Commensal Flora, is it an Unwelcomed Companion as a Triggering Factor of Autoimmune Pancreatitis?

The etiopathogenesis of many autoimmune disorders has not been identified. The aim of this paper is to focus on the involvement of bacterial exposure, as an environmental factor, in the pathogenesis of autoimmune pancreatitis (AIP), which is broadly categorized as autoimmune disorders involving pancreatic lesions. Avirulent and/or commensal bacteria, which may have an important role(s) as initiating/progressing factors in the pathogenesis of autoimmune disorder AIP, will be emphasized

Targeting of MAPK-associated molecules identifies SON as a prime target to attenuate the proliferation and tumorigenicity of pancreatic cancer cells

Abstract Background Pancreatic cancer is characterized by constitutive activation of mitogen-activated protein kinase (MAPK). Activation of MAPK is associated with the upregulation of genes implicated in the proliferation and survival of pancreatic cancer cells. We hypothesized that knockdown of these MAPK-associated molecules could produce notable anticancer phenotypes. Methods A RNA interference-mediated knockdown screening of 78 MAPK-associated molecules previously identified was performed to find molecules specifically associated with proliferation of pancreatic cancer cells in vitro. Expression of an identified molecule in pancreatic cancer tissues was examined by immunohistochemistry. In vivo tumorigenicity of cancer cells with stable knockdown of the molecule was assayed by using xenograft models. Flow cytometry and live cell imaging were employed to assess an association of the molecule with cell cycle. Results The knockdown screening revealed that knockdown of SON, the gene encoding SON, which is a large serine/arginine-rich protein involved in RNA processing, substantially suppressed pancreatic cancer cell proliferation and survival in vitro and tumorigenicity in vivo. SON expression was higher in ductal adenocarcinomas than in cells of normal ducts and precursor lesions in pancreatic cancer tissues. Knockdown of SON induced G2/M arrest and apoptosis in cultured cancer cells. The suppressive effect of SON knockdown on proliferation was less pronounced in cultured normal duct epithelial cells. SON formed nuclear speckles in the interphase of the cell cycle and dispersed in the cytoplasm during mitosis. Live cell imaging showed that SON diffusely dispersed in the early mitotic phase, accumulated in some foci in the cytoplasm in the late mitotic phase, and gradually reassembled into speckles after mitosis. Conclusion These results indicate that SON plays a critical role in the proliferation, survival, and tumorigenicity of pancreatic cancer cells, suggesting that SON is a novel therapeutic molecular target for pancreatic cancer.</p

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 II. Extrapancreatic lesions, differential diagnosis

Published online: 25 March 2014ArticleJOURNAL OF GASTROENTEROLOGY. 49(5):765-784 (2014)journal articl

Association of fear of COVID-19 and resilience with psychological distress among health care workers in hospitals responding to COVID-19: analysis of a cross-sectional study

BackgroundIt remains unclear how fear of COVID-19 and resilience are related to psychological distress based on occupations among healthcare workers (HCWs) in hospitals treating patients with COVID-19. We conducted a survey on the mental health of HCWs during the COVID-19 pandemic to determine the relationship between factors such as fear of COVID-19 and resilience as well as mental distress in each occupation of HCWs.MethodsWe conducted a web-based survey among HCWs at seven hospitals treating COVID-19 patients in Japan from December 24, 2020 to March 31, 2021. A total of 634 participants were analyzed, and information regarding their socio-demographic characteristics and employment status was collected. Several psychometric measures were used, including the Kessler’s Psychological Distress Scale (K6), the fear of COVID-19 Scale (FCV-19S), and the Resilience Scale (RS14). Factors related to psychological distress were identified by logistic regression analysis. The association between job title and psychological scales was examined by one-way ANOVA, and t-tests were conducted to examine the association between the FCV-19S and hospital initiatives.ResultsIt was found that nurses and clerical workers were associated with psychological distress without considering FCV-19S or RS14; in a model that included FCV-19S, FCV-19S was associated with psychological distress, but job title was not; when RS14 was considered, resilience was protective. In terms of occupation, FCV-19S was lower among physicians and higher among nurses and clerical workers, while RS14 was higher among physicians and lower among other occupations. Having access to in-hospital consultation regarding infection control as well as to psychological and emotional support was associated with lower FCV-19S.ConclusionBased on our findings, we can conclude that the level of mental distress differed by occupation and the differences in the fear of COVID-19 and resilience were important factors. In order to provide mental healthcare for HCWs during a pandemic, it is important to create consultation services that enable employees to discuss their concerns. In addition, it is important to take steps to strengthen the resilience of HCWs in preparation for future disasters

Depletion of tumor-associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin.

In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model