scholarly journals Orexins: A promising target to digestive cancers, inflammation, obesity and metabolism dysfunctions

2021 ◽  
Vol 27 (44) ◽  
pp. 7582-7596
Author(s):  
Alain Couvineau ◽  
Thierry Voisin ◽  
Pascal Nicole ◽  
Valerie Gratio ◽  
Anne Blais
Keyword(s):  
Promising Target ◽  
Digestive Cancers

scholarly journals Neurotensin pathway in digestive cancers and clinical applications: an overview

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Niki Christou ◽  
Sabrina Blondy ◽  
Valentin David ◽  
Mireille Verdier ◽  
Fabrice Lalloué ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Biological Effects ◽  
Soluble Form ◽  
Promising Target ◽  
Tumor Tissues ◽  
Digestive Cancers ◽  
The Central Nervous System ◽  
Endocrine Factor ◽  
Vacuolar Protein

AbstractInitially, NEUROTENSIN (NTS) has been shown to play physiological and biological functions as a neuro-transmitter/modulator in the central nervous system and as an endocrine factor in the periphery, through its binding to two kinds of receptors: NTSR1 and 2 (G protein-coupled receptors) and NTSR3/sortilin (a vacuolar protein-sorting 10-domain receptor). NTS also plays oncogenic roles in many types of cancer, including digestive cancers. In tumor tissues, NTS and NTSR1 expression is higher than in healthy ones and is associated with poor prognosis. NTS and NTRS1 promote cancer progression and play key functions in metastatic processes; they modulate several signaling pathways and they contribute to changes in the tumor microenvironment. Conversely, NTRS2 involvement in digestive cancers is poorly understood. Discovered for mediating NTS biological effects, sortilin recently emerged as a promising target as its expression was found to be increased in various types of cancers. Because it can be secreted, a soluble form of sortilin (sSortilin) appears as a new serum biomarker which, on the basis of recent studies, promises to be useful in both the diagnosis and tumor progression monitoring. More precisely, it appears that soluble sortilin can be associated with other receptors like TRKB. These associations occur in exosomes and trigger the aggressiveness of cancers like glioblastoma, leading to the concept of a possible composite theranostic biomarker. This review summarizes the oncogenic roles of the NTS signaling pathways in digestive cancers and discusses their emergence as promising early diagnostic and/or prognostic biomarkers and therapeutic targets.

Gut microbiome a promising target for management of respiratory diseases

2020 ◽  
Vol 477 (14) ◽  
pp. 2679-2696
Author(s):  
Riddhi Trivedi ◽  
Kalyani Barve
Keyword(s):  
Respiratory Diseases ◽  
New Technology ◽  
Bacterial Flora ◽  
Systemic Circulation ◽  
The Body ◽  
Lung Pathology ◽  
Promising Target ◽  
Current Therapies ◽  
Intestinal Microbial Flora ◽  
On Chip

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

Integrin αvβ8 on T Cells is Responsible for Suppression of Anti-Tumor Immunity in Syngeneic Models and is a Promising Target for Tumor Immunotherapy

2020 ◽  
Author(s):  
Eswari Dodagatta-Marri ◽  
Hsiao-Yen Ma ◽  
Benjia Liang ◽  
John Li ◽  
Dominique S. Meyer ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Tumor Immunotherapy ◽  
Promising Target

Glutamyl and Glutaminyl-tRNA Synthetases Are a Promising Target for the Design of Threonine-Producing Strain

2019 ◽  
Vol 35 (6) ◽  
pp. 39-50
Author(s):  
T.V. Yuzbashev ◽  
A.S. Fedorov ◽  
F.V. Bondarenko ◽  
A.S. Savchenko ◽  
T.V. Vybornaya ◽  
...  
Keyword(s):  
Biomass Accumulation ◽  
Trna Synthetase ◽  
Temperature Sensitive ◽  
Original Strain ◽  
Trna Synthetases ◽  
Resource Center ◽  
Promising Target ◽  
The Russian Federation ◽  
Increase In Productivity ◽  
Culture Growth

The present work describes an approach that improves the properties of the strain producing L-threonine via the reduction in the biomass accumulation during fermentation. Glutamyl- and glutaminyl-tRNA synthetases were chosen as targets. Mutants carrying temperature-sensitive alleles were obtained. It was shown that the used system caused the suppression of the function of tRNA synthetases which led to a rapid arrest of the culture growth, and an increase in productivity and yield of the L-threonine synthesis. One of the temperature-sensitive strains was used to obtain under non-permissive conditions of mutants with the suppressed above phenotype. Some of these mutants accumulate less biomass and produce by 10-12% more threonine than the original strain. Escherichia coli, producing strain, threonine, aminoacyl-tRNA synthetase, ts-mutation This work was supported by the Ministry of Science and Higher Education of the Russian Federation (project code RFMEFI61017X0011), and it was carried out using the equipment of the National Bio-Resource Center All-Russian Collection of Industrial Microorganisms, NRC «Kurchatov Institute» - GosNIIgenetika.

