Monocyte chemoattractant protein-1 derived from biliary innate immunity contributes to hepatic fibrogenesis

金沢大学医薬保健研究域医学系Aims: Monocyte chemoattractant protein-1 (MCP-1) is a major chemotactic factor for hepatic stellate cells (HSCs) associated with hepatic fibrosis. In this study, among several fibrogenetic factors derived from biliary epithelial cells (BECs), MCP-1 produced by the biliary innate immune system was found to be most critical in the histogenesis of hepatic fibrogenesis. Methods: Using cultured human BECs, the expression of five fibrogenetic factors including MCP-1 on stimulation with Toll-like receptor ligands, inflammatory cytokines or bile acids was examined. Moreover, in situ detection of MCP-1 and α-smooth muscle actin proteins was performed using sections from normal and diseased livers by immunohistochemistry. Results: All fibrogenetic factors were detected in BECs, but only MCP-1 expression was upregulated, by all the Toll-like receptor ligands, IL-1β, and tumour necrosis factor-alpha. Proliferating bile ductules in interface areas expressed MCP-1 in diseased livers accompanying α-smooth muscle actin-positive activated HSCs. Conclusions: Bile ductules proliferate in various hepatobiliary diseases, and its significance is still unknown. This study demonstrated that BECs in bile ductules could produce MCP-1, particularly, via biliary innate immunity, suggesting that MCP-1 derived from BECs plays an important role in the recruitment of HSCs to interface areas and the activation of HSCs resulting in the progression of periportal fibrosis. Copyright Article author (or their employer) 2011

Encouraging death communication in a death-avoidant society: analysis of interviews with death café organizers

Abstract Background Post-war Japanese tend to avoid discussion of death, resulting in a lack of death communication within clinical settings. However, with the aging of society, the significance of conversations and decisions related to end-of-life issues has grown. In 2007, the government established guidelines for decision-making in end-of-life care. Nonetheless, death communication remains a challenge for healthcare professionals in clinical settings. In contrast, death cafés have spontaneously emerged within communities as informal gatherings to openly discuss and explore death. Learning from death café organizers may help healthcare professionals encourage death communication in a death-avoidant society. Therefore, a qualitative study was conducted to describe death cafés by examining the underlying motivation and practices through interviews with death café organizers. Methods Individual in-depth interviews were conducted with death café organizers. Two key aspects were explored: 1) the underlying motivations of organizers; and 2) the practices and challenges encountered in running death cafés. The interviews were transcribed verbatim and analyzed using a qualitative descriptive approach. Thematic analysis was used. Results The study identified two themes representing the underlying motivation of death café organizers: individually-oriented and community-oriented. These themes exhibited contrasting orientations and were collectively termed “individual-community orientation”. Regarding the practice of death cafés, the focus was on the “attitude towards having attendees with and without grief in the same session.” Participants’ attitudes towards this aspect fell into two categories with opposing orientations: “purification” and “inclusion.” The “purification-inclusion orientation” was more prevalent among organizers who initiated death cafés due to their personal experiences. A matrix was created to categorize death cafés based on their underlying motivations (individual vs. community-oriented) and practices (purification vs. inclusion). This classification resulted in quadrant 1 (community-oriented, inclusive) and quadrant 3 (individually-oriented, purification). Notably, death cafés in quadrant 1 were often held in temples. Conclusions Japanese death cafés can be classified into two categories: individually and purification-oriented and community and inclusive-oriented categories. Healthcare professionals can learn valuable insights from death café organizers, particularly in promoting death communication. Specifically, temple death cafés, with their inclusive practices and orientation towards community, can be particularly beneficial in fostering inclusivity and community engagement

Inaccessibility, unresponsiveness, inconsistency, and invisibility of informal caregivers of older persons with cognitive impairment: community-based participatory research

Abstract Background Studies on informal caregivers in Japan have been limited to family caregivers and largely conducted where family caregivers generally gather. Family caregivers who do not visit such places or non-family caregivers are generally overlooked, and data on these informal caregivers remains scant. Consequently, a framework is needed through which healthcare professionals can approach the informal caregivers of community-dwelling older persons. Therefore, this study approaches such informal caregivers and proposes a classification system for them from the starting point of older persons living in the community with cognitive impairment. Methods In 2016, we conducted an epidemiological survey of 7000 + community-dwelling older persons and identified 198 residents with Mini-mental state examination scores less than 23. A team of healthcare professionals contacted them regularly. By 2022, 92 people were still living in the community, and we systematically asked them about their informal caregivers. After approaching the caregivers and obtaining informed consent, we mailed separate questionnaires to older persons and informal caregivers. Results Among the caregivers, 59%, 34%, and 3% were the child, spouse, and sibling of the older person, while the remaining 4% were non-family caregivers. Except for two daughters-in-laws, all children were biological children of the older person. Male caregivers (46%) tended to have full-time jobs, whereas female caregivers (54%) tended to face financial difficulties. Only 3% of the caregivers had joined a family caregivers’ association. Caregivers’ reason for not joining such organizations was a lack of time and knowledge. A 3-tiered classification system was developed for these informal caregivers: (1) the household form, (2) accessibility, and (3) the reciprocal awareness of caregiving. Furthermore, family caregivers who lived with the older person or visited them more than once a week with reciprocal awareness of caring and being cared, or “traditional caregivers,” accounted for 68% of the caregivers in this study. Conclusion Core family caregivers can be easily approached at places where such caregivers generally gather. However, there also exists a group of informal caregivers who are sometimes inaccessible, unresponsive, and invisible to healthcare professionals. Moreover, their awareness of caregiving is sometimes inconsistent