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Neurobiology of Disease Jun 2024Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has... (Meta-Analysis)
Meta-Analysis Review
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Topics: Humans; Diabetes Mellitus, Type 2; Alzheimer Disease; Animals; Epigenesis, Genetic
PubMed: 38643861
DOI: 10.1016/j.nbd.2024.106485 -
Frontiers in Neuroscience 2021There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is...
There is a substantial need for new pharmacological treatments of addiction, and appetite-regulatory peptides are implied as possible candidates. Appetite regulation is complex and involves anorexigenic hormones such as glucagon-like peptide-1 (GLP-1) and amylin, and orexigenic peptides like ghrelin and all are well-known for their effects on feeding behaviors. This overview will summarize more recent physiological aspects of these peptides, demonstrating that they modulate various aspects of addiction processes. Findings from preclinical, genetic, and experimental clinical studies exploring the association between appetite-regulatory peptides and the acute or chronic effects of addictive drugs will be introduced. Short or long-acting GLP-1 receptor agonists independently attenuate the acute rewarding properties of addictive drugs or reduce the chronic aspects of drugs. Genetic variation of the GLP-1 system is associated with alcohol use disorder. Also, the amylin pathway modulates the acute and chronic behavioral responses to addictive drugs. Ghrelin has been shown to activate reward-related behaviors. Moreover, ghrelin enhances, whereas pharmacological or genetic suppression of the ghrelin receptor attenuates the responses to various addictive drugs. Genetic studies and experimental clinical studies further support the associations between ghrelin and addiction processes. Further studies should explore the mechanisms modulating the ability of appetite-regulatory peptides to reduce addiction, and the effects of combination therapies or different diets on substance use are warranted. In summary, these studies provide evidence that appetite-regulatory peptides modulate reward and addiction processes, and deserve to be investigated as potential treatment target for addiction.
PubMed: 34955726
DOI: 10.3389/fnins.2021.774050 -
Journal of Integrative Neuroscience Dec 2021Vasoactive peptides constitute a heterogenous family of mediators exerting various physiological functions, mostly studied for their vasotropic effects and role as...
Vasoactive peptides constitute a heterogenous family of mediators exerting various physiological functions, mostly studied for their vasotropic effects and role as peripheral neurotransmitters/neuromodulators, mainly involved in nociceptive transmission modulation. They have been divided into vasodilatory or vasoconstrictive peptides, according to their predominant effects on vascular tone. Recent research has shown in the Central Nervous System effects as transmitters and "growth factor-like" signals. Therefore, deregulation of their signaling systems has been thought to play a role in neural cell death and in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease, since these peptides can regulate neuronal stress signaling, survival cascades, synaptic plasticity. This review considers evidence about the implication of neuropeptide systems in Alzheimer's disease while focusing mainly on calcitonin gene-related peptide-alpha. In vitro and in vivo studies have shown potential implications in its pathogenesis. It has been possibly proposed as a neuroprotective agent, considering not only its pleiotropic actions on blood vessels, neurovascular coupling, energy metabolism, but also its potential actions on neuronal, glial, and immune system stress signaling, which might also derive from its structural homology to amylin. Amylin signaling is thought to be disrupted in Alzheimer's disease, and amylin itself takes part in the composition of senile plaques. Calcitonin gene-related peptide-containing systems seem more closely related to Alzheimer's disease pathogenesis than other neuropeptidergic systems, and their regulation might represent an interesting mechanism in developing novel therapeutic approaches.
Topics: Alzheimer Disease; Animals; Calcitonin Gene-Related Peptide; Humans; Neuroprotection
PubMed: 34997729
DOI: 10.31083/j.jin2004107 -
The Journal of Headache and Pain Jul 2021the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment...
BACKGROUND
the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present systematic review aims at identifying genetic variants occurring along the CGRP pathway and at verifying whether these can affect the clinical features and the course of disease and the responsiveness of patients to therapy.
METHODS
the literature search has been conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science, the Human Genome Epidemiology (HuGE) Published Literature database (Public Health Genomics Knowledge Base) and Clinicaltrials.gov from database inception until April 1, 2021. The process of identification and selection of the studies included in the analysis has followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses and the guidance from the Human Genome Epidemiology Network for reporting gene-disease associations.
RESULTS
the search has retrieved 800 results, among which only 7 studies have met the eligibility criteria for inclusion in the analysis. The latter are case-control studies of genetic association and an exploratory analysis and two polymorphisms have been detected as the most recurring: the rs3781719 (T > C) of the CALC A gene encoding CGRP and the rs7590387 of the gene encoding the receptor activity-modifying protein (RAMP) 1 (C > G). Only one study assessing the methylation pattern with regard to CGRP pathway has been found from the search. No genetic association studies investigating the possible effect of genetic variants affecting CGRP signaling on the responsiveness to the most recent pharmacological approaches, i.e. anti-CGRP(R) mAbs, gepants and ditans, have been published. According to the Human Genome Epidemiology (HuGE) systematic reviews and meta-analyses risk-of-bias score for genetic association studies, the heterogeneity between and across studies and the small sample size do not allow to draw conclusions and prompt future studies.
CONCLUSIONS
adequately powered, good quality genetic association studies are needed to understand the impact of genetic variants affecting the pathway of CGRP on migraine susceptibility and clinical manifestation and to predict the response to therapy in terms of efficacy and safety.
Topics: Antibodies, Monoclonal; Calcitonin; Calcitonin Gene-Related Peptide; Calcitonin Gene-Related Peptide Receptor Antagonists; Humans; Migraine Disorders
PubMed: 34330208
DOI: 10.1186/s10194-021-01295-7 -
PloS One 2019Cluster-randomized trials (CRTs) are being increasingly used to test a range of interventions, including medical interventions commonly used in clinical practice....
