scholarly journals Mitochondrial Metabolism in Melanoma

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3197
Author(s):  
Christina Huang ◽  
Rakan H. Radi ◽  
Jack L. Arbiser
Keyword(s):  
Therapeutic Benefit ◽  
Biological Pathways ◽  
Mitochondrial Metabolism ◽  
Mechanisms Of Resistance ◽  
It Impacts ◽  
Cellular Pathways ◽  
Areas Of Interest ◽  
Interest In Research ◽  
Mitochondrial Adaptation

Melanoma and its associated alterations in cellular pathways have been growing areas of interest in research, especially as specific biological pathways are being elucidated. Some of these alterations include changes in the mitochondrial metabolism in melanoma. Many mitochondrial metabolic changes lead to differences in the survivability of cancer cells and confer resistance to targeted therapies. While extensive work has gone into characterizing mechanisms of resistance, the role of mitochondrial adaptation as a mode of resistance is not completely understood. In this review, we wish to explore mitochondrial metabolism in melanoma and how it impacts modes of resistance. There are several genes that play a major role in melanoma mitochondrial metabolism which require a full understanding to optimally target melanoma. These include BRAF, CRAF, SOX2, MCL1, TRAP1, RHOA, SRF, SIRT3, PTEN, and AKT1. We will be discussing the role of these genes in melanoma in greater detail. An enhanced understanding of mitochondrial metabolism and these modes of resistance may result in novel combinatorial and sequential therapies that may lead to greater therapeutic benefit.

scholarly journals Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yawei Wang ◽  
Binlin Tang ◽  
Lei Long ◽  
Peng Luo ◽  
Wei Xiang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxidative Phosphorylation ◽  
Near Infrared ◽  
Mitochondrial Metabolism ◽  
Diet Induced Obesity ◽  
Adipose Tissue Macrophages ◽  
Inflammatory Activation ◽  
Treatment Of Obesity ◽  
Pharmaceutical Agents

AbstractPro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.

scholarly journals Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 304
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Javier Molina-Cerrillo ◽  
Teresa Alonso-Gordoa
Keyword(s):  
Adrenocortical Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
Response Efficacy ◽  
Predictors Of Response ◽  
Primary Endpoints ◽  
Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

Forensic learning disability nursing: what's it really like?

2014 ◽  
Vol 5 (4) ◽  
pp. 167-177
Author(s):  
Mark F Dalgarno ◽  
Sharon A Riordan
Keyword(s):  
Learning Disability ◽  
Design Methodology ◽  
Nursing Practice ◽  
Structured Interview ◽  
Phenomenological Analysis ◽  
Forensic Nursing ◽  
Content Type ◽  
Emotional Challenge ◽  
Areas Of Interest

Purpose – The purpose of this paper is to explore the lived experiences of learning disability nurses working within forensic services, and their views on their practice as a speciality. Design/methodology/approach – A qualitative, semi-structured interview-based design was used and participant's voices were examined through interpretive phenomenological analysis. Findings – Nurses explored a range of topics related to their practice and overall, five superordinate themes were developed. Forensic nursing as being both the same and different to generic nursing, the journey, and the emotional challenge of forensic nursing, the balancing act of everyday practice and the role of language within forensic nursing practice. Originality/value – Very little research has examined the views of learning disability nurses within the forensic field. This study gives both a voice to these nurses and suggests areas of interest both for research and for clinicians to consider in their practice.

An Overview of the Latest Applications of Platelet-Derived Microparticles and Nanoparticles in Medical Technology 2010-2020

2021 ◽  
Vol 21 ◽  
Author(s):  
Tahereh Zadeh Mehrizi
Keyword(s):  
Drug Delivery ◽  
Cell Types ◽  
Current Status ◽  
Target Cells ◽  
Interesting Point ◽  
Large Size ◽  
Review Study ◽  
Cellular Pathways ◽  
Different Cell Types

