Processed Food as a Risk Factor for the Development and Perpetuation of Crohn's Disease-The ENIGMA Study.

(1) Background: Developing countries have experienced a rapid recent rise in Inflammatory Bowel Disease (IBD) incidence and emerging evidence suggests processed foods and food additives may predispose one to the development and perpetuation of Crohn's disease (CD). The aim of this study was to evaluate processed food and food additive intake in CD patients and controls, in Australia (high CD incidence), Hong Kong (intermediate incidence) and mainland China (emerging incidence). (2) Methods: In 274 CD patients (CD), 82 first-degree relatives (FDR), 83 household members (HM) and 92 healthy unrelated controls (HC) from Australia (n = 180), Hong Kong (HK) (n = 160) and mainland China (n = 191) we estimated early life (0-18 years), recent (12 months), and current processed and food additive intake, using validated questionnaires and a 3-day-food diary. (3) Results: Early life processed food intake: Combining all regions, CD were more likely to have consumed soft drinks and fast foods than HM, more likely to have consumed processed fruit and snacks than their FDR, and more likely to have consumed a range of processed foods than HC. HK and China CD patients were more likely to have consumed a range of processed foods than HC. Recent food-additive intake (12-months): Combining all regions, CD patients had significantly higher intakes of aspartame and sucralose, and polysorbate-80, than HC, and more total emulsifiers, artificial sweeteners, and titanium dioxide than FDR and HC. HK and China CD patients had a higher intake of almost all food additives than all controls. Current additive intake (3-days): Australian and HK CD patients had higher total food-additive intake than FDR, and HK CD patients had a higher intake of total food-additives and emulsifiers than HM. (4) Conclusions: CD patients have been exposed to more processed food and food additives than control groups, which may predispose them to CD development and ongoing inflammation.

Childhood antibiotics as a risk factor for Crohn's disease: The ENIGMA International Cohort Study.

Background and Aim: Environmental factors play a key role in development of Crohn's disease (CD), thought to be mediated by changes in the gut microbiota. We aimed to delineate the potential contribution of antibiotic exposure to subsequent development of CD, across diverse geographical populations. Methods: This case-control study in Australia and three cities in China (Hong Kong, Guangzhou, and Kunming) included four groups: patients with CD, at-risk individuals including non-affected first-degree relatives (FDRs) and household members of CD patients (HM), and unrelated healthy controls (HCs). Environmental risk factors, including childhood antibiotic use and 13 other categories, were assessed using a self-developed questionnaire. Logistic regression and conditional logistic regression were used to determine environmental factors associated with CD development. Results: From 2017 to 2019, a total of 254 patients with CD (mean age: 37.98 ± 13.76 years; 58.3% male), 73 FDR (mean age: 49.35 ± 13.28 years; 46.6% male), 122 HMs (including FDR) (mean age: 45.50 ± 13.25 years; 47.5% male), and 78 HC (mean age: 45.57 ± 11.24; 47.4% male) were included. Comparing CD patients with their FDR and HMs, antibiotic use before 18 years old was a risk factor for CD development (adjusted odds ratio [OR] 3.46, 95% confidence interval [CI] 1.38-8.69; P = 0.008). There were no significant differences in other childhood environmental risk factors between CD and their FDR or HMs. Subgroup analysis showed that antibiotic use <18 years old was a risk factor for CD development in the Chinese (adjusted OR 4.80, 95% CI 1.62-12.24; P = 0.005) but not in Australian populations (OR 1.80, 95% CI 0.33-9.95; P = 0.498). Conclusion: Use of antibiotics <18 years was a risk factor for CD development. Attention should be paid to identifying modifiable environmental risk factors in early childhood, especially in at-risk families.

Family carers' expectations regarding dementia care services and support in China: A qualitative study.

