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Maria Shvedova

Bio: Maria Shvedova is an academic researcher from Harvard University. The author has contributed to research in topics: Medicine & Senescence. The author has an hindex of 4, co-authored 10 publications receiving 79 citations. Previous affiliations of Maria Shvedova include Boston University & Siberian State Medical University.

Papers
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Journal ArticleDOI
TL;DR: According to reviewed literature, JNKs represent promising therapeutic targets for protection of the brain and the heart against ischemic stroke and myocardial infarction, respectively, but different members of the JNK family exert diverse physiological properties which may not allow for systemic administration of non-specific JNK inhibitors for therapeutic purposes.
Abstract: In this article, we review the literature regarding the role of c-Jun N-terminal kinases (JNKs) in cerebral and myocardial ischemia/reperfusion injury. Numerous studies demonstrate that JNK-mediated signaling pathways play an essential role in cerebral and myocardial ischemia/reperfusion injury. JNK-associated mechanisms are involved in preconditioning and post-conditioning of the heart and the brain. The literature and our own studies suggest that JNK inhibitors may exert cardioprotective and neuroprotective properties. The effects of modulating the JNK-depending pathways in the brain and the heart are reviewed. Cardioprotective and neuroprotective mechanisms of JNK inhibitors are discussed in detail including synthetic small molecule inhibitors (AS601245, SP600125, IQ-1S, and SR-3306), ion channel inhibitor GsMTx4, JNK-interacting proteins, inhibitors of mixed-lineage kinase (MLK) and MLK-interacting proteins, inhibitors of glutamate receptors, nitric oxide (NO) donors, and anesthetics. The role of JNKs in ischemia/reperfusion injury of the heart in diabetes mellitus is discussed in the context of comorbidities. According to reviewed literature, JNKs represent promising therapeutic targets for protection of the brain and the heart against ischemic stroke and myocardial infarction, respectively. However, different members of the JNK family exert diverse physiological properties which may not allow for systemic administration of non-specific JNK inhibitors for therapeutic purposes. Currently available candidate JNK inhibitors with high therapeutic potential are identified. The further search for selective JNK3 inhibitors remains an important task.

81 citations

Journal ArticleDOI
01 Feb 2022-Cells
TL;DR: This review will highlight the changes in chromatin, DNA methylation, and histone alterations that establish and maintain cellular senescence, alongside the specific epigenetic regulation of the senescENCE-associated secretory phenotype (SASP).
Abstract: Senescence is a complex cellular stress response that abolishes proliferative capacity and generates a unique secretory pattern that is implicated in organismal aging and age-related disease. How a cell transitions to a senescent state is multifactorial and often requires transcriptional regulation of multiple genes. Epigenetic alterations to DNA and chromatin are powerful regulators of genome architecture and gene expression, and they play a crucial role in mediating the induction and maintenance of senescence. This review will highlight the changes in chromatin, DNA methylation, and histone alterations that establish and maintain cellular senescence, alongside the specific epigenetic regulation of the senescence-associated secretory phenotype (SASP).

28 citations

Journal ArticleDOI
TL;DR: It is hypothesize that the disruption of electrical syncytium of the myocardium may underly myocardial stunning and hibernation, and how NO-mediated signaling is involved in myocardian stunning and Siberian hibernation.
Abstract: Irreversible myocardial damage happens in the presence of prolonged and severe ischemia. Several phenomena protect the heart against myocardial infarction and other adverse outcomes of ischemia and reperfusion (IR), namely: hibernation related to stunned myocardium, ischemic preconditioning (IPC), ischemic post-conditioning, and their pharmacological surrogates. Ischemic preconditioning consists in the induction of a brief IR to reduce damage of the tissue caused by prolonged and severe ischemia. Nitric oxide (NO) signaling plays an essential role in IPC. Nitric oxide-sensitive guanylate cyclase/cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase type I-signaling pathway protects against the IR injury during myocardial infarction. Mitochondrial ATP-sensitive and Ca2+-activated K+ channels are involved in NO-mediated signaling in IPC. Independently of the cGMP-mediated induction of NO production, S-nitrosation represents a regulatory molecular mechanism similar to phosphorylation and is essential for IPC. Unlike conditioning phenomena, the mechanistic basis of myocardial stunning and hibernation remains poorly understood. In this review article, we hypothesize that the disruption of electrical syncytium of the myocardium may underly myocardial stunning and hibernation. Considering that the connexins are the building blocks of gap junctions which represent primary structural basis of electrical syncytium, we discuss data on the involvement of connexins into myocardial conditioning, stunning, and hibernation. We also show how NO-mediated signaling is involved in myocardial stunning and hibernation. Connexins represent an essential element of adaptation phenomena of the heart at the level of both the cardio- myocytes and the mitochondria. Nitric oxide targets mitochondrial connexins which may affect electrical syncytium continuum in the heart. Mitochondrial connexins may play an essential role in NO-dependent mechanisms of myocardial adaptation to ischemia.

12 citations

Journal ArticleDOI
TL;DR: A protective role of cGKI is identified in vascular smooth muscle cells during ischemic stroke injury for the first time and was found to be independent of gender and was mediated via improved reperfusion.
Abstract: Recent works highlight the therapeutic potential of targeting cyclic guanosine monophosphate (cGMP)-dependent pathways in the context of brain ischemia/reperfusion injury (IRI). Although cGMP-depen...

