Calcineurin inhibitors: status quo and perspectives

2011 ◽  
Vol 2 (1-2) ◽  
pp. 65-78 ◽  
Author(s):  
Frank Erdmann ◽  
Matthias Weiwad
Keyword(s):  
Calcineurin Inhibitor ◽  
Biological Effects ◽  
Calcineurin Inhibitors ◽  
Basic Research ◽  
Status Quo ◽  
The Past ◽  
Compound Libraries ◽  
High Incidence ◽  
A Current ◽  
Structure Properties

AbstractDespite the fact that cyclosporin A (CsA) and tacrolimus (FK506) are very potent drugs in the treatment of serious autoimmune diseases and in the prevention of graft vs. host reactions or tissue rejections after allo- or xenotransplantations, modern transplantation medicine attempts to develop alternative medication regimes without these calcineurin inhibitors. The primary motivation for this endeavor is the high incidence of dramatic side effects upon immunosuppressive therapy. CsA and FK506 target not only the calcineurin/NFAT pathway, but they also bind and inhibit members of distinct peptidyl-prolyl cis/trans isomerase families, which are involved in numerous important signal transduction pathways. Therefore, the development of a potent calcineurin inhibitor that discriminates between calcineurin and other protein phosphatases and peptidyl-prolyl cis/trans isomerases, respectively, should improve the drug safety in clinical use and represent a valuable tool in basic research to investigate calcineurin modulated pathways. This review gives a current overview about novel calcineurin inhibitors, which were identified by screening of compound libraries and in natural materials or were derived from known inhibitors in the past decades. Thereby, we focus on their structure, properties and biological effects.

Hydraulic Laboratory at University of Liège

2018 ◽  
pp. 80-89
Author(s):  
Willi H. Hager
Keyword(s):  
Basic Research ◽  
The Novel ◽  
University Campus ◽  
Current Position ◽  
Professional Background ◽  
The Past ◽  
Comprehensive Picture

The Hydraulic Laboratory of Liège University, Belgium, is historically considered from its foundation in 1937 to the mid-1960s. The technical facilities of the various Buildings are highlighted, along with canals and instrumentation available. It is noted that in its initial era, comparatively few basic research has been conducted, mainly due to the professional background of the professors leading the establishment. This state was improved in the past 50 years, however, particularly since the Laboratory was dislocated to its current position in the novel University Campus. Biographies of the leading persons associated with the Liège Hydraulic Laboratory are also presented, so that a comprehensive picture is given of one of the currently leading hydraulic Laboratories of Europe.

Post-Soviet economy development: From the past to the future

2017 ◽  
pp. 5-21 ◽  
Author(s):  
E. Yasin
Keyword(s):  
Present Situation ◽  
Soviet Economy ◽  
Market Reforms ◽  
Democratic Development ◽  
The Past ◽  
Current Period ◽  
The Future ◽  
History Of ◽  
Working Out ◽  
A Current

The article is devoted to major events in the history of the post-Soviet economy, their influence on forming and development of modern Russia. The author considers stages of restructuring, market reforms, transformational crisis, and recovery growth (1999-2011), as well as a current period which started in2011 and is experiencing serious problems. The present situation is analyzed, four possible scenarios are put forward for Russia: “inertia”, “mobilization”, “decisive leap”, “gradual democratic development”. More than 30 experts were questioned in the process of working out the scenarios.

Music and Memory: The Tlatelolco Refrain

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Josh Kun
Keyword(s):  
State Violence ◽  
First Century ◽  
Student Movements ◽  
Octavio Paz ◽  
Mexican History ◽  
The Past ◽  
Rock Bands ◽  
To Come ◽  
Musical Memory ◽  
A Current

Ever since the 1968 student movements and the events surrounding the Tlatelolco massacre, Mexico City rock bands have openly engaged with the intersection of music and memory. Their songs offer audiences a medium through which to come to terms with the events of the past as a means of praising a broken world, to borrow the poet Adam Zagajewski’s phrase. Contemporary songs such as Saúl Hernández’s “Fuerte” are a twenty-first-century voicing of the ceaseless revolutionary spirit that John Gibler has called “Mexico unconquered,” a current of rebellion and social hunger for justice that runs in the veins of Mexican history. They are the latest additions to what we might think about as “the Mexico unconquered songbook”: musical critiques of impunity and state violence that are rooted in the weaponry of memory, refusing to focus solely on the present and instead making connections with the political past. What Octavio Paz described as a “swash of blood” that swept across “the international subculture of the young” during the events in Tlatelolco Plaza on October 2, 1968, now becomes a refrain of musical memory and political consciousness that extends across eras and generations. That famous phrase of Paz’s is a reminder that these most recent Mexican musical interventions, these most recent formations of a Mexican subculture of the young, maintain a historically tested relationship to blood, death, loss, and violence.

