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Expert Review of Hematology Oct 2015To report on molecular mechanisms of fetal hemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of sickle cell disease. (Meta-Analysis)
Meta-Analysis Review
AIM
To report on molecular mechanisms of fetal hemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of sickle cell disease.
STUDY DESIGN
Systematic review.
RESULTS
Studies have provided consistent associations between genomic variations in HbF-promoting loci and variable HbF level in response to HU. Numerous signal transduction pathways have been implicated, through the identification of key genomic variants in BCL11A, HBS1L-MYB, SAR1 or XmnI polymorphism that predispose the response to the treatment, and signal transduction pathways that modulate γ-globin expression (cAMP/cGMP; Giα/c-Jun N-terminal kinase/Jun; methylation and miRNA). Three main molecular pathways have been reported: i) Epigenetic modifications, transcriptional events and signaling pathways involved in HU-mediated response, ii) Signaling pathways involving HU-mediated response and iii) Post-transcriptional pathways (regulation by miRNAs).
CONCLUSIONS
The complete picture of HU-mediated mechanisms of HbF production in Sickle Cell Disease remains elusive. Research on post-transcriptional mechanisms could lead to therapeutic targets that may minimize alterations to the cellular transcriptome.
Topics: Anemia, Sickle Cell; Antisickling Agents; Cyclic AMP; Cyclic GMP; Epigenesis, Genetic; Fetal Hemoglobin; Gene Expression Regulation; Genetic Variation; Humans; Hydroxyurea; MicroRNAs; Pharmacogenetics; Polymorphism, Single Nucleotide; RNA Processing, Post-Transcriptional; Signal Transduction; gamma-Globins
PubMed: 26327494
DOI: 10.1586/17474086.2015.1078235 -
Clinics in Liver Disease Aug 2011This article introduces one of the most diverse classes of direct-acting antivirals for hepatitis C, the nucleoside and non-nucleoside NS5B polymerase inhibitors.... (Review)
Review
This article introduces one of the most diverse classes of direct-acting antivirals for hepatitis C, the nucleoside and non-nucleoside NS5B polymerase inhibitors. Through a systematic review of the published literature, we describe their structure, mechanism of action, issues with resistance, and clinical effectiveness shown in the latest clinical trials. Direct-acting antiviral combination trials that have already shown some early promising results even in the setting of interferon-sparing antiviral regimens are discussed.
Topics: Antiviral Agents; Clinical Trials as Topic; Deoxycytidine; Guanosine Monophosphate; Hepatitis C; Humans; Sofosbuvir; Uridine Monophosphate; Viral Nonstructural Proteins
PubMed: 21867940
DOI: 10.1016/j.cld.2011.05.003 -
Mitochondrion Sep 2013Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in... (Review)
Review
Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized. An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched. From one hundred twenty five retrieved titles, 12 (three case control study and 9 case reports) articles met inclusion criteria. All of the included studies indicated dysfunction of electron transport chain in autism. The mitochondrial electron transfer chain seems impaired in some children with autism and ROS production is additionally enhanced. It is hypothesized that interventions involving alternative electron shuttling may improve autism through lowering the production of ROS. In addition, it is expected that this alternative electron shuttling to cytochrome c might enhance the production of ATP which is impaired in the disorder.
Topics: Adenosine Triphosphate; Autistic Disorder; Electron Transport; Humans; Mitochondria; Reactive Oxygen Species
PubMed: 23063712
DOI: 10.1016/j.mito.2012.10.001 -
International Urology and Nephrology Jul 2017We aimed to systematically assess the effect of adipose tissue-derived stem cell (ADSC) therapy and its influential factors on the treatment of erectile dysfunction (ED)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to systematically assess the effect of adipose tissue-derived stem cell (ADSC) therapy and its influential factors on the treatment of erectile dysfunction (ED) in rats.
METHODS
Two authors independently searched for published studies through PubMed and EMBASE from study inception until August 31, 2016. A meta-analysis was used to combine the effect estimate from the published studies. A subgroup analysis was performed to identify the effect of some influential factors. The pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model analysis.
RESULTS
Twenty studies with a total of 248 rats were included in this meta-analysis. The pooled analysis showed that ADSC therapy significantly increased the ratio of intracavernous pressure and mean arterial pressure (ICP/MAP; SMD 3.46, 95% CI 2.85-4.06; P < 0.001) compared to control therapy. The levels of neuronal nitric oxide synthase (nNOS; SMD 6.37, 95% CI 4.35-8.39; P < 0.001), the cavernous smooth muscle content (CSMC; SMD 3.65, 95% CI 2.65-4.65; P < 0.001), the ratio of cavernous smooth muscle and collagen (CSM/collagen; SMD 4.16, 95% CI 2.59-5.72; P < 0.001), and the cyclic guanosine monophosphate (cGMP; SMD 7.12, 95% CI 2.76-11.48; P = 0.001) were higher following ADSC therapy than following control therapy. Subgroup analysis showed that ADSCs modified by growth or neurotrophic factors significantly recovered erectile function (P < 0.001) compared with ADSC therapy.
