The Effects on Angiogenesis of Relevant Inorganic Chemotherapeutics

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666201126163436 ◽

2020 ◽

Vol 20 ◽

Author(s):

Tiziano Marzo ◽

Diego La Mendola

Keyword(s):

Metal Ions ◽

Anticancer Agents ◽

Review Article ◽

Pharmacological Effects ◽

Complex Interactions ◽

Pathological Conditions ◽

Copper Zinc ◽

Antiangiogenic Factors ◽

The Impact

: Angiogenesis is a key process allowing the formation of blood vessels. It is crucial for all the tissue and organs, ensuring their function and growth. Angiogenesis is finely controlled by several mechanisms involving complex interactions between pro- or antiangiogenic factors and an imbalance in this control chain may result in pathological conditions. Metals as copper, zinc and iron cover an essential role in regulating angiogenesis, thus therapies having physiological metals as target have been proposed. Also, some complexes of heavier metal ions (e.g Pt, Au, Ru) are currently used as established or experimental anticancer agents targeting genomic or non-genomic targets. These molecules may affect the angiogenic mechanisms determining different effects that have been only poorly and non-systematically investigated so far. Accordingly, in this review article we aim to recapitulate the impact on the angiogenic process of some reference anticancer drugs, and how it is connected to the overall pharmacological effects. Also, we highlight how the activity of these drugs can be related to the role of biological essential metal ions. Overall, this may allow a deeper description and understanding of the antineoplastic activity of both approved or experimental metal complexes, providing important insights for the synthesis of new inorganic drugs able to overcome resistance and recurrence phenomena.

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MYOSTATIN - A MODERN UNDERSTANDING OF THE PHYSIOLOGICAL ROLE AND SIGNIFICANCE IN THE DEVELOPMENT OF AGE-ASSOCIATED DISEASES

Успехи геронтологии ◽

10.34922/ae.2021.34.5.005 ◽

2021 ◽

pp. 701-706

Author(s):

А.А. Газданова ◽

В.Г. Кукес ◽

О.К. Парфенова ◽

Н.Г. Сидоров ◽

А.В. Перков ◽

...

Keyword(s):

Muscle Growth ◽

Physiological Role ◽

Review Article ◽

Negative Regulator ◽

Transforming Growth Factors ◽

Endogenous Factors ◽

Pathological Conditions ◽

Physiological Properties ◽

The Family

Миостатин - белок, принадлежащий к классу миокинов, семейству трансформирующих факторов роста β (TGF-β). В обзорной статье, анализирующей данные литературы, показана ключевая роль миостатина в развитии старческой саркопении и кахексии при различных патологических состояниях, таких как рак, ХСН, ХБП, ХОБЛ и др. В статье рассматривается структура миостатина, подробная схема синтеза и его активации, механизм действия как негативного регулятора роста и дифференцировки мышц при этих патологических состояниях. Выделены основные физиологические свойства и клиническое значение. Рассмотрены экзогенные и эндогенные факторы, регулирующие экспрессию миостатина, и возможные механизмы их действия. Myostatin is a protein belonging to the myokine class, the family of transforming growth factors β (TGF-β). The review article, based on the analysis of literature data, shows the key role of myostatin in the development of senile sarcopenia and cachexia in various pathological conditions, such as cancer, chronic heart failure, chronic renal failure, COPD, etc. The article discusses the structure of myostatin, provides a detailed diagram of the synthesis and activation of myostatin, the ways of implementing the mechanism of action as a negative regulator of muscle growth and differentiation in these pathological conditions. The main physiological properties and clinical significance are highlighted. Exogenous and endogenous factors regulating myostatin expression and possible mechanisms of their action are considered.

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Pathogenesis of Ischemic Stroke: Role of Epigenetic Mechanisms

Genes ◽

10.3390/genes11010089 ◽

2020 ◽

Vol 11 (1) ◽

pp. 89 ◽

Cited By ~ 3

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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Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Cancers ◽

10.3390/cancers12071946 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1946

Author(s):

Yaroslav Teper ◽

Guido Eibl

Keyword(s):

Pancreatic Cancer ◽

Immune Cells ◽

Current Knowledge ◽

Review Article ◽

Cancer Development ◽

Detailed Knowledge ◽

Inflammatory Macrophages ◽

Pancreatic Neoplasia ◽

The Impact

Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

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The effect of magnesium ions on triphosphate hydrolysis

