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1.
Biochem Biophys Res Commun ; 707: 149783, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38493746

RESUMEN

Ingestion of Porphyromonas gingivalis, a periodontal pathogen, disrupts the intestinal barrier in mice. However, the involvement of outer membrane vesicles (OMVs) secreted from P. gingivalis in the destruction of the intestinal barrier remains unclear. In this study, we tested the hypothesis that OMVs carrying gingipains, the major cysteine proteases produced by P. gingivalis, affects the intestinal barrier function. OMVs increased the permeability of the Caco-2 cell monolayer, a human intestinal epithelial cell line, accompanied by degradation of the tight junction protein occludin. In contrast, OMVs prepared from mutant strains devoid of gingipains failed to induce intestinal barrier dysfunction or occludin degradation in Caco-2 cells. A close histological examination revealed the intracellular localization of gingipain-carrying OMVs. Gingipain activity was detected in the cytosolic fraction of Caco-2 cells after incubation with OMVs. These results suggest that gingipains were internalized into intestinal cells through OMVs and transported into the cytosol, where they then directly degraded occludin from the cytosolic side. Thus, P. gingivalis OMVs might destroy the intestinal barrier and induce systemic inflammation via OMV itself or intestinal substances leaked into blood vessels, causing various diseases.


Asunto(s)
Adhesinas Bacterianas , Porphyromonas gingivalis , Animales , Ratones , Humanos , Cisteína-Endopeptidasas Gingipaínas/metabolismo , Células CACO-2 , Porphyromonas gingivalis/fisiología , Citosol/metabolismo , Ocludina/metabolismo , Adhesinas Bacterianas/metabolismo
2.
J Radiol Prot ; 44(2)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38834049

RESUMEN

It is crucial to anticipate nuclear emergency scenarios and implement effective measures. Japan's climate and topography make it vulnerable to natural disasters; thus, it is necessary to address compounding and cascading disaster scenarios involving the simultaneous occurrence of natural and nuclear disasters. On 1 January 2024, an earthquake hit the Noto region of Ishikawa Prefecture, resulting in damage to the area around the Shika Nuclear Power Plant, located 90 km from the epicenter. This earthquake revealed that, in the event of a complex disaster, it is possible that residents living within 30 km of the Shika Nuclear Power Plant will be completely unprepared for a nuclear disaster. In the event of a complex disaster, it is crucial to implement appropriate countermeasures while balancing responses to both nuclear and natural disasters and optimizing radiation disaster prevention measures.


Asunto(s)
Planificación en Desastres , Japón , Humanos , Liberación de Radiactividad Peligrosa/prevención & control , Terremotos , Desastres Naturales , Plantas de Energía Nuclear , Protección Radiológica
3.
J Radiol Prot ; 43(4)2023 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-38052085

RESUMEN

In nuclear disaster prevention, it is essential not only to make daily efforts to prevent accidents from occurring but also to properly apply lessons learnt from actual disasters. Although significant changes have been made to nuclear disaster preparedness in Japan since the Fukushima Daiichi Nuclear Power Plant accident, there is insufficient information on whether these changes have been evaluated as practical and appropriate for the needs of the Japanese public. In this survey, 20 officials of the Cabinet Office and Japan Atomic Energy Agency, in charge of planning nuclear disaster prevention policy, were asked to evaluate the current nuclear disaster prevention plan through a questionnaire, and compare it with that before the accident, and indicate what elements are lacking in the current plan. The survey results revealed that 30% of the participants (six respondents) had a positive view of the enhancement of resources, including physical and human assets. However, as many as 60% (12 respondents) expressed negative sentiments, primarily due to perceived deficiencies in organisational measures, particularly the coordination of these resources. Moreover, the participants expressed keen interest in obtaining health data during evacuation, along with information on the physical and mental effects on evacuees living in evacuation centres. These crucial insights can inform the formulation of effective future preparedness plans for evacuation and radiation protection.