Therapeutic Perspectives of Food Bioactive Peptides: A Mini Review

2019 ◽  
Vol 26 (9) ◽  
pp. 664-675
Author(s):  
Sulochana Priya
Keyword(s):  
Bioactive Peptides ◽  
Marine Organism ◽  
Biological Effects ◽  
Amide Bond ◽  
Therapeutic Effects ◽  
Specific Sequence ◽  
The Past ◽  
Cancer Immunity ◽  
Microbial Infections ◽  
Diverse Origin

Bioactive peptides are short chain of amino acids (usually 2-20) that are linked by amide bond in a specific sequence which have some biological effects in animals or humans. These can be of diverse origin like plant, animal, fish, microbe, marine organism or even synthetic. They are successfully used in the management of many diseases. In recent years increased attention has been raised for its effects and mechanism of action in various disease conditions like cancer, immunity, cardiovascular disease, hypertension, inflammation, diabetes, microbial infections etc. Bioactive peptides are more bioavailable and less allergenic when compared to total proteins. Food derived bioactive peptides have health benefits and its demand has increased tremendously over the past decade. This review gives a view on last two years research on potential bioactive peptides derived from food which have significant therapeutic effects.

Microbial Genetic Screens for Monitoring Protein Misfolding Associated with Neurodegeneration: Tools for Identifying Disease-Relevant Genes and for Screening Synthetic and Natural Compound Libraries for the Discovery of Potential Therapeutics

2018 ◽  
Vol 24 (19) ◽  
pp. 2055-2075 ◽  
Author(s):  
Kalliopi Kostelidou ◽  
Ilias Matis ◽  
Georgios Skretas
Keyword(s):  
Protein Misfolding ◽  
Socioeconomic Impact ◽  
Genetic Screens ◽  
Subsequent Formation ◽  
The Past ◽  
Compound Libraries ◽  
Selection Systems ◽  
Cellular Factors ◽  
Effective Drugs ◽  
Potential Therapeutics

Neurodegenerative Diseases (ND) are a major threat to the aging population and the lack of a single preventive or disease-modifying agent only serves to increase their impact. In the past few years, protein misfolding and the subsequent formation of neurotoxic oligomeric/aggregated protein species have emerged as a unifying theme underlying the pathology of these complex diseases. Recently developed microbial genetic screens and selection systems for monitoring ND-associated protein misfolding have allowed the establishment of highthroughput assays for the identification of cellular factors and processes that are important mediators of NDassociated proteotoxicities. In addition, such systems have facilitated the discovery of synthetic and natural compounds with the ability to rescue the misfolding and the associated pathogenic effects of aggregation-prone proteins associated with NDs. This review outlines such available systems in bacteria and yeast, whose usage will likely accelerate the pre-clinical discovery process for effective drugs against a variety of NDs with high socioeconomic impact.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

scholarly journals Sphingolipid lysosomal storage diseases: from bench to bedside

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Muna Abed Rabbo ◽  
Yara Khodour ◽  
Laurie S. Kaguni ◽  
Johnny Stiban
Keyword(s):  
Basic Research ◽  
Lysosomal Storage Diseases ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Late Nineteenth Century ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
The Past ◽  
Health And Disease ◽  
General Aspects

AbstractJohann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.

scholarly journals Noncompaction Cardiomyopathy—History and Current Knowledge for Clinical Practice

2021 ◽  
Vol 10 (11) ◽  
pp. 2457
Author(s):  
Birgit J. Gerecke ◽  
Rolf Engberding
Keyword(s):  
Clinical Practice ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Clinical Patient ◽  
Noncompaction Cardiomyopathy ◽  
The Past ◽  
Wide Range ◽  
Morphological Variants ◽  
A Current ◽  
Healthy Persons

