scholarly journals Role of Phytochemicals in Perturbation of Redox Homeostasis in Cancer

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 83
Author(s):  
Shreyas Gaikwad ◽  
Sanjay K. Srivastava
Keyword(s):  
Treatment Options ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Threshold Values ◽  
Cellular Death ◽  
External Stimulation ◽  
The Past ◽  
Oncogenic Pathways ◽  
Ros Homeostasis

Over the past few decades, research on reactive oxygen species (ROS) has revealed their critical role in the initiation and progression of cancer by virtue of various transcription factors. At certain threshold values, ROS act as signaling molecules leading to activation of oncogenic pathways. However, if perturbated beyond the threshold values, ROS act in an anti-tumor manner leading to cellular death. ROS mediate cellular death through various programmed cell death (PCD) approaches such as apoptosis, autophagy, ferroptosis, etc. Thus, external stimulation of ROS beyond a threshold is considered a promising therapeutic strategy. Phytochemicals have been widely regarded as favorable therapeutic options in many diseased conditions. Over the past few decades, mechanistic studies on phytochemicals have revealed their effect on ROS homeostasis in cancer. Considering their favorable side effect profile, phytochemicals remain attractive treatment options in cancer. Herein, we review some of the most recent studies performed using phytochemicals and, we further delve into the mechanism of action enacted by individual phytochemicals for PCD in cancer.

scholarly journals The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD

2021 ◽  
Author(s):  
Chandani Patel Chavez ◽  
Kenneth Cusi ◽  
Sushma Kadiyala
Keyword(s):  
Evidence Synthesis ◽  
Clinical Care ◽  
Treatment Options ◽  
Critical Role ◽  
Risk Groups ◽  
The United States ◽  
Multidisciplinary Teams ◽  
Consensus Statements ◽  
Meta Analyses

Abstract Context The burden of cirrhosis from NAFLD is reaching epidemic proportions in the United States. This calls for greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at the highest risk. At the same time, recent studies suggest that GLP-1RAs are beneficial versus steatohepatitis (NASH) in this population. This minireview aims to assist endocrinologists to recognize the condition and recent work on the role of GLP-1RAs in NAFLD/NASH. Evidence acquisition Evidence from observational studies, randomized controlled trials, and meta-analyses. Evidence Synthesis Endocrinologists should lead multidisciplinary teams to implement recent consensus statements on NAFLD that call for screening and treatment of clinically significant fibrosis to prevent cirrhosis, especially in the high-risk groups (i.e., people with obesity, prediabetes or T2D). With no FDA-approved agents, weight loss is central to their successful management, with pharmacological treatment options limited today to vitamin E (in people without T2D) and diabetes medications that reverse steatohepatitis, such as pioglitazone or GLP-1RA. Recently the benefit of GLP-1RAs in NAFLD, suggested from earlier trials, has been confirmed in adults with biopsy-proven NASH. In 2021, the FDA also approved semaglutide for obesity management. Conclusion A paradigm change is developing between the endocrinologist’s greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients.

scholarly journals Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhuo Xie ◽  
Mudan Zhang ◽  
Gaoshi Zhou ◽  
Lihui Lin ◽  
Jing Han ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Critical Role ◽  
Signalling Pathway ◽  
Hedgehog Signalling Pathway ◽  
Inflammatory Bowel ◽  
Effective Drugs

AbstractThe Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted. Targeting the Hh signalling pathway may pave the way for successful IBD treatment. In this review, we introduce the molecular mechanisms underlying the Hh signalling pathway and its role in maintaining intestinal homeostasis. Then, we present interactions between the Hh signalling and other pathways involved in IBD and colitis-associated colorectal cancer (CAC), such as the Wnt and nuclear factor-kappa B (NF-κB) pathways. Furthermore, we summarise the latest research on Hh signalling associated with the occurrence and progression of IBD and CAC. Finally, we discuss the future directions for research on the role of Hh signalling in IBD pathogenesis and provide viewpoints on novel treatment options for IBD by targeting Hh signalling. An in-depth understanding of the complex role of Hh signalling in IBD pathogenesis will contribute to the development of new effective therapies for IBD patients.

scholarly journals CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

Open Biology ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 130217 ◽  
Author(s):  
Puneet Sharma ◽  
Alo Nag
Keyword(s):  
Ubiquitin Ligase ◽  
Drug Target ◽  
Critical Role ◽  
Cellular Transformation ◽  
Biological Processes ◽  
Molecular Architecture ◽  
The Past ◽  
Cullin 4A ◽  
Broad Overview

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.

scholarly journals Glutamine Addiction and Therapeutic Strategies in Lung Cancer

2019 ◽  
Vol 20 (2) ◽  
pp. 252 ◽  
Author(s):  
Karolien Vanhove ◽  
Elien Derveaux ◽  
Geert-Jan Graulus ◽  
Liesbet Mesotten ◽  
Michiel Thomeer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Tricarboxylic Acid Cycle ◽  
Treatment Options ◽  
Redox Homeostasis ◽  
Glutamine Metabolism ◽  
Lung Cancer Cells ◽  
Production Networks ◽  
Tricarboxylic Acid Cycle Intermediates

