scholarly journals Neuroprotective effects of some epigenetic modifying drugs’ on Chlamydia pneumoniae-induced neuroinflammation: A novel model

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260633
Author(s):  
Elif Kaya-Tilki ◽  
Miriş Dikmen
Keyword(s):  
Chlamydia Pneumoniae ◽  
Trichostatin A ◽  
Treatment Options ◽  
Regulatory System ◽  
Intracellular Pathogen ◽  
Neuroprotective Effects ◽  
Neuroprotective Actions ◽  
New Treatment ◽  
Analysis System ◽  
Novel Model

Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer’s disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host’s epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS. The neuroprotective effects of Trichostatin A (TSA), givinostat, and RG108, which are effective on epigenetic mechanisms, and the antibiotic rifampin, were studied in this newly introduced model and in the presence of amyloid beta (Aβ) 1–42. The neuroprotective effects of the drugs, as well as the effects of CFS and LPS, were evaluated in Aβ-induced neurotoxicity using a real-time cell analysis system, total ROS, and apoptotic impact. TSA, RG108, givinostat, and rifampin all demonstrated neuroprotective effects in both this novel model and Aβ-induced neurotoxicity. The findings are expected to provide early evidence on neuroprotective actions against Cpn-induced neuroinflammation and Aβ-induced neurotoxicity, which could represent a new treatment option for AD, for which there are currently few treatment options.

scholarly journals HDAC inhibition protects degenerating cone photoreceptors in vivo

2016 ◽  
Author(s):  
Dragana Trifunović ◽  
Blanca Arango-Gonzalez ◽  
Antonella Comitato ◽  
Melanie Barth ◽  
Ayse Sahaboglu ◽  
...  
Keyword(s):  
Cell Death ◽  
Trichostatin A ◽  
Treatment Options ◽  
Hdac Inhibition ◽  
Neuroprotective Effects ◽  
Histone Deacetylase Inhibitor Trichostatin ◽  
New Treatment ◽  
Future Therapy

AbstractRetinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

scholarly journals Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics

2020 ◽  
Vol 9 (4) ◽  
pp. 1061 ◽  
Author(s):  
Mehdi Sharifi-Rad ◽  
Chintha Lankatillake ◽  
Daniel A. Dias ◽  
Anca Oana Docea ◽  
Mohamad Fawzi Mahomoodally ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Treatment Options ◽  
Neuroprotective Effects ◽  
Herbal Products ◽  
Suitable Alternative ◽  
Age Related ◽  
Regional Sources ◽  
Oxidase Inhibition ◽  
Socioeconomic Burden ◽  
New Treatment

Among the major neurodegenerative disorders (NDDs), Alzheimer’s disease (AD) and Parkinson’s disease (PD), are a huge socioeconomic burden. Over many centuries, people have sought a cure for NDDs from the natural herbals. Many medicinal plants and their secondary metabolites are reported with the ability to alleviate the symptoms of NDDs. The major mechanisms identified, through which phytochemicals exert their neuroprotective effects and potential maintenance of neurological health in ageing, include antioxidant, anti-inflammatory, antithrombotic, antiapoptotic, acetylcholinesterase and monoamine oxidase inhibition and neurotrophic activities. This article reviews the mechanisms of action of some of the major herbal products with potential in the treatment of NDDs according to their molecular targets, as well as their regional sources (Asia, America and Africa). A number of studies demonstrated the beneficial properties of plant extracts or their bioactive compounds against NDDs. Herbal products may potentially offer new treatment options for patients with NDDs, which is a cheaper and culturally suitable alternative to conventional therapies for millions of people in the world with age-related NDDs.

scholarly journals Neuroprotective Activities of Boophone haemanthoides (Amaryllidaceae) Extract and Its Chemical Constituents

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5376
Author(s):  
Abobaker S. Ibrakaw ◽  
Sylvester I. Omoruyi ◽  
Okobi E. Ekpo ◽  
Ahmed A. Hussein
Keyword(s):  
Bioactive Compounds ◽  
Chemical Constituents ◽  
Treatment Options ◽  
Neuroblastoma Cells ◽  
Neuroprotective Effects ◽  
Vitro Model ◽  
New Treatment ◽  
Induced Apoptosis ◽  
Alkaloidal Constituents