Pure and Applied Chemistry ◽

10.1515/pac-2016-1125 ◽

2017 ◽

Vol 89 (6) ◽

pp. 715-727 ◽

Cited By ~ 14

Author(s):

Alexandre Barrozo ◽

David Blaha-Nelson ◽

Nicholas H. Williams ◽

Shina C. L. Kamerlin

Keyword(s):

Transition State ◽

Metal Ions ◽

Density Functional ◽

Reaction Pathway ◽

Enzymatic Reaction ◽

Phosphate Ester ◽

Mechanistic Pathway ◽

Phosphate Hydrolysis ◽

The Impact

AbstractThe role of metal ions in catalyzing phosphate ester hydrolysis has been the subject of much debate, both in terms of whether they change the transition state structure or mechanistic pathway. Understanding the impact of metal ions on these biologically critical reactions is central to improving our understanding of the role of metal ions in the numerous enzymes that facilitate them. In the present study, we have performed density functional theory studies of the mechanisms of methyl triphosphate and acetyl phosphate hydrolysis in aqueous solution to explore the competition between solvent- and substrate-assisted pathways, and examined the impact of Mg2+ on the energetics and transition state geometries. In both cases, we observe a clear preference for a more dissociative solvent-assisted transition state, which is not significantly changed by coordination of Mg2+. The effect of Mg2+ on the transition state geometries for the two pathways is minimal. While our calculations cannot rule out a substrate-assisted pathway as a possible solution for biological phosphate hydrolysis, they demonstrate that a significantly higher energy barrier needs to be overcome in the enzymatic reaction for this to be an energetically viable reaction pathway.

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Molecular Features and Metal Ions That Influence 10-23 DNAzyme Activity

Molecules ◽

10.3390/molecules25133100 ◽

2020 ◽

Vol 25 (13) ◽

pp. 3100 ◽

Cited By ~ 1

Author(s):

Hannah Rosenbach ◽

Julian Victor ◽

Manuel Etzkorn ◽

Gerhard Steger ◽

Detlev Riesner ◽

...

Keyword(s):

Metal Ions ◽

Structure Determination ◽

Structural Information ◽

Pyrimidine Nucleotides ◽

Molecular Features ◽

Biological Studies ◽

Catalytic Loop ◽

The Impact

Deoxyribozymes (DNAzymes) with RNA hydrolysis activity have a tremendous potential as gene suppression agents for therapeutic applications. The most extensively studied representative is the 10-23 DNAzyme consisting of a catalytic loop and two substrate binding arms that can be designed to bind and cleave the RNA sequence of interest. The RNA substrate is cleaved between central purine and pyrimidine nucleotides. The activity of this DNAzyme in vitro is considerably higher than in vivo, which was suggested to be related to its divalent cation dependency. Understanding the mechanism of DNAzyme catalysis is hindered by the absence of structural information. Numerous biological studies, however, provide comprehensive insights into the role of particular deoxynucleotides and functional groups in DNAzymes. Here we provide an overview of the thermodynamic properties, the impact of nucleobase modifications within the catalytic loop, and the role of different metal ions in catalysis. We point out features that will be helpful in developing novel strategies for structure determination and to understand the mechanism of the 10-23 DNAzyme. Consideration of these features will enable to develop improved strategies for structure determination and to understand the mechanism of the 10-23 DNAzyme. These insights provide the basis for improving activity in cells and pave the way for developing DNAzyme applications.

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The Challenging Riddle about the Janus-Type Role of Hsp60 and Related Extracellular Vesicles and miRNAs in Carcinogenesis and the Promises of Its Solution

Applied Sciences ◽

10.3390/app11031175 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1175

Author(s):

Sabrina David ◽

Alessandra Maria Vitale ◽

Alberto Fucarino ◽

Federica Scalia ◽

Giuseppe Vergilio ◽

...

Keyword(s):

Cell Membrane ◽

Extracellular Vesicles ◽

Cancer Development ◽

Cancer Therapies ◽

Ongoing Research ◽

Pathological Conditions ◽

Anti Cancer ◽

Evolutionarily Conserved ◽

The Impact

Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasma-cell membrane, and extracellular vesicles (EVs). Consequently, non-canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi-faceted role of this chaperonin in human cancers, showing the contribution of intra- and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA-mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti-cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro- or anti-tumor.

