bluuebunny/crossref_metadata_2025_split huggingface dataset:
Icarisid I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity
Authors: Gao Yuan , Xu Guang , Ma Li , Shi Wei , Wang Zhilei , Zhan Xiaoyan , Qin Nan , He Tingting , Guo Yuming , Niu Ming , Wang Jiabo , Bai Zhaofang , Xiao Xiaohe 
Published: August 2020

Abstract
Background

Epimedii Folium(EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI.

Methods

Mouse were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo.

Results

Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mice model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation.

Conclusions

Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI.
Social marketing interventions to promote physical activity among 60 years and older: a systematic review of the literature
Authors: Goethals Luc , Barth Nathalie , Hupin David , Mulvey Michael S. , Roche Frederic , Gallopel-Morvan Karine , Bongue Bienvenu 
Published: August 2020

Abstract
Background: Falls are a significant source of morbidity in people aged 65 and over, affecting one in three people in this age group. The scientific evidence indicates that physical activity is the most effective method for preventing falls among seniors. Although public health professionals often use social marketing to design and plan successful interventions, its use to promote physical activity and prevent falls among older people remains low. This article aims to provide a new systematic literature review of social marketing interventions promoting physical activity and targeting people aged 60 and over.Methods: Following CRD’s guidance and PRISMA guidelines, we searched between January 2008 and July 2019 for relevant articles in five primary databases using predefined search and inclusion criteria. Two independent reviewers analysed the selected articles to identify evidence of the seven social marketing benchmark criteria, defined by experts in the field as the common elements that contribute to social marketing success.Results: The final review included nine studies. Of the studies selected, three specifically targeted over 60-year-olds, whereas the others segmented the population into several age-based subcategories, including over 60-year-olds. Eight studies highlighted positive results for the participants with an increase in participation or an increase in physical activity level. None of the nine studies selected for this systematic review implemented the entire social marketing approach.Conclusion: Few published interventions use the seven social marketing criteria. Further research is required to encourage uptake and inclusion in successful social marketing interventions to increase program effectiveness in this target population.
Social participation is an important health behaviour for health and quality of life among chronically ill older Chinese people
Authors: Feng Zeyun , Cramm Jane Murray , Nieboer Anna Petra 
Published: August 2020

Abstract
Background: Health behaviours (physical activity, maintenance of a healthy diet and not smoking) are known to be beneficial to the health and well-being of chronically ill people. With China's ageing population and increased prevalence of people with chronic diseases, the improvement of unhealthy behaviours in this population has become crucial. Although recent studies have highlighted the importance of social participation for health and quality of life (QoL) among older people, no study to date has included social participation along with more traditional health behaviours. Therefore, this study aimed to identify associations of multiple health behaviours (social participation, physical activity, maintenance of a healthy diet and not smoking) with health and QoL outcomes (including cognitive and physical function) among chronically ill older adults in China.Methods: For this nationally representative cross-sectional study, wave 1 data from the World Health Organization’s Study on global AGEing and adult health (China) were examined. In total, 6,629 community-dwelling older adults (mean age, 64.9 years) with at least one chronic disease were included. Multivariate linear regression analyses were used to evaluate associations of health behaviours with health and QoL outcomes while controlling for background characteristics.Results: Greater social participation was associated with better QoL [β = 0.127, standard error (SE) = 0.002, p < 0.001], cognitive function (β = 0.154, SE = 0.033, p < 0.001) and physical function (β = –0.102, SE = 0.008, p < 0.001). Physical activity was associated with better QoL (β = 0.091, SE = 0.015, p < 0.001) and physical function (β = –0.155, SE = 0.062, p < 0.001). Sufficient fruit and vegetable consumption was associated with better QoL (β = 0.087, SE = 0.015, p < 0.001).Conclusions: Our findings suggest that social participation is an important health behaviour for quality of life and cognitive function among chronically ill older people in China. Health promotion programmes should expand their focus to include social participation as a health behaviour, in addition to physical activity, maintenance of a healthy diet and not smoking.
The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis
Authors: Kitajima Takahito , Okita Yoshiki , Kawamura Mikio , Kondo Satoru , Toiyama Yuji , Uchida Keiichi , Kusunoki Masato 
Published: August 2020

