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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 -
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 -
International Journal of Clinical... Jun 2020Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic...
Novel adjunctive screening aids are needed to reduce the morbidity and mortality related to cancer, and every effort should be made for early diagnosis. This systematic review aimed to evaluate salivary metabolites and their diagnostic value in patients with cancer.The systematic review was performed in two phases and included studies that focused on the diagnostic value of salivary metabolites in humans with solid malignant neoplasms. Five electronic databases were searched, and the risk of bias in individual studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies criteria (QUADAS-2). All procedures were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Of the 1151 studies retrieved, 25 were included; 13 studies used targeted and 12 untargeted metabolomics approaches. Most studies included patients with breast and oral cancer. Except for one, all studies had case-control designs, and none fulfilled all quality assessments. Overall, 140 salivary metabolites were described. The most frequently reported metabolites were alanine, valine, and leucine. Among the 11 studies that reported diagnostic test accuracy (DTA) values, proline, threonine, and histidine in combination and monoacylglycerol alone demonstrated the highest DTA for breast cancer. Combined choline, betaine, pipecolinic acid, and L-carnitine showed better discriminatory performance for early oral cancer.This systematic review highlights the current evidence on salivary metabolites that may be used as a future strategy to diagnose cancer. Further studies including larger sample sizes with confirmation of the results by untargeted analysis are warranted.
Topics: Biomarkers, Tumor; Databases, Factual; Humans; Metabolomics; Neoplasms; Saliva
PubMed: 32221803
DOI: 10.1007/s10147-020-01660-7 -
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 -
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 -
American Journal of Medical Genetics.... Feb 2022Variants in the pleckstrin homology domain-interacting protein (PHIP) gene are implicated in the clinical phenotype of Chung-Jansen syndrome, which includes dysmorphic...
Variants in the pleckstrin homology domain-interacting protein (PHIP) gene are implicated in the clinical phenotype of Chung-Jansen syndrome, which includes dysmorphic features, cognitive dysfunction, aberrant behavior, and childhood onset obesity. Following a systematic literature review, 35 patients are reported to have unique PHIP variants impacting the encoded protein product. We summarize the status and frequency of these variants and relationship to clinical presentation. We also describe an additional patient with a rare, pathogenic variant due to a five base pair deletion leading to an altered codon at I307 but with a stop codon at 22 codons downstream; notably, a variant was identified at the same location as seen previously at protein position I307 in one other subject and a frameshift change at that protein position. We compare the clinical characteristics between the two patients and analyze whether certain types of gene defects impact clinical presentation in previously reported individuals. In addition, we predict structural protein models, which yielded unique differences between the wild-type and I307P-related mutant truncated proteins. Protein-protein interactions indicate involvement of POMC and related proteins with potential contribution to obesity, congenital, neuromuscular, and lipid disorders with heart, gastrointestinal, and rheumatoid diseases. With its surrounding proline-rich region, the I307P point mutation increases susceptibility to conformational rigidity and thermodynamic stability, ultimately impacting function as well as a stop codon downstream. Furthermore, the frameshift mutation seen in our patient may result in a truncated protein with a short abnormal region prior to the stop codon due to a five base pair deletion at I307 or target the protein for nonsense-mediated mRNA decay.
Topics: Child; Frameshift Mutation; Humans; Nonsense Mediated mRNA Decay; Phenotype
PubMed: 34773373
DOI: 10.1002/ajmg.a.62557 -
Frontiers in Genetics 2021Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of...
Schizophrenia is a disorder that is characterized by delusions, hallucinations, disorganized speech or behavior, and socio-occupational impairment. The duration of observation and variability in symptoms can make the accurate diagnosis difficult. Identification of biomarkers for schizophrenia (SCZ) can help in early diagnosis, ascertaining the diagnosis, and development of effective treatment strategies. Here we review peripheral blood-based gene expression studies for identification of gene expression biomarkers for SCZ. A literature search was carried out in PubMed and Web of Science databases for blood-based gene expression studies in SCZ. A list of differentially expressed genes (DEGs) was compiled and analyzed for overlap with genetic markers, differences based on drug status of the participants, functional enrichment, and for effect of antipsychotics. This literature survey identified 61 gene expression studies. Seventeen out of these studies were based on expression microarrays. A comparative analysis of the DEGs ( = 227) from microarray studies revealed differences between drug-naive and drug-treated SCZ participants. We found that of the 227 DEGs, 11 genes () also showed genetic and epigenetic changes associated with SCZ. Functional enrichment analysis of the DEGs revealed dysregulation of proline and 4-hydroxyproline metabolism. Also, arginine and proline metabolism was the most functionally enriched pathway for SCZ in our analysis. Follow-up studies identified effect of antipsychotic treatment on peripheral blood gene expression. Of the 27 genes compiled from the follow-up studies , and had no effect on their expression status as a result of antipsychotic treatment. Despite the differences in the nature of the study, ethnicity of the population, and the gene expression analysis method used, we identified several coherent observations. An overlap, though limited, of genetic, epigenetic and gene expression changes supports interplay of genetic and environmental factors in SCZ. The studies validate the use of blood as a surrogate tissue for biomarker analysis. We conclude that well-designed cohort studies across diverse populations, use of high-throughput sequencing technology, and use of artificial intelligence (AI) based computational analysis will significantly improve our understanding and diagnostic capabilities for this complex disorder.
PubMed: 34721526
DOI: 10.3389/fgene.2021.736483 -
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 -
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