CONCLUSION
The adequate data indicated that ADSC therapy recovered erectile function and regenerated cavernous structures in ED rats, and ADSCs modified by some growth and neurotrophic factors accelerated the recovery of erectile function and cavernous structures in ED rats.
Topics: Adipose Tissue; Animals; Arterial Pressure; Collagen; Cyclic GMP; Erectile Dysfunction; Male; Muscle, Smooth; Nitric Oxide Synthase Type I; Penile Erection; Rats; Stem Cell Transplantation
PubMed: 28417342
DOI: 10.1007/s11255-017-1590-2 -
Genes Feb 2023Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have... (Review)
Review
Recently, several studies have highlighted a skewed prevalence of infectious diseases within the African continent. Furthermore, a growing number of studies have demonstrated unique genetic variants found within the African genome are one of the contributing factors to the disease severity of infectious diseases within Africa. Understanding the host genetic mechanisms that offer protection against infectious diseases provides an opportunity to develop unique therapeutic interventions. Over the past two decades, several studies have linked the 2'-5'-oligoadenylate synthetase (OAS) family with a range of infectious diseases. More recently, the gene has also been associated with disease severity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to a global pandemic. The OAS family serves as an antiviral factor through the interaction with Ribonuclease-Latent (RNase-L). This review explores the genetic variants observed within the genes and the associations with various viral infections and how previously reported ethnic-specific polymorphisms drive clinical significance. This review provides an overview of genetic association studies with a particular focus on viral diseases affecting individuals of African descent.
Topics: Humans; SARS-CoV-2; COVID-19; Adenine Nucleotides; Oligoribonucleotides
PubMed: 36833454
DOI: 10.3390/genes14020527 -
European Journal of Clinical... Nov 2020Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Several therapeutic agents have been investigated for treatment of novel coronavirus 2019 (nCOV-2019). We conducted a systematic review and meta-analysis to assess the efficacy of various treatment modalities in nCOV-2019 patients.
METHODS
A literature search was conducted before 29 June 2020 in PubMed, Google Scholar and Cochrane library databases. A fixed-effect model was applied if I < 50%, else results were combined using random-effect model. Risk ratio (RR) or standardized mean difference (SMD) along with 95% confidence interval (95% CI) was used to pool the results. Between-study heterogeneity was explored using influence and sensitivity analyses, and publication bias was assessed using funnel plots. Entire statistical analysis was conducted in R version 3.6.2.
RESULTS
Fifty studies involving 15 in vitro and 35 clinical studies including 9170 nCOV-2019 patients were included. Lopinavir-ritonavir was significantly associated with shorter mean time to clinical recovery (SMD -0.32; 95% CI -0.57 to -0.06), remdesivir was significantly associated with better overall clinical recovery (RR 1.17; 95% CI 1.07 to 1.29), and tocilizumab was associated with less all-cause mortality (RR 0.38; 95% CI 0.16 to 0.93). Hydroxychloroquine was associated with longer time to clinical recovery and less overall clinical recovery. It additionally had higher all-cause mortality and more total adverse events.
CONCLUSION
Our meta-analysis suggests that except in vitro studies, no treatment has shown overall favourable outcomes in nCOV-2019 patients. Lopinavir-ritonavir, remdesivir and tocilizumab may have some benefits, while hydroxychloroquine administration may cause harm in nCOV-2019 patients. Results from upcoming large clinical trials may further clarify role of these drugs.
Topics: Adenosine Monophosphate; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; COVID-19; Coronavirus Infections; Europe; Female; Humans; Lopinavir; Male; Pandemics; Pneumonia, Viral; Prognosis; Ritonavir; Survival Analysis; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32810285
DOI: 10.1111/eci.13383 -
The Journal of Antimicrobial... Jul 2021We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in treating coronavirus disease 2019 (COVID-19).
METHODS
PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020.
RESULTS
Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group [OR = 1.68 (95% CI 1.18-2.40)], with no significant difference observed between the 10 day and placebo groups [OR = 1.23 (95% CI 0.90-1.68)]. Patients receiving remdesivir revealed a greater likelihood of discharge [10 day remdesivir versus control: OR = 1.32 (95% CI 1.09-1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28-2.35)] and recovery [10 day remdesivir versus control: OR = 1.29 (95% CI 1.03-1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31-2.48)] than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events.
CONCLUSIONS
Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.