Asunto(s)
Desastres , Accidente Nuclear de Fukushima , Humanos , Japón , Plantas de Energía Nuclear , Encuestas y Cuestionarios
4.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36499428

RESUMEN

Recently, the effects of antibacterial peptides are suggested to have therapeutic potential in Alzheimer's disease. Furthermore, systemic treatment of Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) induced Alzheimer's disease-like neuropathological changes in middle-aged mice. Then, we examined whether human ß-defensins (hBDs), antimicrobial peptides produced by the oral mucosa and salivary glands, can suppress Pg LPS-induced oxidative and inflammatory responses by microglia. hBD3 (1 µM) significantly suppressed Pg LPS-induced production of nitric oxide and interleukin-6 (IL-6) by MG6 cells, a mouse microglial cell line. hBD3 (1 µM) also significantly inhibited Pg LPS-induced expression of IL-6 by HMC3 cells, a human microglial cell line. In contrast, neither hBD1, hBD2 nor hBD4 failed to inhibit their productions. Furthermore, hBD3 suppressed Pg LPS-induced p65 nuclear translocation through the IκBα degradation. Pg LPS-induced expression of IL-6 was significantly suppressed by E64d, a cysteine protease inhibitor, and CA-074Me, a known specific inhibitor for cathepsin B, but not by pepstatin A, an aspartic protease inhibitor. Interestingly, hBD3 significantly inhibited enzymatic activities of recombinant human cathepsins B and L, lysosomal cysteine proteases, and their intracellular activities in MG6 cells. Therefore, hBD3 suppressed oxidative and inflammatory responses of microglia through the inhibition of cathepsins B and L, which enzymatic activities are necessary for the NF-κB activation.


Asunto(s)
Enfermedad de Alzheimer , beta-Defensinas , Animales , Humanos , Ratones , beta-Defensinas/metabolismo , Catepsina B/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos , Microglía/metabolismo , FN-kappa B/metabolismo , Porphyromonas gingivalis/metabolismo , Catepsina L/metabolismo
5.
J Radiol Prot ; 42(3)2022 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-35764063

RESUMEN

The initial health impact caused by radiation disasters can be broadly classified into direct and indirect effects. Though no direct health hazards caused by radiation, such as acute radiation injury, were observed following the Fukushima Daiichi nuclear power plant accident, indirect deaths have been reported, including those caused by initial emergency evacuation and relocation, medical disruption, and psychological and social health effects. However, these indirect health effects have not been prioritised for addressal. We evaluated the radiation disaster experience with that of the coronavirus disease (COVID-19) pandemic that emerged while facing the challenges from the radiation disaster. Most of the health effects of COVID-19 are directly associated with infection, but indirect health effects of various scales and entities have been reported. The two disasters have similarities in terms of the strain on community healthcare and the large number of deaths. Adapting the measures implemented in the acute to subacute phases of the COVID-19 disaster to radiation disasters may help improve management following future radiation disasters. Based on the experience and findings during the COVID-19 pandemic, the pattern of deaths in radiation disasters can be divided into five major groups: direct deaths, and four indirect patterns of deaths due to a deteriorating supply-demand balance (a hospital-level problem), collapse of the healthcare system (a community-level problem), death due to neglect alongside underlying disease, and diseases other than direct invasion. From the similarities between the two disasters, three main issues should be prioritised as initial emergency evacuation measures in a radiation disaster: emergency exposure medicine, the establishment of a medical system, and protection of death with dignity. The validity of these priority issues needs to be verified in future research.


Asunto(s)
COVID-19 , Desastres , Accidente Nuclear de Fukushima , Humanos , Japón , Plantas de Energía Nuclear , Pandemias
6.
J Radiol Prot ; 42(3)2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-35998567

RESUMEN

Disaster deaths can be classified into direct and indirect deaths. Direct deaths are those caused by the direct physical effects of disasters, such as earthquakes, tsunamis, and radiation exposure. Indirect deaths are those caused by secondary health effects such as emergency evacuation, relocation, evacuation environment, disruption of health care delivery services, and psychosocial effects. In addition, in Japan, the term disaster-related deaths refers to indirect deaths in accordance with the disaster condolence payments system, which provides relief for bereaved families. On 11 March 2011, the Great East Japan Earthquake exposed several issues related to disaster-related deaths in Japan. Therefore, on 1 February 2022, a symposium on disaster-related deaths hosted by this study was held on the website. The symposium discussed the issues and challenges associated with disaster-related deaths for future disaster preparedness. The authors introduced the concept of 'shaking' at the symposium by defining 'shaking' as 'the repeated changes in the social and living environment that worsen health conditions, regardless of the disaster'. It was also pointed out that vulnerable populations are more likely to experience more pronounced health effects. This generalised concept of 'shaking' associated with disaster-related deaths suggests that it is important to anticipate disasters before they occur to take specific preventive measures, targeted at vulnerable populations. This study found that disaster-related deaths in Japan create several problems in terms of future radiation disaster preparedness and medical countermeasures. In the future, there will be a need to examine the relevance of the issues of disaster-related deaths identified as a result of this symposium for future radiation disaster preparedness.


