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Journal of the American Medical... Oct 2017Alzheimer disease (AD) is the major cause of dependency and disability in the elderly. Numerous studies have sought to achieve its prevention and/or management examining... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer disease (AD) is the major cause of dependency and disability in the elderly. Numerous studies have sought to achieve its prevention and/or management examining a role for modifiable risk factors, such as nutrition. This work aims to investigate the effects of food and/or nutrients in the management of AD at different stages.
METHODS
Electronic databases were searched for clinical trials examining the effect of nutrient intervention in individuals with AD, compared with placebo, published up to 2014. The outcomes investigated were neuropsychological assessment scales, neuroimaging, and biomarkers. The Cochrane tool was employed to assess risk of bias. Pairwise meta-analyses were performed in a random-effect model by estimating the weighted mean differences with 95% confidence interval (CI) for each outcome measure. The Network meta-analysis was undertaken on cognitive outcome.
RESULTS
Selected studies used antioxidants, B-vitamins, inositol, medium-chain triglyceride, omega-3, polymeric formulas, polypeptide, and vitamin D. AD outcome measurements were mainly restricted to cognitive state and functional abilities. Estimate treatment effects from pairwise meta-analyses showed large but nonsignificant effect in the supplementation with proline-rich polypeptide [weighted mean difference 6.93 (95% CI -3.04, 16.89); P = .17] and B-vitamins [weighted mean difference 0.52 (95% CI -0.05, 1.09); P = .07) on cognitive function measured by the Mini-Mental State Examination. The other nutrients supplementation did not show any significant effect on any outcome measures.
CONCLUSIONS
Isolated nutrient supplementations show no convincing evidence of providing a significant benefit on clinical manifestations or neuropathology of AD. During the initial stages of AD, nutrient supplementation did not show any effect when delivered individually, probably because of their synergistic function on brain, at different domains.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Female; Humans; Male; Middle Aged; Network Meta-Analysis
PubMed: 28807434
DOI: 10.1016/j.jamda.2017.06.015 -
Nutrition & Metabolism 2017Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with... (Review)
Review
BACKGROUND
Tannins are often cited for antinutritional effects, including chelation of non-heme iron. Despite this, studies exploring non-heme iron bioavailability inhibition with long-term consumption have reported mixed results. Salivary proline-rich proteins (PRPs) may mediate tannin-antinutritional effects on non-heme iron bioavailability.
AIM
To review evidence regarding biochemical binding mechanisms and affinity states between PRPs and tannins, as well as effects of PRPs on non-heme iron bioavailability with tannin consumption in vivo.
METHODS
Narrative systematic review and meta-analysis. Common themes in biochemical modeling and affinity studies were collated for summary and synthesis; data were extracted from in vivo experiments for meta-analysis.
RESULTS
Thirty-two studies were included in analysis. Common themes that positively influenced tannin-PRP binding included specificity of tannin-PRP binding, PRP and tannin stereochemistry. Hydrolyzable tannins have different affinities than condensed tannins when binding to PRPs. In vivo, hepatic iron stores and non-heme iron absorption are not significantly affected by tannin consumption ( = -0.64-1.84; -2.7-0.13 respectively), and PRP expression may increase non-heme iron bioavailability with tannin consumption.
CONCLUSIONS
In vitro modeling suggests that tannins favor PRP binding over iron chelation throughout digestion. Hydrolyzable tannins are not representative of tannin impact on non-heme iron bioavailability in food tannins because of their unique structural properties and PRP affinities. With tannin consumption, PRP production is increased, and may be an initial line of defense against tannin-non-heme iron chelation in vivo More research is needed to compare competitive binding of tannin-PRP to tannin-non-heme iron complexes, and elucidate PRPs' role in adaption to non-heme iron bioavailability in vivo.
PubMed: 28769992
DOI: 10.1186/s12986-017-0197-z -
The American Journal of Clinical... Jul 2017Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently... (Meta-Analysis)
Meta-Analysis
Interaction between genes and macronutrient intake on the risk of developing type 2 diabetes: systematic review and findings from European Prospective Investigation into Cancer (EPIC)-InterAct.
Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date. We aimed to identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study. We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study ( = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and -interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution. Thirteen observational studies met the eligibility criteria ( < 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7-like 2 (), gastric inhibitory polypeptide receptor (), caveolin 2 (), and peptidase D () (-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates. Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.
Topics: Case-Control Studies; Caveolin 2; Diabetes Mellitus; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dipeptidases; Energy Intake; Europe; Feeding Behavior; Female; Gene-Environment Interaction; Humans; Male; Middle Aged; Models, Biological; Receptors, Gastrointestinal Hormone; Risk Factors; Transcription Factor 7-Like 2 Protein
PubMed: 28592605
DOI: 10.3945/ajcn.116.150094 -
Brazilian Oral Research Jun 2017Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions... (Review)
Review
Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.
Topics: DMF Index; Dental Caries; Dental Caries Susceptibility; Female; Genetic Association Studies; Genetic Markers; Humans; Male; Polymorphism, Genetic; Risk Factors; Salivary Proteins and Peptides
PubMed: 28591238
DOI: 10.1590/1807-3107BOR-2017.vol31.0041 -
European Journal of Clinical... Aug 2016Triple therapy with Pegylated-Interferon α (PEG-IFNα)/Ribavirin (RBV) and Boceprevir (Boc) or Telaprevir (Tel) significantly improved sustained virological response... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Triple therapy with Pegylated-Interferon α (PEG-IFNα)/Ribavirin (RBV) and Boceprevir (Boc) or Telaprevir (Tel) significantly improved sustained virological response (SVR) rates for patients with genotype 1 HCV infection compared to PEG-IFNα/RBV alone (dual therapy). However, less is known about factors associated with rates of SVR and of adverse events (AEs).
MATERIAL AND METHODS
The aim of this systematic review was to evaluate the evidence regarding the factors affecting response and rate of AEs associated with triple therapy. We performed systematic electronic searches in Medline, Embase, Scopus and Central as well as a list of reference literature. We included randomised controlled trials examining triple therapy compared with dual therapy and reporting data according to patients features and about AEs. Odds ratios (OR) were pooled using either fixed or random effect model, as appropriate.
RESULTS
We included data from 14 studies. Treatment with triple therapy increased SVR rate compared to dual therapy especially in patients previously treated with PEG-IFNα/RBV and with increased pretreatment alanine aminotransferase (ALT) levels. Higher rate of serious AEs and treatment discontinuation due to AEs was also observed particularly in treatment-experienced patients.
CONCLUSIONS
The present study shows how improved results of triple therapy are mainly observed in some patients' subsets and are accompanied by increased risk of AEs compared to dual therapy. These results might be useful for optimising treatment of chronic hepatitis C when IFN-free regimens are unavailable.
Topics: Adult; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Proline; Recombinant Proteins; Ribavirin; Treatment Outcome
PubMed: 27376688
DOI: 10.1111/eci.12656 -
Journal of Clinical Pathology Aug 2016Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.
METHODS
PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I(2) test of heterogeneity for multiple studies.
RESULTS
One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I(2)=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I(2)=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I(2)=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I(2)=0%).
CONCLUSIONS
We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.
Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms
PubMed: 26951082
DOI: 10.1136/jclinpath-2015-203585 -
Acta Pharmaceutica Sinica. B Nov 2015Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for... (Review)
Review
Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.
PubMed: 26713267
DOI: 10.1016/j.apsb.2015.08.001 -
PloS One 2015Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues.
OBJECTIVE
To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues.
METHODS
We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO.
RESULTS
Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I2 = 44%).
CONCLUSION
ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis.
