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BMC Endocrine Disorders Nov 2020We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis.
METHODS
Four databases, the Cochrane Library, EMBASE, PubMed and Scopus were selected. A random effect model and a fixed effect model were applied to the results of forest plot analyses to determine the standardized mean difference (SMD) and 95% confidence interval (95% CI) for each metabolite. The SMD for every metabolite was then converted into an odds ratio to create an metabolite biomarker profile.
RESULTS
Twenty-four independent studies reported data from 14,131 healthy individuals and 3499 patients with T2DM, and 14 included studies reported 4844 healthy controls and a total of 2139 pre-diabetes patients. In the serum and plasma of patients with T2DM, compared with the healthy participants, the concentrations of valine, leucine, isoleucine, proline, tyrosine, lysine and glutamate were higher and that of glycine was lower. The concentrations of isoleucine, alanine, proline, glutamate, palmitic acid, 2-aminoadipic acid and lysine were higher and those of glycine, serine, and citrulline were lower in prediabetic patients. Metabolite biomarkers of T2DM and pre-diabetes revealed that the levels of alanine, glutamate and palmitic acid (C16:0) were significantly different in T2DM and pre-diabetes.
CONCLUSIONS
Quantified multiple metabolite biomarkers may reflect the different status of pre-diabetes and T2DM, and could provide an important reference for clinical diagnosis and treatment of pre-diabetes and T2DM.
Topics: Biomarkers; Diabetes Mellitus, Type 2; Humans; Metabolome; Prediabetic State; Prognosis
PubMed: 33228610
DOI: 10.1186/s12902-020-00653-x -
Journal of Thermal Biology Apr 2021This study was conducted in order to investigate the effects of heat stress exposure on the concentrations of amino acids within the plasma and the brain of chicks.... (Meta-Analysis)
Meta-Analysis
This study was conducted in order to investigate the effects of heat stress exposure on the concentrations of amino acids within the plasma and the brain of chicks. Methodology: Five electronic databases including; PubMed, Scopus, Web of Science, Embase and ProQuest were reviewed to find relative literature published until the March 8, 2019. A total of eight relative studies and 194 chicks were analyzed. The Random Effects model and the Fixed Effects model were performed. Using the Random Effects model for amino acids, a Standardized mean difference (SMD) of 2.05 and 1.46 was obtained for alanine and threonine concentrations respectively. This indicates a significant increase in the concentration of these amino acids within the plasma. An SMD of -2.68 and -2.46 was obtained for cysteine and proline concentrations respectively, this indicates a significant decrease in the concentration of these amino acids within the plasma. The pooled estimates regarding the effect of heat stress exposure on plasma amino acid concentrations for proline were -0.013. The SMDs obtained for amino acid concentrations within the brain (diencephalon) including leucine, methionine, valine and isoleucine were 1.799, 0.88, 2.11, 1.85, respectively, This indicates a significant increase in the concentration of these amino acids within the brain (P < 0.05). Comparing the SMD obtained for long-term heat exposure (two weeks) with the SMD obtained for short-term heat exposure shows that plasma amino acid concentrations including aspartic acid, glutamic acid, leucine, lysine, methionine, valine, isoleucine, tyrosine, glycine, proline, phenylalanine and threonine had all decreased. The relationship between heat exposure and changes in the concentration of some amino acids in the plasma is an important scientific finding.
Topics: Amino Acids; Animals; Brain; Chickens; Heat-Shock Response; Hot Temperature
PubMed: 33863436
DOI: 10.1016/j.jtherbio.2021.102872 -
Frontiers in Molecular Biosciences 2023Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
PubMed: 37614441
DOI: 10.3389/fmolb.2023.1215039 -
Clinical Drug Investigation Nov 2017Interferon-free regimens are rapidly evolving for patients with chronic hepatitis C virus (HCV) infection. We performed this meta-analysis to investigate the safety and... (Meta-Analysis)
Meta-Analysis Review
Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with or without Ribavirin for Treatment of Hepatitis C Virus Genotype 1: A Systematic Review and Meta-analysis.
BACKGROUND AND OBJECTIVE
Interferon-free regimens are rapidly evolving for patients with chronic hepatitis C virus (HCV) infection. We performed this meta-analysis to investigate the safety and efficacy of a combination regimen (ombitasvir [OBV]/paritaprevir [PTV]/ritonavir [r] ± dasabuvir [DSV]) for the treatment of patients with HCV genotype 1 infection.
