-
Frontiers in Oncology 2022Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by multiple cytogenetic and molecular abnormalities, with a very poor prognosis....
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by multiple cytogenetic and molecular abnormalities, with a very poor prognosis. Current treatments for AML often fail to eliminate leukemic stem cells (LSCs), which perpetuate the disease. LSCs exhibit a unique metabolic profile, especially dependent on oxidative phosphorylation (OXPHOS) for energy production. Whereas, normal hematopoietic stem cells (HSCs) and leukemic blasts rely on glycolysis for adenosine triphosphate (ATP) production. Thus, understanding the regulation of OXPHOS in LSCs may offer effective targets for developing clinical therapies in AML. This review summarizes these studies with a focus on the regulation of the electron transport chain (ETC) and tricarboxylic acid (TCA) cycle in OXPHOS and discusses potential therapies for eliminating LSCs.
PubMed: 35574326
DOI: 10.3389/fonc.2022.899502 -
Drug Discovery Today Jan 2019Chemical-stimuli-responsive nanotherapeutics have gained great interest in drug delivery and diagnosis applications. These nanotherapeutics are designed to respond to...
Chemical-stimuli-responsive nanotherapeutics have gained great interest in drug delivery and diagnosis applications. These nanotherapeutics are designed to respond to specific internal stimuli including pH, ionic strength, redox, reactive oxygen species, glucose, enzymes, ATP and hypoxia for site-specific and responsive or triggered release of payloads and/or biomarker detections. This review systematically and comprehensively addresses up-to-date technological and design strategies, and challenges nanomaterials to be used for triggered release and sensing in response to chemical stimuli.
Topics: Adenosine Triphosphate; Animals; Drug Delivery Systems; Enzymes; Glucose; Humans; Hydrogen-Ion Concentration; Hypoxia; Nanostructures; Osmolar Concentration; Oxidation-Reduction
PubMed: 30292916
DOI: 10.1016/j.drudis.2018.09.019 -
Croatian Medical Journal Apr 2019To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine...
AIM
To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca2+), and hypoxia-inducible factor 1α (HIF1α) in neurorestoration following the application of EMF.
METHODS
We reviewed the existing studies within the public domain and cross-evaluated their results in order to conclude on the molecular mechanisms of microglia-astrocyte crosstalk at work during EMF treatment.
RESULTS
The existing studies suggest that EMF induces the increase of HSP70 expression and inhibition of HIF1α, thus decreasing inflammation and allowing the microglia-astrocyte crosstalk to initiate the formation of a glial scar within the central nervous system. Furthermore, by potentially up-regulating A2A and A3 adenosine receptors, EMF increases cAMP accumulation from astrocytes and reduces the expression of inflammatory cytokines TNF α and IL-8, thus initiating neurorestoration.
CONCLUSION
The microglia-astrocyte crosstalk during EMF treatment is crucial for the initiation of neurorestoration. Elucidating the exact mechanisms of EMF actions upon microglia and astrocytes, and its role in neurorestoration could be a key step in further research of the therapeutic potential of EMFs in various neurological disorders.
Topics: Adenosine Triphosphate; Animals; Astrocytes; Calcium; Cells, Cultured; Cytokines; Electromagnetic Fields; Heat-Shock Proteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Magnetic Field Therapy; Microglia; Neurodegenerative Diseases; Receptor Cross-Talk; Tumor Necrosis Factor-alpha
PubMed: 31044584
DOI: 10.3325/cmj.2019.60.127 -
PloS One 2023The metabolic syndrome (MS) is a leading cause of death worldwide. Several studies have found MS to be prevalent in various African regions. However, no specific... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The metabolic syndrome (MS) is a leading cause of death worldwide. Several studies have found MS to be prevalent in various African regions. However, no specific estimates of MS prevalence in African populations exist. The aim of this study was to estimate the overall prevalence of MS in the African populations.
METHODS
A systematic review was conducted in PubMed, Web of Science, Africa Index Medicus, and African Journal Online Scopus to find studies published up to the 15th of August 2022. Pooled prevalence was calculated based on six diagnostic methods. The pooled prevalence of MS was estimated using a random-effects model. Our risk of bias analysis was based on the Hoy et al. tool. A Heterogeneity (I2) assessment was performed, as well as an Egger test for publication bias. PROSPERO number CRD42021275176 was assigned to this study.