INTRODUCTION: In China, approximately 85% of people with dementia are cared for by family carers. However, limited research has been conducted to examine family carers' expectations regarding what they perceive is required for optimal care. Therefore, this study aimed to explore family carers' expectations regarding dementia care support and services in China. METHODS: A qualitative study employing semi-structured interviews, with data collected from three public tertiary hospitals where the primary family carers of people with dementia (N = 21) were recruited from May to December 2019. Purposive maximum variation sampling was used to recruit participants. Data was interpreted both inductively and deductively using thematic analysis. FINDINGS: Four themes were identified. The family carers reported minimal support regarding dementia care, and they held little hope of receiving support. However, most carers expressed their limited expectations, such as financial support from the government and respite care services from the community. Carers believed that care was their duty, and some of them were unwilling to move their relative with dementia into a nursing home. CONCLUSION: Health and the three-tier long-term care systems in China are inadequately prepared for the challenges of dementia care, suggesting the need to develop health and social services and improve support for family carers to enable improved care for people with dementia.

Energy conservation education intervention for people with end-stage kidney disease receiving haemodialysis (EVEREST): protocol for a cluster randomised control trial.

INTRODUCTION: Multiple symptoms occur in people with kidney failure receiving haemodialysis (HD) and these symptoms have a negative impact on health-related quality of life (HRQoL). Fatigue, the most common symptom, is debilitating and difficult to manage. Educational interventions involving energy conservation strategies are helpful in reducing fatigue, however the effectiveness of energy conservation has not been previously studied in those receiving HD. The aim of this study is to evaluate the effectiveness of an energy conservation education intervention for people with end-stage kidney disease receiving HD (EVEREST trial). METHODS AND ANALYSIS: A pragmatic cluster randomised control trial with repeated measure will be used. One hundred and twenty-six participants from tertiary level dialysis centre will be cluster randomised to the intervention and control group according to HD treatment day. The intervention group will receive usual care along with a structured energy conservation education programme over 12 weeks comprising three individual face-to-face educational intervention sessions, one booster session and a booklet. The control group will receive usual care from their healthcare providers and a booklet at the end of the study. The primary outcome is fatigue, and the secondary outcomes are other Chronic Kidney Disease (CKD) symptoms, occupational performance and HRQoL. Intention-to-treat analysis will occur and will include a change in primary and secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Research Committee of the Griffith University and Nepal Health Research Council. The results of this research will be published and presented in a variety of forums. TRIAL REGISTRATION NUMBER: NCT04360408.

Healthcare professionals' dementia knowledge and attitudes towards dementia care and family carers' perceptions of dementia care in China: An integrative review.

AIMS AND OBJECTIVES: To establish an understanding of healthcare professionals' dementia knowledge and attitudes towards dementia care, and family carers' perceptions of dementia care in China. BACKGROUND: Healthcare professionals and family carers of people with dementia deliver most of the dementia care in China. However, little research on healthcare professionals' dementia knowledge and attitudes towards dementia care, and family carers' dementia care perceptions has been conducted in China. METHODS: An integrative review was conducted and reported based on the PRISMA guidelines and Whittemore and Knafl's framework. Eight English databases were searched without date restriction: CINAHL Plus with Full Text, MEDLINE, PubMed, Web of Science, Cochrane Library, Embase, PsycINFO and Scopus; and three Chinese databases: China National Knowledge Infrastructure, Chongqing Weipu and Wanfang, plus a manual search of reference lists. RESULTS: Thirty-eight primary research papers were included in the review. Three themes were identified from the synthesis: (a) knowledge and competency; (b) attitudes towards dementia care; and (c) carers' burden and unmet needs. Healthcare professionals' dementia knowledge ranged from low to moderate levels and attitudes towards dementia care were generally negative. With low levels of knowledge of dementia and negative attitudes including stigma, family carers were under stress with insufficient support, and they expected more support from community nurses. CONCLUSIONS: There is an apparent need for a national policy on healthcare professional education and training to improve dementia care practice in China. Such a policy may improve support services for family carers. RELEVANCE TO CLINICAL PRACTICE: Nurses, and particularly community nurses, are well-positioned to support family carers in China. However, healthcare professionals in China are not prepared for this. Therefore, education and training on dementia care should be integrated into medical and nursing undergraduate programmes and provided for healthcare professionals after commencing employment, and strategies to reduce stigma are needed.