Noncompaction cardiomyopathy (NCCM) has gained increasing attention over the past twenty years, but in daily clinical practice NCCM is still rarely considered. So far, there are no generally accepted diagnostic criteria and some groups even refuse to acknowledge it as a distinct cardiomyopathy, and grade it as a variant of dilated cardiomyopathy or a morphological trait of different conditions. A wide range of morphological variants have been observed even in healthy persons, suggesting that pathologic remodeling and physiologic adaptation have to be differentiated in cases where this spongy myocardial pattern is encountered. Recent studies have uncovered numerous new pathogenetic and pathophysiologic aspects of this elusive cardiomyopathy, but a current summary and evaluation of clinical patient management are still lacking, especially to avoid mis- and overdiagnosis. Addressing this issue, this article provides an up to date overview of the current knowledge in classification, pathogenesis, pathophysiology, epidemiology, clinical manifestations and diagnostic evaluation, including genetic testing, treatment and prognosis of NCCM.

scholarly journals Receiving threatening or obscene messages from a partner and mental health, self-harm and suicidality: results from the Adult Psychiatric Morbidity Survey

2021 ◽  
Author(s):  
Sally McManus ◽  
Paul E. Bebbington ◽  
Leonie Tanczer ◽  
Sara Scott ◽  
Louise M. Howard
Keyword(s):  
Intimate Partner Violence ◽  
Mental Disorder ◽  
Partner Violence ◽  
Common Mental Disorder ◽  
Psychiatric Morbidity ◽  
Intimate Partner ◽  
Sample Survey ◽  
The Past ◽  
Self Harm ◽  
A Current

Abstract Purpose Threatening or obscene messaging is repeated, unwanted texts, emails, letters or cards experienced by the recipient as threatening or obscene, and causing fear, alarm or distress. It is rarely examined as an aspect of intimate partner violence. We describe the prevalence of exposure to threatening/obscene messaging from a current or ex-partner; characteristics of victims; and associations with other forms of violence and abuse, mental disorder, self-harm, and suicidality. Methods Cross-sectional probability-sample survey of the general population in England aged 16 + . Multivariable regression modelling tested associations between receipt of threatening/obscene messaging and current common mental disorder, past-year self-harm and suicidality. Results Threatening/obscene messages were received from a current/ex-partner by 6.6% (95%CI: 5.9–7.3) of adults who had been in a relationship; 1.7% received these in the past year. Victims were more likely to be female, under 35, single or divorced, socioeconomically disadvantaged, and to have experienced other forms of sexual and partner violence and abuse. Those who received threatening/obscene messages in the past year were more likely to experience common mental disorder (adjusted odds ratio 1.89; 1.01–3.55), self-harm (2.31; 1.00–5.33), and suicidal thoughts (2.00; 1.06–3.78). Conclusion Threatening/obscene messaging commonly occurs in the context of intimate partner violence. While often occurring alongside sexual and physical violence, messaging has an additional association with mental disorder and suicidality. Routine enquiry in service settings concerning safety, including those working with people who have escaped domestic violence, should ask about ongoing contact from previous as well as current partners. This should include asking about messaging, as well as other forms of potentially technology-enabled abuse which may become increasingly common.

scholarly journals Research on the Literature of Green Building Based on the Web of Science: A Scientometric Analysis in CiteSpace (2002–2018)

2019 ◽  
Vol 11 (13) ◽  
pp. 3716 ◽  
Author(s):  
Yingling Shi ◽  
Xinping Liu
Keyword(s):  
Web Of Science ◽  
Green Building ◽  
Development Trend ◽  
Status Quo ◽  
Future Research ◽  
Building Industry ◽  
Scientometric Analysis ◽  
The Past ◽  
Evolution Pattern ◽  
The Status

Since the 21st century, the concept of green building has been gradually popularized and implemented in more countries, which has become a popular direction in the area of sustainability in the building industry. Over the past few decades, many scholars and experts have done extensive research on green building. The purpose of this paper is to systematically analyze and visualize the status quo of green building. Therefore, based on Web of Science (WoS), this paper analyzed the existing knowledge system of green building using CiteSpace, identified keywords related to green building and their frequency of occurrence using the function of keyword co-occurrence analysis, recognized five clusters using the function of cluster analysis, and explored the knowledge evolution pattern of green building using citation bursts analysis in order to reveal how research related to green building has evolved over time. On the basis of aforementioned keywords, clusters, and citation bursts analysis, this paper has built a knowledge graph for green building. This paper can help readers to better understand the status quo and development trend of green building and to easier recognize the shortcomings in the development of green building, so as to provide a promising direction for future research.

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