9 citations

Journal ArticleDOI
31 Jul 2020-Bone
TL;DR: The role of miRNAs in skeletal development is discussed, particularly focusing on those whose physiological roles were revealed in vivo, and pathological mechanisms underlining these skeletal dysplasias are discussed.

8 citations


Cited by
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TL;DR: It is believed that, by improving existing interatomic potentials and currently available enhanced sampling methods, the community can move toward accurate investigations of realistic systems of practical interest, thus bringing simulations a step closer to experiments.
Abstract: The nucleation of crystals in liquids is one of nature's most ubiquitous phenomena, playing an important role in areas such as climate change and the production of drugs. As the early stages of nucleation involve exceedingly small time and length scales, atomistic computer simulations can provide unique insight into the microscopic aspects of crystallization. In this review, we take stock of the numerous molecular dynamics simulations that in the last few decades have unraveled crucial aspects of crystal nucleation in liquids. We put into context the theoretical framework of classical nucleation theory and the state of the art computational methods, by reviewing simulations of e.g. ice nucleation or crystallization of molecules in solutions. We shall see that molecular dynamics simulations have provided key insight into diverse nucleation scenarios, ranging from colloidal particles to natural gas hydrates, and that in doing so the general applicability of classical nucleation theory has been repeatedly called into question. We have attempted to identify the most pressing open questions in the field. We believe that by improving (i.) existing interatomic potentials; and (ii.) currently available enhanced sampling methods, the community can move towards accurate investigations of realistic systems of practical interest, thus bringing simulations a step closer to experiments.

223 citations

Journal ArticleDOI
TL;DR: A comprehensive review was performed evaluating the cardioprotective effects of these 3 dietary supplements with hope to provide updated information, promote further awareness of these supplements, and inspire future studies on their effects on cardiovascular health.

111 citations

Dissertation
01 Apr 2015
TL;DR: The miR-29 family was found to be the negative regulator in both human and murine chondrogenesis, and was also found to involve in murine limb development.
Abstract: MicroRNAs are short endogenous non-coding RNA molecules, typically 19-25 nucleotides in length, which negatively regulate gene expression. In osteoarthritis (OA), several genes necessary for cartilage homeostasis are aberrantly expressed, with a number of miRNAs implicated in this process. However, our knowledge of the earliest stages of OA, prior to the onset of irreversible changes, remains limited. The purpose of this study was to identify miRNAs involved across the time-course of OA using both a murine model and human cartilage, and to define their function. Expression profile of miRNAs (Exiqon) and mRNAs (Illumina) on total RNA purified from whole knee joints taken from mice which underwent destabilisation of the medial meniscus (DMM) surgery at day 1, 3 and 7 post-surgery showed: the miRNA expression in whole mouse joints post DMM surgery increased over 7 days; at day 1 and 3, the expression of only 4 miRNAs altered significantly; at day 7, 19 miRNAs were upregulated and 15 downregulated. Among the modulated miRNAs, the miR-29b was the most interesting and was chosen to further investigate since integrating analysis of the miRNA and mRNA expression array data showed the inverse correlation between miR-29b and its potential targets. In end-stage human OA cartilage and in murine injury model, the miR-29 family was found to increase expression. Moreover, the miR-29 family was found to be the negative regulator in both human and murine chondrogenesis, and was also found to involve in murine limb development. Expression of the miR-29 family was found to suppress by SOX9 at least in part through directly binding to the promoter of the primary miR-29a/b1. Also, TGFβ1/3 decreased expression of the miR-29 family whilst Wnt3a did not have any effect. Lipopolysaccharide suppressed the miR-29 family expression in part through NFκB signalling pathway while the IL-1 strongly induced its expression partly through P38 MAKP signalling. Using luciferase reporter assay, the miR-29 family was showed to suppress the TGFβ, NFκB, and WNT/β-catenin signalling pathways. Gene expression profiles of gain- and-loss-of-function revealed regulation of a large number of previously recognised extracellular matrix-associated genes as well as an additional subset of protease and Wnt signalling pathway-related genes. Among these genes, ADAMTS6, ADAMTS10, ADAMTS14, ADAMTS17, ADAMTS19, FZD3, DVL3, FRAT2, CK2A2 were experimentally validated as direct targets of the miR-29 family.

78 citations

Journal ArticleDOI
TL;DR: The role of autophagy in I/R injury and its targeting as a therapeutic strategy is discussed.
Abstract: Acute myocardial infarction (AMI) is one of the leading causes of morbidity worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species, and so forth. One of the processes that gets activated in response to I/R injury is autophagy. Indeed, autophagy acts as a "double-edged sword" in the pathology of myocardial I/R injury and there is a controversy about autophagy being beneficial or detrimental. On the basis of the autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy.

61 citations

Journal ArticleDOI
TL;DR: Novel information is provided on Curcumin's protective effects against various CVDs and potential molecular signaling targets of Curcume longa that has been used in traditional medicine for treating several diseases for years.

55 citations