Hospital healthcare professionals' knowledge of dementia and attitudes towards dementia care: A cross-sectional study.

AIMS AND OBJECTIVES: To explore hospital healthcare professionals' knowledge and attitudes towards dementia care in China. BACKGROUND: Hospital healthcare professionals deliver most diagnosis and treatment for people with dementia in China. Literature shows that healthcare professionals' knowledge and attitudes are of great importance in providing optimum dementia care. However, there is limited research of healthcare professionals' dementia knowledge and attitudes within hospital contexts in China. DESIGN: A cross-sectional survey was conducted between April and December 2019. METHODS: A self-report questionnaire composed of demographics and knowledge and attitude scales related to dementia was used for doctors and registered nurses working in settings where people with dementia are cared for in eleven public tertiary hospitals in Hebei Province, China. The STROBE checklist was adhered to in this study. RESULTS: In total, 603 healthcare professionals completed the study. The majority of respondents were registered nurses (71.3%). The overall mean knowledge score was 20.7 (SD = 2.9) out of a maximum possible score of 30. The overall mean score for attitudes was 91.3 (SD = 15.9) out of a maximum possible score of 140. Standard multiple linear regression analysis revealed that the highest level of education, the experience of searching for dementia-related information and willingness to receive dementia training or education were significant predictors of knowledge scores. The department, the experience of working with people with dementia, length of dementia care, interest in dementia care and training type were significant predictors of attitude scores. CONCLUSIONS: Deficits in the knowledge of dementia and a low level of positive attitude were identified among the healthcare professionals who work in hospital settings where people with dementia are cared for in China. RELEVANCE TO CLINICAL PRACTICE: Education and training in dementia care should be integrated into undergraduate nursing and medical programmes and provided for healthcare professionals after commencing employment.

Enhancing reflection on medical and surgical nursing among nursing students: A participatory action research study.

BACKGROUND: Medical and Surgical Nursing (MSN) is a core course in baccalaureate nursing programs that requires active and effective teaching and learning strategies to enhance students' engagement. OBJECTIVE: To develop and implement an effective learning process for students undertaking the MSN course. DESIGN: This participatory action research study used reflection as the center of action in the cycle of planning, acting, observing and reflecting and re-planning. SETTING: The study was conducted at a University in southern Taiwan. PARTICIPANTS: Thirty nursing students in their second year of a bachelor program in nursing, aged 19 to 20 years, were recruited via email and completed the study. METHODS: The data were collected from February to June 2019 through reflective workshops, group discussions, individual interviews, and field notes. A qualitative content analysis was performed. Four criteria were considered to ensure the trustworthiness of the study process: reliability, validity, transferability, and authentic citations. RESULTS: Four key themes - two challenges and two adaptive strategies - emerged in relation to the spiral process of improving teaching and learning in the MSN course. Participants experienced two main challenges: the large amount of multidisciplinary knowledge expected, and the rapid pace of the course. The two adaptive strategies were: recognizing their own unique way of learning and becoming an active learner and achiever. CONCLUSIONS: The project helped students to identify their own learning challenges, recognize the need to modify their attitudes and approaches to learning, improve teaching and learning in the MSN course, and identify the characteristics relevant to becoming an active learner and achiever.

Review article: Probiotics, prebiotics and dietary approaches during COVID-19 pandemic.

