2.Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A.actinomycetemcomitans exacerbates arthritis
Okano TOKUJU ; Ashida HIROSHI ; Komatsu NORIKO ; Tsukasaki MASAYUKI ; Iida TAMAKO ; Iwasawa MARIE ; Takahashi YUTO ; Takeuchi YASUO ; Iwata TAKANORI ; Sasai MIWA ; Yamamoto MASAHIRO ; Takayanagi HIROSHI ; Suzuki TOSHIHIKO
International Journal of Oral Science 2024;16(3):499-514
Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1β secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.
3.Predictor of Activities of Daily Living (ADL) Disability in Patients Undergoing Cardiovascular Surgery
Shinji MIZUTA ; Shinya TAKAHASHI ; Mayo OSHITA ; Miwa ARAKAWA ; Akira KATAYAMA
Japanese Journal of Cardiovascular Surgery 2019;48(5):299-304
Objectives: The aim of this study was to investigate the relationship between preoperative 10m gait speed and ADL disability in patients undergoing cardiovascular surgery. Methods: There were 131 patients who underwent scheduled cardiovascular surgery and pre and postoperative ADL evaluation from June 2014 to December 2017 in our hospital. A total of 19 patients, including 13 whose Barthel Index (BI) was lower than before surgery at discharge and 6 who had a long-term hospital stay of 6 weeks or more after surgery, was defined as the ADL disability group. The other 119 patients were defined as the control group. We retrospectively compared the two groups and searched for predictors of postoperative ADL disability. Results and Conclusions: An independent predictor of postoperative ADL disability was identified: more than 7.04seconds for walking 10m.
4.Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
Michihiro IWAKI ; Hideki FUJII ; Hideki HAYASHI ; Hidenori TOYODA ; Satoshi OEDA ; Hideyuki HYOGO ; Miwa KAWANAKA ; Asahiro MORISHITA ; Kensuke MUNEKAGE ; Kazuhito KAWATA ; Tsubasa TSUTSUMI ; Koji SAWADA ; Tatsuji MAESHIRO ; Hiroshi TOBITA ; Yuichi YOSHIDA ; Masafumi NAITO ; Asuka ARAKI ; Shingo ARAKAKI ; Takumi KAWAGUCHI ; Hidenao NORITAKE ; Masafumi ONO ; Tsutomu MASAKI ; Satoshi YASUDA ; Eiichi TOMITA ; Masato YONEDA ; Akihiro TOKUSHIGE ; Yoshihiro KAMADA ; Hirokazu TAKAHASHI ; Shinichiro UEDA ; Shinichi AISHIMA ; Yoshio SUMIDA ; Atsushi NAKAJIMA ; Takeshi OKANOUE ;
Clinical and Molecular Hepatology 2024;30(2):225-234
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study.
Methods:
This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD.
Results:
Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4).
Conclusions
Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.