scholarly journals Investigation of Genetic Variations of IL6 and IL6R as Potential Prognostic and Pharmacogenetics Biomarkers: Implications for COVID-19 and Neuroinflammatory Disorders

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 351
Author(s):  
Claudia Strafella ◽  
Valerio Caputo ◽  
Andrea Termine ◽  
Shila Barati ◽  
Carlo Caltagirone ◽  
...  
Keyword(s):  
Public Health ◽  
Neurodegenerative Diseases ◽  
Multiorgan Failure ◽  
Treatment Strategies ◽  
Genetic Variations ◽  
Binding Ability ◽  
Public Health Emergencies ◽  
Age Related ◽  
Suitable Treatment

In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in IL6 and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within IL6R, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID-19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of IL6-IL6R-related biomarkers for COVID-19 may be helpful to counteract harmful complications and prevent multiorgan failure. At the same time, IL6-IL6R-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients’ prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize personalized medicine protocols for chronic, age-related and modern public health emergencies.

scholarly journals Investigation of genetic variations of IL6 and IL6R as potential prognostic and pharmacogenetics biomarkers: implications for COVID19 and neuroinflammatory disorders.

2020 ◽  
Author(s):  
Claudia Strafella ◽  
Valerio Caputo ◽  
Andrea Termine ◽  
Shila Barati ◽  
Carlo Caltagirone ◽  
...  
Keyword(s):  
Public Health ◽  
Quality Of Life ◽  
Neurodegenerative Diseases ◽  
Treatment Strategies ◽  
Genetic Variations ◽  
Binding Ability ◽  
Public Health Emergencies ◽  
Age Related ◽  
Suitable Treatment

Abstract In the present study, we investigated the distribution of genetic variations in IL6 and IL6R genes, which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19 and neurodegenerative diseases. The study was performed on 271 samples representative of the Italian general population and identified seven variants (rs140764737, rs142164099, rs2069849, rs142759801, rs190436077, rs148171375, rs13306435) in IL6 and five variants (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642) within IL6R, respectively. These variants have been predicted to affect the expression and binding ability of IL6 and IL6R. The Ingenuity Pathway Analysis (IPA) showed that IL6 and IL6R appeared to be implicated in several pathogenetic mechanisms associated with COVID19 severity and mortality as well as with neurodegenerative diseases mediated by neuroinflammation. Thus, the availability of IL6-IL6R-related biomarkers for COVID19 disease may be helpful to counteract harmful complications and prevent multi-organ failure. At the same time, IL6-IL6R-related biomarkers could also be useful for assessing the susceptibility and progression of neuroinflammatory disorders and undertake the most suitable treatment strategies to improve patients’ prognosis and quality of life. In conclusion, this study showed how IL6 pleiotropic activity could be exploited to meet different clinical needs and realize precision medicine protocols for chronic, age-related and modern public health emergencies.

Nanotechnology: its application in treating Neurodegenerative diseases

2020 ◽  
Vol 19 ◽  
Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique
Keyword(s):  
Quality Of Life ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Huntington Disease ◽  
Treatment Strategies ◽  
Present Review ◽  
Brain Barrier ◽  
Treatment Level ◽  
Blood Brain

: Neurodegenerative diseases including Alzheimer’s, Parkinson’s and Huntington disease are have serious concern due to its effect on the quality of life of affected persons. Neurodegenerative diseases have some limitations for both diagnostic as well as at treatment level. Introducing nanotechnology, for the treatment of these diseases may contribute significantly in solving the problem. There are several treatment strategies for the neurodegenerative diseases, but their limitations are the entry into the due to the presence of the blood-brain barrier (BBB). The present review highlights the application of nanotechnology during last 20 years for the treatment of neurodegenerative diseases.

scholarly journals Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1574
Author(s):  
Ciprian N. Silaghi ◽  
Marius Farcaș ◽  
Alexandra M. Crăciun
Keyword(s):  
Neurodegenerative Diseases ◽  
Wide Spectrum ◽  
Metabolic Adaptation ◽  
High Morbidity ◽  
Protective Effects ◽  
Sirtuin 3 ◽  
Age Related ◽  
Genetic Interventions ◽  
Induced Changes

Age-associated cardiovascular and neurodegenerative diseases lead to high morbidity and mortality around the world. Sirtuins are vital enzymes for metabolic adaptation and provide protective effects against a wide spectrum of pathologies. Among sirtuins, mitochondrial sirtuin 3 (SIRT3) is an essential player in preserving the habitual metabolic profile. SIRT3 activity declines as a result of aging-induced changes in cellular metabolism, leading to increased susceptibility to endothelial dysfunction, hypertension, heart failure and neurodegenerative diseases. Stimulating SIRT3 activity via lifestyle, pharmacological or genetic interventions could protect against a plethora of pathologies and could improve health and lifespan. Thus, understanding how SIRT3 operates and how its protective effects could be amplified, will aid in treating age-associated diseases and ultimately, in enhancing the quality of life in elders.