BACKGROUND: Patients with COVID-19 caused by SARS-CoV-2 exhibit diverse clinical manifestations and severity including enteric involvement. Commensal gut bacteria can contribute to defense against potential pathogens by promoting beneficial immune interactions. Interventions targeting the gut microbiome may have systemic anti-viral effects in SARS-CoV-2 infection. SCOPE AND APPROACH: To summarise alterations of gut microbiota in patients with COVID-19 including impact of specific bacteria on disease severity, discuss current knowledge on the role of probiotics, prebiotics and dietary approaches including vitamin D in preventing and reducing disease susceptibility and review clinical studies using probiotics to target coronavirus. A literature review on SARS-CoV-2, COVID-19, gut microbiome and immunity was undertaken and relevant literature was summarised and critically examined. KEY FINDINGS AND CONCLUSIONS: Integrity of gut microbiome was perturbed in SARS-CoV-2 infections and associated with disease severity. Poor prognosis in SARS-CoV-2 infection was observed in subjects with underlying co-morbidities who had increased gut permeability and reduced gut microbiome diversity. Dietary microbes, including probiotics or selected prebiotics of Chinese origin, had anti-viral effects against other forms of coronavirus, and could positively impact host immune functions during SARS-CoV-2 infection. Numerous studies are investigating the role of probiotics in preventing and reducing susceptibility to SARS-CoV-2 infection in healthcare workers, household contacts and affected patients. An approach to strengthen intestinal barrier and lower pro-inflammatory states by adopting a more diversified diet during COVID-19 pandemic.SARS-CoV-2 infection is associated with immune dysfunction and gut microbiota alterations. Delineating mechanisms of probiotics, prebiotics and diet with anti-SARS-CoV-2 immunity present opportunities for discovery of microbial therapeutics to prevent and treat COVID-19.

Expression of Small Noncoding RNAs in Urinary Exosomes Classifies Prostate Cancer into Indolent and Aggressive Disease.

PURPOSE: This is the first report of the development and performance of a platform that interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes. The Sentinel™ PCa Test classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel CS Test stratifies patients with prostate cancer between those with low risk prostate cancer (Grade Group 1) from those with intermediate and high risk disease (Grade Group 2-5), and the miR Sentinel HG Test stratifies patients with prostate cancer between those with low and favorable intermediate risk prostate cancer (Grade Group 1 or 2) and those with high risk (Grade Group 3-5) disease. MATERIALS AND METHODS: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.0 microarrays. Using proprietary selection and classification algorithms, informative sncRNAs were selected to customize an interrogation OpenArray™ platform that forms the basis of the tests. The tests were validated using a case-control sample of 1,436 subjects. RESULTS: The performance of the miR Sentinel PCa Test demonstrated a sensitivity of 94% and specificity of 92%. The Sentinel CS Test demonstrated a sensitivity of 93% and specificity of 90% for prediction of the presence of Grade Group 2 or greater cancer, and the Sentinel HG Test demonstrated a sensitivity of 94% and specificity of 96% for the prediction of the presence of Grade Group 3 or greater cancer. CONCLUSIONS: The Sentinel PCa, CS and HG Tests demonstrated high levels of sensitivity and specificity, highlighting the utility of interrogation of urinary exosomal sncRNAs for noninvasively diagnosing and classifying prostate cancer with high precision.

Development and Validation of Surveys to Estimate Food Additive Intake.

(1) Background: The Food Agricultural Organization/World Health Organization (FAO/WHO) International Food Standards Codex Alimentarius CXS 192e International Food Standards (hereafter, CODEX) declares additives non-toxic, but they have been associated with changes to the microbiota changes and thinning of the mucus layer of the gut. Their widespread use has occurred in parallel with increased inflammatory bowel disease (IBD) incidence. This paper reports on the development and validation of surveys to estimate additive intake. (2) Methods: Dietitians created a food-additive database, with a focus on additives that have been associated with IBD. For each additive, information on the CODEX food-category they are permitted in and the associated maximum permissible levels (mg/kg) was recorded. Based on the database, questions to assess early life (part 1) and recent (part 2) additive intake were written. Forward-backward translation from English to Chinese was undertaken. Thirty-one individuals were evaluated to assess understandability. A further fifty-seven individuals completed the tool on two occasions, a fortnight apart; agreement was assessed using Cohen's kappa coefficient or the intra-class correlation coefficient (ICC). (3) Results: The participants reported that it was difficult to remember food intake and estimate portion sizes. The participants also noted confusion around the term 'home-grown'. Instructions and definitions were added; after this, respondents judged the questionnaires as clear. The average kappa coefficient for part 1 and part 2 questions were 0.61 and 0.67, respectively. The average ICC ranged from 0.30 to 0.94; three food lists were removed due to low reliability. (4) Conclusions: Two tools have been created and validated, in two languages, that reliably assess remote and recent food additive intake.

