The Emerging Role of Ferroptosis in Liver Diseases

Ferroptosis is a newly discovered type of cell death mediated by iron-dependent lipid peroxide. The disturbance of iron metabolism, imbalance of the amino acid antioxidant system, and lipid peroxide accumulation are considered distinct fingerprints of ferroptosis. The dysregulation of ferroptosis has been intensively studied in recent years due to its participation in various diseases, including cancer, kidney injury, and neurodegenerative diseases. Notably, increasing evidence indicates that ferroptosis plays different roles in a wide spectrum of liver diseases. On the one hand, inhibiting ferroptosis may counteract the pathophysiological progression of several liver diseases, such as alcoholic liver injury, nonalcoholic steatosis hepatitis and fibrosis. On the other hand, inducing ferroptosis may restrict the emergence of secondary resistance to current medicines, such as sorafenib, for hepatocellular carcinoma (HCC) therapy. Here, we summarize the biological characteristics and regulatory signalling pathways of ferroptosis involved in liver disease. The current available medical agents targeting ferroptosis, including inducers or inhibitors applied in liver diseases, are also reviewed. This work aims to provide new insight into the emerging role of pathogenesis and therapeutic approaches for liver diseases.

Download Full-text

Mitochondrial Function, Biology, and Role in Disease

Circulation Research ◽

10.1161/res.0000000000000104 ◽

2016 ◽

Vol 118 (12) ◽

pp. 1960-1991 ◽

Cited By ~ 138

Author(s):

Elizabeth Murphy ◽

Hossein Ardehali ◽

Robert S. Balaban ◽

Fabio DiLisa ◽

Gerald W. Dorn ◽

...

Keyword(s):

Cardiovascular Disease ◽

Mitochondrial Function ◽

The United States ◽

Therapeutic Interventions ◽

Therapeutic Approaches ◽

Mitochondrial Defects ◽

Exciting Time ◽

Insight Into ◽

Novel Therapeutic

Cardiovascular disease is a major leading cause of morbidity and mortality in the United States and elsewhere. Alterations in mitochondrial function are increasingly being recognized as a contributing factor in myocardial infarction and in patients presenting with cardiomyopathy. Recent understanding of the complex interaction of the mitochondria in regulating metabolism and cell death can provide novel insight and therapeutic targets. The purpose of this statement is to better define the potential role of mitochondria in the genesis of cardiovascular disease such as ischemia and heart failure. To accomplish this, we will define the key mitochondrial processes that play a role in cardiovascular disease that are potential targets for novel therapeutic interventions. This is an exciting time in mitochondrial research. The past decade has provided novel insight into the role of mitochondria function and their importance in complex diseases. This statement will define the key roles that mitochondria play in cardiovascular physiology and disease and provide insight into how mitochondrial defects can contribute to cardiovascular disease; it will also discuss potential biomarkers of mitochondrial disease and suggest potential novel therapeutic approaches.

Download Full-text

Insight into the Double-Edged Role of Ferroptosis in Disease

Biomolecules ◽

10.3390/biom11121790 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1790

Author(s):

Lei Zhang ◽

Ruohan Jia ◽

Huizhen Li ◽

Huarun Yu ◽

Keke Ren ◽

...

Keyword(s):

Cell Death ◽

Digestive System ◽

Kidney Injury ◽

Oxygen Species ◽

Disease Treatment ◽

The Relationship ◽

Insight Into ◽

New Strategies ◽

Research Hotspots

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.

Download Full-text

Part I General Aspects, 2 The IPO Process, IPO Disclosure, and the Prospectus Regulation

Prospectus Regulation and Prospectus Liability ◽

10.1093/law/9780198846529.003.0002 ◽

2020 ◽

Author(s):

Teerink Han

Keyword(s):

Initial Public Offering ◽

The Other ◽

Business Information ◽

Other Hand ◽

The One ◽

General Aspects ◽

Public Offering ◽

The Right ◽

Insight Into

This chapter offers insight into a typical initial public offering (IPO) process, highlighting key practical and legal considerations around disclosure, through the IPO prospectus and otherwise. The prospectus plays a key role in the preparations for, and execution of, an IPO. As an IPO prospectus typically constitutes a company's first public dissemination of financial and business information, the company and other parties involved in the IPO process must carefully consider the right balance between, on the one hand, drafting the IPO prospectus as a marketing document introducing the company and its business to potential investors, whilst, on the other hand, being able to use the prospectus as a disclosure document that protects the company against liability arising from claims from investors or others after the IPO. Here, the chapter summarizes the different phases in an IPO process and the most important documents and parties involved, focusing on the central role of the IPO prospectus. In addition, a number of changes resulting from the enactment of the Prospectus Regulation are likely to be of particular relevance to IPO processes. The expected impact of these changes is therefore also discussed.