Parkinson’s disease (PD) is a neurodegenerative condition that progresses as age increases, and some of its major symptoms include tremor and postural and movement-related difficulties. To date, the treatment of PD remains a challenge because available drugs only treat the symptoms of the disease or possess serious side effects. In light of this, new treatment options are needed; hence, this study investigates the neuroprotective effects of an organic Boophone haemanthoides extract (BHE) and its bioactive compounds using an in vitro model of PD involving the toxin 1-methyl-4-phenylpyridinium (MPP+) and SH-SY5Y neuroblastoma cells. A total of seven compounds were isolated from BHE, viz distichamine (1), 1α,3α-diacetylnerbowdine (2), hippadine (3), stigmast-4-ene-3,6-dione (4), cholest-4-en-3-one (5), tyrosol (6), and 3-hydroxy-1-(4′-hydroxyphenyl)-1-propanone (7). Six compounds (1, 2, 4, 5, 6 and 7) were investigated, and five showed neuroprotection alongside the BHE. This study gives insight into the bioactivity of the non-alkaloidal constituents of Amaryllidaceae, since the isolated compounds and the BHE showed improved cell viability, increased ATP generation in the cells as well as inhibition of MPP+-induced apoptosis. Together, these findings support the claim that the Amaryllidaceae plant family could be a potential reserve of bioactive compounds for the discovery of neuroprotective agents.

scholarly journals Boophone Haemanthoides (Amaryllidaceae) and Its Bioactive Compounds Attenuate MPP+-Induced Toxicity in an in Vitro Parkinson’s Disease Model

2020 ◽  
Author(s):  
Abobaker S. Ibrakaw ◽  
Sylvester I. Omoruyi ◽  
Okobi E. Ekpo ◽  
Ahmed A. Hussein
Keyword(s):  
Bioactive Compounds ◽  
Treatment Options ◽  
Disease Model ◽  
Neuroblastoma Cells ◽  
Neuroprotective Effects ◽  
Vitro Model ◽  
New Treatment ◽  
Induced Apoptosis ◽  
Alkaloidal Constituents

Parkinson’s disease (PD) is a neurodegenerative disease that progresses with increasing age and some of its major symptoms include tremor, postural and movement related difficulties. Till date, the treatment of PD remains a challenge because available drugs only treat the symptoms of the disease or possess serious side effects. In light of this, new treatment options are needed, hence this study investigates the neuroprotective effects of an organic Boophone haemanthoides extract (BHE) and its bioactive compounds using an in vitro model of PD involving the toxin 1-methyl-4-phenylpyridinium (MPP+) and SH-SY5Y neuroblastoma cells. A total of seven compounds were isolated from BHE viz: distichamine (1), 1α,3α-diacetylnerbowdine (2), hippadine (3), stigmast-4-ene-3, 6-dione (4), cholest-4-en-3-one (5), tyrosol (6), and 3-hydroxy-1-(4`-hydroxyphenyl)-1-propanone (7). Six compounds (1, 2, 4, 5, 6, 7) were investigated and five showed neuroprotection alongside the BHE. This study gives insight into the bioactivity of the non-alkaloidal constituents of Amaryllidaceae since the isolated compounds and the BHE showed improved cell viability, increased ATP generation in the cells as well as inhibition of MPP+-induced apoptosis. Together, these findings support the claim that the Amaryllidaceae plant family could be a potential reserve of bioactive compounds for the discovery of neuroprotective agents.

Chlamydia pneumoniae-Induced Neuroinflammation Cell Model Using Lyophilized Cell-Free Supernatant v1

2021 ◽  
Author(s):  
Elif Kaya Tilki
Keyword(s):  
Inflammatory Response ◽  
Infected Cell ◽  
Chlamydia Pneumoniae ◽  
Cell Model ◽  
Regulatory System ◽  
Host Tissue ◽  
Pulmonary Diseases ◽  
Intracellular Pathogen ◽  
Gram Negative ◽  
Cell Free Supernatant

Chlamydia pneumoniae (Cpn) is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer's disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host's epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS.

