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Life Sciences Nov 2022Eating behavior is regulated by central and peripheral signals, which interact to modulate the response to nutrient intake. Central control is mediated by the... (Review)
Review
Eating behavior is regulated by central and peripheral signals, which interact to modulate the response to nutrient intake. Central control is mediated by the hypothalamus through neuropeptides that activate the orexigenic and anorexigenic pathways. Energy homeostasis depends on the efficiency of these regulatory mechanisms. This neuroendocrine regulation of hunger and appetite can be modulated by nutritional sensors such as adenosine monophosphate-activated protein kinase (AMPK). Thus, this systematic review discusses the literature on correlations between AMPK and hypothalamic neuropeptides regarding control of eating behavior. Lilacs, PubMed/Medline, ScienceDirect, and Web of Science were searched for articles published from 2009 to 2021 containing combinations of the following descriptors: "eating behavior," "hypothalamus," "neuropeptide," and "AMPK." Of the 1330 articles found initially, 27 were selected after application of the inclusion and exclusion criteria. Of the selected articles, 15 reported decreased AMPK activity, due to interventions using angiotensin II infusion, fructose, glucose, cholecystokinin, leptin, or lipopolysaccharide (LPS) injection; dietary control through a low-protein diet or a high-fat diet (60 % fat); induction of hyperthyroidism; or injection of AMPK inhibitors. Seven studies showed a decrease in neuropeptide Y (NPY) through CV4 AICAR administration; fructose, glucose, leptin, or angiotensin II injections; or infusion of LPS from Escherichia coli and liver kinase B1 (LKB1) overexpression. Eleven studies reported a decrease in food consumption due to a decrease in AMPK activity and/or hypothalamic neuropeptides such as NPY. The results indicate that there is a relationship between AMPK and the control of eating behavior: a decrease in AMPK activity due to a dietary or non-dietary stimulus is associated with a consequent decrease in food intake. Furthermore, AMPK activity can be modulated by glucose, thyroid hormones, estradiol, leptin, and ghrelin.
Topics: Leptin; Ghrelin; Neuropeptide Y; AMP-Activated Protein Kinases; Lipopolysaccharides; Angiotensin II; Hypothalamus; Neuropeptides; Feeding Behavior; Eating; Cholecystokinin; Glucose; Thyroid Hormones; Estradiol; Adenosine Monophosphate; Fructose
PubMed: 36096244
DOI: 10.1016/j.lfs.2022.120947 -
Molecular Psychiatry Mar 2012A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First,... (Meta-Analysis)
Meta-Analysis Review
A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.
Topics: Adenosine Triphosphate; Adolescent; Animals; Biomarkers; Brain; Child; Child Development Disorders, Pervasive; Comorbidity; Developmental Disabilities; Disease Models, Animal; Electron Transport; Energy Metabolism; Female; Gastrointestinal Diseases; Humans; Lactates; Male; Mitochondria; Mitochondrial Diseases; Neuroimaging; Prevalence; Pyruvic Acid; Seizures; Sex Distribution; Young Adult
PubMed: 21263444
DOI: 10.1038/mp.2010.136 -
Journal of Pharmacy & Pharmaceutical... 2021To evaluate the safety and efficacy of remdesivir in adult patients with COVID-19. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the safety and efficacy of remdesivir in adult patients with COVID-19.
METHODS
PubMed, Embase, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, and medRxiv databases were searched using a search strategy tailored to each database. The Consolidated Standards of Reporting Trials (CONSORT) and Strengthening the reporting of observational studies in epidemiology (STROBE) checklists were used for the studies' qualitative assessment. The outcomes studied were mortality, all adverse events, serious adverse events, and clinical improvement. The quantitative synthesis was conducted using fixed and random effects models in the CMA 2.2. Heterogeneity was tested using the I-squared (I2) measure.
RESULTS
In general, six studies, including five randomized controlled trials and one cohort study were found eligible. Comparison of the findings related to both groups receiving remdesivir (10-day remdesivir group) and placebo/control group showed that remdesivir treatment had no significant effect on mortality at day 14 of the treatment (RR=0.769; 95% CI :0.563-1.050; p=0.098), and all adverse events (RR= 1.078; 95% CI: 0.908-1.279; p= 0.392). However, remdesivir had a significant effect on clinical improvement at day 14 compared to placebo/control (OR= 1.447; 95% CI: 1.005-2.085; p= 0.047) and reduced serious adverse events (RR= 0.736; 95% CI: 0.611-0.887; p= 0.001).
CONCLUSION
Remdesivir has positive effects on clinical improvement, and reduction of the risk of serious adverse events. However, it does not influence the mortality at day 14 of treatment.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; COVID-19; Humans; Hypoalbuminemia; Hypokalemia; Randomized Controlled Trials as Topic; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34048669
DOI: 10.18433/jpps31870 -
Jornal Brasileiro de Pneumologia :... 2022Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19.