Abstract
Background: Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. Aim: To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. Methods: This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch–anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL‐17A) were determined.Results: Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p=0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p=0.043). Univariate analysis demonstrated a total dose of prednisolone >7000 mg administered before colectomy (p=0.04) and high IFN-γ expression (p=0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p=0.03).Conclusion: IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.
Active constituents of Zanthoxylum nitidum from Yunnan Province against leukemia
Authors: Deng Ying , Ding Tongtong , Deng Lulu , Hao Xiaojiang , Mu Shu Zhen 
Published: August 2020

Abstract
Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, though research on its potential use in treating leukaemia is relatively rare. Twenty-six compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium. They were (+)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1), 8-(3′-oxobut-1′-en-1′-yl)-5, 7-trimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5-(3′, 3′-dimethyl-2′-butenyloxy)-7, 8-dimethoxy-coumarin (4), 2-(5-methoxy-2-methyl-1H-indol-3-yl) methyl acetate (5), 2′-(5,6-dihydrochleletrythrine-6-yl) ethyl acetate (6), 6-acetonyldi-hydrochelerythrine (7), 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12), N-nornitidine (13), nitidine (14), chelerythrine (15), 4-hydroxyl-7,8-dimethoxy-furoquinoline (16), dictamnine (17), γ-fagarine (18), skimmianine (19), robustine (20), R-(+)-platydesmine (21), 4-O-methyl-1-methyl-quinoline-2-one (22), 4-methoxy-2-quinolone (23), liriodenine (24), aurantiamide acetate (25), 10-O-demethyl-12-O-methylarnottianamide (26). Four among them, compounds 4-6 and 16, were first confirmed in this study by UV, IR, 1D, 2D NMR and HR-ESI-MS spectra. Compounds 1-2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, 1, 2, 9, 10, 14, 15 and 24, exhibited good inhibitory activities in the leukaemia cell line HEL, whereas compound 14 (IC50: 3.59 µM) and compound 24 (IC50: 15.95 µM) exhibited potent inhibitory activities. So, to further investigate the possible mechanisms, cell cycle and apoptosis assays were performed, which indicated that compound 14 causes obvious S-phase arrest in HEL cells and induced apoptosis, whereas compound 24 only induced apoptosis. The present results suggested both compounds 14 and 24 are promising potential anti-leukaemia drug candidates.
A comparison of medical student competency, attitudes and knowledge of abortion care after a structured clinical curriculum
Authors: Gardner Hallie , Zimmerman Marguerite , Flanigan Moira , Baldwin Maureen K 
Published: August 2020

Abstract
Background: Abortion care is a core educational objective according to the Association of Professors of Gynecology and Obstetrics (APGO), but clinical exposure is variable in medical education. The authors sought to compare professional competency, attitudes, and knowledge regarding abortion between students who attended a structured clinical experience in abortion care to those who chose a less-structured family planning clinical environment.Methods: All medical students participating in the Obstetrics & Gynecology clerkship from 2014-2015 were invited to complete a pre- and post-clerkship survey and grouped based on their attendance to a structured clinical abortion experience at Planned Parenthood (PPCW) versus an alternative Family Planning Clinic (FPC) experience. Self-assessed competency and attitudes about abortion were measured using a 100-mm visual analog scale (VAS). Authors assessed knowledge about abortion with multiple-choice questions.Results: A total of 89 students completed the surveys (PPCW: 74; FPC: 15). Students attending PPCW were more likely to observe counseling about abortion and ultrasound prior to abortion (PPCW: 67/74, 91%; FPC: 4/15, 27%, p=<0.01). More PPWC students observed a surgical abortion (91% versus 7% of FPC students). Self-assessed competency scores improved with composite mean difference in VAS for PPCW of 42.2 mm and FPC of 27.3 mm (p=0.02). Attitude scores were unchanged in those with initial VAS <80 mm. Knowledge improved overall, with greater changes among the PPCW group.Conclusions: A structured clinical abortion experience met APGO educational objectives more than an alternative experience. Future physicians should universally be exposed to clinical abortion care in order to ensure evidence-based education about abortion.
Socioeconomic status, social capital, health risk behaviors, and health-related quality of life among Chinese older adults
Authors: Yang Ying , Wang Shizhen , Chen Lei , Luo Mi , Xue Lina , Cui Dan , Mao Zongfu 
Published: August 2020