Topics: Adenosine Monophosphate; Alanine; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33758946
DOI: 10.1093/jac/dkab093 -
The American Journal of Cardiology Jun 2014Several prospective studies have shown that high on-clopidogrel platelet reactivity (HPR) in patients undergoing percutaneous coronary intervention (PCI) is a risk... (Meta-Analysis)
Meta-Analysis Review
Several prospective studies have shown that high on-clopidogrel platelet reactivity (HPR) in patients undergoing percutaneous coronary intervention (PCI) is a risk factor for ischemic events. All studies were insufficiently powered to detect differences in stroke between patients with HPR and those without. Therefore, we performed a systematic review and meta-analysis of available publications aimed at determining whether patients undergoing PCI with HPR are also at increased risk of stroke. We searched for prospective studies enrolling patients undergoing PCI and treated with aspirin and clopidogrel that reported on clinical relevance of HPR to adenosine diphosphate. Study end point was the rate of stroke. We also investigated whether there was an interaction on the relative risk of stroke between HPR, clinical presentation, duration of follow-up, or laboratory methods. Fourteen studies including 11,959 patients were deemed eligible. On pooled analysis, the risk of stroke was higher in patients with HPR compared with patients with no HPR (1.2% vs 0.7%, relative risk on fixed effect 1.84, 95% confidence interval 1.21 to 2.80). There was no heterogeneity among the studies (I(2) = 0%, p = 0.5). Clinical presentation (p = 0.39 for interaction), duration of follow-up (p = 0.87 for interaction), and laboratory method for detection of HPR (p = 0.99 for interaction) did not affect the relative increase in the risk of stroke in patients with HPR compared with patients with no HPR. In conclusion, in patients with coronary artery disease undergoing PCI, the presence of HPR to adenosine diphosphate is a risk factor for stroke.
Topics: Adenosine Diphosphate; Blood Platelets; Clopidogrel; Dose-Response Relationship, Drug; Global Health; Humans; Incidence; Myocardial Ischemia; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Postoperative Period; Risk Factors; Stroke; Ticlopidine
PubMed: 24837257
DOI: 10.1016/j.amjcard.2014.03.009 -
Journal of Gynecology Obstetrics and... Apr 2022This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis
PURPOSE
This meta-analysis evaluated the correlation between poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) expression and prognosis in patients with ovarian cancer.
METHODS
Eligible studies were extracted from the electronic databases of PubMed, Web of Science, and EMBASE until 1 August 2019. The included studies investigated the correlation between PARP expression and clinical outcomes in patients with ovarian cancer. Clinical outcomes are overall survival (OS) and progression free survival (PFS). The clinical data of patients, such as clinicopathologic characteristics and survival, were analyzed. The language was limited to English, and studies conducted at the cellular level, animal studies, and non-original research were excluded. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were used for this meta-analysis.
RESULTS
A total of 9 eligible studies involving 1230 patients were included in our meta-analysis. Based on the analysis, higher PARP expression was correlated with worse overall survival [OS] (HR,1.64; 95% CI, 1.08-2.49; P = 0.020) in the univariate analysis, whereas results from multivariate analysis indicated that PARP overexpression wasn't statistically associated with worse OS (HR, 1.36; 95% CI, 0.98-1.90; P = 0.069). Moreover, the pooled results revealed that patients with PARP overexpression were not associated with worse histologic grade (OR,2.22; 95% CI, 0.98-5.02; P = 0.06).
CONCLUSION
PARP overexpression maybe associated with poor prognosis and survival in patients with ovarian cancer. The patients with PARP over expression were not tended to have a worse histologic grade. Findings require further validation.
Topics: Adenosine Diphosphate; Adenosine Diphosphate Ribose; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Prognosis; Ribose
PubMed: 35218983
DOI: 10.1016/j.jogoh.2022.102344 -
Expert Opinion on Drug Safety 2016Dual antiplatelet therapy with aspirin and an oral ADP P2Y12 receptor antagonist is the standard-of-care for treatment of patients undergoing percutaneous coronary... (Review)
Review
INTRODUCTION
Dual antiplatelet therapy with aspirin and an oral ADP P2Y12 receptor antagonist is the standard-of-care for treatment of patients undergoing percutaneous coronary intervention (PCI). However, oral P2Y12 receptor antagonists have several limitations, including inter- and intra-individual response variability, drug-drug interactions, slow onset and offset of action and delayed platelet inhibition in high-risk clinical settings, such as patients with ST-segment elevation myocardial infarction.
AREAS COVERED
Cangrelor is an intravenous, direct-acting, reversible, potent P2Y12 receptor antagonist. It rapidly achieves near complete platelet inhibition and has a very short half-life and a fast offset of action. We conducted a systematic review searching PubMed/MEDLINE for pharmacodynamic/pharmacokinetic studies and clinical trials in which cangrelor was investigated, published from any time up to November 1(st) 2015. For clinical trials, those investigating cangrelor in the setting of PCI were considered for discussion.
EXPERT OPINION
Cangrelor is approved by drug regulating authorities worldwide as adjunctive antithrombotic therapy for the full spectrum of patients undergoing PCI, not pre-treated with a P2Y12 receptor inhibitor and not with intent to receive a glycoprotein IIb/IIIa inhibitor. Its unique pharmacological properties and its favorable safety and efficacy profile make it an attractive treatment strategy, especially in clinical settings where immediate platelet inhibition is required.
Topics: Adenosine Monophosphate; Aspirin; Drug Interactions; Drug Therapy, Combination; Half-Life; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists
PubMed: 26680584
DOI: 10.1517/14740338.2016.1133585