopening of the school in 1952, this study attempts to discuss how the school's reopening influenced the rebuilding of the Japanese-Canadian community in post-war Vancouver, where Japanese Canadians had had a large ethnic community before 1941. B y regarding the Japanese-language school as a means to comprehend trends in the lives of Japanese Canadians, this study seeks to understand how and to what extent the Japanese Canadians in Vancouver were able to reconstruct their ethnic identity: how much they acculturated into anglo-Canadian society after the devastation of their ethnic community; and how differently each successive generation has perceived the significance of ethnic cultural retention, such as the Japanese language. Until the Japanese attack on Pearl Harbour in 1941, the Vancouver Japanese Language School was the largest such school on the Pacific coast of North America, and served the Japanese Canadian community as a transmitter of their ethnic culture and traditions to the next generation. However, after the destruction of the ethnic community by the World War II evacuation of Japanese Canadians in 1942, the leadership of the Japanese Canadians shifted from culturally "Japanese-oriented" issei (first generation) to "more-Canadianized" nisei (second generation). Consequently, demand for fluency in the Japanese language and an understanding of the ethnic culture was replaced with the demand for English and the anglo-Canadian culture. Despite such a huge change in the community, the Vancouver Japanese Language School was reopened, though reduced in size, and continues to operate to the present. This study draws evidence from several works by a long-time principal and teacher of the school, Tsutae Sato, and his wife Hanako, a variety of primary sources from the Sato Collection at the University of British Columbia, and the Japanese ethnic press, as well as the author's interviews with six people who have historical connections to the school reopening and management. By using these sources, this study attempts to examine what the meaning of the school reopening was for the Japanese Canadians after the devastation of their pre-war communities; how the school's function and roles changed from the pre-war to the post-war period; how language education and the Japanese language influenced the formation of Japanese Canadians' particularly that of the nisei ethnic identity as heirs to a Japanese tradition in Canada.Arts, Faculty ofHistory, Department ofGraduat

Autologous Transplantation of the Internal Limiting Membrane for Refractory Macular Hole following Ruptured Retinal Arterial Macroaneurysm: A Case Report

Purpose: To report a case of macular hole (MH) secondary to a retinal arterial macroaneurysm (RAMA) which was successfully treated with an autologous transplantation of internal limiting membrane (ILM). Case Report: An 87-year-old female presented with a sudden decrease in central vision in the right eye. A fundus examination revealed a RAMA in the superonasal macular region, a subretinal hemorrhage (SRH), involving the macula, and a sub-ILM hemorrhage. A pars plana vitrectomy (PPV) was performed. Intraoperatively, an MH filled with coagulum was detected. We tried to blow off and drain the SRH with a current of BSS and a gentle suction with a 27-gauge vitreous cutter from the MH, but some amount of SRH at the bottom of the MH remained. The ILM was peeled off for 2 disc diameters around the MH. The vitreous cavity was filled with air at the end of the operation. Two weeks after the surgery, the MH was not closed. One month following the initial PPV, a second PPV was performed to achieve closure of the MH. Results: An autologous transplantation of ILM was performed as second PPV. Six months after the final surgery, the MH was successfully closed and the best-corrected decimal visual acuity was 0.6. Conclusions: Autologous ILM transplantation can be an effective treatment option for MH closure following RAMA rupture

Fermented Cosmetics and Metabolites of Skin Microbiota—A New Approach to Skin Health

The skin covers our entire body and is said to be the “largest organ of the human body”. It has many health-maintaining functions, such as protecting the body from ultraviolet rays and dryness and maintaining body temperature through energy metabolism. However, the number of patients suffering from skin diseases, including atopic dermatitis, is increasing due to strong irritation of the skin caused by detergents that are spread by the development of the chemical industry. The skin is inhabited by about 102–107 cells/cm2 and 1000 species of commensal bacteria, fungi, viruses, and other microorganisms. In particular, metabolites such as fatty acids and glycerol released by indigenous skin bacteria have been reported to have functional properties for the health of the skin. Therefore, skin-domesticating bacteria and the metabolites derived from those bacteria are used in many skincare product ingredients and function as probiotic cosmetics. Japanese traditional fermented stuff, used as foods in Japan for over 1300 years, are now being applied as fermented cosmetics. Fermented cosmetics are expected to have multifaceted health functionality and continue to grow as products in the natural skincare product market. In this review, we consider approaches to skin health using fermented cosmetics and modulation of skin microflora metabolites

EpisomiR, a New Family of miRNAs, and Its Possible Roles in Human Diseases

MicroRNAs (miRNAs) are synthesized through a canonical pathway and play a role in human diseases, such as cancers and cardiovascular, neurodegenerative, psychiatric, and chronic inflammatory diseases. The development of sequencing technologies has enabled the identification of variations in noncoding miRNAs. These miRNA variants, called isomiRs, are generated through a non-canonical pathway, by several enzymes that alter the length and sequence of miRNAs. The isomiR family is, now, expanding further to include episomiRs, which are miRNAs with different modifications. Since recent findings have shown that isomiRs reflect the cell-specific biological function of miRNAs, knowledge about episomiRs and isomiRs can, possibly, contribute to the optimization of diagnosis and therapeutic technology for precision medicine