Asunto(s)
Desastres , Terremotos , Accidente Nuclear de Fukushima , Humanos , Japón/epidemiología , Plantas de Energía Nuclear , Tsunamis
7.
Exp Cell Res ; 381(1): 10-17, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31063732

RESUMEN

We previously reported that Drosophila phagocytes enhance their phagocytic activity after apoptotic cell engulfment accompanied by the activation of the transcription repressor Tailless and an increase in the levels of engulfment receptors. We herein investigated the underlying mechanisms. We found that Tailless phosphorylation levels decreased in Drosophila phagocytes following the stimulation with apoptotic cells. Anticipating the involvement of another transcription repressor, we examined the possible involvement of Krüppel, a bibliographically identified repressor whose expression is controlled by Tailless. The level of Krüppel in phagocytes decreased after the stimulation in a Tailless-dependent manner. The RNAi knockdown of Krüppel abrogated increases in the levels of engulfment receptors and phagocytic activity in stimulated phagocytes. The binding of Krüppel to the 5'-upstream regions of genes coding for engulfment receptors was demonstrated. These results suggest the following pathway: Tailless is activated by de-phosphorylation; Krüppel expression is inhibited by Tailless; the transcription of engulfment receptors-encoding genes is augmented due to a decrease of inhibition by Krüppel; and finally phagocytic activity is enhanced.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila/genética , Fagocitos/metabolismo , Fagocitosis/genética , Receptores de Superficie Celular/genética , Proteínas Represoras/metabolismo , Animales , Apoptosis , Línea Celular , Drosophila/inmunología , Drosophila/metabolismo , Proteínas de Drosophila/genética , Regulación de la Expresión Génica , Cadenas alfa de Integrinas/genética , Cadenas alfa de Integrinas/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Fosforilación , Receptores de Superficie Celular/metabolismo , Transcripción Genética
8.
Artículo en Inglés | MEDLINE | ID: mdl-32037370

RESUMEN

Responding to the radiation-related concerns of parents/guardians with infants/small children is an important public health issue for regional recovery after radioactive contamination. This study summarizes the results of a systematic internal contamination screening of infants/small children, aged 0-6 years, using BABYSCAN and individual counselling sessions with physicians about radiation concerns from 2014 to 2018 in Minamisoma City. Of 3,114 participants, no one was found to have internal contamination with radioactive caesium with a detection limit of 50 Bq/body. The questionnaire survey showed a decreasing trend of concerns about food contamination and playing outside as possible causes of internal contamination over time. Because people's concerns were diverse in counselling sessions, individual responses are required. This study showed that examinations using BABYSCAN provide an opportunity for direct dialogue between the parents/guardians of infants/small children and experts. This can be considered a model case for risk communication conducted by the local government after a radioactive contamination incident.


Asunto(s)
Radioisótopos de Cesio/análisis , Recuento Corporal Total/estadística & datos numéricos , Niño , Preescolar , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Contaminación Radiactiva de Alimentos/estadística & datos numéricos , Accidente Nuclear de Fukushima , Humanos , Lactante , Recién Nacido , Japón , Masculino , Plantas de Energía Nuclear , Monitoreo de Radiación/estadística & datos numéricos , Liberación de Radiactividad Peligrosa/estadística & datos numéricos , Factores de Riesgo , Encuestas y Cuestionarios
9.
J Biol Chem ; 292(19): 8059-8072, 2017 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-28325838

RESUMEN

The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin αPS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signal-transduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells by stimulated phagocytes and is thus considered as a mechanism to prime phagocytes in innate immunity.