scholarly journals The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases

2020 ◽  
Vol 21 (6) ◽  
pp. 2108 ◽  
Author(s):  
Wioletta Rozpędek-Kamińska ◽  
Natalia Siwecka ◽  
Adam Wawrzynkiewicz ◽  
Radosław Wojtczak ◽  
Dariusz Pytel ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Stress Conditions ◽  
World Population ◽  
Dependent Manner ◽  
Age Related ◽  
The Unfolded Protein Response

Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.

The effects of aging, injury and disease on microglial function: a case for cellular senescence

2007 ◽  
Vol 3 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Kelly R. Miller ◽  
Wolfgang J. Streit
Keyword(s):  
Neurodegenerative Diseases ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Aging Brain ◽  
Normal Brain ◽  
Age Related ◽  
Anti Inflammatory ◽  
Effects Of Aging ◽  
And Function

AbstractNeuroinflammation resulting from chronic reactive microgliosis is thought to contribute to age-related neurodegeneration, as well as age-related neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of this theory comes from studies reporting a progressive, age-associated increase in microglia with an activated phenotype. Although the underlying cause(s) of this microglial reactivity is idiopathic, an accepted therapeutic strategy for the treatment of AD is inhibition of microglial activation using anti-inflammatory agents. Although the effectiveness of anti-inflammatory treatment for AD remains equivocal, microglial inhibition is being tested as a potential treatment for additional neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Given the important and necessary functions of microglia in normal brain, careful evaluation of microglial function in the aged brain is a necessary first step in targeting more precise treatment strategies for aging-related neurodegenerative diseases. Studies from our laboratory have shown multiple age-related changes in microglial morphology and function that are suggestive of cellular senescence. In this manuscript, we review current knowledge of microglia in the aging brain and present new, unpublished work that further supports the theory that microglia experience an age-related decline in proliferative function as a result of cellular senescence.

scholarly journals Convergence of Synapses, Endosomes, and Prions in the Biology of Neurodegenerative Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Gunnar K. Gouras
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Brain Regions ◽  
Neural Function ◽  
Cellular Mechanisms ◽  
Normal Functions ◽  
Age Related ◽  
Cell Propagation

Age-related misfolding and aggregation of disease-linked proteins in selective brain regions is a characteristic of neurodegenerative diseases. Although neuropathological aggregates that characterize these various diseases are found at sites other than synapses, increasing evidence supports the idea that synapses are where the pathogenesis begins. Understanding these diseases is hampered by our lack of knowledge of what the normal functions of these proteins are and how they are affected by aging. Evidence has supported the idea that neurodegenerative disease-linked proteins have a common propensity for prion protein-like cell-to-cell propagation. However, it is not thought that the prion-like quality of these proteins/peptides that allows their cell-to-cell transmission implies a role for human-to-human spread in common age-related neurodegenerative diseases. It will be important to better understand the molecular and cellular mechanisms governing the role of these aggregating proteins in neural function, especially at synapses, how their propagation occurs and how pathogenesis is promoted by aging.

scholarly journals A Stepped Wedge Cluster Randomized Control Trial to Evaluate the Implementation and Effectiveness of Optimized Quality-Improvement Initiatives in Improving Quality of Care for Acute Cardiac Events in Response to the COVID-19 Outbreak

2021 ◽  
Author(s):  
Shuduo Zhou ◽  
Xuejie Dong ◽  
Fangjing Liu ◽  
Yan Zhang ◽  
Dahai Yue ◽  
...  
Keyword(s):  
Public Health ◽  
Health Care ◽  
Randomized Control Trial ◽  
Scale Up ◽  
Stepped Wedge ◽  
Public Health Emergencies ◽  
Cluster Randomized Control Trial ◽  
Randomized Control ◽  
Cluster Randomized

