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.

Factors affecting the amplitude of the τ angle in proteins: a revisitation

2017 ◽  
Vol 73 (7) ◽  
pp. 618-625 ◽  
Author(s):  
Nicole Balasco ◽  
Luciana Esposito ◽  
Luigi Vitagliano
Keyword(s):  
Protein Structures ◽  
Factors Affecting ◽  
X Ray ◽  
Backbone Conformation ◽  
Potential Factors ◽  
The Stability ◽  
Major Factors ◽  
The Impact ◽  
Open Issues

The protein folded state is the result of the fine balance of a variety of different forces. Even minor structural perturbations may have a significant impact on the stability of these macromolecules. Studies carried out in recent decades have led to the convergent view that proteins are endowed with a flexible spine. One of the open issues related to protein local backbone geometry is the identification of the factors that influence the amplitude of the τ (N—Cα—C) angle. Here, statistical analyses performed on an updated ensemble of X-ray protein structures by dissecting the contribution of the major factors that can potentially influence the local backbone geometry of proteins are reported. The data clearly indicate that the local backbone conformation has a prominent impact on the modulation of the τ angle. Therefore, a proper assessment of the impact of the other potential factors can only be appropriately evaluated when small (φ, ψ) regions are considered. Here, it is shown that when the contribution of the backbone conformation is removed by considering small (φ, ψ) areas, an impact of secondary structure, as defined byDSSP, and/or the residue type on τ is still detectable, although to a limited extent. Indeed, distinct τ-value distributions are detected for Pro/Gly and β-branched (Ile/Val) residues. The key role of the local backbone conformation highlighted here supports the use of variable local backbone geometry in protein refinement protocols.

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 Financial Innovations in Proliferation of Economic Instability

2011 ◽  
pp. 56-64
Author(s):  
I. Strelets ◽  
M. Stolbov
Keyword(s):  
Financial Market ◽  
Business Processes ◽  
New Drugs ◽  
Social Progress ◽  
Economic Stability ◽  
Economic Issues ◽  
Financial Innovations ◽  
Financial Products ◽  
The Impact

The authors consider the impact of financial innovations on the macroeconomic situation. The increasing complexity of financial market instruments is the way to decrease its transparency and, consequently, the overall economic stability. The global crisis of 2008-2009 demonstrated the relevance of this problem. However, the authors believe that the nations can take advantage of new financial products, technologies and business processes if the regulators manage to fully track and timely offset the accompanying risks. It is important that execution of the financial innovations correspond with the structure of the funding companies and banks. It is concluded that adequate regulation of financial innovation will allow better use of their potential in order to address a number of important economic issues. In particular, it may help to accelerate the development and introduction of new drugs, to the implementation of environmental projects, the financing of social progress in the developing countries for achieving the Millennium Goals proclaimed by the UN in 2000.

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 GTP metabolic reprogramming by IMPDH2: unlocking cancer cells’ fuelling mechanism

2020 ◽  
Vol 168 (4) ◽  
pp. 319-328 ◽  
Author(s):  
Satoshi Kofuji ◽  
Atsuo T Sasaki
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Metabolic Reprogramming ◽  
Inosine Monophosphate Dehydrogenase ◽  
Metabolic Demand ◽  
Adaptive Mechanisms ◽  
Key Aspects ◽  
Polymerase I ◽  
Rate Limiting

Abstract Growing cells increase multiple biosynthetic processes in response to the high metabolic demands needed to sustain proliferation. The even higher metabolic requirements in the setting of cancer provoke proportionately greater biosynthesis. Underappreciated key aspects of this increased metabolic demand are guanine nucleotides and adaptive mechanisms to regulate their concentration. Using the malignant brain tumour, glioblastoma, as a model, we have demonstrated that one of the rate-limiting enzymes for guanosine triphosphate (GTP) synthesis, inosine monophosphate dehydrogenase-2 (IMPDH2), is increased and IMPDH2 expression is necessary for the activation of de novo GTP biosynthesis. Moreover, increased IMPDH2 enhances RNA polymerase I and III transcription directly linking GTP metabolism to both anabolic capacity as well as nucleolar enlargement historically observed as associated with cancer. In this review, we will review in detail the basis of these new discoveries and, more generally, summarize the current knowledge on the role of GTP metabolism in cancer.

Treatment of metastatic bladder cancer

2017 ◽  
Author(s):  
Fabio Calabrò ◽  
Cora N. Sternberg
Keyword(s):  
Bladder Cancer ◽  
Urothelial Cancer ◽  
Clinical Investigation ◽  
Good Prognosis ◽  
New Drugs ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Molecular Patterns ◽  
The Impact

Although bladder cancer is considered a chemosensitive malignancy, the prognosis of patients with metastatic disease is poor, with a median survival of approximately 12–14 months in good prognosis patients and with cure in only a minority. The addition of new drugs to the standard cisplatin-based regimens has not improved these outcomes. In this chapter, we highlight the role of chemotherapy and the impact of the new targeted agents in the treatment of metastatic bladder carcinoma. A better understanding of the underlying biology and the molecular patterns of urothelial bladder cancer has led to clinical investigation of several therapeutic targets. To date, these agents have yet to demonstrate an improvement in overall survival. Urothelial cancer is extremely sensitive to checkpoint inhibition with both anti PD-1 and anti PDL1 antibodies. The future seems brighter with the advent of these new therapies.

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.

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