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PloS One 2017Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies have investigated the anti-neoplastic properties of CGs since 1960s. Epidemiological studies concerning the association between CGs use and cancer risk yielded inconsistent results. We have performed a systematic review and meta-analysis to summarize the effects of CGs on cancer risk and mortality.
METHODS
PubMed, Scopus, Cochrane library, Medline and Web of Knowledge were searched for identifying relevant studies. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects model.
RESULTS
We included 14 case-control studies and 15 cohort studies published between 1976 and 2016 including 13 cancer types. Twenty-four studies reported the association between CGs and cancer risk and six reported the association between CGs and mortality of cancer patients. Using CGs was associated with a higher risk of breast cancer (RR = 1.330, 95% CI: 1.247-1.419). Subgroup analysis showed that using CGs increased the risk of ER+ve breast cancer but not ER-ve. Using CGs wasn't associated with prostate cancer risk (RR = 1.015, 95% CI: 0.868-1.87). However, CGs decreased the risk in long term users and showed a protective role in decreasing the risk of advanced stages. CGs use was associated with increased all-cause mortality (HR = 1.35, 95% CI: 1.248-1.46) but not cancer-specific mortality (HR = 1.075, 95% CI: 0.968-1.194).
CONCLUSION
The anti-tumor activity of CGs observed in pre-clinical studies requires high concentrations which can't be normally tolerated in humans. However, the estrogen-like activity of CGs could be responsible for increasing the risk of certain types of tumors.
Topics: Cardiac Glycosides; Female; Humans; Male; Neoplasms; Observational Studies as Topic; Risk Factors
PubMed: 28591151
DOI: 10.1371/journal.pone.0178611 -
Biology Apr 2022The use of normobaric hypoxia can bring benefits to sports performance because it improves haematological parameters and/or physical activity tests. Our objective was to... (Review)
Review
BACKGROUND
The use of normobaric hypoxia can bring benefits to sports performance because it improves haematological parameters and/or physical activity tests. Our objective was to conduct a systematic review so as to analyse the methods used in hypoxia and to detect its effects on middle- and/or long-distance runners.
METHODS
Research was conducted using five electronic databases (PubMed, SportDiscus, Cochrane Library, Scopus and PEDro) until December 2021. The methodological quality of the included studies was assessed using the PEDro scale.
RESULTS
Having analysed 158 studies, 12 were chosen for the qualitative and quantitative synthesis. A significant improvement on time until exhaustion was detected, and oxygen saturation decreased after the intervention. There were no significant changes in the 3000-metre time trial or in the haematocrit percentage. The changes in percentage of reticulocytes, heart rate, maximal heart rate, lactate concentration and erythropoietin were heterogeneous between the different research studies.
CONCLUSION
short exposure (less than 3 h to normobaric hypoxia significantly increases the time to exhaustion). However, longer exposure times are necessary to increase haemoglobin. Altitude and exposure time are highly heterogeneous in the included studies.
PubMed: 35625417
DOI: 10.3390/biology11050689 -
Scientific Reports Jun 2023Hyperuricemia as a risk factor for metabolic diseases is proved to be profoundly modified by dietary approaches. This systematic review and meta-analysis of randomized... (Meta-Analysis)
Meta-Analysis
The effect of dietary approaches to stop hypertension and ketogenic diets intervention on serum uric acid concentration: a systematic review and meta-analysis of randomized controlled trials.
Hyperuricemia as a risk factor for metabolic diseases is proved to be profoundly modified by dietary approaches. This systematic review and meta-analysis of randomized control trials (RCT) was conducted to investigate the effect of two nutritional interventions; dietary approaches to stop hypertension (DASH) diet and ketogenic diet (KD) on serum uric acid (UA) concentrations. Our systematic search was for RCTs in which KD or DASH diet were assigned to adults for at least 2 weeks or more. Until March 2023 in Embase, Web of Science, PubMed, and Scopus databases, 10 eligible RCTs that intervened with DASH diet (n = 4) or KD (n = 6) and had provided laboratory data on serum UA were found. Summary effect was calculated by random-effects model. Results from the meta-analysis of the 4 DASH diet RCTs with a total of 590 participants revealed significant decrease in serum UA after at least 4 weeks of interventions (mean difference (MD) = ‒0.25; 95% CI ‒0.4 to ‒0.1 mg/dL; p < 0.01; I = 0%). The pooled meta-analysis of the 6 included RCTs of KD reporting data of 267 participants showed no significant changes in serum UA (MD = 0.26; 95% CI ‒0.47 to 0.98 mg/dL, I = 95.32%). However, a non-significant reduction of UA in the subgroup analysis of very low-calorie KD (VLCKD) studies (MD = ‒0.04; 95% CI ‒0.29 to 0.22, I = 0%) was obtained. DASH diet has an ameliorating effect on serum UA and may be recommended for hyperuricemia states such as gout. In addition, we have shown that serum UA level following KD remained unchanged. Although, in view of the heterogeneity across the studies, further investigations are needed to determine the effect of KD and VLKD on serum UA concentrations.
