Molecular Pathways of Ischemic Stroke and Advanced Therapeutic Strategies

2018 ◽  
Vol 4 (1-2) ◽  
Author(s):  
Preeti Singh
Keyword(s):  
Ischemic Stroke ◽  
New Technologies ◽  
Treatment Strategies ◽  
Molecular Pathways ◽  
Therapeutic Approaches ◽  
Permanent Disability ◽  
Acute Cerebral Ischemia ◽  
Tremendous Progress ◽  
New Treatment

Ischemic stroke is a leading cause of death and permanent disability. This disease may affect any age group and especially in old age and pregnancy. All the responsible mechanisms are yet not completely understood. There is limited therapeutic intervention beyond prevention, yet tremendous progress in understanding cause of stroke at molecular level has been going on. A lot of advancement has occurred in the prevention and treatment of stroke during the past decade. In this review an update work of causeways of stroke and its therapeutic approaches have been discussed. The relevance of excitotoxicity (role of glutamate receptor), inflammation, ischemic penumbra, apoptosis, to delayed mechanisms and, damage and treatment strategies have been hasted out. Although the results among clinical studies, conflict regarding several experimental data of different therapies, and it may improve neurological outcome after acute cerebral ischemia. Along this several other interventions and new technologies such as stroke detector microwave helmet are being assessed and many other advanced techniques developed by researchers. Even the development of other novel and new treatment strategies (regarding molecular pathways and risk to benefit therapeutic ratio) for stroke are still required in future for better treatment.

scholarly journals Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xu Zhou ◽  
Jingliang He ◽  
Jinbo Chen ◽  
Yu Cui ◽  
Zhenyu Ou ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Leydig Cells ◽  
Treatment Strategies ◽  
Pten Expression ◽  
Luciferase Reporter ◽  
Western Blots ◽  
New Treatment ◽  
Lps Treatment

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

scholarly journals The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

2021 ◽  
Author(s):  
Natalia Bryniarska-Kubiak ◽  
Andrzej Kubiak ◽  
Małgorzata Lekka ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Nervous System ◽  
Physical Factors ◽  
Nervous System Diseases ◽  
Therapeutic Approaches ◽  
System Disease ◽  
New Therapeutic Approaches ◽  
The Subject ◽  
Topographical Factors ◽  
New Treatment

AbstractNervous system diseases are the subject of intensive research due to their association with high mortality rates and their potential to cause irreversible disability. Most studies focus on targeting the biological factors related to disease pathogenesis, e.g. use of recombinant activator of plasminogen in the treatment of stroke. Nevertheless, multiple diseases such as Parkinson’s disease and Alzheimer’s disease still lack successful treatment. Recently, evidence has indicated that physical factors such as the mechanical properties of cells and tissue and topography play a crucial role in homeostasis as well as disease progression. This review aims to depict these factors’ roles in the progression of nervous system diseases and consequently discusses the possibility of new therapeutic approaches. The literature is reviewed to provide a deeper understanding of the roles played by physical factors in nervous system disease development to aid in the design of promising new treatment approaches. Graphic abstract

Thrombolysis in Ischemic Stroke: Focus on New Treatment Strategies

2012 ◽  
Vol 7 (1) ◽  
pp. 42-52
Author(s):  
Rocco S. Calabro ◽  
Giuseppe Gervasi ◽  
Placido Bramanti ◽  
Anna Cavallini
Keyword(s):  
Ischemic Stroke ◽  
Treatment Strategies ◽  
New Treatment

scholarly journals Extracellular Vesicles: A Possible Link between HIV and Alzheimer’s Disease-Like Pathology in HIV Subjects?

