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Metabolites Sep 2020Globally, lung cancer is the most prevalent cancer type. However, screening and early detection is challenging. Previous studies have identified metabolites as promising... (Review)
Review
Globally, lung cancer is the most prevalent cancer type. However, screening and early detection is challenging. Previous studies have identified metabolites as promising lung cancer biomarkers. This systematic literature review and meta-analysis aimed to identify metabolites associated with lung cancer risk in observational studies. The literature search was performed in PubMed and EMBASE databases, up to 31 December 2019, for observational studies on the association between metabolites and lung cancer risk. Heterogeneity was assessed using the I statistic and Cochran's Q test. Meta-analyses were performed using either a fixed-effects or random-effects model, depending on study heterogeneity. Fifty-three studies with 297 metabolites were included. Most identified metabolites (252 metabolites) were reported in individual studies. Meta-analyses were conducted on 45 metabolites. Five metabolites (cotinine, creatinine riboside, N-acetylneuraminic acid, proline and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene) and five metabolite groups (total 3-hydroxycotinine, total cotinine, total nicotine, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (sum of concentrations of the metabolite and its glucuronides), and total nicotine equivalent (sum of total 3-hydroxycotinine, total cotinine and total nicotine)) were associated with higher lung cancer risk, while three others (folate, methionine and tryptophan) were associated with lower lung cancer risk. Significant heterogeneity was detected across most studies. These significant metabolites should be further evaluated as potential biomarkers for lung cancer.
PubMed: 32899527
DOI: 10.3390/metabo10090362 -
Renal Failure Nov 2020Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are orally active first-in-class new generation drugs for renal anemia. This extensive meta-analysis of... (Meta-Analysis)
Meta-Analysis
Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are orally active first-in-class new generation drugs for renal anemia. This extensive meta-analysis of randomized controlled trials (RCTs) was designed to provide clear information on the efficacy and safety of HIF-PHIs on anemia in chronic kidney disease (CKD) patients. Searches included PubMed, Web of Science, Ovid MEDLINE, and Cochrane Library database up to October 2019. RCTs of patients with CKD comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in the treatment of anemia. The primary outcome was hemoglobin change from baseline (Hb CFB); the secondary outcomes included iron-related parameters and the occurrence of each adverse event. 26 trials in 17 articles were included, with a total of 2804 dialysis or patients with CKD. HIF-PHIs treatment produced a significant beneficial effect on Hb CFB compared with the placebo group (MD, 0.69; 95% CI, 0.36 to 1.02). However, this favored effect of HIF-PHIs treatment was not observed in subgroup analysis among trials compared with ESAs (MD, 0.06; 95% CI, -0.20 to 0.31). The significant reduction in hepcidin by HIF-PHIs was observed in all subgroups when compared with the placebo group, whereas this effect was observed only in NDD-CKD patients when compared with ESAs. HIF-PHIs increased the risk of nausea (RR, 2.20; 95% CI, 1.06 to 4.53) and diarrhea (RR, 1.75; 95% CI, 1.06 to 2.92). We conclude that orally given HIF-PHIs are at least as efficacious as ESAs treatment to correct anemia short term in patients with CKD. In addition, HIF-PHIs improved iron metabolism and utilization in patients with CKD.
Topics: Anemia; Erythropoietin; Hematinics; Hepcidins; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Prolyl-Hydroxylase Inhibitors; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 32869703
DOI: 10.1080/0886022X.2020.1811121 -
European Journal of Neurology Nov 2020The present systematic review and meta-analysis aims to establish the possible value of cerebrospinal fluid (CSF) and serum/plasma levels of amino acids as markers of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The present systematic review and meta-analysis aims to establish the possible value of cerebrospinal fluid (CSF) and serum/plasma levels of amino acids as markers of Parkinson's disease (PD).
METHODS
This is a review of four databases (PubMed, Embase, MEDLINE and Web of Science - Core Collection) from 1966 to 14 March 2020, with identification of references of interest for the topic. The meta-analysis of eligible studies was done using R software package meta, following the PRISMA and MOOSE guidelines.