METHODS
This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls.
RESULTS
A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = -0.01 (95% CI, -0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, -0.08 to 0.01]; p = 0.09).
CONCLUSIONS
The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; Observational Studies as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 35137874
DOI: 10.36416/1806-3756/e20210393 -
PloS One 2020Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19.
METHODS
Studies evaluating remdesivir in adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed.
RESULTS
We included four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed.
CONCLUSIONS
There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33301514
DOI: 10.1371/journal.pone.0243705 -
Lasers in Medical Science Oct 2022Low-level laser therapy (LLLT)-induced photobiomodulation (PBM) stimulates bone tissue regeneration by inducing osteoblast differentiation and mitochondrial activation.... (Review)
Review
Low-level laser therapy (LLLT)-induced photobiomodulation (PBM) stimulates bone tissue regeneration by inducing osteoblast differentiation and mitochondrial activation. However, the role of reactive oxygen species (ROS) in this process remains controversial. The aim of this systematic review was to collect and analyze the available literature on the cellular and molecular effects of LLLT on osteoblasts and the role of ROS in this process. A search was conducted in PubMed, ScienceDirect, Scopus, and Web of Science. Studies published in English over the past 15 years were selected. Fourteen articles were included with moderate (n = 9) and low risk of bias (n = 5). Thirteen studies reported the use of diode lasers with wavelengths (λ) between 635 and 980 nm. One study used an Nd:YAG laser (λ1064 nm). The most commonly used λ values were 808 and 635 nm. The energy densities ranged from 0.378 to 78.75 J/cm, and irradiation times from 1.5 to 300 s. Most studies found increases in proliferation, ATP synthesis, mitochondrial activity, and osteoblastic differentiation related to moderate and dose-dependent increases in intracellular ROS levels. Only two studies reported no significant changes. The data presented heterogeneity owing to the variety of LLLT protocols. Although several studies have shown a positive role of ROS in the induction of proliferation, migration, and differentiation of different cell types, further research is required to determine the specific role of ROS in the osteoblastic cell response and the molecular mechanisms involved in triggering previously reported cellular events.
Topics: Adenosine Triphosphate; Cell Proliferation; Lasers, Semiconductor; Low-Level Light Therapy; Osteoblasts; Reactive Oxygen Species
PubMed: 35751706
DOI: 10.1007/s10103-022-03587-z -
The Journal of Sexual Medicine Sep 2009The endothelial monolayer plays a crucial role in the vasodilation and hemodynamic events involved in erection physiology. Due to its relevant functions, a close link... (Review)
Review
INTRODUCTION
The endothelial monolayer plays a crucial role in the vasodilation and hemodynamic events involved in erection physiology. Due to its relevant functions, a close link has been established between endothelial integrity and erectile dysfunction (ED). Endothelial dysfunction is induced by the detrimental actions of vascular risk factors (VRFs), identified as common correlates for the development of cardiovascular disease and ED. It is currently recognized that ED is the early harbinger of a more generalized vascular systemic disorder, and, therefore, an evaluation of endothelial health in ED patients should be of prime relevance. Several noninvasive methods for endothelial function assessment have been proposed, including the Penile Nitric Oxide Release Test (PNORT).
AIM
To highlight the most recent gathered knowledge on basic and clinical mechanisms underlying loss of cavernosal endothelial function promoted by VRFs and to discuss local and systemic methods for endothelial function assessment in ED individuals, focusing on the PNORT.
MAIN OUTCOME MEASURES
A complete revision on the novel basic and clinical links between endothelial and ED.
METHODS
A systematic review of the literature regarding the aforementioned issues.
RESULTS
Risk factor-associated cavernosal endothelial dysfunction is mostly induced by unifying mechanisms, including oxidative stress and impaired endothelial nitric oxide functional activities, which present clinically as ED. Several techniques to evaluate endothelial dysfunction were revised, with advantages and limitations debated, focusing on our detailed expertise using the PNORT method.
CONCLUSIONS
The established endothelial-erectile dysfunction connection was thoroughly revised, from basic mechanisms to the clinical importance of endothelial dysfunction assessment as diagnosis for generalized vascular disease. Further studies are required to disclose efficient approaches to repair disabled endothelium and both restore and prevent endothelial dysfunction.