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 968 ◽  
Author(s):  
Sunitha Kodidela ◽  
Kelli Gerth ◽  
Sanjana Haque ◽  
Yuqing Gong ◽  
Saifudeen Ismael ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Progressive Dementia ◽  
Hiv Patients ◽  
Age Related ◽  
Infected Cells ◽  
New Treatment

The longevity of people with HIV/AIDS has been prolonged with the use of antiretroviral therapy (ART). The age-related complications, especially cognitive deficits, rise as HIV patients live longer. Deposition of beta-amyloid (Aβ), a hallmark of Alzheimer’s disease (AD), has been observed in subjects with HIV-associated neurocognitive disorders (HAND). Various mechanisms such as neuroinflammation induced by HIV proteins (e.g., Tat, gp120, Nef), excitotoxicity, oxidative stress, and the use of ART contribute to the deposition of Aβ, leading to dementia. However, progressive dementia in older subjects with HIV might be due to HAND, AD, or both. Recently, extracellular vesicles (EVs)/exosomes, have gained recognition for their importance in understanding the pathology of both HAND and AD. EVs can serve as a possible link between HIV and AD, due to their ability to package and transport the toxic proteins implicated in both AD and HIV (Aβ/tau and gp120/tat, respectively). Given that Aß is also elevated in neuron-derived exosomes isolated from the plasma of HIV patients, it is reasonable to suggest that neuron-to-neuron exosomal transport of Aβ and tau also contributes to AD-like pathology in HIV-infected subjects. Therefore, exploring exosomal contents is likely to help distinguish HAND from AD. However, future prospective clinical studies need to be conducted to compare the exosomal contents in the plasma of HIV subjects with and without HAND as well as those with and without AD. This would help to find new markers and develop new treatment strategies to treat AD in HIV-positive subjects. This review presents comprehensive literatures on the mechanisms contributing to Aβ deposition in HIV-infected cells, the role of EVs in the propagation of Aβ in AD, the possible role of EVs in HIV-induced AD-like pathology, and finally, possible therapeutic targets or molecules to treat HIV subjects with AD.

Role of the intestinal microbiome in liver fibrosis development and new treatment strategies

2019 ◽  
Vol 209 ◽  
pp. 22-38 ◽  
Author(s):  
Rongrong Zhou ◽  
Xuegong Fan ◽  
Bernd Schnabl
Keyword(s):  
Liver Fibrosis ◽  
Treatment Strategies ◽  
Intestinal Microbiome ◽  
New Treatment

scholarly journals Endovascular Intervention for Acute Ischemic Stroke in Light of Recent Trials

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kenan Alkhalili ◽  
Nohra Chalouhi ◽  
Stavropoula Tjoumakaris ◽  
David Hasan ◽  
Robert M. Starke ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Treatment Strategies ◽  
Endovascular Intervention ◽  
Treatment Modalities ◽  
Efficacy And Safety ◽  
The Past ◽  
Endovascular Approach

Three recently published trials, MR RESCUE, IMS III, and SYNTHESIS Expansion, evaluating the efficacy and safety of endovascular treatment of acute ischemic stroke have generated concerns about the future of endovascular approach. However, the tremendous evolution that imaging and endovascular treatment modalities have undergone over the past several years has raised doubts about the validity of these trials. In this paper, we review the role of endovascular treatment strategies in acute ischemic stroke and discuss the limitations and shortcomings that prevent generalization of the findings of recent trials. We also provide our experience in endovascular treatment of acute ischemic stroke.

The role of methylglyoxal and the glyoxalase system in diabetes and other age-related diseases

2015 ◽  
Vol 128 (12) ◽  
pp. 839-861 ◽  
Author(s):  
Dionne E.M. Maessen ◽  
Coen D.A. Stehouwer ◽  
Casper G. Schalkwijk
Keyword(s):  
Advanced Glycation Endproducts ◽  
Treatment Strategies ◽  
Glyoxalase System ◽  
Dicarbonyl Compound ◽  
Glycation Endproducts ◽  
Age Related ◽  
Key Enzyme ◽  
The Central Nervous System ◽  
New Treatment

The formation and accumulation of advanced glycation endproducts (AGEs) are related to diabetes and other age-related diseases. Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is the major precursor in the formation of AGEs. MGO is mainly formed as a byproduct of glycolysis. Under physiological circumstances, MGO is detoxified by the glyoxalase system into D-lactate, with glyoxalase I (GLO1) as the key enzyme in the anti-glycation defence. New insights indicate that increased levels of MGO and the major MGO-derived AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1), and dysfunctioning of the glyoxalase system are linked to several age-related health problems, such as diabetes, cardiovascular disease, cancer and disorders of the central nervous system. The present review summarizes the mechanisms through which MGO is formed, its detoxification by the glyoxalase system and its effect on biochemical pathways in relation to the development of age-related diseases. Although several scavengers of MGO have been developed over the years, therapies to treat MGO-associated complications are not yet available for application in clinical practice. Small bioactive inducers of GLO1 can potentially form the basis for new treatment strategies for age-related disorders in which MGO plays a pivotal role.