Download Full-text

Autophagy Function and Regulation in Kidney Disease

Biomolecules ◽

10.3390/biom10010100 ◽

2020 ◽

Vol 10 (1) ◽

pp. 100 ◽

Cited By ~ 5

Author(s):

Gur P. Kaushal ◽

Kiran Chandrashekar ◽

Luis A. Juncos ◽

Sudhir V. Shah

Keyword(s):

Cell Death ◽

Renal Injury ◽

Mammalian Target Of Rapamycin ◽

Kidney Injury ◽

Therapeutic Approaches ◽

Regulated Necrosis ◽

Atg Genes ◽

Cellular Components ◽

The Impact

Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

Download Full-text

Bestuursetiek in bestuursopleiding: Retoriek of realiteit

SA Journal of Industrial Psychology ◽

10.4102/sajip.v19i3.564 ◽

1993 ◽

Vol 19 (3) ◽

Author(s):

S. Kruger

Keyword(s):

Business Ethics ◽

The Other ◽

Literature Study ◽

Business Training ◽

Other Hand ◽

The Future ◽

The Subject ◽

The One ◽

Insight Into

Business ethics in business training: Oratory or the actuality. This article is the culmination of an in-depth literature study. On the one hand an attempt is made to incorporate the views of different authors, while on the other hand an attempt is made to take part in the debate which is initiated by the current renewal of interest in the subject Business Ethics. Within this framework attention is paid to the question of whether business ethics can be taught and if so, to what extent it's influence will be felt. Secondly, an insight into the teaching of business ethics in the future is provided. Within this context the approach to the teaching, the content, the role of the student and the responsibility of the educator in particular are addressed. Opsomming Hierdie artikel is die resultaat van 'n indringende literatuurstudie. Daar word gepoog om enersyds verskillende skrywers se standpunte saam te vat, maar andersyds ook kritiese kommentaar te lower en deel te neem aan die debat wat deur die huidige opiewing in die belangstelling in Bestuursetiek bestaan. Binne die raamwerk sal aandag aan die volgende geskenk word: Die beantwoording van die vraag of Bestuursetiek onderrig kan word en indien wel die trefwydte daarvan. Tweedens 'n toekomsblik op die onderrig van Bestuursetiek. Binne die konteks word die benadering tot die onderrig/ die inhoud en die rol van die student en die verantwoordelikheid van die dosent bekvk.

Download Full-text

Perioperative Organ Injury

Anesthesiology ◽

10.1097/aln.0000000000000022 ◽

2013 ◽

Vol 119 (6) ◽

pp. 1474-1489 ◽

Cited By ~ 86

Author(s):

Karsten Bartels ◽

Jörn Karhausen ◽

Eric T. Clambey ◽

Almut Grenz ◽

Holger K. Eltzschig

Keyword(s):

Distress Syndrome ◽

Kidney Injury ◽

Organ Injury ◽

Therapeutic Approaches ◽

The Past ◽

Novel Treatment ◽

Current Review ◽

Common Causes ◽

Treatment Concepts ◽

Insight Into

Abstract Despite the fact that a surgical procedure may have been performed for the appropriate indication and in a technically perfect manner, patients are threatened by perioperative organ injury. For example, stroke, myocardial infarction, acute respiratory distress syndrome, acute kidney injury, or acute gut injury are among the most common causes for morbidity and mortality in surgical patients. In the current review, the authors discuss the pathogenesis of perioperative organ injury, and provide select examples for novel treatment concepts that have emerged over the past decade. Indeed, the authors are of the opinion that research to provide mechanistic insight into acute organ injury and identification of novel therapeutic approaches for the prevention or treatment of perioperative organ injury represent the most important opportunity to improve outcomes of anesthesia and surgery.

Download Full-text

The emerging role of ferroptosis in non-cancer liver diseases: hype or increasing hope?

Cell Death and Disease ◽

10.1038/s41419-020-2732-5 ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 5

Author(s):

Lihong Mao ◽

Tianming Zhao ◽

Yan Song ◽

Lin Lin ◽

Xiaofei Fan ◽

...