: Today, Platelets and platelet-derived nanoparticles and microparticles have found many applications in nanomedical technology. The results of our review study show that no article has been published in this field to review the current status of applications of these platelet derivatives so far. Therefore, in present study, our goal is to compare the applications of platelet derivatives and review their latest status between 2010 and 2020 to present the latest findings to researchers. A very interesting point about the role of platelet derivatives is the presence of molecules on their surface which makes them capable of hiding from the immune system, reaching different target cells, and specifically attaching to different cell types. According to the results of this study, most of their applications include drug delivery, diagnosis of various diseases, and tissue engineering. However, their application in drug delivery is limited due to heterogeneity, large size, and the possibility of interference with cellular pathways in microparticles derived from other cells. On the other hand, platelet nanoparticles are more controllable and have been widely used for drug delivery in treatment of cancer, atherosclerosis, thrombosis, infectious diseases, repair of damaged tissue, and photothermal therapy. The results of this study show that platelet nanoparticles are more controllable than platelet microparticles and have a higher potential for use in medicine.

Re-Examination of the Exacerbating Effect of Inflammasome Components during Radiation Injury

2021 ◽  
Author(s):  
W. June Brickey ◽  
Michael A. Thompson ◽  
Zhecheng Sheng ◽  
Zhiguo Li ◽  
Kouros Owzar ◽  
...  
Keyword(s):  
Cellular Response ◽  
Radiation Injury ◽  
Therapeutic Benefit ◽  
Acute Radiation ◽  
Cellular Damage ◽  
Inflammatory Factors ◽  
Experimental Conditions ◽  
Acute Radiation Injury ◽  
Radiation Induced

Radiation can be applied for therapeutic benefit against cancer or may result in devastating harm due to accidental or intentional release of nuclear energy. In all cases, radiation exposure causes molecular and cellular damage, resulting in the production of inflammatory factors and danger signals. Several classes of innate immune receptors sense the released damage associated molecules and activate cellular response pathways, including the induction of inflammasome signaling that impacts IL-1β/IL-18 maturation and cell death. A previous report indicated inflammasomes aggravate acute radiation syndrome. In contrast, here we find that inflammasome components do not exacerbate gamma-radiation-induced injury by examining heterozygous and gene-deletion littermate controls in addition to wild-type mice. Absence of some inflammasome genes, such as caspase-1/11 and Nlrp3, enhance susceptibility of treated mice to acute radiation injury, indicating importance of the inflammasome pathway in radioprotection. Surprisingly, we discover that the survival outcome may be sex-dependent as more inflammasome-deficient male mice are susceptible to radiation-induced injury. We discuss parameters that may influence the role of inflammasomes as radioprotective or radioexacerbating factors in recovery from radiation injury including the use of littermate controls, the sex of the animals, differences in microbiota within the colonies and other experimental conditions. Under the conditions tested, inflammasome components do not exacerbate radiation injury, but rather provide protective benefit.

scholarly journals The Role of the Passive Voice Mindset in Regulating Healthy Eating

2017 ◽  
Vol 9 (2) ◽  
pp. 37
Author(s):  
Ibrahim Senay ◽  
Muhammet Usak ◽  
Zeynep Ceren Acarturk
Keyword(s):  
Healthy Eating ◽  
Eating Habits ◽  
Passive Voice ◽  
Active Voice ◽  
The Past ◽  
It Impacts ◽  
Unhealthy Eating

Talking about eating in the passive, as opposed to the active voice, (e.g., The cake will be eaten vs. I will eat the cake) can lead people to see the act of eating to be triggered by the food to a greater extent, leading to the continuation of past eating habits. Depending on whether or not the past habits are healthy, the motivation for healthy eating may change as a result. In study 1, writing passive sentences increased the motivation for healthy eating to the extent that people reported eating healthy in the past. Moreover, in study 2 across 127 languages spoken in 94 countries, when the acted-upons of actions (e.g., the food in the act of eating) became relatively more salient in a language, people became more likely to act on cultural habits that may be relatively healthier, decreasing unhealthy eating. The results are important for understanding the perceived role of food in starting eating as it impacts healthy eating across cultures.

