Cyclic nigerosylnigerose ameliorates DSS-induced colitis with restoration of goblet cell number and increase in IgA reactivity against gut microbiota in mice

Cyclic nigerosylnigerose (CNN) is a cyclic oligosaccharide. Oral administration of CNN promotes immunoglobulin A (IgA) secretion in the gut. IgA is a major antibody secreted into the gut and plays a crucial role in suppressing gut inflammation due to commensal gut microbiota. To investigate the effect of administration of CNN to promote IgA secretion on gut inflammation, experimental colitis was induced with dextran sulfate sodium (DSS) in Balb/c mice after 6 weeks of CNN pre-feeding. The severity of colitis was evaluated based on a disease activity index (DAI), the gene expression of inflammatory cytokines, and a histological examination. The CNN-treated mice with DSS-induced colitis (CNN-DSS group) showed significantly lower DAI scores and mRNA levels of interleukin-1 compared with the CNN-untreated mice with DSS-induced colitis (DSS group). Histological examination of the colon revealed that the pathological score was significantly lower in the CNN-DSS group compared with the DSS group due to the reduced infiltration of immune cells. The number of goblet cells was significantly higher in the CNN-DSS group compared with the DSS group. The IgA concentration and the ratio of microbiota coated with IgA were evaluated in the cecal content. Although there was no difference in the IgA concentration among groups, a higher proportion of cecal microbiota were coated with IgA in the CNN-DSS group compared with that in the DSS group. These results suggest that CNN might preserve goblet cells in the colon and promote IgA coating of gut microbiota, which synergistically ameliorate gut inflammation in mice with DSS-induced colitis

Are topical steroids essential after an uneventful cataract surgery?

Purpose : To access the necessity of topical steroids after uneventful cataract surgery, phaco-emulsification/aspiration plus intraocular lens (PEA+IOL) implantation. Design : Single-blind, randomized, prospective study. Participants : Twenty-one patients were prospectively randomized, 11 patients were assigned to the steroid group, and 10 to the non-steroid group. Methods : Between March and September 2007, in Mino Tanaka Hospital in Tokushima Prefecture, Japan, we performed PEA+IOL in 28 eyes of 21 patients and examined the visual acuity, corneal endothelium cell density, and anterior aqueous flare value after dividing all the patients into 2 groups, the topical steroid use and the non-steroid group. Results : At 1 month postoperatively, no difference was observed between the 2 groups in terms of the outcomes described, and no cystoid macular edema was detected. Conclusion : Topical steroid medication may not be absolutely essential after uneventful PEA+IOL

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ABSTRACT. Objective. Recent advances in the management of patients with rheumatoid arthritis (RA) increased the rates of disease remission and patient life expectancy, while malignancy has become a more common cause of death. Here, we report the incidence of malignancy in a nationwide survey of Japanese patients with RA compared to the general population, focusing on the risk of lymphoma, which often arises in patients with RA. Methods. Data on the occurrence of malignancy were collected from patients registered in a nationwide Japanese cohort database, the National Database of Rheumatic Diseases by iR-net in Japan, from 2003 to 2012. To adjust for different population composition and to compare the incidence of malignancy with the general population, standardized incidence rates (SIR) were calculated. To identify risk factors for lymphoma, individual patient data were obtained for multivariate analysis for the year before lymphoma diagnosis. Results. In 10 years, the cohort composed of 66,953 patient-years yielded 559 malignancies, most frequently lung cancer, followed by gastric cancer, breast cancer, and lymphoma. The overall incidence of malignancies in patients with RA was slightly lower than in the general population (SIR 0.89, 95% CI 0.82-0.97). However, lymphoma risk was significantly higher (SIR 3.43, 95% CI 2.59-4.28), whereas risk of colon, rectal, or liver cancer was lower. Significant risk factors for lymphoma were the use of methotrexate or tacrolimus, and higher age. Conclusion. Patients with RA had no higher overall incidence of malignancies, but lymphoma was significantly more frequent than in the general population

Development of an Oropharyngeal Scope with an Integrated Tongue Depressor: NTOP2013 Study

The oropharynx is examined with a light source such as an electric light, a penlight, or a forehead mirror based on an acquired visual field using a tongue depressor. However, it is extremely difficult to obtain objective and reproducible images of tissue within the pharynx required in recent years with these methods, and insufficient progress in the examination tools has been made. There is an increasing need to develop a method for display during oropharyngeal examination. We conducted the present study to develop a novel oropharyngeal endoscope as an objective observation method

Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts

Background: Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. Methods and Findings: We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y. Conclusions: Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.</p

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.ArticleeNeuro.4(2):e0250(2017)journal articl

Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts

Background:Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.Methods and Findings:We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: A 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.Conclusions:Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.Please see later in the article for the Editors' Summary. © 2014 Zheng et al

Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium

10.1371/journal.pone.0019930PLoS ONE66

Fluorinated Derivatives of Digalloyl-Flavan-3-ol Induce Autophagic Cell Death by Forming Granular Aggregates Containing Mitochondria

Flavan-3-ol derivatives are polyphenolic compounds with multifunctional properties. One of the flavan-3-ol derivatives, green tea catechin epigallocatechin gallate, is known to have anticancer activity as one of its multifunctional properties. We have studied the synthesis of flavan-3-ol derivatives and conducted structure-activity relationship studies; we found that the fluorinated derivatives exhibited high toxicity against HeLa and A549 cells. It was confirmed that the cytotoxicity was affected by the conformation of the flavan-3-ol skeleton and that the 2,3-cis form was dominant. The addition of fluorinated compounds increased the amount of intracellular mitochondrial superoxide, abolished the membrane potential of mitochondria, and, interestingly, formed granular aggregates containing mitochondria. When the level of LC3-II, a marker of autophagy induction, was confirmed, it suggested that the addition of the fluorinated compounds promoted autophagy. These results suggest that the novel highly cytotoxic fluorinated flavan-3-ol compound synthesized in this study promotes autophagy and induces cell death by triggering mitochondrial dysfunction. We believe that these results suggest the possibility of conferring more functionality through structural transformations of flavan-3-ol derivatives