BACKGROUND
Cluster-randomized trials (CRTs) are being increasingly used to test a range of interventions, including medical interventions commonly used in clinical practice. Policies created by the NIH and the Food and Drug Administration (FDA) require the reporting of demographics and the examination of demographic heterogeneity of treatment effect (HTE) for individually randomized trials. Little is known about how frequent demographics are reported and HTE analyses are conducted in CRTs.
OBJECTIVES
We sought to understand the prevalence of HTE analyses and the statistical methods used to conduct them in CRTs focused on treating cardiovascular disease, cancer, and chronic lower respiratory diseases. Additionally, we also report on the proportion of CRTs that reported on baseline demographics of its populations and conducted demographic HTE analyses.
DATA SOURCES
We searched PubMed and Embase for CRTs published between 1/1/2010 and 3/29/2016 that focused on treating the top 3 Center for Disease Control causes of death (cardiovascular disease, chronic lower respiratory disease, and cancer). Evidence Screening And Review: Of 1,682 unique titles, 117 abstracts were screened. After excluding 53 articles, we included 64 CRT publications and abstracted information on study characteristics and demographic information, statistical analysis, HTE analysis, and study quality.
RESULTS
Age and sex were reported in greater than 95.3% of CRTs, while race and ethnicity were reported in only 20.3% of CRTs. HTE analyses were conducted in 28.1% (n = 18) of included CRTs and 77.8% (n = 12) were prespecified analyses. Four CRTs conducted a demographic subgroup analysis. Only 6/18 CRTs used interaction testing to determine whether HTE existed.
CONCLUSIONS
Baseline demographic reporting was high for age and sex in CRTs, but was uncommon for race and ethnicity. HTE analyses were uncommon and was rare for demographic subgroups, which limits the ability to examine the extent of benefits or risks for treatments tested with CRT designs.
Topics: Cardiovascular Diseases; Data Collection; Delivery of Health Care; Humans; Information Storage and Retrieval; Neoplasms; Randomized Controlled Trials as Topic; Research Design; Respiration Disorders
PubMed: 31404063
DOI: 10.1371/journal.pone.0219894 -
BMJ Simulation & Technology Enhanced... 2021The need for healthcare workers (HCWs) to have skills and knowledge in non-cancer palliative care has been recognised. Simulation is increasingly being used for...
BACKGROUND
The need for healthcare workers (HCWs) to have skills and knowledge in non-cancer palliative care has been recognised. Simulation is increasingly being used for palliative care training, offering participants the opportunity to learn in a realistic environment and fully interactive way.
OBJECTIVE
The aim of this systematic review was to summarise and critically appraise controlled studies on simulation training in non-cancer palliative care for HCWs.
SELECTION
Medline, CINAHL, PubMed and Cochrane Library databases were searched using palliative care and simulation terms. Randomised controlled trials (RCTs), non-randomised RCTs and controlled before-and-after (CBA) studies were included. Two reviewers independently screened titles and abstracts and undertook full article review using predefined selection criteria. Studies that met the inclusion criteria had data extracted and risk of bias assessed using the Cochrane Effective Practice and Organisation of Care risk of bias criteria.
FINDINGS
Five articles were included: three RCTs and two CBA studies. All studies assessed learners' palliative care communication skills, most studies evaluated learners' perception of change in skills and one study assessed impact on patient outcomes and learners' change in behaviour when applied in practice. There was variation in intervention content, intensity and duration, outcome measures and study design, making it difficult to compare and synthesise results.
CONCLUSION
There is a paucity of evidence to support simulation training to improve non-cancer palliative care. This review highlights the need for more robust research, including multicentre studies that use standardised outcome measures to assess clinician skills, changes in clinical practice and patient-related outcomes.
PubMed: 35516824
DOI: 10.1136/bmjstel-2019-000570 -
World Journal of Diabetes Aug 2021The prevalence of diabetes as a catastrophic disease in childhood is growing in the world. The search for novel biomarkers of β-cell failure has been an elusive task...
BACKGROUND
The prevalence of diabetes as a catastrophic disease in childhood is growing in the world. The search for novel biomarkers of β-cell failure has been an elusive task because it requires several clinical and biochemical measurements in order to integrate the risk of metabolic syndrome.
AIM
To determine which biomarkers are currently used to identify β-cell failure among children and adolescents with high risk factors for diabetes mellitus.
METHODS
This systematic review was carried out using a modified version of the PICO protocol (Participants/Intervention/Comparison/Outcome). Once our research question was established, terms were individually researched on three different databases (PubMed, BIREME and Web of Science). The total articles obtained underwent a selection process from which the 78 most relevant articles were retrieved to undergo further analysis. They were assessed individually according to quality criteria.
RESULTS
First, we made the classification of the β-cell-failure biomarkers by the target tissue and the evolution of the disease, separating the biomarkers in relation to the types of diabetes. Second, we demonstrated that most biomarkers currently used as early signs of β-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Third, we explored the novelties of diabetes as a protein conformational disease and the novel biomarker called real human islet amyloid polypeptide amyloid oligomers. Finally, we ended with a discussion about the best practice of validation and individual control of using different types of biomarkers in type 1 and type 2 diabetes in order to assess the role they play in the progress of diabetes in childhood.
CONCLUSION
This review makes widely evident that most biomarkers currently used as early signs of β-cell failure are those that concern local or systemic inflammation processes and oxidative stress as well as those related to endothelial dysfunction processes. Landing in the clinical practice we propose that real human islet amyloid polypeptide amyloid oligomers is good for identifying patients with β-cell damage and potentially could substitute many biomarkers.
PubMed: 34512897
DOI: 10.4239/wjd.v12.i8.1325