scholarly journals The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Zhu ◽  
Yangong Liu ◽  
Yuanxiu Song ◽  
Shiqin Zhang ◽  
Chengwen Hang ◽  
...  

Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.

2020 ◽  
Vol 27 (40) ◽  
pp. 6815-6824 ◽  
Author(s):  
Yuan Jiang ◽  
Chuanshan Xu ◽  
Wingnang Leung ◽  
Mei Lin ◽  
Xiaowen Cai ◽  
...  

Photodynamic Therapy (PDT) is a promising alternative treatment for malignancies based on photochemical reaction induced by Photosensitizers (PS) under light irradiation. Recent studies show that PDT caused the abundant release of exosomes from tumor tissues. It is well-known that exosomes as carriers play an important role in cell-cell communication through transporting many kinds of bioactive molecules (e.g. lipids, proteins, mRNA, miRNA and lncRNA). Therefore, to explore the role of exosomes in photodynamic anticancer therapy has been attracting significant attention. In the present paper, we will briefly introduce the basic principle of PDT and exosomes, and focus on discussing the role of exosomes in photodynamic anticancer therapy, to further enrich and boost the development of PDT.


2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.


Author(s):  
Adrián Yoris ◽  
Adolfo M. García ◽  
Paula Celeste Salamone ◽  
Lucas Sedeño ◽  
Indira García-Cordero ◽  
...  

Dimensional and transdiagnostic approaches have revealed multiple cognitive/emotional alterations shared by several neuropsychiatric conditions. While this has been shown for externally triggered neurocognitive processes, the disruption of interoception across neurological disorders remains poorly understood. This chapter aims to fill this gap while proposing cardiac interoception as a potential common biomarker across disorders. It focuses on key aspects of interoception, such as the mechanisms underlying different interoceptive dimensions; the relationship among interoception, emotion, and social cognition; and the roles of different interoceptive pathways. It considers behavioral and brain evidence in the context of an experimental and clinical agenda to evaluate the potential role of interoception as a predictor of clinical outcomes, a marker of neurocognitive deficits across diseases, and a general source of insights for breakthroughs in the treatment and prevention of multiple disorders. Finally, future directions to improve the dimensional and transdiagnostic assessment of interoception are outlined.


Modern Italy ◽  
2016 ◽  
Vol 21 (2) ◽  
pp. 157-170
Author(s):  
Mila Milani

Long neglected by critical literature and historians, the Neapolitan journalSud(1945–1947) shared similar aims and objectives with the more famousIl Politecnico, although the two journals were inserted into and connected with lively yet different cultural environments and networks, which crucially influenced their outputs. Most notably, both journals paid significant attention to politically committed literary and essay translations. By combining an analysis of the journals’ articles and translations with the editors’ published and unpublished correspondence, the article reassesses the journals’ relationship and illuminates theengagementof the two editorial boards through translations. The analysis of the two intellectual networks and projects will re-establish the relevance ofSudin stimulating a transnational dialogue and will reconsider the role of translation in shaping the editors’ political identities. Finally, the article offers a geo-cultural perspective on post-war Italianimpegnoby charting its multiple, both national and transnational, identities.


Universe ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 66
Author(s):  
Jenni Kotila

Single-particle level energies form a significant input in nuclear physics calculations where single-particle degrees of freedom are taken into account, including microscopic interacting boson model investigations. The single-particle energies may be treated as input parameters that are fitted to reach an optimal fit to the data. Alternatively, they can be calculated using a mean field potential, or they can be extracted from available experimental data, as is done in the current study. The role of single-particle level energies in the microscopic interacting boson model calculations is discussed with special emphasis on recent double beta decay calculations.