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New work: New motivation? A comprehensive literature review on the impact of workplace technologies

Management Review Quarterly ◽

10.1007/s11301-020-00204-7 ◽

2020 ◽

Author(s):

Yvonne Schmid ◽

Michael Dowling

Keyword(s):

Literature Review ◽

New Technologies ◽

Performance Outcomes ◽

Complex Interactions ◽

Comprehensive Literature Review ◽

Job Motivation ◽

Points Of View ◽

State Of Research ◽

The Impact

Abstract The role of work and the characteristics of the workplace have changed greatly in recent decades. Today, new technologies enable an almost seamless interaction between machines and humans and allow teams in different countries and time zones to collaborate effectively. In this paper, we focus on the question of how job motivation is affected by technologies in the changing workplace. First, we review the state of research on job motivation and examine challenges in light of current technology trends and predicted developments for the workplace of the future. Job motivation is a well-documented construct connected to several company-relevant performance outcomes. However, our comprehensive literature review reveals a fragmented picture, with several disciplines addressing the topic from various points of view. We identify the four following schools of thought on workplace technologies and motivation: Technology as 1. background music, 2. hygiene factor, 3. motivator, and 4. influencer of mediators. While some scholars neglect technology in their considerations, others describe complex frameworks. This lack of unity reveals a further need for research. We suggest further research to develop holistic frameworks including moderators and to collect empirical data on the complex interactions between technology and job motivation.

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Themes in the Socioeconomic History of China, 1840–1949—A Review Article

The Journal of Asian Studies ◽

10.2307/2055758 ◽

1984 ◽

Vol 43 (3) ◽

pp. 459-473

Author(s):

David D. Buck

Keyword(s):

Review Article ◽

New Order ◽

Socioeconomic History ◽

History Of ◽

Foreign Governments ◽

Agrarian Crisis ◽

Nationalist Government ◽

The Impact ◽

Trade And Investment

This article discusses two collections (seventy-seven titles) of reprints edited by Ramon H. Myers. He does not provide an interpretative essay for either collection; his choices for inclusion are reviewed in terms of the opinions that he has expressed in a textbook and in other works. The choices reveal that Myers, along with other specialists, views 1895 to 1937 as a key period in which the old socioeconomic order disintegrated and a new order took shape. Scholarly interest concerning those years has focused on the nature of the agrarian crisis, the impact of foreign trade and investment, the contribution of the Chinese bourgeoisie, and the role of the new Nationalist government. The author discusses the views of Myers and others on these topics, and, in addition, the author points out that these collections suggest that another topic—the expanded control of foreign governments over the economic affairs of the Chinese state—is worthy of investigation.

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The role of microRNAs in angiogenesis

Pomeranian Journal of Life Sciences ◽

10.21164/pomjlifesci.631 ◽

2019 ◽

Vol 65 (4) ◽

Author(s):

Joanna Bujak ◽

Patrycja Kopytko ◽

Małgorzata Lubecka ◽

Katarzyna Sokołowska ◽

Maciej Tarnowski

Keyword(s):

Regulation Of Gene Expression ◽

Tumor Development ◽

Main Function ◽

Rna Molecules ◽

Pathological Conditions ◽

Non Coding Rna ◽

Antiangiogenic Factors ◽

And Migration ◽

Post Transcriptional Regulation

Angiogenesis is the process that leads to the formation of new blood vessels. Under physiological conditions it occurs, inter alia, during corpus luteum formation and in some stages of the menstrual cycle. However, angiogenesis plays an essential role in many pathological conditions, particularly cancer. New blood vessel formation provides cancer cells with oxygen and essential nutrients, which stimulates tumor growth and facilitates its metastasis. Increasing evidence indicates that angiogenesis is regulated by microRNAs (miRNAs), which are small non-coding RNA molecules of 19–25 nucleotides. The main function of miRNAs is post-transcriptional regulation of gene expression, which controls many key biological processes, including cell proliferation, differentiation and migration. Endothelial miRNAs, known as angiomiRs, are presumably involved in tumor development and angiogenesis through regulation of pro- and antiangiogenic factors. To date, the miRNAs that stimulate angiogenesis are: miR-9, miR-27a, miR-30d, miR0-130b, miR-139, miR-146a, miR-150, miR-155, miR-200c, miR-296 and miR-558. Conversely, miRNAs that inhibit angiogenesis are: miR-145, miR-519c, miR-22, miR-20a, miR-92, miR-7b, miR-221, miR-222, miR-328 and miR-101.

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