The effectiveness of nurse-led interventions for preventing urinary tract infections in older adults in residential aged care facilities: A systematic review.

AIMS AND OBJECTIVES: To explore the effectiveness of nurse-led interventions to prevent urinary tract infections in older adults living in residential aged care facilities. BACKGROUND: While most empirical studies focus on the treatment of urinary tract infections, few studies have examined the effectiveness of nurse-led interventions in preventing urinary tract infections. DESIGN: Systematic review. METHODS: Eight electronic databases were searched for relevant studies published between 2008-2018. The inclusion criteria were as follows: (a) a focus on older adults, (b) evaluation of nurse-led interventions, focusing on prevention of urinary tract infection, (c) implemented in residential aged care facilities, and (d) outcomes reported as incidence or prevalence of urinary tract infection. The selected papers were critically appraised using the Mixed Methods Appraisal Tool. The data were analysed with narrative synthesis, and findings were reported following the PRISMA guidelines. RESULTS: A review of 1,614 titles and abstracts identified four studies that met the inclusion criteria. Three types of nurse-led interventions were identified: (a) the appointment of advanced practice nurses, (b) those focused on a single specific nursing intervention, and (c) implementation of a multicomponent nursing intervention. All included studies reported at least some positive outcomes. However, the included studies were highly heterogeneous and it was impossible to determine the most effective intervention approach. CONCLUSIONS: Nurses are leaders in health care and are well placed to lead prevention of urinary tract infections in residential aged care; however, evidence of the effectiveness of a nurse-led approach is limited. High-quality randomised controlled trials are warranted to address the knowledge gap and advance practice in this area. RELEVANCE TO CLINICAL PRACTICE: When developing an effective nurse-led intervention programme, the programme should be grounded in nurse-led principles and consider the complex staffing factors to ensure that nurse-led programmes are tailored to an effective level.

Vitamin D and testosterone co-ordinately modulate intracellular zinc levels and energy metabolism in prostate cancer cells.

Vitamin D3 and its receptor are responsible for controlling energy expenditure in adipocytes and have direct roles in the transcriptional regulation of energy metabolic pathways. This phenomenon also has a significant impact on the etiology of prostate cancer (PCa). Using several in vitro models, the roles of vitamin D3 on energy metabolism and its implication in primary, early, and late invasive PCa were investigated. BODIPY staining and qPCR analyses show that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) up-regulates de novo lipogenesis in PCa cells by orchestrating transcriptional regulation that affects cholesterol and lipid metabolic pathways. This lipogenic effect is highly dependent on the interaction of several nuclear receptors and their corresponding ligands, including androgen receptor (AR), vitamin D receptor (VDR), and retinoid X receptor (RXR). In contrast, inhibition of peroxisome proliferator-activated receptor alpha (PPARα) signaling blocks the induction of the lipogenic phenotype induced by these receptors. Furthermore, 1,25(OH)2D3, T, and 9 cis-retinoic acid (9-cis RA) together redirect cytosolic citrate metabolism toward fatty acid synthesis by restoring normal prostatic zinc homeostasis that functions to truncate TCA cycle metabolism. 1,25(OH)2D3, T, and 9-cis RA also exert additional control of TCA cycle metabolism by down-regulating SLC25A19, which limits the availability of the co-factor thiamine pyrophosphate (TPP) that is required for enzymatic catalyzation of citrate oxidation. This extensive metabolic reprogramming mediated by 1,25(OH)2D3, T, and 9-cis RA is preserved in all in vitro cell lines investigated. These data suggest that 1,25(OH)2D3 and T are important regulators of normal prostatic energy metabolism. Based on the close association between energy metabolism and cancer progression, supplementation of vitamin D3 and testosterone can restrict the energy production that is required to drive PCa progression by maintaining proper zinc homeostasis and inhibiting TCA cycle activity in PCa cells.