Topics: Angiotensin-Converting Enzyme Inhibitors; Fibrosis; Humans; Myocardium; Oligopeptides; Patient Selection; Pericarditis, Tuberculous; Prospective Studies; Renal Insufficiency
PubMed: 26656271
DOI: 10.1371/journal.pone.0143338 -
PloS One 2015The lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations,... (Meta-Analysis)
Meta-Analysis Review
Influence of the Lactotripeptides Isoleucine-Proline-Proline and Valine-Proline-Proline on Systolic Blood Pressure in Japanese Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
The lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to decrease systolic blood pressure (SBP) in several populations, but the size of the effect varies among studies. We performed a meta-analysis including all published studies to evaluate the SBP-lowering effect of IPP/VPP in Japanese subjects more comprehensively.
METHODS AND FINDINGS
Eligible randomized controlled trials were searched for within four bibliographic databases, including two Japanese ones. Eighteen studies (including a total of 1194 subjects) were included in the meta-analysis. A random effect model using the restricted maximum likelihood (REML) estimator was used for the analysis. The analysis showed that consumption of IPP/VPP induced a significant reduction in SBP as compared with placebo in Japanese subjects, with an estimated effect of -5.63 mm Hg (95% CI, -6.87 to -4.39, P<0.0001) and no evidence of publication bias. A significant heterogeneity between series was evident, which could be explained by a significant influence of the baseline blood pressure status of the subjects, the effect of IPP/VPP on SBP being stronger in hypertensive subjects (-8.35 mm Hg, P<0.0001) than in non-hypertensive subjects (-3.42mm Hg, P<0.0001). Furthermore, the effect of IPP/VPP on SBP remained significant when limiting the analysis to series that tested the usual doses of IPP/VPP consumed daily (below 5 mg/d), with estimated effects of -6.01 mm Hg in the overall population and -3.32 mm Hg in non-hypertensive subjects.
CONCLUSIONS
Results from this meta-analysis show that IPP/VPP lactotripeptides can significantly reduce office SBP in Japanese subjects with or without overt hypertension, and for doses that can potentially be consumed as an everyday supplement. This suggests that these peptides could play a role in controlling blood pressure in Japanese subjects. The systematic review protocol was published on the PROSPERO register (CRD42014014322).
Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Humans; Hypertension; Japan; Middle Aged; Oligopeptides; Randomized Controlled Trials as Topic
PubMed: 26536628
DOI: 10.1371/journal.pone.0142235 -
Reproductive Biomedicine Online Aug 2015The p53 tumour suppressor gene plays an important role in angiogenesis and apoptosis. The association between Arg72Pro polymorphism and recurrent pregnancy loss (RPL)... (Meta-Analysis)
Meta-Analysis Review
The p53 tumour suppressor gene plays an important role in angiogenesis and apoptosis. The association between Arg72Pro polymorphism and recurrent pregnancy loss (RPL) has been studied but with inconsistent results. A meta-analysis was conducted to examine whether p53 Arg72Pro polymorphism is a risk factor for RPL. Electronic searches of PubMed, Embase and Web of Knowledge were conducted to identify relevant studies. The final meta-analysis included six published articles with 730 RPL cases and 613 controls. The pooled results suggested that the variant genotype was associated with the RPL risk in additive model (Pro versus Arg; odds ratio [OR] = 1.28; 95% confidence interval [CI]: 1.06 to 1.54) and recessive model (Pro/Pro versus Arg/Pro + Arg/Arg; OR = 1.82; 95% CI: 1.21 to 2.73). In the stratified analysis by ethnicity, for white people the results were consistent. The Egger's regression asymmetry test suggested a lack of publication bias. Results of this meta-analysis suggest that p53 codon 72 polymorphism is associated with RPL, especially in white people. Identification of p53 codon 72 mutation would have some implication for primary prevention of RPL and screening of high-risk individuals. Large well-designed studies are needed to fully describe the association between this polymorphism and RPL.
Topics: Abortion, Habitual; Arginine; Codon; Female; Humans; Polymorphism, Single Nucleotide; Proline; Tumor Suppressor Protein p53
PubMed: 26099444
DOI: 10.1016/j.rbmo.2015.05.003