NXC736 Attenuates Radiation-Induced Lung Fibrosis via Regulating NLRP3/IL-1ß Signaling Pathway.

Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1ß and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial-mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.

Interferon-γ elicits the ocular surface pathology mimicking dry eye through direct modulation of resident corneal cells.

Despite accumulating evidence indicating a key role of interferon-γ (IFN-γ)-producing immune cells in ocular infection and immunity, little is known about the direct effects of IFN-γ on resident corneal cells or on the ocular surface. Here, we report that IFN-γ impacts corneal stromal fibroblasts and epithelial cells to promote inflammation, opacification, and barrier disruption on the ocular surface, leading to dry eye. Our results demonstrated that IFN-γ dose-dependently induced cytotoxicity, pro-inflammatory cytokine/chemokine production, and expression of major histocompatibility complex class II and CD40 in cultures of corneal stromal fibroblasts and epithelial cells while increasing myofibroblast differentiation of corneal stromal fibroblasts. In mice, subconjunctival IFN-γ administration caused corneal epithelial defects and stromal opacity in dose- and time-dependent manners while promoting neutrophil infiltration and inflammatory cytokine expression in the cornea. Moreover, IFN-γ reduced aqueous tear secretion and the number of conjunctival goblet cells responsible for mucinous tear production. Together, our findings suggest that IFN-γ induces the ocular surface changes characteristic of dry eye disease at least in part through its direct effects on resident corneal cells.

The Relationship Between Lower Urinary Tract Symptoms and Osteoarthritis Symptoms Among Vendors in a Conventional Market.

PURPOSE: This study aimed to investigate lower urinary tract symptoms (LUTS) and the correlation between LUTS and osteoarthritis (OA) symptoms in the vendors working in a conventional market. METHODS: This cross-sectional study was conducted on 153 vendors aged 40 and over from August 10th to September 8th, 2020, in a conventional market. Data were collected via the self-reported questionnaires. We assessed LUTS by International Prostate Symptom Score (IPSS) and OA symptoms by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The mean age of 153 subjects was 61.31±9.92 years old. The mean score of IPSS and WOMAC was 5.37±5.68 (range, 0-35) and 16.89±19.61 (range, 0-96). Fifty-one percent of subjects had urinary incontinence at least monthly. Twenty-four point two percent of subjects had moderate-to-severe LUTS which were defined as a score of IPSS ≥8. LUTS were positively correlated with OA symptoms (r=0.41, P<0.001). CONCLUSION: The results showed that LUTS were associated with OA symptoms, and it also emphasized the need for vendors to be provided with a health education program to manage and prevent their LUTS and OA symptoms.

Lower urinary tract symptoms and erectile dysfunction in men with type 2 diabetes mellitus.

PURPOSE: To assess the prevalence of lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) and the relationships between LUTS, ED, depression, and other factors in Korean men with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study included 124 male patients with T2DM who attended a university hospital diabetes clinic between October 2010 and April 2012. Data were collected using structured interviews and chart reviews. LUTS were measured using the International Prostate Symptom Score (IPSS), ED using the five-item Korean version of the International Index of Erectile Function (IIEF), depression using the Center for Epidemiologic Studies Depression Scale, and glycosylated hemoglobin level from clinical data. RESULTS: The IPSS score was 9.2±6.6. The total IPSS scores indicated that 53.3% of the subjects had either moderate or severe symptoms. The mean IIEF score was 7.3±8.6, indicating the severity of ED to be mild, mild to moderate, moderate, and severe in 10.5%, 9.7%, 1.6%, and 66.9% of the participants, respectively. LUTS showed a significant negative correlation with ED (r=-0.26, P=0.003) and a significant positive correlation with depression (r=0.33, P<0.001). ED was negatively correlated with age (r=-0.44, P<0.001), duration of diabetes (r=-0.26, P=0.004), and depression (r=-0.24, P=0.008). CONCLUSIONS: LUTS and ED were found to have a high prevalence among Korean men with T2DM. More severe ED was associated with worse LUTS, whereas more severe depressive symptoms were found to be associated with more severe ED and LUTS.

Impact of lower urinary tract symptoms and depression on health-related quality of life in older adults.

PURPOSE: We aimed primarily to investigate the level of health-related quality of life (HRQoL), lower urinary tract symptoms (LUTS), and depression in older adults and secondly to identify the impact of LUTS and depression on HRQoL. METHODS: A community-based cross-sectional study was conducted from April to November 2010. Participants were recruited from five community senior centers serving community dwelling older adults in Jeju city. Data analysis was based on 171 respondents. A structured questionnaire was used to guide interviews; the data were collected including demographic characteristics, body mass index, adherence to regular exercise, comorbidities (hypertension, diabetes mellitus, and osteoarthritis), depression, urinary incontinence, LUTS (measured via the International Prostate Symptom Score [IPSS]), and HRQoL as assessed by use of the EQ-5D Index. Stepwise multiple regression analysis was used to test predictors of HRQoL. RESULTS: Eighteen percent (18.6%) of the respondents reported depressive symptoms. The mean LUTS score was 8.9 (IPSS range, 0 to 35). The severity of LUTS, was reported to be mild (score, 0 to 7) by 53% of the respondents, moderate (score, 8 to 19) by 34.5%, and severe (score, 20 to 35) by 12.5%. HRQoL was significantly predicted by depression (Partial R(2)=0.193, P<0.01) and LUTS (Partial R(2)=0.048, P=0.0047), and 24% of the variance in HRQoL was explained. CONCLUSIONS: LUTS and depression were the principal predictors of HRQoL in older adults.

Constipation in community-dwelling elders: prevalence and associated factors.