Quality Improvement Initiative to Improve Abuse Screening Among Infants With Extremity Fractures.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of clinical pathway implementation and quality improvement (QI) interventions to increase the percentage of infants with extremity fractures undergoing evaluation for suspected physical abuse, including skeletal survey (SS), and consultation with social work, and/or Child Protection Team. METHODS: Charts were retrospectively reviewed to establish percentage of infants less than 12 months old with extremity fractures undergoing an SS and consultation during the prepathway (January 1, 2012 to December 31, 2013) and postpathway (January 1, 2014 to June 30, 2015) periods. Using an Ishikawa framework, key process drivers were identified and additional QI interventions (clinical decision support and provider education) were developed and implemented. Impact of QI interventions on study metrics during active QI (July 1, 2015 to June 30, 2016) and post-QI periods (July 1, 2016 to December 31, 2016) was monitored using statistical process control charts. Logistic regression assessed predictors of obtaining an SS, consultation use, and occult fracture detection. RESULTS: Skeletal survey use pre- and postpathway averaged 40%, surpassing 60% on average during active QI and post-QI periods. Consultation performance averaged 46% pre- and postpathway, increasing to nearly 67% during active QI; consultation performance decreased during post-QI to 60%. A lack of trauma history and presence of femur or humerus fracture were associated with increased SS use and consultation (both P < 0.001). Overall 20% of SS revealed occult fractures.

Real-Time Interactive Tree Animation.

We present a novel method for posing and animating botanical tree models interactively in real time. Unlike other state of the art methods which tend to produce trees that are overly flexible, bending and deforming as if they were underwater plants, our approach allows for arbitrarily high stiffness while still maintaining real-time frame rates without spurious artifacts, even on quite large trees with over ten thousand branches. This is accomplished by using an articulated rigid body model with as-stiff-as-desired rotational springs in conjunction with our newly proposed simulation technique, which is motivated both by position based dynamics and the typical algorithms for articulated rigid bodies. The efficiency of our algorithm allows us to pose and animate trees with millions of branches or alternatively simulate a small forest comprised of many highly detailed trees. Even using only a single CPU core, we can simulate ten thousand branches in real time while still maintaining quite crisp user interactivity. This has allowed us to incorporate our framework into a commodity game engine to run interactively even on a low-budget tablet. We show that our method is amenable to the incorporation of a large variety of desirable effects such as wind, leaves, fictitious forces, collisions, fracture, etc.

Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer.

Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in prostate cancer cells and tumors. This isoform is transcribed from an alternative promoter and results in a protein with an amino-terminal extension. Prostate cancer cell lines and prostate tumors express more BTK-C transcript than the malignant NAMALWA B-cell line or human lymphomas. BTK protein expression is also observed in tumor tissue from prostate cancer patients. Down regulation of this protein with RNAi or inhibition with BTK-specific inhibitors, Ibrutinib, AVL-292 or CGI-1746 decrease cell survival and induce apoptosis in prostate cancer cells. Microarray results show that inhibiting BTK under these conditions increases expression of apoptosis related genes, while overexpression of BTK-C is associated with elevated expression of genes with functions related to cell adhesion, cytoskeletal structure and the extracellular matrix. These results are consistent with studies that show that BTK signaling is important for adhesion and migration of B cells and suggest that BTK-C may confer similar properties to prostate cancer cells. Since BTK-C is a survival factor for these cells, it represents both a potential biomarker and novel therapeutic target for prostate cancer.

The role of Hibiscus sabdariffa L. (Roselle) in maintenance of ex vivo murine bone marrow-derived hematopoietic stem cells.

Hematopoietic stem cells- (HSCs-) based therapy requires ex vivo expansion of HSCs prior to therapeutic use. However, ex vivo culture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role of Hibiscus sabdariffa L. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0-1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival (P < 0.05) of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1(+) cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased (P < 0.05) the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.