Topics: Adult; Humans; Dietary Approaches To Stop Hypertension; Diet, Ketogenic; Uric Acid; Hyperuricemia; Randomized Controlled Trials as Topic
PubMed: 37380733
DOI: 10.1038/s41598-023-37672-2 -
Oxidative Medicine and Cellular... 2018Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years,... (Meta-Analysis)
Meta-Analysis Review
Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years, particular focus has been put on mitochondria-targeted antioxidants, to decrease the concentration of reactive oxygen species and help alleviate the accumulation of oxidative damage and associated aging. MitoQ is a mitochondria-targeted antioxidant of which is reported to support healthy aging. The aim of this systematic review is to investigate the effects of MitoQ on oxidative outcomes related to the aging process. A predeveloped search strategy was run against MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, which identified 10,255 articles of interest, with 27 of these finalised for use after screening. Three outcomes had sufficient data to meta-analyse nitrotyrosine concentration (190 animals, SMD -0.67, 95% CI (-1.30, -0.05), = 0.04), membrane potential (63 animals, MD 11.44, 95% CI (1.28-21.60), = 0.03), and protein carbonyl concentration (182 animals, SMD -0.13, 95% CI (-0.44, 0.18), = 0.41). MitoQ intervention produced a statistically significant reduction in nitrotyrosine concentration and increased membrane potential. MitoQ may be of some benefit in alleviating oxidative stress related to aging.
Topics: Aging; Biomarkers; Humans; Mitochondria; Organophosphorus Compounds; Ubiquinone
PubMed: 30116495
DOI: 10.1155/2018/8575263 -
Cardiology Research and Practice 2022Coronary heart disease is a major cause of mortality in developed and developing countries. Changes in the trace element concentration in the human body are one of the...
AIM
Coronary heart disease is a major cause of mortality in developed and developing countries. Changes in the trace element concentration in the human body are one of the main reasons for the transition of the human body from a healthy to a diseased state. In this meta-analysis, we have studied the relationship between the reduction in serum zinc ion concentration and coronary heart disease.
METHODS
We used PubMed and Cochrane (as of June 30, 2021) databases for the literature search. Per the requirements of this systematic review, case-control studies involving serum zinc ion concentration and coronary heart disease were searched, and the quality of the included studies was evaluated before the meta-analysis.
RESULTS
A total of 3,981 cases were found across seven articles. The standard mean deviation (SMD) of serum zinc ion concentration was -0.22 [-0.28, -0.15], = 6.52, and < 0.05 indicated that the difference was statistically significant. The forest plot results show that = 34% < 50%, and the test showed =0.17 > 0.1. These results suggest a lack of heterogeneity among the selected articles. Results from the funnel chart indicated that this study was free from publication bias.
CONCLUSION
The results of this meta-analysis reveal that a decrease in serum zinc ion concentration is related to the occurrence of coronary heart disease. Clinically, monitoring the serum zinc ion levels is proven to be of great significance for patients with coronary heart disease.
PubMed: 36247185
DOI: 10.1155/2022/4352484 -
Advances in Nutrition (Bethesda, Md.) Jan 2023The effects of exercise training (Ex), dietary interventions (DIs), and a combination of Ex and DI (Ex + DI) on leptin and adiponectin have been established. However,... (Meta-Analysis)
Meta-Analysis Review
The impact of exercise and dietary interventions on circulating leptin and adiponectin in individuals who are overweight and those with obesity: A systematic review and meta-analysis.