Lung cancer cells are well-documented to rewire their metabolism and energy production networks to support rapid survival and proliferation. This metabolic reorganization has been recognized as a hallmark of cancer. The increased uptake of glucose and the increased activity of the glycolytic pathway have been extensively described. However, over the past years, increasing evidence has shown that lung cancer cells also require glutamine to fulfill their metabolic needs. As a nitrogen source, glutamine contributes directly (or indirectly upon conversion to glutamate) to many anabolic processes in cancer, such as the biosynthesis of amino acids, nucleobases, and hexosamines. It plays also an important role in the redox homeostasis, and last but not least, upon conversion to α-ketoglutarate, glutamine is an energy and anaplerotic carbon source that replenishes tricarboxylic acid cycle intermediates. The latter is generally indicated as glutaminolysis. In this review, we explore the role of glutamine metabolism in lung cancer. Because lung cancer is the leading cause of cancer death with limited curative treatment options, we focus on the potential therapeutic approaches targeting the glutamine metabolism in cancer.

scholarly journals Therapeutic Effects of Melatonin on Ocular Diseases: Knowledge Map and Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Haozhe Yu ◽  
Qicong Wang ◽  
Wenyu Wu ◽  
Weizhen Zeng ◽  
Yun Feng
Keyword(s):  
Clinical Evidence ◽  
Critical Role ◽  
Knowledge Map ◽  
Therapeutic Effects ◽  
Ocular Diseases ◽  
Ocular Tissues ◽  
The Past ◽  
Clinical Transformation ◽  
And Oxidative Stress

Melatonin plays a critical role in the pathophysiological process including circadian rhythm, apoptosis, and oxidative stress. It can be synthesized in ocular tissues, and its receptors are also found in the eye, triggering more investigations concentrated on the role of melatonin in the eye. In the past decades, the protective and therapeutic potentials of melatonin for ocular diseases have been widely revealed in animal models. Herein, we construct a knowledge map of melatonin in treating ocular diseases through bibliometric analysis and review its current understanding and clinical evidence. The overall field could be divided into twelve topics through keywords co-occurrence analysis, in which the glaucoma, myopia, and retinal diseases were of greatest research interests according to the keywords burst detection. The existing clinical trials of melatonin in ocular diseases mainly focused on the glaucoma, and more research should be promoted, especially for various diseases and drug administration. We also discuss its bioavailability and further research topics including developing melatonin sensors for personalized medication, acting as stem cell therapy assistant drug, and consuming food-derived melatonin for facilitating its clinical transformation.

scholarly journals Multifaceted Functional Role of Semaphorins in Glioblastoma

2019 ◽  
Vol 20 (9) ◽  
pp. 2144 ◽  
Author(s):  
Cristiana Angelucci ◽  
Gina Lama ◽  
Gigliola Sica
Keyword(s):  
Axon Guidance ◽  
Treatment Options ◽  
Migration And Invasion ◽  
Tumor Type ◽  
Metastatic Progression ◽  
Oncogenic Pathways ◽  
Membrane Bound ◽  
Wide Group

Glioblastoma (GBM) is the most malignant tumor type affecting the adult central nervous system. Despite advances in therapy, the prognosis for patients with GBM remains poor, with a median survival of about 15 months. To date, few treatment options are available and recent trials based on the molecular targeting of some of the GBM hallmark pathways (e.g., angiogenesis) have not produced any significant improvement in overall survival. The urgent need to develop more efficacious targeted therapies has led to a better molecular characterization of GBM, revealing an emerging role of semaphorins in GBM progression. Semphorins are a wide group of membrane-bound and secreted proteins, originally identified as axon guidance cues, signaling through their receptors, neuropilins, and plexins. A number of semaphorin signals involved in the control of axonal growth and navigation during development have been found to furthermore participate in crosstalk with different dysfunctional GBM pathways, controlling tumor cell proliferation, migration, and invasion, as well as tumor angiogenesis or immune response. In this review, we summarize the regulatory activities mediated by semaphorins and their receptors on the oncogenic pathways implicated in GBM growth and invasive/metastatic progression.

Precision medicine: Driving the evolution of biobanking quality

2020 ◽  
Vol 33 (3) ◽  
pp. 102-106 ◽  
Author(s):  
Rebecca O. Barnes ◽  
Peter H. Watson
Keyword(s):  
Data Quality ◽  
Precision Medicine ◽  
Healthcare System ◽  
Biological Samples ◽  
Critical Role ◽  
Quality Requirements ◽  
The Past ◽  
The Impact ◽  
Research Domain

The promise of precision medicine will only be realized if the healthcare system adapts to meet some key infrastructure needs. Among these needs are adequate biobanking practices, capable of producing the biological samples and data that precision medicine relies upon in both the research and clinical phases. Within the research domain, there have been significant improvements to biobanking processes over the past two decades, driven by increased understanding of the impact of pre-analytical variability and the critical role of biospecimen and data quality. In the era of precision medicine, biobanking to support clinical needs has similar quality requirements. The extensive knowledge and resources that have been developed by the research biobanking community are available for adoption by clinical biobanking. The challenge and opportunity now presented to the healthcare system is to adopt or adapt these resources, for example, external biobanking standards and verification programs.