RESULTS
Compared with age- and sex-matched controls, PD patients showed decreased CSF levels of glutamate and taurine and increased CSF levels of tyrosine; decreased serum/plasma levels of aspartate, serine, tryptophan and lysine, and increased serum/plasma proline and homocysteine levels.
CONCLUSION
Despite the limitations of this study due to the important variability of results between different series, our findings suggest the value of CSF or serum/plasma levels of several amino acids in the discrimination of PD patients from healthy subjects, related to the levels of some amino acids.
Topics: Amino Acids; Biomarkers; Humans; Parkinson Disease
PubMed: 32777152
DOI: 10.1111/ene.14470 -
Joint Bone Spine Oct 2020A systematic review and analysis of data from several rheumatoid arthritis metabolomics studies attempts to determine which metabolites can be used as potential...
OBJECTIVE
A systematic review and analysis of data from several rheumatoid arthritis metabolomics studies attempts to determine which metabolites can be used as potential biomarkers for the diagnosis of rheumatoid arthritis and to explore the pathogenesis of rheumatoid arthritis.
METHODS
We searched all the subject-related documents published by EMBASE, PubMed, Web of Science, and Cochrane Library from the database to the September 2019 publication. Two researchers independently screened the literature and extracted the data. QUADOMICS tool was used to assess the quality of studies included in this systematic review.
RESULTS
A total of 10 studies met the inclusion criteria of systematic review, including 502 patients with rheumatoid arthritis and 373 healthy people. Among them, the biological samples utilised for metabolomic analysis include: serum (n=8), urine (n=1) and synovial fluid (n=1). Some metabolites play an important role in rheumatoid arthritis: glucose, lactic acid, citric acid, leucine, methionine, isoleucine, valine, phenylalanine, threonine, serine, proline, glutamate, histidine, alanine, cholesterol, glycerol, and ribose.
CONCLUSIONS
Metabolomics provides important new opportunities for further research in rheumatoid arthritis and is expected to elucidate the pathogenesis of rheumatoid arthritis that has not been fully understood before.
Topics: Arthritis, Rheumatoid; Biomarkers; Humans; Metabolomics; Synovial Fluid
PubMed: 32473419
DOI: 10.1016/j.jbspin.2020.05.005 -
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 -
Pharmacological Research May 2020Stachydrine is extracted from the leaves of Leonurus japonicus Houtt (or Motherwort, "Yi Mu Cao" in Traditional Chinese Medicine) and is the major bioactive ingredient....
Stachydrine is extracted from the leaves of Leonurus japonicus Houtt (or Motherwort, "Yi Mu Cao" in Traditional Chinese Medicine) and is the major bioactive ingredient. So far, stachydrine has demonstrated various bioactivities for the treatment of fibrosis, cardiovascular diseases, cancers, uterine diseases, brain injuries, and inflammation. The pharmacological and pharmacokinetic properties of stachydrine up to 2019 have been comprehensively searched and summarized. This review provides an updated summary of recent studies on the pharmacological activities of stachydrine. Many studies have demonstrated that stachydrine has strong anti-fibrotic properties (on various types of fibrosis) by inhibiting ECM deposition and decreasing inflammatory and oxidative stress through multiple molecular mechanisms (including TGF-β, ERS-mediated apoptosis, MMPs/TIMPs, NF-κB, and JAK/STAT). The cardioprotective and vasoprotective activities of stachydrine are related to its inhibition of β-MHC, excessive autophagy, SIRT1, eNOS uncoupling and TF, promotion of SERCA, and angiogenesis. In addition to its anticancer action, regulation of the uterus, neuroprotective effects, etc. the pharmacokinetic properties of stachydrine are also discussed.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Cardiotonic Agents; Female; Fibrosis; Humans; Neuroprotective Agents; Proline; Uterus
PubMed: 32173585
DOI: 10.1016/j.phrs.2020.104755 -
Pharmacological Research May 2020The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study... (Meta-Analysis)
Meta-Analysis
Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta-analysis.