Histone deacetylase inhibitors modulate miRNA and mRNA expression, block metaphase, and induce apoptosis in inflammatory breast cancer cells.

To develop new therapies for inflammatory breast cancer (IBC) we have compared the effects of two hydroxamic acid-based histone deacetylase (HDAC) inhibitors, CG-1521 and Trichostatin A (TSA) on the biology of two IBC cell lines: SUM149PT and SUM190PT. CG-1521 and TSA induce dose (0-10 µM) and time-dependent (0-96 h) increases in the proportion of cells undergoing cell cycle arrest and apoptosis in the presence or absence of 17ß-estradiol. In SUM 149PT cells, both CG-1521 and TSA increase the levels of acetylated α-tubulin; however the morphological effects are different: CG-1521 blocks mitotic spindle formation and prevents abscission during cytokinesis while TSA results in an increase in cell size. In SUM190PT cells CG-1521 does not cause an increase in acetylated-α-tubulin and even though TSA significantly increases the levels of acetylated tubulin, neither inhibitor alters the morphology of the cells. Microarray analysis demonstrates that CG-1521 modulates the expression of 876 mRNAs and 63 miRNAs in SUM149PT cells, and 1227 mRNAs and 35 miRNAs in SUM190PT cells. Only 9% of the genes are commonly modulated in both cell lines, suggesting that CG-1521 and TSA target different biological processes in the two cell lines most likely though the inhibition of different HDACs in these cell lines. Gene ontology (GO) analysis reveals that CG-1521 affects the expression of mRNAs that encode proteins associated with the spindle assembly checkpoint, chromosome segregation, and microtubule-based processes in both cell lines and has cell-type specific effects on lipid biosynthesis, response to DNA damage, and cell death.

1,25-Dihydroxyvitamin D3 modulates lipid metabolism in prostate cancer cells through miRNA mediated regulation of PPARA.

Previous studies from our laboratory have shown that testosterone (T) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) co-operate to inhibit cell proliferation and induce significant changes in gene expression and differentiation in LNCaP cells. The data presented here demonstrate that the two agents alter fatty acid metabolism, and accumulation of neutral lipid. Concurrent genome wide analysis of mRNA and miRNA in LNCaP cells reveals an extensive transcription regulatory network modulated by T and 1,25(OH)2D3. This involves not only androgen receptor (AR)- and vitamin D receptor (VDR)-mediated transcription, but also transcription factors E2F1- and c-Myc-dependent transcription. Changes in the activities of these transcription factors alter the steady state levels of several miRNAs, including the miR-17/92 cluster. These changes correlate with the up-regulation of the mRNA encoding peroxisome proliferator-activated receptor alpha (PPARA) and its downstream targets, leading to increased lipogenesis. These data suggest that the coordinated effect of T and 1,25(OH)2D3 in prostate cancer cells increases lipogenesis, diverting energy away from Warburg-based tumor energy metabolism, which slows or halts cell growth and tumor progression. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Release of retinal growth hormone in the chick embryo: local regulation?

The neural retina is an extrapituitary site of growth hormone (GH) production and an autocrine or paracrine site of retinal GH action. Retinal GH is released from retinal tissue and may be secreted into the vitreous. Ontogenetic changes in the abundance of retinal GH during embryogenesis indicate that the amount of GH released may be regulated. The presence of pituitary GH secretagogues (GH-releasing hormone, GHRH; thyrotropin-releasing hormone, TRH; and ghrelin) and pituitary GH inhibitors (somatostatin, SRIF and insulin-like growth factor, IGF-1) within the neural retina may indicate the involvement of these factors in retinal GH release. This possibility is supported by the finding that GHRH is colocalized with GH in chick retinal ganglion cells (RGCs) and in immortalized cells (QNRD) derived from quail neuroretinal cells and by the induction of GH mRNA in incubated QNRD cells. In summary, these results provide evidence for the autocrine or paracrine regulation of retinal GH release in the ganglion cells of the embryonic chick retina.