scholarly journals Oxidative Stress and Thrombosis during Aging: The Roles of Oxidative Stress in RBCs in Venous Thrombosis

2020 ◽  
Vol 21 (12) ◽  
pp. 4259
Author(s):  
Qinhong Wang ◽  
Rahima Zennadi
Keyword(s):  
Oxidative Stress ◽  
Venous Thrombosis ◽  
Life Stage ◽  
Redox Homeostasis ◽  
Critical Role ◽  
Membrane Integrity ◽  
Accelerated Aging ◽  
Coagulation Factors ◽  
Membrane Structure And Function

Mid-life stage adults are at higher risk of developing venous thrombosis (VT)/thromboembolism (VT/E). Aging is characterized by an overproduction of reactive oxygen species (ROS), which could evoke a series of physiological changes involved in thrombosis. Here, we focus on the critical role of ROS within the red blood cell (RBC) in initiating venous thrombosis during aging. Growing evidence has shifted our interest in the role of unjustifiably unvalued RBCs in blood coagulation. RBCs can be a major source of oxidative stress during aging, since RBC redox homeostasis is generally compromised due to the discrepancy between prooxidants and antioxidants. As a result, ROS accumulate within the RBC due to the constant endogenous hemoglobin (Hb) autoxidation and NADPH oxidase activation, and the uptake of extracellular ROS released by other cells in the circulation. The elevated RBC ROS level affects the RBC membrane structure and function, causing loss of membrane integrity, and decreased deformability. These changes impair RBC function in hemostasis and thrombosis, favoring a hypercoagulable state through enhanced RBC aggregation, RBC binding to endothelial cells affecting nitric oxide availability, RBC-induced platelet activation consequently modulating their activity, RBC interaction with and activation of coagulation factors, increased RBC phosphatidylserine exposure and release of microvesicles, accelerated aging and hemolysis. Thus, RBC oxidative stress during aging typifies an ultimate mechanism in system failure, which can affect major processes involved in the development of venous thrombosis in a variety of ways. The reevaluated concept of the critical role of RBC ROS in the activation of thrombotic events during aging will help identify potential targets for novel strategies to prevent/reduce the risk for VT/E or VT/E recurrences in mid-life stage adults.

Performance Feedback Persistence: Comparative Effects of Historical Versus Peer Performance Feedback on Innovative Search

2020 ◽  
pp. 014920632091622 ◽  
Author(s):  
Yang Ye ◽  
Wei Yu ◽  
Robert Nason
Keyword(s):  
Performance Feedback ◽  
Critical Role ◽  
Theory Of The Firm ◽  
Theoretical Development ◽  
Panel Regression ◽  
The Past ◽  
Likelihood Analysis ◽  
Peer Performance ◽  
Quasi Maximum Likelihood

Firms use aspirations to regulate innovative search activities, but peer and historical referents may contain different signals regarding performance feedback. Integrating insights from the literature on profit persistence with the behavioral theory of the firm, we propose a persistence-based framework of organizational innovative search that connects the persistence characteristics of feedback from peer and historical referents with innovative search. We first predict that feedback from peer referents is more persistent than feedback from historical referents. Further, we theorize that peer performance feedback produces more pronounced effects: Performance above (below) peer aspiration leads to less (more) innovative search compared with performance above (below) the historical aspiration level. In addition, because industries impose heterogeneous levels of profit persistence, the differential effect between peer and historical performance feedback on innovative search is likely to be more evident in highly persistent industries. Examining the research-and-development intensity of a comprehensive panel of Compustat manufacturing firms over the past 45 years, our results from quasi–maximum likelihood analysis and fixed-effect panel regression largely support our theoretical development. Our study extends a nascent understanding of aspiration heterogeneity by revealing and empirically confirming the critical role of persistence.

The Critical Role of Microscopy and Spectroscopy in the Development of New Materials for Microelectronics Packaging

1996 ◽  
Vol 54 ◽  
pp. 634-635
Author(s):  
R.A. Youngman
Keyword(s):  
Thermal Conductivity ◽  
Critical Role ◽  
New Materials ◽  
Considerable Time ◽  
Microelectronics Packaging ◽  
Sintered Ceramic ◽  
The Past ◽  
Sintered Aluminum ◽  
New Material

It has been over thirty years since sintered aluminum nitride (AIN) has been the focus of many research and development activities in Japan, the U.S., and Europe. Only in the past 5 years has there been significant use of this material in microelectronics. There are many reasons for this considerable time for application including, technology needs and acceptance of a new material. Also important has been the role of materials understanding of AIN through the use of microscopy and spectroscopy. We illustrate the use of both standard and unique characterization techniques to elucidate the nature of the crystalline defects which control the important property of thermal conductivity.The thermal conductivity of pure AIN is 320 W/mK. This value has never been achieved in a sintered ceramic. In order to develop a sintered AIN with a high thermal conductivity it is necessary to understand the factors which control the thermal conductivity.

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