The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study was to evaluate the efficacy of roxadustat for the treatment of anemia in patients who are dialysis dependent (DD) or dialysis independent (NDD) CKD. We performed a systematic review of randomised controlled trials (RCTs) comparing treatment with roxadustat versus placebo or epoetin alfa up to November 2019. We investigated the efficacy of roxadustat in the levels of hemoglobin and other clinical parameters in renal anemia in patients with NDD and DD-CKD. We estimated weighted-mean difference (WMD) using random effect models. We included six RCTs comprising 1001 patients of whom 70.6 % were treated with roxadustat and 294 controls. The control group for studies of NDD-CKD patients was placebo whereas an active control of epoetin-alfa was used in studies of DD-CKD patients. Median follow-up time was 8 weeks. All trials were industry-sponsored. Overall, roxadustat increased hemoglobin levels by 1.20 g/dl (95 % CI:0.66, 1.75,P < 0.0001,I = 99.3 %). Hemoglobin levels increased by 1.99 g/dl in NDD-CKD patients versus placebo and 0.52 g/dl in DD-CKD patients versus epoetin-alfa. Roxadustat was associated with a decrease the levels of hepcidin by -49.3 ng/dl (-38.5 ng/dl in NDD patients versus placebo and -27.7 ng/dl in DD patients versus epoetin alfa), a decrease in ferritin of -49.7 μmol/l (-52.2 μmol/l in NDD patients versus placebo and -7.3 μmol/l in DD patients versus epoetin alfa), and increase in total iron-binding capacity of 32.2 μmol/l (14.1 μmol/l in NDD patients versus placebo and 13.6 μmol/l in DD patients versus epoetin alfa). The percentage change in the transferrin saturation levels was -2.07 % (-6%, NDD patients versus placebo, and +3.7 % in DD patients versus epoetin alfa) in anemia associated CKD patients. This review found roxadustast increases the levels of hemoglobin, serum transferrin, intestinal iron absorption, and reduces hepcidin in both NDD and DD-CKD patients. Safety data is still emerging.
Topics: Anemia; Glycine; Humans; Isoquinolines; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 32171893
DOI: 10.1016/j.phrs.2020.104747 -
Minerva Urologica E Nefrologica = the... Aug 2020To systematically review the effect of additional drug therapy as metaphylaxis in patients with cystinuria.
INTRODUCTION
To systematically review the effect of additional drug therapy as metaphylaxis in patients with cystinuria.
EVIDENCE ACQUISITION
A literature search of three databases (MEDLINE, Embase and the Cochrane Library) was performed according to the PRISMA-guidelines enclosing articles published up to May 2019. A total of 1117 articles were screened. Thirty-four publications met the inclusion criteria for this review.
EVIDENCE SYNTHESIS
Male-female ratio in the studied cohorts was 49.9% - 50.1%. The majority of studies showed a positive effect in reducing stone events and/or urinary cystine excretion. D-Penicillamine showed success in 13/14 (92%) studies, whereas Tiopronin-treatment showed a reduction in all (8/8; 100%) studies. All studies on Captopril (4/4) showed a decrease, however not all significant. The same is true for studies on Thiols in combination with Captopril (2/2). Furthermore, Tiopronin showed less side effects compared to D-penicillamine, respectively 30% and 37%. Captopril showed the least adverse events, with one event in nine patients.
CONCLUSIONS
The evidence on benefit of additional drug therapy in patients with cystinuria is scarce. All studied medications showed an effect on stone event and urinary cystine excretion, when used in addition to hyperhydration, alkalization and a diet low on methionine. Based on this systematic review, no drug can be preferred over another. An important aspect in the choice of drug is the risk of side effects. Therefore, the choice of additional drug should be personalized for every patient where the risk of side effects should be taken into consideration.
Topics: Captopril; Cystine; Cystinuria; Drug Therapy, Combination; Evidence-Based Medicine; Female; Humans; Male; Penicillamine; Tiopronin
PubMed: 32083421
DOI: 10.23736/S0393-2249.20.03704-2 -
Alimentary Pharmacology & Therapeutics Mar 2020The effect of baseline resistance-associated substitutions (RAS) on the sustained virologic response at 12 weeks (SVR12) among chronic hepatitis C (CHC) patients... (Meta-Analysis)
Meta-Analysis
Systematic review with meta-analysis: impact of baseline resistance-associated substitutions on the efficacy of glecaprevir/pibrentasvir among chronic hepatitis C patients.
