scholarly journals HDAC6 Inhibition Extinguishes Autophagy in Cancer: Recent Insights

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6280
Author(s):  
Eugenia Passaro ◽  
Chiara Papulino ◽  
Ugo Chianese ◽  
Antonella Toraldo ◽  
Raffaella Congi ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Hdac Inhibitors ◽  
Research Community ◽  
Mechanisms Of Resistance ◽  
Ubiquitin Binding ◽  
Important Player ◽  
Targeted Drug ◽  
Cellular Tolerance ◽  
The Impact

Autophagy is an essential intracellular catabolic mechanism involved in the degradation and recycling of damaged organelles regulating cellular homeostasis and energy metabolism. Its activation enhances cellular tolerance to various stresses and is known to be involved in drug resistance. In cancer, autophagy has a dual role in either promoting or blocking tumorigenesis, and recent studies indicate that epigenetic regulation is involved in its mechanism of action in this context. Specifically, the ubiquitin-binding histone deacetylase (HDAC) enzyme HDAC6 is known to be an important player in modulating autophagy. Epigenetic modulators, such as HDAC inhibitors, mediate this process in different ways and are already undergoing clinical trials. In this review, we describe current knowledge on the role of epigenetic modifications, particularly HDAC-mediated modifications, in controlling autophagy in cancer. We focus on the controversy surrounding their ability to promote or block tumor progression and explore the impact of HDAC6 inhibitors on autophagy modulation in cancer. In light of the fact that targeted drug therapy for cancer patients is attracting ever increasing interest within the research community and in society at large, we discuss the possibility of using HDAC6 inhibitors as adjuvants and/or in combination with conventional treatments to overcome autophagy-related mechanisms of resistance.

scholarly journals Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 909
Author(s):  
Krzysztof Kotowski ◽  
Jakub Rosik ◽  
Filip Machaj ◽  
Stanisław Supplitt ◽  
Daniel Wiczew ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Treatment Options ◽  
Protein Structures ◽  
New Drugs ◽  
Proliferating Cells ◽  
Cancer Tissues ◽  
The Impact ◽  
Rate Limiting ◽  
Synthesis And Degradation

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

scholarly journals Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Lucía Fuentes ◽  
Tamás Rőszer ◽  
Mercedes Ricote
Keyword(s):  
Insulin Resistance ◽  
Nuclear Receptor ◽  
Cytokine Production ◽  
Current Knowledge ◽  
Liver Steatosis ◽  
Visceral Obesity ◽  
M2 Macrophage ◽  
Low Grade ◽  
The Impact

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

Social capital in the theory and research of LIS professionals in the light of the literature on the subject. Review of current knowledge

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Maja Dorota Wojciechowska
Keyword(s):  
Social Capital ◽  
Current Knowledge ◽  
Future Research ◽  
Content Type ◽  
Individual Social Capital ◽  
Rural Libraries ◽  
The Subject ◽  
The Moment ◽  
The Impact

Purpose The purpose of the paper is to present the latest scholarly trends in the field of social capital in libraries, to review research concepts published by LIS professionals and to suggest further research possibilities in this area. Design/methodology/approach This paper presents a review and critical analysis of literature associated with research on social capital in libraries to highlight its importance for the development of LIS and its impact on the functioning of environments linked with various types of libraries. The goal of literature analysis was to determine the current condition of research on social capital in libraries. The main trends were identified and the need for further qualitative analyses, which are missing at the moment, was confirmed. Findings It was determined that, so far, LIS professionals have focussed mainly on the role of municipal libraries in developing social capital, the problem of building trust, especially in immigrant circles and the impact of libraries on promoting a civil society. Academic libraries, rural libraries, organisational capital in libraries and individual social capital of librarians were a much less frequent subject of research. The role of libraries in developing social capital in educational (primary and secondary education) and professional (non-university professionals) circles is practically non-existent in research, and it will require in-depth studies and analyses in the coming years. Originality/value This paper constitutes a synthetic review of the latest research concepts concerning social capital in libraries. It identifies the most important research trends and areas that so far have not been explored and suggests research methods to help LIS professionals design future research in this area more effectively.

