scholarly journals Role of Autophagy in Cadmium-Induced Hepatotoxicity and Liver Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Suryakant Niture ◽  
Minghui Lin ◽  
Qi Qi ◽  
John T. Moore ◽  
Keith E. Levine ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Pulmonary Toxicity ◽  
Molecular Level ◽  
Lysosomal Degradation ◽  
Cell Organelles ◽  
Air Contamination ◽  
Recent Developments ◽  
Toxic Pollutant ◽  
Catabolic Process

Cadmium (Cd) is a toxic pollutant that is associated with several severe human diseases. Cd can be easily absorbed in significant quantities from air contamination/industrial pollution, cigarette smoke, food, and water and primarily affects the liver, kidney, and lungs. Toxic effects of Cd include hepatotoxicity, nephrotoxicity, pulmonary toxicity, and the development of various human cancers. Cd is also involved in the development and progression of fatty liver diseases and hepatocellular carcinoma. Cd affects liver function via modulation of cell survival/proliferation, differentiation, and apoptosis. Moreover, Cd dysregulates hepatic autophagy, an endogenous catabolic process that detoxifies damaged cell organelles or dysfunctional cytosolic proteins through vacuole-mediated sequestration and lysosomal degradation. In this article, we review recent developments and findings regarding the role of Cd in the modulation of hepatotoxicity, autophagic function, and liver diseases at the molecular level.

scholarly journals Targeting Autophagy to Treat Cancer: Challenges and Opportunities

2020 ◽  
Vol 11 ◽  
Author(s):  
Junghyun Lim ◽  
Aditya Murthy
Keyword(s):  
Cancer Therapy ◽  
Tumor Progression ◽  
Treatment Resistance ◽  
Tissue Homeostasis ◽  
Lysosomal Degradation ◽  
Growing Body ◽  
Challenges And Opportunities ◽  
Established Disease ◽  
Catabolic Process

Autophagy is a catabolic process that targets its cargo for lysosomal degradation. In addition to its function in maintaining tissue homeostasis, autophagy is recognized to play a context-dependent role in cancer. Autophagy may inhibit tumor initiation under specific contexts; however, a growing body of evidence supports a pro-tumorigenic role of this pathway in established disease. In this setting, autophagy drives treatment resistance, metabolic changes, and immunosuppression both in a tumor-intrinsic and extrinsic manner. This observation has prompted renewed interest in targeting autophagy for cancer therapy. Novel genetic models have proven especially insightful, revealing unique and overlapping roles of individual autophagy-related genes in tumor progression. Despite identification of pharmacologically actionable nodes in the pathway, fundamental challenges still exist for successful therapeutic inhibition of autophagy. Here we summarize the current understanding of autophagy as a driver of resistance against targeted and immuno-therapies and highlight knowledge gaps that, if addressed, may provide meaningful advances in the treatment of cancer.

scholarly journals Tumor Suppression and Promotion by Autophagy

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Yenniffer Ávalos ◽  
Jimena Canales ◽  
Roberto Bravo-Sagua ◽  
Alfredo Criollo ◽  
Sergio Lavandero ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Metabolic Stress ◽  
Lysosomal Degradation ◽  
Tumor Suppressor Proteins ◽  
Pathological Conditions ◽  
Suppressor Mechanism ◽  
Resistance To Chemotherapy ◽  
Catabolic Process

Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless, autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion on this ambiguous role of autophagy in the development and progression of cancer.

An integrated screening method for evaluating the pulmonary toxicity of inhaled particulates: Role of microscopic techniques in assessing pulmonary macrophage clearance functions

1990 ◽  
Vol 48 (3) ◽  
pp. 826-827
Author(s):  
David B. Warheit ◽  
Lena Achinko ◽  
Mark A. Hartsky
Keyword(s):  
Bronchoalveolar Lavage ◽  
Pulmonary Toxicity ◽  
Screening Method ◽  
Pulmonary Response ◽  
Inhaled Particles ◽  
Cytochemical Analysis ◽  
Pulmonary Macrophages ◽  
Integrated Screening