BACKGROUND
The effect of baseline resistance-associated substitutions (RAS) on the sustained virologic response at 12 weeks (SVR12) among chronic hepatitis C (CHC) patients receiving the second generation, pan-genotypic glecaprevir/pibrentasvir (G/P) regimen is unclear.
AIM
To assess the effect of RAS on the SVR12 in CHC patients treated with G/P regimen.
METHODS
The EMBASE, MEDLINE and Cochrane central register of controlled trials databases were searched for relevant studies published before 1 March 2019. The principal outcome was to compare the SVR12 in CHC patients with and without baseline RAS, particularly in genotype-1, genotype-3 and direct-acting anti-virals (DAAs) failure patients. The outcomes were pooled using a random-effects model and odds ratio (OR) was calculated. The risk of bias was assessed using the Cochrane risk of bias tools for randomised and nonrandomised interventional studies.
RESULTS
After initially identifying 410 studies, 3302 patients from 17 studies were included. Among 50 cases of virologic failures, 48% had genotype-3 infection, 44% genotype-1 infection and 36% DAA-failure patients. Baseline RAS were present in 44(88%) patients. The most common NS5a and NS3 mutations were Y93H and A166S respectively. The odds of SVR12 were significantly reduced in patients with any baseline RAS (NS3 and/or NS5a) (OR 0.32, 95%C I[0.15, 0.65], I = 0%) and NS5a substitutions (OR 0.36, 95%CI [0.18,0.73]). The impact of RAS on SVR12 was significant among genotype-3 patients, but not among genotype-1 or DAA-failure cases. The presence of Y93H and A30K mutations significantly impacted SVR12 rates in genotype-3 patients.
CONCLUSION
Baseline NS3 or NS5a RAS, especially the NS5a substitutions-A30K, Y93H, decrease the odds of achieving SVR12 in genotype-3 CHC patients.
Topics: Amino Acid Substitution; Aminoisobutyric Acids; Antiviral Agents; Benzimidazoles; Cyclopropanes; Drug Resistance, Viral; Drug Therapy, Combination; Genotype; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Leucine; Non-Randomized Controlled Trials as Topic; Proline; Pyrrolidines; Quinoxalines; Randomized Controlled Trials as Topic; Sulfonamides; Sustained Virologic Response; Treatment Outcome; Viral Nonstructural Proteins
PubMed: 31943236
DOI: 10.1111/apt.15633 -
Archives of Gynecology and Obstetrics Nov 2019Galectin-3 is a M 31,000 protein that belongs to a family of carbohydrate-binding proteins. Galectin-3 has already been associated with protection against apoptosis...
PURPOSE
Galectin-3 is a M 31,000 protein that belongs to a family of carbohydrate-binding proteins. Galectin-3 has already been associated with protection against apoptosis through cell to cell or cell to matrix adhesion processes. It seems that galectin-3 plays an important role in tumor progression, cell growth, invasion and metastasis. Galectin-3 is the only member of the chimeric galectins that has an N-terminal glycine and proline domain and a C-terminal carbohydrate recognition domain that allows galectin-3 to accommodate larger structures such us polylactosaminoglycans and intervene to DNA damage repair process. In this systematic review, our primary goal is to identify the effect of galectin-3 expression in association with drug resistance and apoptosis inhibition in breast cancer.
MATERIALS AND METHODS
Scopus and PubMed databases were searched on 26 November 2018 using the following combination of keywords: (galectin-3 OR gal-3 OR LGALS3) AND (breast cancer) AND (chemoresistance OR (drug resistance) OR chemosensitivity). All the articles in English, regardless the time of publication, text availability and species included were initially accepted.
RESULTS
In the majority of the included studies, the expression of galectin-3 had a protective role in cell survival via different pathways such as the response to DNA damage and repair or the inhibition of apoptosis after treatment with a chemotherapeutic agent.
CONCLUSION
Galectin-3 expression in breast tumors might be an important factor in the selection of the most suitable treatment.
Topics: Antineoplastic Agents; Apoptosis; Blood Proteins; Breast Neoplasms; Drug Resistance, Neoplasm; Female; Galectin 3; Galectins; Humans
PubMed: 31502061
DOI: 10.1007/s00404-019-05292-9