scholarly journals HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

Reproduction ◽  
2021 ◽  
Vol 161 (1) ◽  
pp. F1-F17
Author(s):  
Rocío Martínez-Aguilar ◽  
Lucy E Kershaw ◽  
Jane J Reavey ◽  
Hilary O D Critchley ◽  
Jacqueline A Maybin
Keyword(s):  
Current Knowledge ◽  
Abnormal Uterine Bleeding ◽  
Future Research ◽  
Hypoxic Episode ◽  
Optimal Function ◽  
Pros And Cons ◽  
The Impact ◽  
Review Current

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

Role of the gut microbiota in airway immunity and host defense against respiratory infections

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maike Willers ◽  
Dorothee Viemann
Keyword(s):  
Gut Microbiota ◽  
Host Defense ◽  
Gut Microbiome ◽  
Respiratory Infections ◽  
Current Knowledge ◽  
Viral Pathogens ◽  
Commensal Microbiota ◽  
Enhanced Resistance ◽  
The Impact

Abstract Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a focus on consequences for the host defense against respiratory infections. Specific gut commensal microbiota compositions and functions are depicted that mediate protection against respiratory infections with bacterial and viral pathogens. Lastly, we highlight factors that have imprinting effects on the establishment of the gut microbiota early in life and are potentially relevant in the context of respiratory infections. Deepening our understanding of these relationships will allow to exploit the knowledge on how gut microbiome maturation needs to be modulated to ensure lifelong enhanced resistance towards respiratory infections.

scholarly journals The Emerging Role of Microbiota and Microbiome in Pancreatic Ductal Adenocarcinoma

Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 565
Author(s):  
Sona Ciernikova ◽  
Maria Novisedlakova ◽  
Danka Cholujova ◽  
Viola Stevurkova ◽  
Michal Mego
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Early Stage ◽  
Poor Response ◽  
Response To Therapy ◽  
Oral Microbiome ◽  
Ductal Adenocarcinoma ◽  
The Impact

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant tumors due to the absence of biomarkers for early-stage detection and poor response to therapy. Since mounting evidence supports the role of microbiota composition in tumorigenesis and cancer treatment, the link between microbiome and PDAC has been described. In this review, we summarize the current knowledge regarding the impact of the gut and oral microbiome on the risk of PDAC development. Microenvironment-driven therapy and immune system interactions are also discussed. More importantly, we provide an overview of the clinical trials evaluating the microbiota role in the risk, prognosis, and treatment of patients suffering from PDAC and solid tumors. According to the research findings, immune tolerance might result from the microbiota-derived remodeling of pancreatic tumor microenvironment. Thus, microbiome profiling and targeting represent the potential trend to enhance antitumor immunity and improve the efficacy of PDAC treatment.

scholarly journals Management of Soil-Borne Fungi and Root-Knot Nematodes in Cucurbits through Breeding for Resistance and Grafting

Agronomy ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1641
Author(s):  
Alejandro Ayala-Doñas ◽  
Miguel de Cara-García ◽  
Miguel Talavera-Rubia ◽  
Soledad Verdejo-Lucas
Keyword(s):  
Current Knowledge ◽  
Pathogenic Fungi ◽  
Nematode Species ◽  
Mechanisms Of Resistance ◽  
Root Knot Nematodes ◽  
Breeding For Resistance ◽  
Root Diseases ◽  
Soil Borne Pathogens ◽  
The Right ◽  
The Impact