Topics: Aging; Cyclic GMP; Endothelium, Vascular; Hemodynamics; Humans; Impotence, Vasculogenic; Male; Nitric Oxide; Penile Erection; Penis; Plethysmography; Risk Factors; Signal Transduction; Statistics as Topic
PubMed: 19523038
DOI: 10.1111/j.1743-6109.2009.01356.x -
European Journal of Pharmacology Apr 2021The coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis. Considering the recent food and drug administration (FDA) approval of remdesivir as... (Meta-Analysis)
Meta-Analysis
The coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis. Considering the recent food and drug administration (FDA) approval of remdesivir as the first officially approved agent for COVID-19 treatment, we performed this systematic review and meta-analysis to evaluate the efficacy and safety of remdesivir administration in COVID-19 patients. A systematic literature search was done through MEDLINE, Google Scholar, Web of Science, Scopus, Science Direct, Cochrane Library, medRxiv, and bioRxiv from their inception to December 22nd, 2020. Five randomized controlled trials (RCTs) and five non-randomized studies of intervention (NRSI) were entered into the meta-analysis. The results showed that remdesivir administration was associated with a significant improvement in the 28-day recovery (RR = 1.09, 95%CI, 1.04-1.15), low flow oxygen support through days one to 14 (RR = 2.88, 95%CI, 1.80-4.60), and invasive mechanical ventilation or extracorporeal membrane oxygenation requirement through days 14-28 of the follow-up time (RR = 5.34, 95%CI, 2.37-12.05). The risk of experiencing serious adverse drug reactions (ADRs) was significantly lower (RR = 0.75, 95%CI, 0.63-0.90) in the remdesivir group than the comparison/control group. The pooled median difference of the time to clinical improvement was 2.99 (95%CI = 2.71-3.28), which did not remain significant during the sensitivity analysis. The clinical output comparison of the 5-day and 10-day remdesivir courses revealed that the 5-day regimen might provide similar benefits while causing fewer serious ADRs than 10-day. The current meta-analysis provided an updated evaluation of scientific evidence on the use of remdesivir in COVID-19 patients. Performing adequate well-designed RCTs are needed to show more accurate results.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; Pandemics; Randomized Controlled Trials as Topic; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33549577
DOI: 10.1016/j.ejphar.2021.173926 -
Molecular Biology Reports Apr 2023FF adenosine triphosphate (ATP) synthase, also known as the complex V, is the central ATP-producing unit in the cells arranged in the mitochondrial and plasma membranes.... (Review)
Review
FF adenosine triphosphate (ATP) synthase, also known as the complex V, is the central ATP-producing unit in the cells arranged in the mitochondrial and plasma membranes. FF ATP synthase also regulates the central metabolic processes in the human body driven by proton motive force (Δp). Numerous studies have immensely contributed toward highlighting its regulation in improving energy homeostasis and maintaining mitochondrial integrity, which otherwise gets compromised in illnesses. Yet, its role in the implication of non-communicable diseases remains unknown. FF ATP synthase dysregulation at gene level leads to reduced activity and delocalization in the cristae and plasma membranes, which is directly associated with non-communicable diseases: cardiovascular diseases, diabetes, neurodegenerative disorders, cancer, and renal diseases. Individual subunits of the FF ATP synthase target ligand-based competitive or non-competitive inhibition. After performing a systematic literature review to understand its specific functions and its novel drug targets, the present article focuses on the central role of FF ATP synthase in primary non-communicable diseases. Next, it discusses its involvement through various pathways and the effects of multiple inhibitors, activators, and modulators specific to non-communicable diseases with a futuristic outlook.
Topics: Humans; Adenosine Triphosphate; Glycogen Synthase; Noncommunicable Diseases; Mitochondria; Mitochondrial Membranes; Mitochondrial Proton-Translocating ATPases
PubMed: 36715790
DOI: 10.1007/s11033-023-08299-3 -
Expert Review of Anti-infective Therapy Apr 2021Coronavirus Disease 2019 is a contagious infection that has infected millions worldwide. The objective of this systematic review is to identify studies pertaining to...
INTRODUCTION
Coronavirus Disease 2019 is a contagious infection that has infected millions worldwide. The objective of this systematic review is to identify studies pertaining to antivirals, both as sole and combined therapies, in COVID-19 patients and review the clinical outcomes of these treatment methods.
AREAS COVERED
A systematic review was conducted using Preferred Reporting Items or Systematic Reviews and Meta-analysis (PRISMA) guidelines. A literature search was done on Medline, Global Health, and EMBASE using keywords and MeSH terms relevant to COVID- 19 and antivirals. Limits were put on date to obtain articles between December 2019 to May 2020 (the time at which the search was performed). 776 articles were identified and screened. After screening, 16 studies were included. The narrative synthesis revealed three key themes (1) Use of antivirals only (such as lopinavir, umifenovir, and remdesivir), (2) Use of lopinavir-ritonavir alongside other treatments, and (3) Use of other antivirals in combination with other treatments.
EXPERT OPINION
Using antivirals in combination with other treatments has potential; however, further randomized controlled trials with larger sample sizes are required to identify the best candidate components that should comprise combined treatments for COVID-19. This should optimize treatment efficacy and improve patient outcomes.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; COVID-19; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Ritonavir; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 32924650
DOI: 10.1080/14787210.2021.1823832