Asunto(s)
Apoptosis , Fagocitos/citología , Transducción de Señal , Animales , Línea Celular , Núcleo Celular/metabolismo , Cicloheximida/química , Proteínas del Citoesqueleto/metabolismo , ADN/análisis , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Hemocitos/citología , Inmunidad Innata , Cadenas alfa de Integrinas/metabolismo , Proteínas de la Membrana/metabolismo , Proteína Oncogénica v-crk/metabolismo , Fagocitosis , Interferencia de ARN , Proteínas Represoras/metabolismo
10.
Biochem Biophys Res Commun ; 506(3): 510-515, 2018 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-30361090

RESUMEN

The Drosophila Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the Toll-1 receptor, only Spätzle (Spz) has been identified and characterized. We previously reported that Drosophila larva-derived tissue extract contains ligand activity for the Toll-1 receptor, which differs from Spz based on the observation that larval extract prepared from spz mutants possessed full ligand activity. Here, we demonstrate that Spz5, a member of the Spz family of proteins, functions as a ligand for the Toll-1 receptor. Processing of Spz5 by Furin protease, which is known to be important for ligand activity of Spz5 to Toll-6, is not required for its function to the Toll-1 receptor. By generating a spz5 null mutant, we further showed that the Toll-1 ligand activity of larva-derived extract is mainly derived from Spz5. Finally, we found a genetic interaction between spz and spz5 in terms of developmental processes. This study identified a novel ligand for the Drosophila Toll-1 receptor, providing evidence that Toll-1 is a multi-ligand receptor, similar to the mammalian Toll-like receptor.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Receptores Toll-Like/metabolismo , Animales , Epistasis Genética , Larva/metabolismo , Ligandos , Proteolisis , Extractos de Tejidos
11.
Biol Pharm Bull ; 40(11): 1819-1827, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29093328

RESUMEN

Cells that have become unwanted by the body need to be selectively, rapidly, and safely removed. The removal of these cells is achieved by apoptosis-dependent phagocytosis: unwanted cells are induced to undergo apoptosis and given susceptibility to phagocytosis. Phagocytes recognize these cells using engulfment receptors that bind substances expressed on the surface of target cells during the apoptotic process. The phagocytic elimination of cells undergoing apoptosis is a mechanism that is conserved among multicellular organisms. Malfunctions in this process may lead to structural and functional defects in morphogenesis and tissue homeostasis. Therefore, molecules involved in this phenomenon may be targeted in medical treatments. The mechanisms responsible for the apoptosis-dependent phagocytosis of unwanted cells as well as its physiological and pathological consequences are described herein.


Asunto(s)
Apoptosis/fisiología , Fagocitos/fisiología , Fagocitosis/fisiología , Transducción de Señal/fisiología , Citoesqueleto de Actina/fisiología , Animales , Presentación de Antígeno/fisiología , Humanos , Morfogénesis/fisiología , Fosfatidilserinas/fisiología
13.
J Biol Chem ; 288(15): 10374-80, 2013 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-23426364

RESUMEN

Integrins exert a variety of cellular functions as heterodimers of two transmembrane subunits named α and ß. Integrin ßν, a ß-subunit of Drosophila integrin, is involved in the phagocytosis of apoptotic cells and bacteria. Here, we searched for an α-subunit that forms a complex and cooperates with ßν. Examinations of RNAi-treated animals suggested that αPS3, but not any of four other α-subunits, is required for the effective phagocytosis of apoptotic cells in Drosophila embryos. The mutation of αPS3-encoding scb, deficiency, insertion of P-element, or alteration of nucleotide sequences, brought about a reduction in the level of phagocytosis. The defect in phagocytosis by deficiency was reverted by the forced expression of scb. Furthermore, flies in which the expression of both αPS3 and ßν was inhibited by RNAi showed a level of phagocytosis almost equal to that observed in flies with RNAi for either subunit alone. A loss of αPS3 also decreased the activity of larval hemocytes in the phagocytosis of Staphylococcus aureus. Finally, a co-immunoprecipitation analysis using a Drosophila cell line treated with a chemical cross-linker suggested a physical association between αPS3 and ßν. These results collectively indicated that integrin αPS3/ßν serves as a receptor in the phagocytosis of apoptotic cells and bacteria by Drosophila phagocytes.