There is a great need for the development of a rapid and reliable bioassay to evaluate the pulmonary toxicity of inhaled particles. A number of methods have been proposed, including lung clearance studies, bronchoalveolar lavage analysis, and in vitro cytotoxicity tests. These methods are often limited in scope inasmuch as they measure only one dimension of the pulmonary response to inhaled, instilled or incubated dusts. Accordingly, a comprehensive approach to lung toxicity studies has been developed.To validate the method, rats were exposed for 6 hours or 3 days to various concentrations of either aerosolized alpha quartz silica (Si) or carbonyl iron (CI) particles. Cells and fluids from groups of sham and dust-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, LDH and protein values were measured in BAL fluids at several time points postexposure. Cells were counted and evaluated for viability, as well as differential and cytochemical analysis. In addition, pulmonary macrophages (PM) were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy.

Shot-noise simulations of HREM images of polymer crystals

1989 ◽  
Vol 47 ◽  
pp. 342-343
Author(s):  
Philippe Pradère ◽  
Edwin L. Thomas
Keyword(s):  
Low Dose ◽  
Molecular Level ◽  
High Resolution Electron Microscopy ◽  
Crystal Defects ◽  
Inorganic Materials ◽  
Photographic Emulsion ◽  
Polymer Crystals ◽  
Resolution Electron ◽  
Recent Developments ◽  
Lattice Images

High Resolution Electron Microscopy (HREM) is a very powerful technique for the study of crystal defects at the molecular level. Unfortunately polymer crystals are beam sensitive and are destroyed almost instantly under the typical HREM imaging conditions used for inorganic materials. Recent developments of low dose imaging at low magnification have nevertheless permitted the attainment of lattice images of very radiation sensitive polymers such as poly-4-methylpentene-1 and enabled molecular level studies of crystal defects in somewhat more resistant ones such as polyparaxylylene (PPX) [2].With low dose conditions the images obtained are very noisy. Noise arises from the support film, photographic emulsion granularity and in particular, the statistical distribution of electrons at the typical doses of only few electrons per unit resolution area. Figure 1 shows the shapes of electron distribution, according to the Poisson formula :

How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

2020 ◽  
Vol 48 (3) ◽  
pp. 1019-1034 ◽  
Author(s):  
Rachel M. Woodhouse ◽  
Alyson Ashe
Keyword(s):  
Histone Modifications ◽  
Molecular Mechanisms ◽  
Epigenetic Inheritance ◽  
Nematode Caenorhabditis Elegans ◽  
Histone Methyltransferases ◽  
Transgenerational Epigenetic Inheritance ◽  
C Elegans ◽  
Recent Developments ◽  
Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

The miR-21 potential of serving as a biomarker for liver diseases in clinical practice

2020 ◽  
Vol 48 (5) ◽  
pp. 2295-2305
Author(s):  
Jiawei Zhang ◽  
Dandan Li ◽  
Rui Zhang ◽  
Peng Gao ◽  
Rongxue Peng ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Liver Diseases ◽  
Hepatic Disease ◽  
Noninvasive Detection ◽  
Diagnosis And Prognosis ◽  
Expected Performance ◽  
Potential Biomarker ◽  
Disease Condition ◽  
Complex Regulatory Network

The role of miR-21 in the pathogenesis of various liver diseases, together with the possibility of detecting microRNA in the circulation, makes miR-21 a potential biomarker for noninvasive detection. In this review, we summarize the potential utility of extracellular miR-21 in the clinical management of hepatic disease patients and compared it with the current clinical practice. MiR-21 shows screening and prognostic value for liver cancer. In liver cirrhosis, miR-21 may serve as a biomarker for the differentiating diagnosis and prognosis. MiR-21 is also a potential biomarker for the severity of hepatitis. We elucidate the disease condition under which miR-21 testing can reach the expected performance. Though miR-21 is a key regulator of liver diseases, microRNAs coordinate with each other in the complex regulatory network. As a result, the performance of miR-21 is better when combined with other microRNAs or classical biomarkers under certain clinical circumstances.