PURPOSE: The purpose of this study was to measure the prevalence of constipation in community-dwelling elders and to analyze associated factors. SUBJECTS AND SETTING: The study sample comprised 186 elders from 5 Senior Citizen Centers in Jeju-si. DESIGN: This community-based cross-sectional study used a structured questionnaire to collect data via interviews with respondents. METHODS: Interviews were completed by the principal investigator and an assistant. Interviews required approximately 20 minutes and were completed in the senior centers. Respondents were queried about demographic characteristics, body mass index, alcohol consumption, level of exercise, depression, and lower urinary tract symptoms including urinary incontinence. Bowel elimination symptoms were queried, and the presence of constipation was established using Rome II criteria. Multiple logistic regression analysis was used to test for associations between potential risk factors and constipation. RESULTS: The prevalence of constipation in this community-dwelling sample population was 25.8%. The most common symptoms were "hard or lumpy stools" reported by 30.8% and "straining during a bowel movement" reported by 27.1%. Analysis via logistic regression found that constipation is associated with lower urinary tract symptoms (odds ratio = 1.1; 95% confidence interval: 1.03-1.14) and obesity (body mass index ≥ 25 kg/m) (odds ratio = 2.4; 95% confidence interval: 1.01-5.57). CONCLUSIONS: Slightly more than one quarter of the elderly reported symptoms of constipation. Associated factors were presence of lower urinary tract symptoms and obesity.

[Factors associated with lower urinary tract symptoms for patients with Parkinson's disease].

PURPOSE: The study was done to identify lower urinary tract symptoms (LUTS) and to evaluate the factors affecting LUTS for the people with Parkinson's disease. METHODS: The research design was a cross-sectional study with interviews using a structured questionnaire. The participants were 72 patients with Parkinson's disease who were seen in the Neurology clinic of a university hospital from September to November 2005. RESULTS: Mean score of LUTS for the participants was 10.11. In each symptom score of LUTS (range 0-5), weak stream was the highest 2.06, followed by nocturia 1.71, and urgency 1.61. The severity of LUTS was moderate to severe group for 51%. LUTS were significantly different by regular exercise. Positive correlations were observed between Hoehn and Yahr stage (stage of disease severity) and frequency and between Hoehn and Yahr stage and urgency (r=.280, p=.018; r=.328, p=.005). LUTS were significantly predicted by regular exercise (p=.001) which explained 15.0% of the variance in LUTS. CONCLUSION: Regular exercise was found to be a very important factor associated with LUTS for patients with Parkinson's disease.

Prevalence of urinary incontinence and lower urinary tract symptoms for community-dwelling elderly 85 years of age and older.

OBJECTIVE: We sought to identify the prevalence of urinary incontinence (UI) and lower urinary tract symptoms (LUTS) and to evaluate the risk factors of community-dwelling South Korean elders for developing UI. DESIGN: We undertook a cross-sectional study based on interviews using a structured questionnaire. SETTING AND SUBJECTS: One hundred thirty-five community-dwelling elders, aged 85 years and older residing in 9 villages of Jeju Island, South Korea, were interviewed. Of 218 persons registered by the provincial government, interviews with 135 (62%) persons were completed. METHODS: Between April 5, 2004 and May 31, 2004, a researcher or 1 of 3 research assistants visited each subject's home. The interview took approximately 40 minutes to complete. Data were recorded by a research assistant and interviews were performed by the primary investigator or research assistant. INSTRUMENTS: LUTS severity was assessed by the Korean version of the International Prostate Symptom Score (IPSS) (7 items), and 3 additional items that specifically queried Urinary Incontinence (UI). Cognitive function and depression were assessed using the Korean version of the Mini Mental State Examination (MMSE-K) (13 items) and Geriatric Depression Scale Short Form Korean Version (GDSSF-K) (15 items). RESULTS: Forty-seven elderly (34.8%) reported UI more than once a week during the prior 12 months. Mixed UI symptoms were reported by 29 subjects (61.7%), pure urge UI symptoms by 16 (34.0%), and pure stress UI symptoms by 2 respondents (4.3%). The mean IPSS score of the subjects was 6.0 +/- 6.3 (range: 0-35). Risk factors for developing UI were moderate (odds ratio (OR) 17.6; 95% confidence interval (CI) 6.87-45.30) and severe LUTS (OR 36.5; 95% CI 3.86-345.07) measured by the IPSS. CONCLUSIONS: UI was found to affect 34.8% (47) of the community-dwelling elders 85 years or older in this study and mixed UI symptoms were predominant. LUTS was associated with an increased risk of UI.

A study of lower urinary tract symptoms for the Korean women aged 30 and over.

The purposes of this study were (1) to identify the prevalence of urinary incontinence (UI) and lower urinary tract symptoms (LUTS) for Korean women, (2) to evaluate the LUTS scores of the subjects in relation with each UI patterns and general characteristics, and (3) to identify affecting factors developing LUTS by using self-administered questionnaire. Community-based cross-sectional study was conducted for 3,371 women aged 30 to 89 years old who were allocated at six provinces in South Korea. UI and LUTS were assessed by validated symptom scales including the International Prostate Symptom Score. Of all the respondents, 63.4% had experienced UI more than once a month during the prior 12 months. Among the respondents, 36.6% had no UI, 47.5% had stress UI, 0.4% had urge UI, and 15.5% had mixed UI. The mean LUTS score of the total respondents was 7.8 +/- 4.1. The LUTS was significantly predicted by age (p < .0001) and mixed UI (p < .0001), and 79.4% of variance in LUTS was explained. The highest LUTS scores were shown in the subjects with mixed UI, and we found that LUTS scores increased with age.