scholarly journals Ankhd1 enhances polycystic kidney disease development via promoting proliferation and fibrosis

2020 ◽  
Author(s):  
Foteini Patera ◽  
Guillaume M Hautbergue ◽  
Patricia Wilson ◽  
Paul C Evans ◽  
Albert CM Ong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Therapeutic Benefit ◽  
Polycystic Kidney ◽  
Molecular Events ◽  
Proliferative Growth ◽  
Kh Domain ◽  
Autosomal Dominant Polycystic Kidney

ABSTRACTAutosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic kidney disorder resulting in 10% of patients with renal failure. The molecular events responsible for the relentless growth of cysts are not defined. Thus, identification of novel drivers of ADPKD may lead to new therapies. Ankyrin Repeat and Single KH domain-1 (ANKHD1) controls cancer cell proliferation, yet its role in ADPKD is unexplored. Here, we present the first data that identify ANKHD1 as a driver of proliferative growth in cellular and mouse models of ADPKD. Using the first Ankhd1-deficient mice, we demonstrate that Ankhd1 heterozygosity potently reduces cystic growth and fibrosis, in a genetically orthologous mouse model of ADPKD. We performed transcriptome-wide profiling of patient-derived ADPKD cells with and without ANKHD1 siRNA silencing, revealing a major role for ANKHD1 in the control of cell proliferation and matrix remodelling. We validated the role of ANKHD1 in enhancing proliferation in patient-derived cells. Mechanistically ANKHD1 promotes STAT5 signalling in ADPKD mice. Hence, ANKHD1 is a novel driver of ADPKD, and its inhibition may be of therapeutic benefit.

scholarly journals Protection of the Child’s Creative Output Including Its Legal Protection

2014 ◽  
Vol 12 (1) ◽  
Author(s):  
Anna Sokołowska
Keyword(s):  
Creative Process ◽  
Legal Protection ◽  
Legal Aspects ◽  
Rights Of The Child ◽  
Starting Point ◽  
The Subject ◽  
Education And Development ◽  
Areas Of Interest ◽  
Education Process

AbstractThis paper is an attempt to analyze the necessity of defining and extending the protection of the child’s creative process. The starting point for consideration is the key role of artistic instruction in the child’s education and development which justifies providing appropriate framework for that process. The present text defines artistic output as a personal good covered by legal protection and specifies relevant legal regulations underlying the subject. It also reveals the position of the child as a creator with his/her specific characteristics and possible dangers arising from those characteristics. Another issue discussed here is the creative process and its components. In a further part, legal aspects of the child’s situation in the context of creative activity are analyzed with references to the UN Convention on the Rights of the Child (1989), the (Polish) Family and Guardianship Code (1964), the UN Declaration on Rights of the Child (1959) and other legal acts. Finally, the paper addresses objectives of arts education in the light of the discussed issues. Conclusions include an indication of certain similarity between some areas of interest in pedagogy and in law. The main conclusion comes down to a statement that in the education process we should take into consideration so-called creative integrity which constitutes a personal good of both the adult and the child, and which is covered by legal protection.

scholarly journals Angiogenesis and Anti-Angiogenic Treatment in Prostate Cancer: Mechanisms of Action and Molecular Targets

2021 ◽  
Vol 22 (18) ◽  
pp. 9926
Author(s):  
Evangelia Ioannidou ◽  
Michele Moschetta ◽  
Sidrah Shah ◽  
Jack Steven Parker ◽  
Mehmet Akif Ozturk ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Chemotherapeutic Agents ◽  
Combination Therapies ◽  
Mechanisms Of Resistance ◽  
Marginal Benefit ◽  
Antiangiogenic Activity ◽  
Castration Resistant ◽  
Common Cancer

Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance.

scholarly journals Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism

2019 ◽  
Vol 71 ◽  
pp. 34-40 ◽  
Author(s):  
Caitlyn E. Bowman ◽  
Michael J. Wolfgang
Keyword(s):  
Mitochondrial Metabolism ◽  
Malonyl Coa
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