Asunto(s)
Apoptosis/fisiología , Proteínas de Drosophila/metabolismo , Embrión no Mamífero/metabolismo , Hemocitos/metabolismo , Cadenas alfa de Integrinas/metabolismo , Cadenas beta de Integrinas/metabolismo , Fagocitosis/fisiología , Staphylococcus aureus , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster , Embrión no Mamífero/citología , Hemocitos/citología , Cadenas alfa de Integrinas/genética , Cadenas beta de Integrinas/genética , Mutación
14.
Cogn Emot ; 28(2): 375-83, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-23971527

RESUMEN

Autobiographical memories can be recalled from either a field (first-person) or an observer (third-person) perspective. Previous studies have reported that field-to-observer perspective change reduced the emotional intensity of recalled events. In the present study, we examined whether this effect has a long duration by employing follow-up measurements. The participants were asked to recall the same events repeatedly across three sessions (S1, S2, and S3): S2 was conducted about three days after S1, and S3 was conducted about four weeks after S2. The results showed a reduction in the emotional intensity of the recalled events when the perspective was changed from field to observer at S2. More importantly, this reduction in emotional intensity persisted until S3. These effects were not observed under observer-to-field perspective change at S2. These results suggest that observer perspective taking can cause plastic change in the autobiographical memory system.


Asunto(s)
Emociones , Memoria Episódica , Recuerdo Mental , Ego , Humanos , Factores de Tiempo
15.
Vaccines (Basel) ; 12(5)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38793750

RESUMEN

This online survey of unvaccinated people living in Japan aimed to identify the reasons for declining vaccination and to develop effective countermeasures. We conducted a hierarchical class analysis to classify participants, examine factors influencing their classification, and provide the information they needed about coronavirus disease 2019 (COVID-19) and trusted sources of COVID-19 information for each group. A total of 262 participants were classified into three groups: Group 1 with no specific reason (28 participants, 10.69%); Group 2 with clear concerns about trust in the vaccine (85 participants, 32.44%), and Group 3 with attitudinal barriers, such as distrust of the vaccine and complacency towards COVID-19, and structural barriers, such as vaccination appointments (149 participants, 56.87%). For each group, females tended to be classified in Group 2 more than Group 1 (Odds ratio (OR) [95% confidential intervals (95%CI)] = 1.64 (0.63 to 2.66), p = 0.001) and in Group 3 more than Group 1 (OR [95%CI] = 1.16 (0.19 to 2.12), p = 0.019). The information that the participants wanted to know about COVID-19 was different among each group (Safety: p < 0.001, Efficacy: p < 0.001, Genetic effects: p < 0.001). Those who did not receive the COVID-19 vaccine also had lower influenza vaccination coverage (8.02%). Additionally, 38 participants (14.50%) were subject to social disadvantages because they had not received the COVID-19 vaccine. Countermeasures should be carefully tailored according to the target population, reasons for hesitancy, and specific context. The findings of this study may help develop individualized countermeasures to address vaccine hesitancy.