The effects of exercise training (Ex), dietary interventions (DIs), and a combination of Ex and DI (Ex + DI) on leptin and adiponectin have been established. However, less is known regarding the comparisons of Ex with DI and of Ex + DI with either Ex or DI alone. The aim of the present meta-analysis is to compare the effects of Ex with those of DI and those of Ex + DI with those of either Ex or DI alone on circulating leptin and adiponectin in individuals who are overweight and those with obesity. PubMed, Web of Science, and MEDLINE were searched to identify original articles, published through June 2022, that compared the effects of Ex with those of DI and/or the effects of Ex + DI with those of Ex and/or DI on leptin and adiponectin in individuals with BMIs (in kg/m) of ≥25 and aged 7-70 y. Standardized mean differences (SMDs), weighted mean differences, and 95% CIs were calculated using random-effect models for outcomes. Forty-seven studies, comprising 3872 participants who were overweight and those with obesity, were included in the current meta-analysis. DI reduced the concentration of leptin (SMD: -0.30; P = 0.001) and increased the concentration of adiponectin (SMD: 0.23; P = 0.001) compared with Ex, as did Ex + DI (leptin: SMD: -0.34; P = 0.001; adiponectin: SMD: 0.37; P = 0.004) compared with Ex alone. However, Ex + DI did not affect the concentration of adiponectin (SMD: 0.10; P = 0.11) and led to inconsistent and nonsignificant changes in the concentration of leptin (SMD: -0.13; P = 0.06) compared with DI alone. Subgroup analyses showed that age, BMI, duration of intervention, type of supervision, quality of the study, and magnitude of energy restriction are sources of heterogeneity. Our results suggest that Ex alone was not as effective as DI or Ex + DI for decreasing leptin and increasing adiponectin in individuals with overweight and obesity. However, Ex + DI was not more effective than DI alone, suggesting that diet plays a critical role in beneficially altering the concentrations of leptin and adiponectin. This review was registered at PROSPERO as CRD42021283532.
Topics: Humans; Leptin; Overweight; Adiponectin; Obesity; Exercise
PubMed: 36811585
DOI: 10.1016/j.advnut.2022.10.001 -
The Lancet. Microbe Apr 2023The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy.
METHODS
We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238.
FINDINGS
28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies.
INTERPRETATION
The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues.
FUNDING
Shenzhen Science and Technology Programs.
Topics: Humans; COVID-19 Vaccines; Asymptomatic Infections; COVID-19; SARS-CoV-2; Immunoglobulin G; Randomized Controlled Trials as Topic
PubMed: 36868258
DOI: 10.1016/S2666-5247(22)00390-1 -
ACS Pharmacology & Translational Science Jul 2023Methamphetamine exists as two stereoisomers: -(+)-methamphetamine ((+)-MAMP) and -(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central... (Review)
Review
Methamphetamine exists as two stereoisomers: -(+)-methamphetamine ((+)-MAMP) and -(-)-methamphetamine ((-)-MAMP). The (+)-MAMP stereoisomer is a well-known central nervous system stimulant, available as a pharmaceutical and clandestine drug of abuse. However, the (-)-MAMP stereoisomer is less well understood despite commercial availability for over 30 years as an over-the-counter (OTC) nasal decongestant in the Vicks Vapor Inhaler (a product of Procter & Gamble). Recently, several generic versions have become available, decreasing the cost and increasing the availability of (-)-MAMP-containing nasal sprays to consumers. Despite widespread commercial availability and use in the United States, a paucity of literature exists on the pharmacology of (-)-MAMP in humans. This knowledge gap is problematic, given the difficulty in separating (-)-MAMP and (+)-MAMP isomers in laboratory assays for workplace drug testing, suspected impaired drivers, post-mortem investigations, and assessment of drug involvement in crimes. In response, this systematic review of the literature coalesces and summarizes available knowledge of (-)-MAMP pharmacology in humans. It was found that available knowledge relies heavily on urine drug and metabolite concentrations, systematic pharmacokinetics studies are lacking, and existing knowledge has been derived from a total of 99 unique participants. The impacts of highlighted gaps in the literature are discussed, focusing on forensic toxicology and law enforcement, and future research directions are suggested.
PubMed: 37470013
DOI: 10.1021/acsptsci.3c00019 -
A systematic review and meta-analysis of macrolides in the management of adult patients with asthma.Allergology International : Official... Jul 2024The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma.
METHODS
Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides.
RESULTS
Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo.
CONCLUSIONS
Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma.
Topics: Humans; Asthma; Macrolides; Adult; Treatment Outcome; Anti-Asthmatic Agents; Randomized Controlled Trials as Topic; Quality of Life
PubMed: 38296770
DOI: 10.1016/j.alit.2024.01.002 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468