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Advances in the Prevention and Treatment of Ischemic Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 5127

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Special Issue Editor

Prof. Dr. Egor Yu. Plotnikov

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Guest Editor

A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia
Interests: acute kidney injury; renal progenitor cells; mitochondria; mesenchymal stromal cells; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce a Special Issue on "Advances in the Prevention and Treatment of Ischemic Diseases." Ischemic diseases such as stroke, myocardial infarction, and renal and hepatic ischemia are among the leading causes of death worldwide. Therefore, it is critical to stay abreast of the latest research and advances in this field. In recent years, there have been significant advances in the treatment of ischemic pathologies. In addition to traditional therapies such as angioplasty and stenting, there are a number of cutting-edge approaches to treating ischemic disease. One of the most promising treatments for ischemic pathologies is the use of stem cells and various regenerative therapies. Another promising treatment is gene therapy to promote the growth of new blood vessels. In addition, dietary approaches or their pharmacological mimics are also being investigated to prevent ischemia or reduce its negative consequences, such as fibrosis. Overall, current advances in the treatment of ischemic diseases offer hope for patients with these conditions. These innovative therapies, in combination with traditional methods, provide a comprehensive approach to treating ischemic pathologies and improving patient outcomes.

The goal of this Special Issue is to bring together the latest research and emerging technologies that have the potential to improve the prevention and treatment of ischemic diseases. We invite researchers and experts in related fields to submit their work and contribute to this Special Issue.

Submissions of original research articles, review articles, case reports, and perspectives are invited. All submissions will be peer-reviewed, and the accepted articles will be published in the upcoming Special Issue. We welcome contributions from a wide range of disciplines, including, but not limited to, cardiology, neurology, pharmacology, nephrology, hepatology, and gastroenterology.

This Special Issue provides a unique opportunity for researchers to present their work, share their findings, and contribute to the advancement of this field.

Prof. Dr. Egor Yu. Plotnikov
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

stroke
acute kidney injury
dietary approaches
liver ischemia
heart attack
stem cells
hypoxia
preconditioning
antioxidants

Published Papers (4 papers)

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Research

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20 pages, 7951 KiB

Open AccessArticle

Monomeric CXCL12-Engineered Adipose-Derived Stem Cells Transplantation for the Treatment of Ischemic Stroke

by Haoran Zheng, Khan Haroon, Mengdi Liu, Xiaowen Hu, Qun Xu, Yaohui Tang, Yongting Wang, Guo-Yuan Yang and Zhijun Zhang

Int. J. Mol. Sci. 2024, 25(2), 792; https://doi.org/10.3390/ijms25020792 - 08 Jan 2024

Viewed by 839

Abstract

Adipose-derived stem cells (ASCs) possess therapeutic potential for ischemic brain injury, and the chemokine CXCL12 has been shown to enhance their functional properties. However, the cumulative effects of ASCs when combined with various structures of CXCL12 on ischemic stroke and its underlying molecular mechanisms remain unclear. In this study, we genetically engineered mouse adipose-derived ASCs with CXCL12 variants and transplanted them to the infarct region in a mice transient middle cerebral artery occlusion (tMCAO) model of stroke. We subsequently compared the post-ischemic stroke efficacy of ASC-mCXCL12 with ASC-dCXCL12, ASC-wtCXCL12, and unmodified ASCs. Neurobehavior recovery was assessed using modified neurological severity scores, the hanging wire test, and the elevated body swing test. Changes at the tissue level were evaluated through cresyl violet and immunofluorescent staining, while molecular level alterations were examined via Western blot and real-time PCR. The results of the modified neurological severity score and cresyl violet staining indicated that both ASC-mCXCL12 and ASC-dCXCL12 treatment enhanced neurobehavioral recovery and mitigated brain atrophy at the third and fifth weeks post-tMCAO. Additionally, we observed that ASC-mCXCL12 and ASC-dCXCL12 promoted angiogenesis and neurogenesis, accompanied by an increased expression of bFGF and VEGF in the peri-infarct area of the brain. Notably, in the third week after tMCAO, the ASC-mCXCL12 exhibited superior outcomes compared to ASC-dCXCL12. However, when treated with the CXCR4 antagonist AMD3100, the beneficial effects of ASC-mCXCL12 were reversed. The AMD3100-treated group demonstrated worsened neurological function, aggravated edema volume, and brain atrophy. This outcome is likely attributed to the interaction of monomeric CXCL12 with CXCR4, which regulates the recruitment of bFGF and VEGF. This study introduces an innovative approach to enhance the therapeutic potential of ASCs in treating ischemic stroke by genetically engineering them with the monomeric structure of CXCL12. Full article

(This article belongs to the Special Issue Advances in the Prevention and Treatment of Ischemic Diseases)

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24 pages, 13674 KiB

Open AccessArticle

Pilot Study of Cytoprotective Mechanisms of Selenium Nanorods (SeNrs) under Ischemia-like Conditions on Cortical Astrocytes

by Elena G. Varlamova, Egor Y. Plotnikov, Ilya V. Baimler, Sergey V. Gudkov and Egor A. Turovsky

Int. J. Mol. Sci. 2023, 24(15), 12217; https://doi.org/10.3390/ijms241512217 - 30 Jul 2023