scholarly journals Neuroprotective activity of orexin system in ischemic stroke

2018 ◽  
Vol 17 (2) ◽  
pp. 4-11
Author(s):  
I. A. Filchenko ◽  
Yu. V. Sviryaev ◽  
T. D. Vlasov
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Neuroprotective Activity ◽  
Therapeutic Approaches ◽  
Common Features ◽  
Protective Potential ◽  
New Methods ◽  
New Therapeutic Approaches ◽  
The Common

The protective potential of orexin system is a field of interest in the search of the new methods to diminish brain damage in ischemic stroke. The cytoprotective potential of orexins in hypoxic damage is associated with their antioxidant, anti-inflammatory and anti-apoptotic properties and with their ability to activate proliferation and normalize metabolism. Even though today little is known about the role of orexins in memory and pain in ischemic stroke, the common features of the pathogenesis of these disruptions and the mechanisms of orexin-associated protection could suggest the opportunity to use of orexins for correction of these complications following ischemic stroke. Further studies of the orexin-associated neuroprotection could become the further step on the way to the new therapeutic approaches in ischemic stroke.

scholarly journals Role of fatty acids in inflammation, atherosclerosis, metabolic disorders and gout

2021 ◽  
Vol 15 (6) ◽  
pp. 124-129
Author(s):  
M. A. Gromova ◽  
V. V. Tsurko ◽  
O. A. Kislyak ◽  
E. V. Kiseleva
Keyword(s):  
Fatty Acids ◽  
Metabolic Disorders ◽  
Treatment Strategies ◽  
Endothelial Activation ◽  
Transport Systems ◽  
Membrane Phospholipids ◽  
Inflammatory Reactions ◽  
New Treatment ◽  
Urate Crystals

Fatty acids (FA) are present in all types of organisms and play an important role in energy metabolism. The length and number of double bonds in the FA of membrane phospholipids determine the viscosity, the activity of transport systems and enzymes, and also the susceptibility to lipid peroxidation. The review discusses the influence of free unsaturated FAs with short and long chains on various inflammatory mechanisms, including atherosclerosis. It has been shown that FAs can reduce endothelial activation and affect the metabolism of eicosanoids. A new model of fundamental factors determining the variability of the timing, degree and duration of acute inflammatory reactions in the deposition of urate crystals in tissues, in which FAs play an important role is considered, using gout as an example. In the future, the study of FAs will expand the understanding of the pathophysiology of chronic inflammation in various diseases, metabolic disorders and atherosclerosis and enable the development of new treatment strategies. 

scholarly journals Pathogenesis of Ischemic Stroke: Role of Epigenetic Mechanisms

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 89 ◽  
Author(s):  
Rosita Stanzione ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Simona Marchitti ◽  
Maurizio Forte ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Epigenetic Modifications ◽  
Review Article ◽  
Epigenetic Changes ◽  
Therapeutic Approaches ◽  
Nutritional Factors ◽  
New Therapeutic Approaches ◽  
Different Types ◽  
The Impact

Epigenetics is the branch of molecular biology that studies modifications able to change gene expression without altering the DNA sequence. Epigenetic modulations include DNA methylation, histone modifications, and noncoding RNAs. These gene modifications are heritable and modifiable and can be triggered by lifestyle and nutritional factors. In recent years, epigenetic changes have been associated with the pathogenesis of several diseases such as diabetes, obesity, renal pathology, and different types of cancer. They have also been related with the pathogenesis of cardiovascular diseases including ischemic stroke. Importantly, since epigenetic modifications are reversible processes they could assist with the development of new therapeutic approaches for the treatment of human diseases. In the present review article, we aim to collect the most recent evidence concerning the impact of epigenetic modifications on the pathogenesis of ischemic stroke in both animal models and humans.

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