Author(s):  
Kalin Z. Salinas ◽  
Amanda Venta

The current study proposed to determine whether adolescent emotion regulation is predictive of the amount and type of crime committed by adolescent juvenile offenders. Despite evidence in the literature linking emotion regulation to behaviour problems and aggression across the lifespan, there is no prior longitudinal research examining the predictive role of emotion regulation on adolescent recidivism, nor data regarding how emotion regulation relates to the occurrence of specific types of crimes. Our primary hypothesis was that poor emotion regulation would positively and significantly predict re-offending among adolescents. We tested our hypothesis within a binary logistic framework utilizing the Pathways to Desistance longitudinal data. Exploratory bivariate analyses were conducted regarding emotion regulation and type of crime in the service of future hypothesis generation. Though the findings did not indicate a statistically significant relation between emotion regulation and reoffending, exploratory findings suggest that some types of crime may be more linked to emotion regulation than others. In sum, the present study aimed to examine a hypothesized relation between emotion regulation and juvenile delinquency by identifying how the individual factor of dysregulated emotion regulation may have played a role. This study’s findings did not provide evidence that emotion regulation was a significant predictor of recidivism over time but did suggest that emotion regulation is related to participation in certain types of crime one year later. Directions for future research that build upon the current study were described. Indeed, identifying emotion regulation as a predictor of adolescent crime has the potential to enhance current crime prevention efforts and clinical treatments for juvenile offenders; this is based on the large amount of treatment literature, which documents that emotion regulation is malleable through treatment and prevention programming.


2021 ◽  
Vol 94 (1) ◽  
Author(s):  
Rafael Vicuña ◽  
Bernardo González

Abstract Background In this article we would like to touch on the key role played by the microbiota in the maintenance of a sustainable environment in the entire planet. For obvious reasons, this article does not intend to review thoroughly this extremely complex topic, but rather to focus on the main threats that this natural scenario is presently facing. Methods Recent literature survey. Results Despite the relevance of microorganisms have in our planet, the effects of climate change on microbial communities have been scarcely and not systematically addressed in literature. Although the role of microorganisms in emissions of greenhouse gases has received some attention, there are several microbial processes that are affected by climate change with consequences that are presently under assessment. Among them, host-pathogen interactions, the microbiome of built environment, or relations among plants and beneficial microbes. Conclusions Further research is required to advance in knowledge of the effect of climate change on microbial communities. One of the main targets should be a complete evaluation of the global microbial functional diversity and the design of new strategies to cope with limitations in methods to grow microorganisms in the laboratory. These efforts should contribute to raise a general public awareness on the major role played by the microbiota on the various Earth ecosystems.


2021 ◽  
Vol 22 (5) ◽  
pp. 2754
Author(s):  
Naila Qayyum ◽  
Muhammad Haseeb ◽  
Moon Suk Kim ◽  
Sangdun Choi

Thioredoxin-interacting protein (TXNIP), widely known as thioredoxin-binding protein 2 (TBP2), is a major binding mediator in the thioredoxin (TXN) antioxidant system, which involves a reduction-oxidation (redox) signaling complex and is pivotal for the pathophysiology of some diseases. TXNIP increases reactive oxygen species production and oxidative stress and thereby contributes to apoptosis. Recent studies indicate an evolving role of TXNIP in the pathogenesis of complex diseases such as metabolic disorders, neurological disorders, and inflammatory illnesses. In addition, TXNIP has gained significant attention due to its wide range of functions in energy metabolism, insulin sensitivity, improved insulin secretion, and also in the regulation of glucose and tumor suppressor activities in various cancers. This review aims to highlight the roles of TXNIP in the field of diabetology, neurodegenerative diseases, and inflammation. TXNIP is found to be a promising novel therapeutic target in the current review, not only in the aforementioned diseases but also in prolonged microvascular and macrovascular diseases. Therefore, TXNIP inhibitors hold promise for preventing the growing incidence of complications in relevant diseases.


Author(s):  
Demosthenes G. Papamatheakis ◽  
Srilakshmi Vemulakonda ◽  
Jay Patel ◽  
Quintin Blood ◽  
Travis Merritt ◽  
...  

2006 ◽  
Vol 173 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Weigang Wang ◽  
Ghassan Mouneimne ◽  
Mazen Sidani ◽  
Jeffrey Wyckoff ◽  
Xiaoming Chen ◽  
...  

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine–threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119–1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868–36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247–7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349–359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.


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