Role of scavenger receptors in the pathophysiology of chronic liver diseases

2013 ◽  
Author(s):  
Carolina Armengol ◽  
Ramon Bartoli ◽  
Lucia Sanjurjo ◽  
Isabel Serra ◽  
Nuria Amezaga ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Chronic Liver ◽  
Scavenger Receptors ◽  
Chronic Liver Diseases

Wilfred Ethier. Modern International Economics. New York: W. W. Norton and Company. 1983. xviii + 588 pp.

1988 ◽  
Vol 27 (1) ◽  
pp. 81-83
Author(s):  
Nadeem A. Burney
Keyword(s):  
International Economic ◽  
New York ◽  
Economic Theory ◽  
International Economics ◽  
International Monetary System ◽  
International Markets ◽  
The Past ◽  
Monetary System ◽  
Recent Developments

Its been long recognized that various economies of the world are interlinked through international trade. The experience of the past several years, however, has demonstrated that this economic interdependence is far greater than was previously realized. In this context, the importance of international economic theory as an area distinct from general economics hardly needs any mentioning. What gives international economic theory this distinction is international markets for some goods and effects of national sovereignty on the character of economic activity. Wilfred Ethier's book, which incorporates recent developments in the field, is an excellent addition to textbooks on international economics for one- or twosemester undergraduate courses. The book mostly covers standard topics. A distinguishing feature of this book is its detailed analysis of the flexible exchange rates and a discussion of the various approaches used for their determination. Within each chapter, the author has extensively used facts, figures and major events to clarify the concepts in the light of the theoretical framework. The book also discusses, in a fair amount of detail, the existing international monetary system and the role of various international organizations.

Can the Lewis basicity of an isolated solvent molecule be used for characterizing solvent effects?

2020 ◽  
Vol 16 ◽  
Author(s):  
Jean-François Gal ◽  
Pierre-Charles Maria
Keyword(s):  
Solvent Effects ◽  
Molecular Level ◽  
Solvent Molecule ◽  
Lewis Base ◽  
Bulk Liquid ◽  
Donor Number ◽  
Special Focus ◽  
Solution Processes ◽  
Inert Solvent

Background: The ubiquitous Lewis acid/base interactions are important in solution processes. Analytical chemistry may benefit of a better understanding of the role of Lewis basicity, at the molecular level or acting through a bulk solvent effect. Objective: To clearly delineate (i) the basicity at a molecular level, hereafter referred as solute basicity, and (ii) the solvent basicity, which is a bulk-liquid property. Method: The literature that relates Lewis basicity scales and solvent effects is analyzed. A special focus is placed on two extensive scales, the Donor Number, DN, and the BF3 affinity scale, BF3A, which were obtained by calorimetric measurement on molecules as solutes diluted in a quasi-inert solvent, and therefore define a molecular Lewis basicity. We discuss the validity of these solute scales when regarded as solvent scales, in particular when the basicity of strongly associated liquids is discussed. Results: We demonstrate the drawbacks of confusing the Lewis basicity of a solvent molecule, isolated as solute, and that of the bulk liquid solvent itself. Conclusion: Consequently, we recommend a reasoned use of the concept of Lewis basicity taking clearly into account the specificity of the process for which a Lewis basicity effect may be invoked. In particular, the action of the Lewis base, either as an isolated entity, or as a bulk liquid, must be distinguished.

The Role of Financial Innovation in EU Market Integration and the Capital Markets Union

2018 ◽  
Author(s):  
Emilios Avgouleas
Keyword(s):  
Capital Markets ◽  
Risk Sharing ◽  
Market Integration ◽  
Financial Innovation ◽  
The European Union ◽  
Recent Developments ◽  
Capital Markets Union ◽  
Critical Overview ◽  
The Eu

This chapter offers a critical overview of the issues that the European Union 27 (EU-27) will face in the context of making proper use of financial innovation to further market integration and risk sharing in the internal financial market, both key objectives of the drive to build a Capital Markets Union. Among these is the paradigm shift signalled by a technological revolution in the realm of finance and payments, which combines advanced data analytics and cloud computing (so-called FinTech). The chapter begins with a critical analysis of financial innovation and FinTech. It then traces the EU market integration efforts and explains the restrictive path of recent developments. It considers FinTech's potential to aid EU market integration and debates the merits of regulation dealing with financial innovation in the context of building a capital markets union in EU-27.

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