METHODS
A computerized literature search for relevant clinical trials was conducted during May 2017. Data on sustained virological response (SVR), virological relapse, and safety outcomes were extracted and calculated as pooled proportion (PP) or risk ratio (RR) with their 95% confidence interval (CI), using StatsDirect and RevMan software.
RESULTS
The final analysis included 13 studies for HCV genotype 1 (3115 patients). The pooled effect estimate showed that 12-week treatment of genotype 1 patients with the OBV/PTV/r regimen achieved a high SVR rate (PP = 94%, 95% CI 92-96) that increased to (PP = 97%, 95% CI 96-98) upon the addition of DSV. These results were consistent when independent subgroup analyses were conducted based on viral subgenotypes, the presence of cirrhosis, or former treatment failure. Adding ribavirin (RBV) to this regimen was not associated with increased SVR rates (risk ratio = 1, 95% CI 0.98-1.02), while it increased the risk of serious adverse events (p = 0.02), insomnia (p = 0.001), and pruritus (p < 0.001).
CONCLUSION
The current meta-analysis showed a high efficacy for the OBV/PTV/r regimen in the treatment of HCV genotype 1 (with DSV) infection, regardless of the presence of cirrhosis or former treatment failure. Adding RBV to this regimen slightly decreased the relapse rate. Future studies with larger sample sizes are required to investigate the efficacy of this regimen in other HCV genotypes and to establish the evidence about the effect of adding RBV to OBV/PTV/r + DSV.
Topics: 2-Naphthylamine; Anilides; Antiviral Agents; Carbamates; Cyclopropanes; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Liver Cirrhosis; Macrocyclic Compounds; Proline; Ribavirin; Ritonavir; Sulfonamides; Sustained Virologic Response; Uracil; Valine
PubMed: 28871475
DOI: 10.1007/s40261-017-0565-5 -
Metabolites Sep 2023Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the... (Review)
Review
Response to radiotherapy (RT) includes tissue toxicity, which may involve inflammatory reactions. We aimed to compare changes in metabolic patterns induced at the systemic level by radiation and inflammation itself. Patients treated with RT due to head and neck cancer and patients with inflammation-related diseases located in the corresponding anatomical regions were selected. PubMed and Web of Science databases were searched from 1 January 2000 to 10 August 2023. Twenty-five relevant studies where serum/plasma metabolic profiles were analyzed using different metabolomics approaches were identified. The studies showed different metabolic patterns of acute and chronic inflammatory diseases, yet changes in metabolites linked to the urea cycle and metabolism of arginine and proline were common features of both conditions. Although the reviewed reports showed only a few specific metabolites common for early RT response and inflammatory diseases, partly due to differences in metabolomics approaches, several common metabolic pathways linked to metabolites affected by radiation and inflammation were revealed. They included pathways involved in energy metabolism (e.g., metabolism of ketone bodies, mitochondrial electron transport chain, Warburg effect, citric acid cycle, urea cycle) and metabolism of certain amino acids (Arg, Pro, Gly, Ser, Met, Ala, Glu) and lipids (glycerolipids, branched-chain fatty acids). However, metabolites common for RT and inflammation-related diseases could show opposite patterns of changes. This could be exemplified by the lysophosphatidylcholine to phosphatidylcholine ratio (LPC/PC) that increased during chronic inflammation and decreased during the early phase of response to RT. One should be aware of dynamic metabolic changes during different phases of response to radiation, which involve increased levels of LPC in later phases. Hence, metabolomics studies that would address molecular features of both types of biological responses using comparable analytical and clinical approaches are needed to unravel the complexities of these phenomena, ultimately contributing to a deeper understanding of their impact on biological systems.