Keyword(s):

Cell Death ◽

Liver Diseases ◽

Therapeutic Strategy ◽

Kidney Injury ◽

Hepatic Disease ◽

Therapeutic Concept ◽

Regulated Cell Death ◽

Dependent Form ◽

Molecular Machinery

Abstract Ferroptosis is an iron- and lipotoxicity-dependent form of regulated cell death (RCD). It is morphologically and biochemically distinct from characteristics of other cell death. This modality has been intensively investigated in recent years due to its involvement in a wide array of pathologies, including cancer, neurodegenerative diseases, and acute kidney injury. Dysregulation of ferroptosis has also been linked to various liver diseases and its modification may provide a hopeful and attractive therapeutic concept. Indeed, targeting ferroptosis may prevent the pathophysiological progression of several liver diseases, such as hemochromatosis, nonalcoholic steatohepatitis, and ethanol-induced liver injury. On the contrary, enhancing ferroptosis may promote sorafenib-induced ferroptosis and pave the way for combination therapy in hepatocellular carcinoma. Glutathione peroxidase 4 (GPx4) and system xc− have been identified as key players to mediate ferroptosis pathway. More recently diverse signaling pathways have also been observed. The connection between ferroptosis and other forms of RCD is intricate and compelling, where discoveries in this field advance our understanding of cell survival and fate. In this review, we summarize the central molecular machinery of ferroptosis, describe the role of ferroptosis in non-cancer hepatic disease conditions and discuss the potential to manipulate ferroptosis as a therapeutic strategy.

Download Full-text

Renal cell carcinoma: a review of biology and pathophysiology

F1000Research ◽

10.12688/f1000research.13179.1 ◽

2018 ◽

Vol 7 ◽

pp. 307 ◽

Cited By ~ 25

Author(s):

Shahzaib Nabi ◽

Elizabeth R. Kessler ◽

Brandon Bernard ◽

Thomas W. Flaig ◽

Elaine T. Lam

Keyword(s):

Renal Cell Carcinoma ◽

Immune System ◽

Cell Carcinoma ◽

Renal Cell ◽

Disease Process ◽

Genetic Alterations ◽

Therapeutic Approaches ◽

Main Emphasis ◽

Insight Into

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC.

Download Full-text

The art of non-verbal communication in perlocutionary giftedness

Linguistics Beyond and Within (LingBaW) ◽

10.31743/lingbaw.5385 ◽

2019 ◽

Vol 5 (1) ◽

pp. 135-147

Author(s):

Adam Świątek

Keyword(s):

Speech Act ◽

Individual Case ◽

Willingness To Communicate ◽

Language Aptitude ◽

Fundamental Factor ◽

Considerable Impact ◽

The One ◽

Pragmatic Aspects ◽

Insight Into

Language aptitude and perlocutionary acts and effects have been subjects of extensive research since their true beginnings in the 1950’s and 1960’s, respectively. On the one hand, Carroll and Sapon (1959), Pimsleur (1966), or Biedroń (2012) aimed at revealing the factors responsible for a learner’s sixth sense for languages. On the other hand, almost simultaneously, Austin (1962) introduced the tripartite division of a speech act, with locutions, illocutions, and perlocutions as the integral components, later developed by Searle (1969), who shed new light on the Speech Act Theory (SAT). At that time, however, the role of the perlocutionary component was significantly diminished, since the primary goal of pragmatics was to investigate the speaker’s intentions. Gradually, the role of perlocutionary acts and effects changed and more attention was drawn to the perlocutionary aspect. In 1979, Cohen, Davis and Gaines highlighted the fact that perlocutionary acts have perlocutionary goals, which might be observed by the subsequent effects utterance have on the listener. In 2013, Post offered a new insight into the SAT and suggested that the role of perlocution ought not to be diminished, but enhanced and intensified. In 2015, Świątek suggested a contrasting approach to both concepts and combined them to investigate the role of individual differences responsible for one’s verbal perlocutionary giftedness. The research revealed that the aspects like verbal aptitude, anxiety, willingness to communicate, or personality type had considerable impact on perlocutionary skills and the desired perlocutionary effects. Świątek’s approach shed new light on the research on pragmatic aspects of glottodidactics and opened a new chapter in that field of science. The aim of the presentation is to concentrate on yet another fundamental factor of perlocutionary giftedness, i.e. non-verbal aspects in its manifestation. The research, based on experiential and comparative methods as well as individual case analysis, aimed at revealing a strong link between verbal perlocutionary giftedness and the accompanying non-verbal aspects of communication, such as kinesics, proxemics, vocalics, or posture, which affect the listener’s decisions, who then complies with the speaker’s will.

Download Full-text

Insight into Salivary Gland Aquaporins

Cells ◽

10.3390/cells9061547 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1547 ◽

Cited By ~ 2

Author(s):

Claudia D’Agostino ◽

Osama A. Elkashty ◽

Clara Chivasso ◽

Jason Perret ◽

Simon D. Tran ◽

...

Keyword(s):

Molecular Mechanisms ◽

Physiological Role ◽

Main Role ◽

Osmotic Gradient ◽

Therapeutic Approaches ◽

Potential Therapeutic Target ◽

Transmembrane Channel ◽

Saliva Secretion ◽

Insight Into

The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren’s syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.

Download Full-text