Abstract
Background: There is limited knowledge on the mediating role of different health risk behavior on the relationship between social capital, socioeconomic status (SES), and health-related quality of life (HRQoL) in Chinese older adults. We conducted this study to (a) investigate the condition of health risk behaviors of the Chinese elderly, and (b) assess the relationship between SES, social capital, health risk behaviors, and HRQoL.Methods: A sample of 4,868 adults aged 60 years and older were included in this study, from the China’s Health-related Quality of Life Survey for Older Adults 2018. Participants’ demographic characteristics, SES (education level, family income), health risk behaviors (smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder) were collected. Social capital and HRQoL were assessed by the 16-item Personal Social Capital Scale (PSCS-16) and WHOQOL-Old, respectively. Structural equation modeling (SEM) was applied to examine the associations between variables.Results: The proportion of smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder were 32.1%, 36.3%, 62.5%, 45.7%, 31.8%, and 45.5%, respectively. Significant differences were observed in education level, family income, and social capital between elderly individuals with and without each of the six health risk behavior (all p-values < 0.05). Elderly individuals who reported smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder had significantly lower HRQoL than those without these unhealthy behaviors (all p-values < 0.05). SEM analysis showed that SES and social capital positively associated with alcohol consumption. Social capital negatively associated with smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder. SES negatively associated with smoking, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder. Smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder correlated with poorer HRQoL.Conclusions: Chinese older adults demonstrated a high incidence of health risk behaviors, especially for physical inactivity (62.5%) and unhealthy dietary behavior (45.7%). Social capital and SES were correlated with the elderly’s HRQoL, as well as with the health risk behaviors. Health risk behaviors played potential mediating role on the relationship between social capital, SES, and HRQoL in Chinese older adults.
Patients with pheochromocytoma exhibit low aldosterone renin ratio-preliminary reports
Authors: Yamada Tomoko , Fukuoka Hidenori , Hosokawa Yusei , Odake Yukiko , Yoshida Kenichi , Matsumoto Ryusaku , Bando Hironori , Okada Yuko , Hirota Yushi , Iguchi Genzo , Ogawa Wataru , Takahashi Yutaka 
Published: August 2020

Abstract
Background

Plasma renin activity (PRA) is generally increased in patients with pheochromocytoma (PCC) due to low circulating plasma volume and activation of β-1 adrenergic receptor signaling. However, there has been no study on the aldosterone renin ratio (ARR) in patients with PCC. To elucidate the issue, this study aimed to determine the PRA, plasma aldosterone concentration (PAC), and ARR in patients with PCC and compare them with those in patients with subclinical Cushing’s syndrome (SCS) and non-functioning adrenal adenoma (NFA).

Methods

In this retrospective single-center, cross-sectional study, 67 consecutive patients with adrenal tumors (PCC (n =18), SCS (n =18), and NFA (n =31)) diagnosed at Kobe University Hospital between 2008 and 2014 were enrolled.

Results

PRA was significantly higher in patients with PCC than in those with SCS and NFA (2.1 (1.3~2.8) vs. 0.7 (0.5~1.8) and 0.9 (0.6~1.4) ng/mL/h; p =0.018 and p =0.025). Although PACs were comparable among the three groups, ARR was significantly lower in patients with PCC than in those with SCS and NFA (70.5 (45.5~79.5) vs. 156.0 (92.9~194.5) and 114.9 (90.1~153.4); p =0.001 and p <0.001). Receiver operating characteristic curve analysis demonstrated that, in differentiating PCC from NFA, PRA >1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR <95.4 showed a sensitivity of 83.3% and specificity of 86.7%, which were higher than those in PRA.

Conclusions

ARR decreased in patients with PCC, which was a more sensitive marker than PRA. Further study is necessary to understand the usefulness of this convenient marker in the detection of PCC.
The Combination of an Inflammatory Peripheral Blood Gene Expression and Imaging Biomarkers Enhance Prediction of Radiographic Progression in Knee Osteoarthritis.
Authors: Attur Mukundan , Krasnokutsky Svetlana , Zhou Hua , Samuels Jonathan , Chang Gregory , Bencardino Jenny T. , Rosenthal Pamela , Rybak Leon , Huebner Janet L. , Kraus Virginia B. , Abramson Steven B. 
Published: August 2020

