181 research outputs found

    CRX controls retinal expression of the X-linked juvenile retinoschisis (RS1) gene

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    X-linked juvenile retinoschisis is a heritable condition of the retina in males caused by mutations in the RS1 gene. Still, the cellular function and retina-specific expression of RS1 are poorly understood. To address the latter issue, we characterized the minimal promoter driving expression of RS1 in the retina. Binding site prediction, site-directed mutagenesis, and reporter assays suggest an essential role of two nearby cone-rod homeobox (CRX)-responsive elements (CRE) in the proximal −177/+32 RS1 promoter. Chromatin immunoprecipitation associates the RS1 promoter in vivo with CRX, the coactivators CBP, P300, GCN5 and acetylated histone H3. Transgenic Xenopus laevis expressing a green fluorescent protein (GFP) reporter under the control of RS1 promoter sequences show that the −177/+32 fragment drives GFP expression in photoreceptors and bipolar cells. Mutating either of the two conserved CRX binding sites results in strongly decreased RS1 expression. Despite the presence of sequence motifs in the promoter, NRL and NR2E3 appear not to be essential for RS1 expression. Together, our in vitro and in vivo results indicate that two CRE sites in the minimal RS1 promoter region control retinal RS1 expression and establish CRX as a key factor driving this expression

    Moxibustion for ulcerative colitis: a systematic review and meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Complementary and alternative medicine (CAM) is increasingly used for treatment of inflammatory bowel disease (IBD). Acupuncture-type treatments are among the most popular options. Several studies have reported that moxibustion is effective in ulcerative colitis (UC). The objective of this review was to assess the clinical evidence for or against moxibustion as a treatment for UC.</p> <p>Methods</p> <p>We searched the literature using 18 databases from their inception to February 10, 2010, without language restrictions. We included randomized clinical trials (RCTs), in which human patients with UC were treated with moxibustion. Studies were included if they were placebo-controlled or controlled against a drug therapy or no treatment group. The methodological quality of all RCTs was assessed using the Cochrane risk of bias.</p> <p>Results</p> <p>In total, five RCTs were included. All were of low methodological quality. They compared the effects of moxibustion with conventional drug therapy. Three tested moxibustion against sulfasalazine and two against sulfasalazine plus other drugs. A meta-analysis of five RCTs showed favorable effects of moxibustion on the response rate compared to conventional drug therapy (n = 407; risk ratio = 1.24, 95% CI = 1.11 to 1.38; P < 0.0001; heterogeneity: I<sup>2 </sup>= 16%).</p> <p>Conclusions</p> <p>Current evidence is insufficient to show that moxibustion is an effective treatment of UC. Most of included trials had high risk of bias. More rigorous studies seem warranted.</p

    Evidence-based hydro- and balneotherapy in Hungary-a systematic review and meta-analysis

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    Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis. © 2013 The Author(s)

    Effect of garlic on blood pressure: A systematic review and meta-analysis

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    The electronic version of this article is the complete one and can be found online at the publisher's website.Background: Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure. Methods: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment. Results: Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 ± 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 ± 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02). Conclusion: Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.Karin Ried, Oliver R. Frank, Nigel P. Stocks, Peter Fakler and Thomas Sulliva

    Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial

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    <p>Abstract</p> <p>Background</p> <p>Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing <it>Glycine max </it>leaves extract (EGML) or <it>Garcinia cambogia </it>extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles.</p> <p>Methods</p> <p>Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants.</p> <p>Results</p> <p>EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group.</p> <p>Conclusions</p> <p>Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.</p

    Naturopathic Care for Anxiety: A Randomized Controlled Trial ISRCTN78958974

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    BACKGROUND: Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life. Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity. This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a randomized trial. METHODS: Employees with moderate to severe anxiety of longer than 6 weeks duration were randomized based on age and gender to receive naturopathic care (NC) (n = 41) or standardized psychotherapy intervention (PT) (n = 40) over a period of 12 weeks. Blinding of investigators and participants during randomization and allocation was maintained. Participants in the NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% with anolides, prepared from root). The PT intervention received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Participants were blinded to the placebo-controlled intervention. RESULTS: Seventy-five participants (93%) were followed for 8 or more weeks on the trial. Final BAI scores decreased by 56.5% (p<0.0001) in the NC group and 30.5% (p<0.0001) in the PT group. BAI group scores were significantly decreased in the NC group compared to PT group (p = 0.003). Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the NC group exhibiting greater clinical benefit. No serious adverse reactions were observed in either group. RELEVANCE: Many patients seek alternatives and/or complementary care to conventional anxiety treatments. To date, no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety. Knowledge of the efficacy, safety or risk of natural health products, and naturopathic treatments is important for physicians and the public in order to make informed decisions. INTERPRETATION: Both NC and PT led to significant improvements in patients' anxiety. Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group. Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT. The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN78958974

