Tobacco smoking continues to be a major risk factor for cardiovascular disease (CVD) and the leading avoidable cause of death worldwide. Tobacco smoking has declined in high-income countries, but the ...average smoking rate in Japan remains high: 29.4% for men and 7.2% for women in 2017. Of note, the average smoking rate among middle-aged men remains approximately 40%, indicating that a high incidence of smoking-related CVD will continue for a couple of decades in Japan. The adverse effects of tobacco smoking on CVD are more extensive than previously thought. Physicians should be particularly alert to the development and progression of heart failure, atrial fibrillation, and venous thromboembolism, as well as ischemic CVD among tobacco smokers. Increasing use of heat-not-burn tobacco as cigarette alternatives is an emerging issue. Harmful effects do not disappear just by changing the delivery system of tobacco.
Background
Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression ...in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs’ ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation.
Methods
Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
Results
AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase.
Conclusions
We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease.
Background:Pulmonary embolism (PE) is a potentially fatal form of venous thromboembolism (VTE). This study compares the mortality, incidence of recurrent VTE, and incidence of major bleeding between ...non-cancer and cancer-associated PE patients treated with direct oral anticoagulants (DOACs).Methods and Results:This was a retrospective, observational, single-center study involving 130 consecutive patients (87 with active cancer; 43 without cancer) who received DOAC treatment for PE between January 2016 and December 2019. Kaplan-Meier analysis showed significantly higher mortality in cancer-associated PE patients than in non-cancer patients (35/87 40% vs. 1/43 2%, P<0.001, log-rank test, HR 18.6 95% CI: 2.5–136.0). In contrast, the cumulative incidences of recurrent VTE and major bleeding were comparable between the 2 groups. Among the cancer-associated PE patients, the incidence for the composite outcome of recurrent VTE or major bleeding was significantly higher in patients undergoing chemotherapy than in those not undergoing chemotherapy (9/37 24% vs. 2/50 4%, P=0.004, log-rank test, HR 6.9 95% CI: 1.5–32.0).Conclusions:Although cancer-associated PE patients treated with DOACs showed higher mortality compared with non-cancer patients, presumably because of the presence of cancer, the risk of recurrent VTE or major bleeding was comparable between the 2 groups. Thus, DOAC is an important treatment option for cancer-associated PE, although underlying cancer-related risks (e.g., chemotherapy) remain.
Background: The term "nonrestorative sleep (NRS)" refers to unrefreshed feeling at wake-up and is a domain of poor sleep quality. Previous researches have demonstrated that NRS is linked to a number ...of diseases and adverse health outcomes, but less is known regarding the link between NRS and diabetes, particularly in Japanese.Methods: We studied 3665 middle-aged male participants of the Aichi Workers' Cohort Study who were followed-up from 2002 to 2019. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of incident type 2 diabetes mellitus (T2DM) in relation to NRS adjusted for potential confounding variables.Results: During a median follow-up of 14.6 years, 421 type 2 diabetes cases were identified. Participants with NRS had a higher crude incidence rate of T2DM (11.2/1,000 person-years), compared to participants without NRS (9.3/1,000 person-years). In the fully adjusted model, individuals who reported having NRS had a significantly higher risk of developing T2DM (HR: 1.36, 95% CI: 1.10-1.67). The association was observed only in participants under 50 years old (HR: 1.82, 95% CI: 1.36-2.43), not in the older (50 years or older) participants (P for interaction =0.025). In contrast, stratified analyses by the presence of shift work, obesity or sleep duration showed similar associations in all the strata.Conclusions: NRS was associated with higher risk of T2DM in middle-aged Japanese male workers independent of a variety of lifestyle factors and other sleep problems.
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