RESULTS
In total, 297 studies corresponding to 345 prevalence data from 29 African countries and involving 156 464 participants were included. The overall prevalence of MS in Africa was 32.4% (95% CI: 30.2-34.7) with significant heterogeneity (I2 = 98.9%; P<0.001). We obtained prevalence rates of 44.8% (95% CI: 24.8-65.7), 39.7% (95% CI: 31.7-48.1), 33.1% (95% CI: 28.5-37.8), 31.6% (95% CI: 27.8-35.6) and 29.3% (95% CI: 25.7-33) using the WHO, revised NCEP-ATP III, JIS, NCEP/ATP III and IDF definition criteria, respectively. The prevalence of MS was significantly higher in adults >18 years with 33.1% (95%CI: 30.8-35.5) compared to children <18 years with 13.3% (95%CI: 7.3-20.6) (P<0.001). MS prevalence was significantly higher in females with 36.9% (95%CI: 33.2-40.7) compared to males with 26.7% (95%CI: 23.1-30.5) (P<0.001). The prevalence of MS was highest among Type 2 diabetes patients with 66.9% (95%CI: 60.3-73.1), followed by patients with coronary artery disease with 55.2% (95%CI: 50.8-59.6) and cardiovascular diseases with 48.3% (95%CI: 33.5-63.3) (P<0.001). With 33.6% (95% CI: 28.3-39.1), the southern African region was the most affected, followed by upper-middle income economies with 35% (95% CI: 29.5-40.6).
CONCLUSION
This study, regardless of the definition used, reveals a high prevalence of MS in Africa, confirming the ongoing epidemiological transition in African countries. Early prevention and treatment strategies are urgently needed to reverse this trend.
Topics: Male; Adult; Child; Female; Humans; Metabolic Syndrome; Prevalence; Diabetes Mellitus, Type 2; Africa; Adenosine Triphosphate
PubMed: 37498832
DOI: 10.1371/journal.pone.0289155 -
Cardiovascular Diabetology Jul 2022The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is lacking. We performed this systematic review and meta-analysis to address this controversy.
METHODS
We systematically searched the PubMed, Embase, Web of Science and Cochrane Library databases to collect relevant literature. Fixed and random effects models were used to estimate the hazard ratio (HR) with 95% CIs.
RESULTS
Thirty-six articles reporting on 162,780 ICD recipients were included in this analysis. Compared with nondiabetic ICD recipients, diabetic ICD recipients had higher all-cause mortality (HR = 1.45, 95% CI 1.36-1.55). The subgroup analysis showed that secondary prevention patients with diabetes may suffer a higher risk of all-cause mortality (HR = 1.89, 95% CI 1.56-2.28) (for subgroup analysis, P = 0.03). Cardiac mortality was also higher in ICD recipients with diabetes (HR = 1.68, 95% CI 1.35-2.08). However, diabetes had no significant effect on the risks of ICD therapies, including appropriate or inappropriate therapy, appropriate or inappropriate shock and appropriate anti-tachycardia pacing (ATP). Diabetes was associated with a decreased risk of inappropriate ATP (HR = 0.56, 95% CI 0.39-0.79).
CONCLUSION
Diabetes is associated with an increased risk of mortality in ICD recipients, especially in the secondary prevention patients, but does not significantly influence the risks of ICD therapies, indicating that the increased mortality of ICD recipients with diabetes may not be caused by arrhythmias. The survival benefits of ICD treatment in diabetes patients are limited.
Topics: Adenosine Triphosphate; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Defibrillators, Implantable; Diabetes Mellitus; Humans; Proportional Hazards Models; Risk Factors
PubMed: 35906611
DOI: 10.1186/s12933-022-01580-y -
Frontiers in Cardiovascular Medicine 2022Cardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial...
OBJECTIVE
Cardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial respiration and cardiac mitochondrial quality control in IHD.
METHODS
A narrative synthesis was conducted after searching animal studies written in English in three databases (PubMed, Web of Science, and EMBASE) until December 2020. Studies that used aerobic exercise as an intervention for at least 3 weeks and had at least normal, negative (sedentary IHD), and positive (exercise-trained IHD) groups were included. The CAMARADES checklist was used to check the quality of the included studies.
RESULTS
The 10 included studies (CAMARADES score: 6-7/10) used swimming or treadmill exercise for 3-8 weeks. Seven studies showed that ET ameliorated cardiac mitochondrial respiratory function as manifested by decreased reactive oxygen species (ROS) production and increased complexes I-V activity, superoxide dismutase 2 (SOD2), respiratory control ratio (RCR), NADH dehydrogenase subunits 1 and 6 (ND1/6), Cytochrome B (CytB), and adenosine triphosphate (ATP) production. Ten studies showed that ET improved cardiac mitochondrial quality control in IHD as manifested by enhanced and/or controlled mitochondrial biogenesis, dynamics, and mitophagy. Four other studies showed that ET resulted in better cardiac mitochondrial physiological characteristics.
CONCLUSION
Exercise training could improve cardiac mitochondrial functions, including respiration, biogenesis, dynamics, and mitophagy in IHD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/ display_record.php?RecordID=226817, identifier: CRD42021226817.