PubMed: 37755280
DOI: 10.3390/metabo13091000 -
Pharmacological Reports : PR Apr 2019Oxaceprol, a derivative of l-proline, is an established drug for managing osteoarthritis (OA) with better safety profile than non-steroidal anti-inflammatory drugs... (Comparative Study)
Comparative Study Meta-Analysis
Oxaceprol, a derivative of l-proline, is an established drug for managing osteoarthritis (OA) with better safety profile than non-steroidal anti-inflammatory drugs (NSAIDs). This systematic review and meta-analysis, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, evaluated the efficacy, safety and tolerability of oxaceprol in OA. Electronic databases for published and grey (unpublished) literature were searched to identify parallel-group randomized controlled trials (RCTs) evaluating the impact of oxaceprol in patients with OA. Risk of bias was assessed using the Cochrane collaboration's tool. A total of seven parallel-group RCTs involving 1087 participants were included in the systematic review. Meta-analysis, in Review Manager, demonstrated numerically greater/significant improvements compared to active control [diclofenac/ibuprofen]/placebo in pain and function of joint; similar improvement vs. active control in global treatment efficacy; no difference/significant difference vs. active control/placebo in NSAIDs as rescue medication. Treatment with oxaceprol showed numerically less adverse events (AEs) than active control (diclofenac: risk ratio [RR], 0.71; 95% confidence interval [CI], 0.45 to 1.11; p=0.14: ibuprofen: RR, 0.73; 95% CI, 0.30 to 1.78; p=0.49) and significantly fewer AEs compared to placebo (RR, 0.76; 95% CI, 0.63 to 0.92; p=0.004). Given the nature of small-to-moderate sample size and short duration of eligible studies, the available clinical evidence of oxaceprol in the management of OA is modest - though looks promising. New and better RCTs with larger sample size and longer follow-up are warranted to strengthen the use of oxaceprol in clinical setting for managing OA.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Diclofenac; Humans; Hydroxyproline; Ibuprofen; Osteoarthritis; Randomized Controlled Trials as Topic; Sample Size
PubMed: 30851540
DOI: 10.1016/j.pharep.2018.12.010 -
Heliyon Jan 2024Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. : This systematic review...
Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. : This systematic review summarizes the insights gleaned from metabolomic analyses of individuals afflicted with this cancer variant. The overarching goal was to delineate the molecular alterations associated with triple-negative breast cancer, pinpointing potential therapeutic targets and novel biomarkers. We systematically searched for evidence using the PubMed database and followed the PRISMA and STARLITE guidelines. The search parameters were delimited to articles published within the last 13 years. From an initial pool of 148 scrutinized articles, 17 studies involving 1686 participants were deemed eligible for inclusion. The current body of research shows a paucity of studies, and the available evidence presents conflicting outcomes. Notwithstanding, Pathway Enrichment Analysis identified the urea and glucose-alanine cycles as the most affected metabolic pathways, followed by arginine, proline, and aspartate metabolism. Future investigations need to focus on elucidating which of those metabolites and/or pathways might be reliable candidates for novel therapeutic interventions or reliable biomarkers for diagnosis and prognosis of this subtype of breast cancer.
PubMed: 38187259
DOI: 10.1016/j.heliyon.2023.e23628 -
Annals of Hepatology 2015Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability.
AIM
Assess benefits and harms of boceprevir (BOC) and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit.
MATERIAL AND METHODS
Search from 2009-2013 in PubMed, EMBASE, and "gray literature" of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed.
RESULTS
33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis, statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels. In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Oligopeptides; Polyethylene Glycols; Proline; RNA, Viral; Recombinant Proteins; Ribavirin; Treatment Outcome; Viral Load
PubMed: 25536641
DOI: No ID Found -
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 -
Shoulder & Elbow Apr 2021The EVOLVE implant (Wright Medical Technology, Arlington, TN, USA) is a modular loose-fitting radial head prosthesis. The primary objective was to synthesize all... (Review)
Review
INTRODUCTION
The EVOLVE implant (Wright Medical Technology, Arlington, TN, USA) is a modular loose-fitting radial head prosthesis. The primary objective was to synthesize all available literature investigating the midterm clinical outcomes of the EVOLVE implant.
MATERIALS AND METHODS
An electronic literature search in Pubmed/Medline, Scopus, EMBASE, and Cochrane library was performed querying for studies published in 2000-2017. Articles describing clinical and radiographical outcomes as well as reoperation were included. Outcomes of interest included range of motion, Mayo Elbow Performance Score, Disabilities of the Arm Shoulder and Hand, radiographic outcome, and reason for reoperation.
RESULTS
A total of five articles consisting of 146 patients with EVOLVE implants were included. Mean patient age was 57.4 years (range 22-84), and 43.8% were males (n = 64). Mean follow-up was 4.8 years (range 1-14). Mean Mayo Elbow Performance Score and Disabilities of the Arm Shoulder and Hand score were 87.6 (range 30-100) and 18.9 (range 0-82), respectively. Midterm clinical results were good or excellent (Mayo Elbow Performance Score > 74) in 94 patients. Reoperation was observed in 12 patients, with implant revision required in 2 patients. The primary reason for reoperation was persistent stiffness (n = 9).
CONCLUSION
Midterm outcomes of EVOLVE radial head prosthesis are satisfactory, and associated complication rates are low. Loose-fit implant method appears to be a reliable approach to avoid failure of radial head prosthesis by painful loosening.
PubMed: 33897852
DOI: 10.1177/1758573219850111