Cited by 3 | Viewed by 1065

Abstract

The cytoprotective properties of the trace element selenium, its nanoparticles, and selenium nanocomplexes with active compounds are shown using a number of models. To date, some molecular mechanisms of the protective effect of spherical selenium nanoparticles under the action of ischemia/reoxygenation on brain cells have been studied. Among other things, the dependence of the effectiveness of the neuroprotective properties of nanoselenium on its diameter, pathways, and efficiency of penetration into astrocytes was established. In general, most research in the field of nanomedicine is focused on the preparation and study of spherical nanoparticles of various origins due to the ease of their preparation; in addition, spherical nanoparticles have a large specific surface area. However, obtaining and studying the mechanisms of action of nanoparticles of a new form are of great interest since nanorods, having all the positive properties of spherical nanoparticles, will also have a number of advantages. Using the laser ablation method, we managed to obtain and characterize selenium nanorods (SeNrs) with a length of 1 μm and a diameter of 100 nm. Using fluorescence microscopy and inhibitory analysis, we were able to show that selenium nanorods cause the generation of Ca²⁺ signals in cortical astrocytes in an acute experiment through the mobilization of Ca²⁺ ions from the thapsigargin-sensitive pool of the endoplasmic reticulum. Chronic use of SeNrs leads to a change in the expression pattern of genes encoding proteins that regulate cell fate and protect astrocytes from ischemia-like conditions and reoxygenation through the inhibition of a global increase in the concentration of cytosolic calcium ([Ca²⁺]_i). An important component of the cytoprotective effect of SeNrs during ischemia/reoxygenation is the induction of reactive A2-type astrogliosis in astrocytes, leading to an increase in both baseline and ischemia/reoxygenation-induced phosphoinositide 3-kinase (PI3K) activity and suppression of necrosis and apoptosis. The key components of this cytoprotective action of SeNrs are the actin-dependent process of endocytosis of nanoparticles into cells and activation of the Ca²⁺ signaling system of astrocytes. Full article

(This article belongs to the Special Issue Advances in the Prevention and Treatment of Ischemic Diseases)

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Review

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28 pages, 2920 KiB

Open AccessReview

Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia

by Pavel P. Tregub, Vladimir P. Kulikov, Irada Ibrahimli, Oksana F. Tregub, Artem V. Volodkin, Michael A. Ignatyuk, Andrey A. Kostin and Dmitrii A. Atiakshin

Int. J. Mol. Sci. 2024, 25(7), 3665; https://doi.org/10.3390/ijms25073665 - 25 Mar 2024

Viewed by 1079

Abstract

The review introduces the stages of formation and experimental confirmation of the hypothesis regarding the mutual potentiation of neuroprotective effects of hypoxia and hypercapnia during their combined influence (hypercapnic hypoxia). The main focus is on the mechanisms and signaling pathways involved in the formation of ischemic tolerance in the brain during intermittent hypercapnic hypoxia. Importantly, the combined effect of hypoxia and hypercapnia exerts a more pronounced neuroprotective effect compared to their separate application. Some signaling systems are associated with the predominance of the hypoxic stimulus (HIF-1α, A1 receptors), while others (NF-κB, antioxidant activity, inhibition of apoptosis, maintenance of selective blood–brain barrier permeability) are mainly modulated by hypercapnia. Most of the molecular and cellular mechanisms involved in the formation of brain tolerance to ischemia are due to the contribution of both excess carbon dioxide and oxygen deficiency (ATP-dependent potassium channels, chaperones, endoplasmic reticulum stress, mitochondrial metabolism reprogramming). Overall, experimental studies indicate the dominance of hypercapnia in the neuroprotective effect of its combined action with hypoxia. Recent clinical studies have demonstrated the effectiveness of hypercapnic–hypoxic training in the treatment of childhood cerebral palsy and diabetic polyneuropathy in children. Combining hypercapnic hypoxia with pharmacological modulators of neuro/cardio/cytoprotection signaling pathways is likely to be promising for translating experimental research into clinical medicine. Full article

(This article belongs to the Special Issue Advances in the Prevention and Treatment of Ischemic Diseases)

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20 pages, 911 KiB

Open AccessReview

Cell Therapy in the Treatment of Coronary Heart Disease

by Elena V. Chepeleva

Int. J. Mol. Sci. 2023, 24(23), 16844; https://doi.org/10.3390/ijms242316844 - 28 Nov 2023

Viewed by 1497

Abstract

Heart failure is a leading cause of death in patients who have suffered a myocardial infarction. Despite the timely use of modern reperfusion therapies such as thrombolysis, surgical revascularization and balloon angioplasty, they are sometimes unable to prevent the development of significant areas of myocardial damage and subsequent heart failure. Research efforts have focused on developing strategies to improve the functional status of myocardial injury areas. Consequently, the restoration of cardiac function using cell therapy is an exciting prospect. This review describes the characteristics of various cell types relevant to cellular cardiomyoplasty and presents findings from experimental and clinical studies investigating cell therapy for coronary heart disease. Cell delivery methods, optimal dosage and potential treatment mechanisms are discussed. Full article

(This article belongs to the Special Issue Advances in the Prevention and Treatment of Ischemic Diseases)

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