Abstract Background: The National Chest Pain Center Accreditation Program (CHANGE) is the first hospital-based, multifaceted, nationwide quality improvement (QI) initiative, to monitor and improve quality of ST-segment elevation myocardial infarction (STEMI) care in China. The QI initiatives, as implementation strategies, include a bundle of evidence-based interventions adapted for implementation in China. During the pandemic of coronavirus disease 2019 (COVID-19), fear of infection with severe acute respiratory syndrome coronavirus 2, national lockdowns, and altered health care priorities have highlighted the program’s importance in improving STEMI care quality. This study aims to minimize the adverse impact of the COVID-19 pandemic on the quality of STEMI care, by developing interventions that optimize the QI initiatives, implementing and evaluating the optimized QI initiatives, and developing scale-up activities of the optimized QI initiatives in response to COVID-19 and other public health emergencies.Methods: A stepped wedge cluster randomized control trial will be conducted in three selected cities of China: Wuhan, Suzhou, and Shenzhen. Two districts have been randomly selected in each city, yielding a total of 24 registered hospitals. This study will conduct a rollout in these hospitals every 3 months. The 24 hospitals will be randomly assigned to four clusters, and each cluster will commence the intervention (optimized QI initiatives) at one of the four steps. We will conduct hospital-based assessments, questionnaire surveys among health care providers, community-based household surveys, and key informant interviews during the trial. All outcome measures will be organized using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, including implementation outcomes, service outcomes (e.g., treatment time), and patient outcomes (e.g., in-hospital mortality and 1-year complication). The Consolidated Framework for Implementation Research framework will be used to identify factors that influence implementation of the optimized QI interventions.Discussion: The study findings could be translated into a systematic solution to implementing QI initiatives in response to COVID-19 and future potential major public health emergencies. Such actionable knowledge is critical for implementors of scale-up activities in low- and middle-income settings.Trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR 2100043319), registered 10 February 2021

scholarly journals The management of the patient with osteoporosis: from evidence to clinical practice

2017 ◽  
Vol 11 (3) ◽  
pp. 253
Author(s):  
Immacolata Ambrosino ◽  
Angela Riccardo ◽  
Paola Gnerre ◽  
Grace Massiah ◽  
Laura Castelnovo ◽  
...  
Keyword(s):  
Public Health ◽  
Clinical Practice ◽  
Economic Impact ◽  
Bone Disease ◽  
Careful Evaluation ◽  
Treatment Of Osteoporosis ◽  
Diagnosis And Therapy ◽  
Age Related ◽  
Efficacious Treatment

Osteoporosis is the most common bone disease and is an important problem of public health. In fact, it represents the main cause of age-related fractures and disabilities with a consequent increasing sanitary, social and economic impact. Unfortunately, often osteoporosis is not as thoroughly investigated as it would be desirable and it is underestimated in diagnosis and therapy. The aim of this monograph is to sensitize medical internists to a careful evaluation and an efficacious treatment of osteoporosis in order to reduce the risks of this disease, in particular the fractures, with a view to improving the quality of patients’ life.

scholarly journals Community resilience monitoring and evaluation under the prevention and control of public health emergencies

2021 ◽  
Vol 251 ◽  
pp. 03013
Author(s):  
Shuang Liu ◽  
Yixi Wang ◽  
Zixiao Li ◽  
Dandan Zhang ◽  
Kuntai Yu
Keyword(s):  
Public Health ◽  
Medical Staff ◽  
Prevention And Control ◽  
Community Resilience ◽  
Living Environment ◽  
Assessment Model ◽  
Medical Resources ◽  
Public Health Emergencies ◽  
And Control

In order to monitor the level of community resilience and the quality of the living environment under public health emergencies, 13 communities in Xingfu Street, Dujiangyan City are taken as the empirical research objects, and the PSR model-entropy method is used to construct a community-based public health emergency prevention and control resilience assessment model to explore the existing problems of the community’s epidemic prevention capabilities and the quality of the human settlement environment. The results show that: ①The resilience level and the quality of the living environment of the series of communities under Xingfu Street are generally average, and there are big differences in resilience between communities. ②In the construction indicators, “Total per capita income loss” and “Proportion of population over 65” have significant negative impact, “Application level of new prevention and control technology”, “Number of community medical staff”, “Proportion of medical staff with intermediate and above titles”, “ Exchangeability and sharing of health information resources” and “Number of hospital beds” have significant positive impact. ③The resilience of the prevention and control of public health emergencies in the community is most significantly affected by medical resources, but the community medical resources are generally scarce and the development is not coordinated. Xingfu Street series communities should focus on improving the level of basic medical services, promote resilience building in stages, and realize the organic combination of dynamic epidemic prevention and sustainable development.

Autophagy and ageing: implications for age-related neurodegenerative diseases

2013 ◽  
Vol 55 ◽  
pp. 119-131 ◽  
Author(s):  
Bernadette Carroll ◽  
Graeme Hewitt ◽  
Viktor I. Korolchuk
Keyword(s):  
Neurodegenerative Diseases ◽  
Energy Availability ◽  
Future Studies ◽  
Intracellular Degradation ◽  
Age Related ◽  
Autophagy Induction ◽  
Social Importance ◽  
Cellular Dysfunction ◽  
Autophagy Activity ◽  
Intense Research

Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our ‘ageing’ world.

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