16.
Medicine (Baltimore) ; 103(18): e37942, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701284

RESUMEN

Radiation disasters pose distinctive medical challenges, requiring diverse care approaches. Beyond radiation exposure assessment, addressing health impacts due to lifestyle changes, especially among vulnerable populations, is vital. Evacuation orders issued in radiation-affected areas introduce unique healthcare dynamics, with their duration significantly influencing the recovery process. Understanding evolving patient demographics and medical needs after lifting evacuation orders is crucial for post-disaster care planning. Minamisoma Municipal Odaka Hospital, located 13 to 20 km from Fukushima Daiichi Nuclear power plant in a post-evacuation zone, was greatly affected by the Great East Japan Earthquake and subsequent radiation disaster. Data were retrospectively collected from patient records, including age, gender, visit date, diagnoses, and addresses. Patient records from April 2014 to March 2020 were analyzed, comparing data before and after the July 2016 evacuation order lift. Data was categorized into pre and post-evacuation order lifting periods, using International Classification of Diseases, Tenth Edition codes, to identify the top diseases. Statistical analyses, including χ-square tests, assessed changes in disease distributions. Population data for Odaka Ward and Minamisoma City fluctuated after lifting evacuation orders. As of March 11, 2011, Odaka Ward had 12,842 residents (27.8% aged 65+ years), dropping to 8406 registered residents and 2732 actual residents by April 30, 2018 (49.7%). Minamisoma City also saw declines, with registered residents decreasing from 71,561 (25.9%) to 61,049 (34.1%). The study analyzed 11,100 patients, mostly older patients (75.1%), between 2014 and 2020. Post-lifting, monthly patient numbers surged from an average of 55.2 to 213.5, with female patients increasing from 33.8% to 51.7%. Disease patterns shifted, with musculoskeletal cases declining from 23.8% to 13.0%, psychiatric disorders increasing from 9.3% to 15.4%, and trauma-related cases decreasing from 14.3% to 3.9%. Hypertension (57.1%) and dyslipidemia (29.2%) prevailed post-lifting. Urgent cases decreased from 1.3% to 0.1%. This study emphasizes the importance of primary care in post-evacuation zones, addressing diverse medical needs, including trauma, noncommunicable diseases, and psychiatric disorders. Changing patient demographics require adaptable healthcare strategies and resource allocation to meet growing demands. Establishing a comprehensive health maintenance system tailored to these areas' unique challenges is crucial for future disaster recovery efforts.


Asunto(s)
Terremotos , Accidente Nuclear de Fukushima , Atención Primaria de Salud , Humanos , Estudios Retrospectivos , Japón , Femenino , Masculino , Anciano , Persona de Mediana Edad , Adulto , Atención Primaria de Salud/estadística & datos numéricos , Adolescente , Adulto Joven , Niño , Planificación en Desastres , Anciano de 80 o más Años , Preescolar , Lactante , Instituciones de Atención Ambulatoria/estadística & datos numéricos
17.
Cells ; 13(3)2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38334675

RESUMEN

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer's disease-like pathologies in mice, including interleukin-1ß (IL-1ß) production and cognitive decline. However, little is known about the role of CatB in Pg virulence factor-induced IL-1ß production by microglia. We first subjected IL-1ß-luciferase reporter BV-2 microglia to inhibitors of Toll-like receptors (TLRs), IκB kinase, and the NLRP3 inflammasome following stimulation with Pg LPS and outer membrane vesicles (OMVs). To clarify the involvement of CatB, we used several known CatB inhibitors, including CA-074Me, ZRLR, and human ß-defensin 3 (hBD3). IL-1ß production in BV-2 microglia induced by Pg LPS and OMVs was significantly inhibited by the TLR2 inhibitor C29 and the IκB kinase inhibitor wedelolactonne, but not by the NLRPs inhibitor MCC950. Both hBD3 and CA-074Me significantly inhibited Pg LPS-induced IL-1ß production in BV-2 microglia. Although CA-074Me also suppressed OMV-induced IL-1ß production, hBD3 did not inhibit it. Furthermore, both hBD3 and CA-074Me significantly blocked Pg LPS-induced nuclear NF-κB p65 translocation and IκBα degradation. In contrast, hBD3 and CA-074Me did not block OMV-induced nuclear NF-κB p65 translocation or IκBα degradation. Furthermore, neither ZRLR, a specific CatB inhibitor, nor shRNA-mediated knockdown of CatB expression had any effect on Pg virulence factor-induced IL-1ß production. Interestingly, phagocytosis of OMVs by BV-2 microglia induced IL-1ß production. Finally, the structural models generated by AlphaFold indicated that hBD3 can bind to the substrate-binding pocket of CatB, and possibly CatL as well. These results suggest that Pg LPS induces CatB/CatL-dependent synthesis and processing of pro-IL-1ß without activation of the NLRP3 inflammasome. In contrast, OMVs promote the synthesis and processing of pro-IL-1ß through CatB/CatL-independent phagocytic mechanisms. Thus, hBD3 can improve the IL-1ß-associated vicious inflammatory cycle induced by microglia through inhibition of CatB/CatL.