Structure and Function of Angiopoietin-like Protein 3 (ANGPTL3) in Atherosclerosis

2020 ◽  
Vol 27 (31) ◽  
pp. 5159-5174 ◽  
Author(s):  
Xinjie Lu
Keyword(s):  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
Biological Functions ◽  
Pharmacological Management ◽  
Vascular Growth ◽  
Promising Target ◽  
And Function ◽  
Systematic Appraisal

Background:Angiopoietin-Like Proteins (ANGPTLs) are structurally related to the angiopoietins. A total of eight ANGPTLs (from ANGPTL1 to ANGPTL8) have been identified so far. Most ANGPTLs possess multibiological functions on lipid metabolism, atherosclerosis, and cancer. Among them, ANGPTL3 has been shown to regulate the levels of Very Low-Density Lipoprotein (VLDL) made by the liver and play a crucial role in human lipoprotein metabolism.Method:A systematic appraisal of ANGPTLs was conducted, focusing on the main features of ANGPTL3 that has a significant role in atherosclerosis.Results:Angiopoietins including ANGPTL3 are vascular growth factors that are highly specific for endothelial cells, perform a variety of other regulatory activities to influence inflammation, and have been shown to possess both pro-atherosclerotic and atheroprotective effects.Conclusion:ANGPTL3 has been demonstrated as a promising target in the pharmacological management of atherosclerosis. However, many questions remain about its biological functions.

The Next Generation of Pattern Recognition Receptor Agonists: Improving Response Rates in Cancer Immunotherapy

2020 ◽  
Vol 27 (34) ◽  
pp. 5654-5674 ◽  
Author(s):  
Daniel H. O’ Donovan ◽  
Yumeng Mao ◽  
Deanna A. Mele
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Cancer Immunotherapy ◽  
Anticancer Agents ◽  
Adaptive Immune System ◽  
Antitumor Effects ◽  
Tlr Agonists ◽  
Recent Success ◽  
Promising Target ◽  
Tumor Types

The recent success of checkpoint blocking antibodies has sparked a revolution in cancer immunotherapy. Checkpoint inhibition activates the adaptive immune system leading to durable responses across a range of tumor types, although this response is limited to patient populations with pre-existing tumor-infiltrating T cells. Strategies to stimulate the immune system to prime an antitumor response are of intense interest and several groups are now working to develop agents to activate the Pattern Recognition Receptors (PRRs), proteins which detect pathogenic and damageassociated molecules and respond by activating the innate immune response. Although early efforts focused on the Toll-like Receptor (TLR) family of membrane-bound PRRs, TLR activation has been associated with both pro- and antitumor effects. Nonetheless, TLR agonists have been deployed as potential anticancer agents in a range of clinical trials. More recently, the cytosolic PRR Stimulator of IFN Genes (STING) has attracted attention as another promising target for anticancer drug development, with early clinical data beginning to emerge. Besides STING, several other cytosolic PRR targets have likewise captured the interest of the drug discovery community, including the RIG-Ilike Receptors (RLRs) and NOD-like Receptors (NLRs). In this review, we describe the outlook for activators of PRRs as anticancer therapeutic agents and contrast the earlier generation of TLR agonists with the emerging focus on cytosolic PRR activators, both as single agents and in combination with other cancer immunotherapies.

Plasmodium falciparum M1-Aminopeptidase: A Promising Target for the Development of Antimalarials

2014 ◽  
Vol 15 (12) ◽  
pp. 1144-1165 ◽  
Author(s):  
Jorge Gonzalez-Bacerio ◽  
Rafael Fando ◽  
Alberto Monte-Martinez ◽  
Jean-Louis Charli ◽  
Maria Chávez
Keyword(s):  
Plasmodium Falciparum ◽  
Promising Target ◽  
Aminopeptidase A

Development of an HPLC-UV Method for Quantification of Stattic

2019 ◽  
Vol 15 (6) ◽  
pp. 568-573
Author(s):  
Soheil Sedaghat ◽  
Ommoleila Molavi ◽  
Akram Faridi ◽  
Ali Shayanfar ◽  
Mohammad Reza Rashidi
Keyword(s):  
High Performance ◽  
Accurate Method ◽  
Plasma Samples ◽  
Promising Target ◽  
Relative Standard ◽  
Dimerization Inhibitor ◽  
Oncogenic Protein ◽  
First Time ◽  
Transcription 3

Background: Signal transducer and activator of transcription 3 (STAT3), an oncogenic protein found constitutively active in many types of human malignancies, is considered to be a promising target for cancer therapy. Objective: In this study for the first time, a simple and accurate method has been developed for the determination of a STAT3 dimerization inhibitor called stattic in aqueous and plasma samples. Methods: A reverse-phase high-performance liquid chromatography (RP-HPLC) composed of C18 column as stationary phase, and the mixture of acetonitrile (60%) and water (40%) as mobile phase with a UV detection at 215 nm were applied for quantification of stattic. The developed method was validated by Food and Drug Administration (FDA) guideline. Results: The method provided a linear range between 1-40 and 2.5-40 µg mL-1 for aqueous and plasma samples, respectively, with a correlation coefficient of 0.999. The accuracy (as recovery) of the developed method was found to be between 95-105% for aqueous medium and 85-115% for plasma samples. The precision (as relative standard deviation) for aqueous and plasma samples was less than 6% and 15%, respectively. The sensitivity of the developed method based on FDA guideline was 1 µg mL-1 for aqueous and 2.5 µg mL-1 for plasma samples. Conclusion: These results show that the established method is a fast and accurate quantification for stattic in aqueous and plasma samples.

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