    Transcriptional Regulation of Rod Photoreceptor Homeostasis Revealed by In Vivo NRL Targetome Analysis

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    A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–Seq) data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP–Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP–Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s) for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis

    An update on the strategies in multicomponent activity monitoring within the phytopharmaceutical field

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    <p>Abstract</p> <p>Background</p> <p>To-date modern drug research has focused on the discovery and synthesis of single active substances. However, multicomponent preparations are gaining increasing importance in the phytopharmaceutical field by demonstrating beneficial properties with respect to efficacy and toxicity.</p> <p>Discussion</p> <p>In contrast to single drug combinations, a botanical multicomponent therapeutic possesses a complex repertoire of chemicals that belong to a variety of substance classes. This may explain the frequently observed pleiotropic bioactivity spectra of these compounds, which may also suggest that they possess novel therapeutic opportunities. Interestingly, considerable bioactivity properties are exhibited not only by remedies that contain high doses of phytochemicals with prominent pharmaceutical efficacy, but also preparations that lack a sole active principle component. Despite that each individual substance within these multicomponents has a low molar fraction, the therapeutic activity of these substances is established via a potentialization of their effects through combined and simultaneous attacks on multiple molecular targets. Although beneficial properties may emerge from such a broad range of perturbations on cellular machinery, validation and/or prediction of their activity profiles is accompanied with a variety of difficulties in generic risk-benefit assessments. Thus, it is recommended that a comprehensive strategy is implemented to cover the entirety of multicomponent-multitarget effects, so as to address the limitations of conventional approaches.</p> <p>Summary</p> <p>An integration of standard toxicological methods with selected pathway-focused bioassays and unbiased data acquisition strategies (such as gene expression analysis) would be advantageous in building an interaction network model to consider all of the effects, whether they were intended or adverse reactions.</p

    Moxibustion for cancer care: a systematic review and meta-analysis

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    <p>Abstract</p> <p>Background</p> <p>Moxibustion is a traditional Chinese method that uses the heat generated by burning herbal preparations containing <it>Artemisia vulgaris </it>to stimulate acupuncture points. Considering moxibustion is closely related to acupuncture, it seems pertinent to evaluate the effectiveness of moxibustion as a treatment of symptoms of cancer. The objective of this review was to systematically assess the effectiveness of moxibustion for supportive cancer care.</p> <p>Methods</p> <p>We searched the literature using 11 databases from their inceptions to February 2010, without language restrictions. We included randomised clinical trials (RCTs) in which moxibustion was employed as an adjuvant treatment for conventional medicine in patients with any type of cancer. The selection of studies, data extraction, and validations were performed independently by two reviewers.</p> <p>Results</p> <p>Five RCTs compared the effects of moxibustion with conventional therapy. Four RCTs failed to show favourable effects of moxibustion for response rate compared with chemotherapy (n = 229, RR, 1.04, 95% CI 0.94 to 1.15, P = 0.43). Two RCTs assessed the occurrence of side effects of chemotherapy and showed favourable effects of moxibustion. A meta-analysis showed significant less frequency of nausea and vomiting from chemotherapy for moxibustion group (n = 80, RR, 0.38, 95% CIs 0.22 to 0.65, P = 0.0005, heterogeneity: χ<sup>2 </sup>= 0.18, P = 0.67, I<sup>2 </sup>= 0%).</p> <p>Conclusion</p> <p>The evidence is limited to suggest moxibustion is an effective supportive cancer care in nausea and vomiting. However, all studies have a high risk of bias so effectively there is not enough evidence to draw any conclusion. Further research is required to investigate whether there are specific benefits of moxibustion for supportive cancer care.</p
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