Soil-borne pathogenic fungi (SBPF) and root-knot nematodes (RKN) co-exist in the rhizosphere and are major pathogens causing root diseases in cucurbits. Current knowledge on soil-borne pathogens of cucurbit crops grown under protected cultivation, their host-pathogen interactions, and mechanisms of resistance has been reviewed. Plant resistance is an effective and sustainable method to control soil-borne diseases and the available resistant cultivars and rootstocks to key soil-borne pathogens are reported. The importance of proper pathogen diagnosis in the right choice of cultivar or rootstock is highlighted because of the specificity in the response of the cucurbit crops to fungal and nematode species and races. Plants protect themselves through common mechanisms of resistance against SBPF and RKN including hardening of their cell walls, pathogenesis-related (PR) proteins, and production of antimicrobial molecules. The activity of some enzymes, such as peroxidases and phenylalanine lyase, is increased after pathogen infection and is higher on SBPF and RKN resistant than susceptible cucurbits. Plant hormones such as salicylic acid, jasmonic acid, and ethylene are involved in the response of cucurbits to SBPF. Most mechanisms of resistance to RKN affect post-infection development of the nematode, which results in a delay or disruption of the life cycle. Traditional and biotechnological tools used for breeding for resistance in cucurbits are described. Grafting is an effective non-host resistance method to control primarily Fusarium wilt but not to control RKN. However, new rootstocks with resistance to both pathogens have been developed recently and their effects on fruit quality and yield stability need additional studies. The impact of grafting on yield in pathogen-infested soils is discussed.

Determining the impact of knowledge sharing initiatives in international organizations: Case studies

IFLA Journal ◽  
2019 ◽  
Vol 46 (1) ◽  
pp. 64-71
Author(s):  
Linda Stoddart
Keyword(s):  
United Nations ◽  
Knowledge Sharing ◽  
International Organizations ◽  
Current Knowledge ◽  
Senior Management ◽  
The United Nations ◽  
United Nations System ◽  
The Impact ◽  
Nations System

No one disputes that knowledge is the lifeblood of international organizations and especially specialized agencies of the United Nations. However, there has been little consensus on the best methods to share knowledge, leverage the extensive international expertise and make it available to the constituents and partners of these organizations. What is their strategy for managing knowledge? Do they have one? What impact does it have? What is the role of senior management in championing knowledge sharing in these international organizations? These are the questions this paper addresses through the lenses of the evaluations of current knowledge sharing practices in two institutions located in Geneva, Switzerland, both part of the United Nations system.

scholarly journals Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ilse Bollaerts ◽  
Jessie Van houcke ◽  
Lien Andries ◽  
Lies De Groef ◽  
Lieve Moons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Current Knowledge ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Novel Therapeutic Strategies ◽  
The Impact ◽  
Vertebrate Central Nervous System

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

The Oxford Handbook of Hope

2017 ◽  
Keyword(s):  
Current Knowledge ◽  
Physical And Mental Health ◽  
Comprehensive Overview ◽  
Future Directions ◽  
Theoretical Perspectives ◽  
The Many ◽  
The Impact ◽  
Made In

The Oxford Handbook of Hope provides a comprehensive overview of current knowledge regarding the science and practice of hope. Hope has long been a topic of interest to philosophers and the general public, but it was only in recent decades that hope became a focus of psychological science. Rick Snyder defined hope as a cognitive trait that helps individuals to identify and pursue goals and consists of two components: pathways, the perceived capacity to identify strategies necessary to achieve goals, and agency, the willpower or motivation to pursue those pathways to achieve goals. Hope has become one of most robust and promising topics in the burgeoning field of positive psychology. This book reviews the progress that has been made in the past 25 years regarding the origins and influence of hope. Topics covered include current theoretical perspectives on how best to define hope and how it is distinct from related constructs, current best practices for measuring and quantifying hope, interventions and strategies for promoting hope across different settings and the lifespan, the impact that hope has on many dimensions and domains of physical and mental health, and the many ways and contexts in which hope promotes resilience and positive functioning. Experts in the field both review what is currently known about the role of hope in different domains and identify topics and questions that can help to guide the next decade of research. The handbook concludes with a collaborative vision on the future directions of the science of hope.

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