PubMed: 36304547
DOI: 10.3389/fcvm.2022.949744 -
The Cochrane Database of Systematic... Aug 2016Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical... (Review)
Review
BACKGROUND
Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. This review is an update of a previously published Cochrane review.
OBJECTIVES
To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions, or no treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2015, Issue 8), MEDLINE/PubMed (1949 to September 2015), and EMBASE/Ovid (1980 to September 2015) for potentially relevant articles. In addition, we searched reference lists of relevant articles, conference proceedings of the International Society for Paediatric Oncology (SIOP), the American Society of Clinical Oncology (ASCO), the American Society of Hematology (ASH), the International Conference on Long-Term Complications of Treatment of Children & Adolescents for Cancer, and the European Symposium on Late Complications from Childhood Cancer (from 2005 to 2015), and ongoing trial databases (the ISRCTN Register, the National Institutes of Health (NIH) Register, and the trials register of the World Health Organization (WHO); all searched in September 2015).
SELECTION CRITERIA
Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions, or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments, which another review author checked. We performed analyses according to the guidelines in the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
In the original version of the review we identified two RCTs; in this update we identified no additional studies. One trial (135 participants) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline-induced cardiac dysfunction. The other trial (68 participants) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, adenosine triphosphate, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations.The RCT on enalapril showed no statistically significant differences in overall survival, mortality due to heart failure, development of clinical heart failure, and quality of life between treatment and control groups. A post-hoc analysis showed a decrease (that is improvement) in one measure of cardiac function (left ventricular end-systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Participants treated with enalapril had a higher risk of dizziness or hypotension (risk ratio 7.17, 95% confidence interval 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function, and adverse events between treatment and control groups.
AUTHORS' CONCLUSIONS
Only one trial evaluated the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.Only one trial evaluated the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatments on echocardiographic function and clinical outcomes.We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.High-quality studies should be performed.
Topics: Adult; Adult Survivors of Child Adverse Events; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antibiotics, Antineoplastic; Cardiotonic Agents; Child; Enalapril; Heart Failure; Humans; Neoplasms; Phosphocreatine; Randomized Controlled Trials as Topic
PubMed: 27552363
DOI: 10.1002/14651858.CD008011.pub3 -
Journal of Animal Science Jan 2024Improving the feeding efficiency of dairy cows is a key component to improve the utilization of land resources and meet the demand for high-quality protein. Advances in... (Meta-Analysis)
Meta-Analysis
Improving the feeding efficiency of dairy cows is a key component to improve the utilization of land resources and meet the demand for high-quality protein. Advances in genomic methods and omics techniques have made it possible to breed more efficient dairy cows through genomic selection. The aim of this review is to obtain a comprehensive understanding of the biological background of feed efficiency (FE) complex traits in purebred Holstein dairy cows including heritability estimate, and genetic markers, genes, and pathways participating in FE regulation mechanism. Through a literature search, we systematically reviewed the heritability estimation, molecular genetic markers, genes, biomarkers, and pathways of traits related to feeding efficiency in Holstein dairy cows. A meta-analysis based on a random-effects model was performed to combine reported heritability estimates of FE complex. The heritability of residual feed intake, dry matter intake, and energy balance was 0.20, 0.34, and 0.22, respectively, which proved that it was reasonable to include the related traits in the selection breeding program. For molecular genetic markers, a total of 13 single-nucleotide polymorphisms and copy number variance loci, associated genes, and functions were reported to be significant across populations. A total of 169 reported candidate genes were summarized on a large scale, using a higher threshold (adjusted P value < 0.05). Then, the subsequent pathway enrichment of these genes was performed. The important genes reported in the articles were included in a gene list and the gene list was enriched by gene ontology (GO):biological process (BP), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Three GO:BP terms and four KEGG terms were statistically significant, which mainly focused on adenosine triphosphate (ATP) synthesis, electron transport chain, and OXPHOS pathway. Among these pathways, involved genes such as ATP5MC2, NDUFA, COX7A2, UQCR, and MMP are particularly important as they were previously reported. Twenty-nine reported biological mechanisms along with involved genes were explained mainly by four biological pathways (insulin-like growth factor axis, lipid metabolism, oxidative phosphorylation pathways, tryptophan metabolism). The information from this study will be useful for future studies of genomic selection breeding and genetic structures influencing animal FE. A better understanding of the underlying biological mechanisms would be beneficial, particularly as it might address genetic antagonism.
Topics: Female; Cattle; Animals; Lactation; Genetic Markers; Phenotype; Genome; Eating; Animal Feed; Milk
PubMed: 38354297
DOI: 10.1093/jas/skae040