Abstract
Objective. Predictive biomarkers of progression in knee osteoarthritis are sought to enable clinical trials of structure modifying drugs. A peripheral blood leukocyte (PBL) inflammatory gene signature, MRI-based bone marrow lesions (BML) and meniscus extrusion scores), meniscal lesions, and osteophytes on x-ray each have been shown separately to predict radiographic joint space narrowing (JSN) in subjects with symptomatic knee osteoarthritis (SKOA). In these studies, we determined whether the combination of the PBL inflammatory gene expression and these imaging findings at baseline enhanced the prognostic value of either alone.Methods. PBL inflammatory gene expression (increased mRNA for IL-1β, TNFα, and COX-2), routine radiographs, and 3T knee MRI were assessed in two independent populations with SKOA: an NYU cohort, and the Osteoarthritis Initiative (OAI). At baseline and 24 months, subjects underwent standardized fixed-flexion knee radiographs and knee MRI. Medial JSN (mJSN) was determined as the change in medial JSW. Progressors were defined by an mJSN cut-point (≥0.5 mm/24 months). Models were evaluated by odds ratios (OR) and area under the receiver operating characteristic curve (AUC).Results. We validated our prior finding in these two independent (NYU and OAI) cohorts, individually and combined, that an inflammatory PBL inflammatory gene expression predicted radiographic progression of SKOA after adjustment for age, sex, and BMI. Similarly, the presence of baseline BML and meniscal lesions by MRI or semi-quantitative osteophyte score on x-ray each predicted radiographic medial JSN at 24 months. The combination of the PBL inflammatory gene expression and medial BML increased the AUC from 0.66 (p=0.004) to 0.75 (p<0.0001) and the odds ratio from 6.31 to 19.10 (p<0.0001) in the combined cohort of 473 subjects. The addition of osteophyte score to BML and PBL inflammatory gene expression further increased the predictive value of any single biomarker. A causal analysis demonstrated that the PBL inflammatory gene expression and BML independently influenced mJSN.Conclusion. The use of the PBL inflammatory gene expression together with imaging biomarkers as combinatorial predictive biomarkers, markedly enhances the identification of radiographic progressors. The identification of the SKOA population at risk for progression will help in the future design of disease-modifying OA drug trials and personalized medicine strategies.
The β-catenin/TCF-4 pathway regulates the expression of OPN in human osteoarthritic chondrocytes
Authors: Tian Jian , Gao Shu-Guang , Li Yu-Sheng , Cheng Chao , Deng Zhen-Han , Luo Wei , Zhang Fang-Jie 
Published: August 2020

Abstract
Background: Cartilage destruction is the main characteristic of osteoarthritis (OA), and osteopontin (OPN) is elevated in OA articular cartilage; however, the reason for the increased OPN level is not determined. In addition, Wnt/β-catenin signaling participates in the progression of OA. The aim of the present study was to evaluate whether canonical Wnt signaling could regulate the expression of OPN in human chondrocytes in vitro.Methods: Human chondrocytes were cultured in vitro, and we first assayed the mRNA levels of OPN and β-catenin in chondrocytes. Next, we performed transient transfection of TCF 4 shRNA into chondrocytes to inhibit TCF 4 expression and explore changes in the OPN level. Then, the Wnt/β-catenin signaling inhibitor Dickkopf-1 (Dkk-1) was incubated with chondrocytes, and we assayed the changes in β-catenin and OPN.Results: Our results showed that the expression of both β-catenin and OPN was increased in OA chondrocytes, but there were no correlations between β-catenin and OPN expression. TCF4 shRNA downregulated the expression of TCF 4 and OPN in chondrocytes, while after treatment with rDKK-1 at a concentration of 400 ng/ml for 24 h, the mRNA and protein expression of both β-catenin and OPN was significantly decreased in chondrocytes.Conclusions: Elevated OPN expression might be regulated by the β-catenin/TCF-4 pathway, and the Wnt/β-catenin inhibitor DKK1 could inhibit the expression of β-catenin and OPN in OA chondrocytes.
Protocol for CardioCluster Creation
Authors: Monsanto Megan M , Sussman Mark A 
Published: August 2020

Abstract
Cellular therapy to treat heart failure is an ongoing focus of intense research, but with limited progress due to limitations in engraftment and persistence of injected cells. Engineered augmentation of established cellular effectors overcomes impediments, enhancing reparative activity. Such ‘next generation’ implementation includes delivery of combinatorial cell populations working together synergistically to improve heart function following injury. Concurrent isolation and expansion of 3 distinct cardiac-derived interstitial cell types from human heart tissue prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Here we describe a method wherein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments we have termed 'CardioClusters'.