Management of thoracic aortic lesions - the future is endovascular

VASA ◽  
2012 ◽  
Vol 41 (3) ◽  
pp. 163-176 ◽  
Author(s):  
Weidenhagen ◽  
Bombien ◽  
Meimarakis ◽  
Geisler ◽  
A. Koeppel
Keyword(s):  
Thoracic Aorta ◽  
Clinical Decision Making ◽  
Treatment Options ◽  
Clinical Decision ◽  
Clinical Results ◽  
Treatment Modalities ◽  
Traumatic Rupture ◽  
Descending Thoracic Aorta ◽  
New Treatment ◽  
Aneurysm Dissection

Open surgical repair of lesions of the descending thoracic aorta, such as aneurysm, dissection and traumatic rupture, has been the “state-of-the-art” treatment for many decades. However, in specialized cardiovascular centers, thoracic endovascular aortic repair and hybrid aortic procedures have been implemented as novel treatment options. The current clinical results show that these procedures can be performed with low morbidity and mortality rates. However, due to a lack of randomized trials, the level of reliability of these new treatment modalities remains a matter of discussion. Clinical decision-making is generally based on the experience of the vascular center as well as on individual factors, such as life expectancy, comorbidity, aneurysm aetiology, aortic diameter and morphology. This article will review and discuss recent publications of open surgical, hybrid thoracic aortic (in case of aortic arch involvement) and endovascular repair in complex pathologies of the descending thoracic aorta.

A Genomic Approach to Characterize the Vulnerable Patient – a Clinical Update

2019 ◽  
Vol 4 (3) ◽  
pp. 141-144
Author(s):  
Evelin Szabó ◽  
Zsolt Parajkó ◽  
Diana Opincariu ◽  
Monica Chițu ◽  
Nóra Raț ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Ischemia ◽  
Treatment Options ◽  
Ischemic Heart ◽  
Pathophysiological Mechanism ◽  
Ischemia And Reperfusion Injury ◽  
Myocardial Ischemia And Reperfusion ◽  
Vulnerable Patient ◽  
Traditional Risk Factors ◽  
New Treatment

Abstract Atherosclerosis is the elemental precondition for any cardiovascular disease and the predominant cause of ischemic heart disease that often leads to myocardial infarction. Systemic risk factors play an important role in the starting and progression of atherosclerosis. The complexity of the disease is caused by its multifactorial origin. Besides the traditional risk factors, genetic predisposition is also a strong risk factor. Many studies have intensively researched cardioprotective drugs, which can relieve myocardial ischemia and reperfusion injury, thereby reducing infarct size. A better understanding of abnormal epigenetic pathways in the myocardial pathology may result in new treatment options. Individualized therapy based on genome sequencing is important for an effective future medical treatment. Studies based on multiomics help to better understand the pathophysiological mechanism of several diseases at a molecular level. Epigenomic, transcriptomic, proteomic, and metabolomic research may be essential in detecting the pathological phenotype of myocardial ischemia and ischemic heart failure.

U.S. Regulatory Approaches: A Critical Appraisal

1992 ◽  
Vol 25 (3) ◽  
pp. 13-21
Author(s):  
R. L. Williamson
Keyword(s):  
Decision Making ◽  
Command And Control ◽  
Regulatory System ◽  
Federal Agencies ◽  
Toxic Substances ◽  
Use Of Technology ◽  
Treatment Technologies ◽  
New Treatment ◽  
And Control ◽  
The Impact

The American approach to environmental regulation is characterized by fragmentation of responsibilities, primary reliance on command and control regulations, extraordinary complexity, a preference for identifiable standards, and heavy resort to litigation. This system has provided important benefits, including significant reduction of environmental contamination, substantial use of science in decision-making, broad participatory rights, and the stimulation of new treatment technologies. However, these gains have been achieved at excessive cost. Too much reliance is placed on command and control methods and especially on technology-based standards. There is too much resort to litigation, and inadequate input from science. Participatory rights are being undermined, and there is a poor allocation of decision-making among the federal agencies and the states. Over-regulation sometimes leads to under-regulation, and insufficient attention is given to the impact on small entities. The responsibility for these difficulties rests with everyone, including the federal agencies, the Congress, the general public and the courts. Changes in the regulatory system are needed. We should abandon the use of technology-based standards to control toxic substances under the Clean Water Act in favor of strong health- and environmentally based standards, coupled with taxes on toxic substances in wastewater.

Proteomic Analysis of the Vitreous Body in Proliferative and Non-Proliferative Diabetic Retinopathy

2020 ◽  
Vol 17 ◽  
Author(s):  
Van-An Duong ◽  
Jeeyun Ahn ◽  
Na-Young Han ◽  
Jong-Moon Park ◽  
Jeong-Hun Mok ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Vitreous Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Protein Protein Interaction ◽  
Alpha Beta ◽  
New Treatment

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

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