Asunto(s)
Microglía , beta-Defensinas , Humanos , beta-Defensinas/metabolismo , Catepsina B/metabolismo , Quinasa I-kappa B/metabolismo , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos , Microglía/metabolismo , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factores de Virulencia/metabolismo
18.
Sci Rep ; 14(1): 2946, 2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316846

RESUMEN

The medical situation during disasters often differs from that at usual times. Disasters can lead to significant mortality that can be difficult to monitor. The types of disaster-related deaths are largely unknown. In this study, we conducted a survey to categorize the disaster-related deaths caused by a radiation disaster. A total of 520 people living in Minamisoma City, Fukushima Prefecture, at the time of the Fukushima Daiichi Nuclear Power Plant accident, who were certified to have died due to disaster-related causes were surveyed. We divided the participants into those who were at home at the time of the earthquake and those who were in hospitals or facilities when the disaster struck and conducted a hierarchical cluster analysis of the two groups. Disaster-related deaths could be divided into seven groups for those who were at home at the time of the disaster and five groups for those who were in hospitals or facilities at the time of the disaster. Each group showed different characteristics, such as "the group with disabilities," "the group receiving care," and "the group with depression," and it became evident that not only uniform post-disaster support, but support tailored to the characteristics of each group is necessary.


Asunto(s)
Desastres , Terremotos , Accidente Nuclear de Fukushima , Humanos , Hospitales , Análisis por Conglomerados , Japón/epidemiología , Plantas de Energía Nuclear
19.
PLOS Digit Health ; 3(5): e0000497, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38701055

RESUMEN

As we learned during the COVID-19 pandemic, vaccines are one of the most important tools in infectious disease control. To date, an unprecedentedly large volume of high-quality data on COVID-19 vaccinations have been accumulated. For preparedness in future pandemics beyond COVID-19, these valuable datasets should be analyzed to best shape an effective vaccination strategy. We are collecting longitudinal data from a community-based cohort in Fukushima, Japan, that consists of 2,407 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time courses of the vaccine-elicited antibody response based on mathematical modeling, we first identified basic demographic and health information that contributed to the main features of the antibody dynamics, i.e., the peak, the duration, and the area under the curve. We showed that these three features of antibody dynamics were partially explained by underlying medical conditions, adverse reactions to vaccinations, and medications, consistent with the findings of previous studies. We then applied to these factors a recently proposed computational method to optimally fit an "antibody score", which resulted in an integer-based score that can be used as a basis for identifying individuals with higher or lower antibody titers from basic demographic and health information. The score can be easily calculated by individuals themselves or by medical practitioners. Although the sensitivity of this score is currently not very high, in the future, as more data become available, it has the potential to identify vulnerable populations and encourage them to get booster vaccinations. Our mathematical model can be extended to any kind of vaccination and therefore can form a basis for policy decisions regarding the distribution of booster vaccines to strengthen immunity in future pandemics.

20.
Disaster Med Public Health Prep ; 17: e332, 2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36815358

RESUMEN

OBJECTIVE: People with psychiatric disorders are one of the most vulnerable populations in disasters, and the 2011 Great East Japan Earthquake reported higher post-evacuation mortality rates among psychiatric inpatients. A psychiatric hospital evacuated after the nuclear accident was surveyed to gain valuable insights for future disaster preparedness. METHODS: The authors interviewed two Odaka Akasaka Hospital (a private psychiatric hospital) staff responsible for evacuation due to the nuclear accident. RESULTS: At the time of the earthquake, 104 patients had been admitted to the hospital. They were instructed to evacuate on the grounds that they existed within a 20 km radius of Fukushima Daiichi Nuclear Power Station. Although the evacuation process was extraordinarily demanding, the staff acted professionally, and no patient experienced a significant deterioration in health during the evacuation. CONCLUSION: It was reasonable to follow the evacuation order because of the difficulty of obtaining accurate information about radiation exposure and staff availability in high-risk situations. The staff's knowledgeable and attentive care of the patients was one of the factors that enabled them to successfully carry out this severe evacuation. However, this may be related to the high mortality rate after the evacuation of patients who were separated from such caregivers.


Asunto(s)
Desastres , Terremotos , Accidente Nuclear de Fukushima , Humanos , Hospitales Psiquiátricos , Japón
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