scholarly journals The Emerging Role of Macrophages in Chronic Cholangiopathies Featuring Biliary Fibrosis: An Attractive Therapeutic Target for Orphan Diseases

2020 ◽  
Vol 7 ◽  
Author(s):  
Massimiliano Cadamuro ◽  
Noemi Girardi ◽  
Gregory J. Gores ◽  
Mario Strazzabosco ◽  
Luca Fabris
Keyword(s):  
Therapeutic Target ◽  
Orphan Diseases ◽  
Attractive Therapeutic Target

AMPK as a New Attractive Therapeutic Target for Disease Prevention: The Role of Dietary Compounds AMPK and Disease Prevention

2016 ◽  
Vol 17 (8) ◽  
pp. 865-889 ◽  
Author(s):  
Massimiliano Gasparrini ◽  
Francesca Giampieri ◽  
Josè M. Alvarez Suarez ◽  
Luca Mazzoni ◽  
Tamara Y. Forbes Hernandez ◽  
...  
Keyword(s):  
Disease Prevention ◽  
Therapeutic Target ◽  
Attractive Therapeutic Target

The role of interleukin-17 in the pathogenesis of systemic sclerosis: Pro-fibrotic or anti-fibrotic?

2021 ◽  
pp. 239719832110394
Author(s):  
Silvia Bellando-Randone ◽  
Emanuel Della-Torre ◽  
Andra Balanescu
Keyword(s):  
Systemic Sclerosis ◽  
Therapeutic Target ◽  
Inflammatory Diseases ◽  
Adaptive Immune System ◽  
Disease Stage ◽  
Target Cells ◽  
Interleukin 17 ◽  
T Helper 17 ◽  
Attractive Therapeutic Target

Systemic sclerosis is characterized by widespread fibrosis of the skin and internal organs, vascular impairment, and dysregulation of innate and adaptive immune system. Growing evidence indicates that T-cell proliferation and cytokine secretion play a major role in the initiation of systemic sclerosis, but the role of T helper 17 cells and of interleukin-17 cytokines in the development and progression of the disease remains controversial. In particular, an equally distributed body of literature supports both pro-fibrotic and anti-fibrotic effects of interleukin-17, suggesting a complex and nuanced role of this cytokine in systemic sclerosis pathogenesis that may vary depending on disease stage, target cells in affected organs, and inflammatory milieu. Although interleukin-17 already represents an established therapeutic target for several immune-mediated inflammatory diseases, more robust experimental evidence is required to clarify whether it may become an attractive therapeutic target for systemic sclerosis as well.

scholarly journals Emerging Role of the NLRP3 Inflammasome and Interleukin-1β in Neonates

Neonatology ◽  
2020 ◽  
pp. 1-10
Author(s):  
Murwan Omer ◽  
Ashanty Maggvie Melo ◽  
Lynne Kelly ◽  
Emma Jane Mac Dermott ◽  
Timothy Ronan Leahy ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Target ◽  
Inflammasome Activation ◽  
Neonatal Brain ◽  
Persistent Inflammation ◽  
Attractive Therapeutic Target ◽  
Clinical Models ◽  
Novel Therapeutic

Infection and persistent inflammation have a prominent role in the pathogenesis of brain injury and cerebral palsy, as well as other conditions associated with prematurity such as bronchopulmonary dysplasia. The NLRP3 inflammasome-interleukin (IL)-1β pathway has been extensively studied in adults and pre-clinical models, improving our understanding of innate immunity and offering an attractive therapeutic target that is already contributing to clinical management in many auto-inflammatory disorders. IL-1 blockade has transformed the course and outcome of conditions such as chronic infantile neurological, cutaneous, articular (CINCA/NOMID) syndrome. Inflammasome activation and upregulation has recently been implicated in neonatal brain and lung inflammatory disease and may be a novel therapeutic target.

PI3K/ Akt/ mTOR Pathway as a Therapeutic Target for Colorectal Cancer: A Review of Preclinical and Clinical Evidence

2019 ◽  
Vol 20 (12) ◽  
pp. 1217-1226 ◽  
Author(s):  
Arunaksharan Narayanankutty
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Therapeutic Target ◽  
Clinical Evidence ◽  
Mtor Pathway ◽  
Colorectal Cancers ◽  
Patent Literature ◽  
Mtor Signalling ◽  
Natural And Synthetic

Background: Phosphoinositide 3-kinase (PI3Ks) is a member of intracellular lipid kinases and involved in the regulation of cellular proliferation, differentiation and survival. Overexpression of the PI3K/Akt/mTOR signalling has been reported in various forms of cancers, especially in colorectal cancers (CRC). Due to their significant roles in the initiation and progression events of colorectal cancer, they are recognized as a striking therapeutic target. Objective: The present review is aimed to provide a detailed outline on the role of PI3K/Akt/mTOR pathway in the initiation and progression events of colorectal cancers as well as its function in drug resistance. Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed. The review contains preclinical and clinical evidence as well as patent literature of the pathway inhibitors which are natural and synthetic in origin. Methods: The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results: PI3K/Akt/mTOR signalling is an important event in colorectal carcinogenesis. In addition, it plays significant roles in acquiring drug resistance as well as metastatic initiation events of CRCs. Several small molecules of natural and synthetic origin have been found to be potent inhibitors of CRCs by effectively downregulating the pathway. Data from various clinical studies also support these pathway inhibitors and several among them are patented. Conclusion: Inhibitors of the PI3K/mTOR pathway have been successful for the treatment of primary and metastatic colorectal cancers, rendering the pathway as a promising clinical cancer therapeutic target.

scholarly journals Osteopontin in Cardiovascular Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1047
Author(s):  
Kohsuke Shirakawa ◽  
Motoaki Sano
Keyword(s):  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Therapeutic Target ◽  
Gene Mutations ◽  
Major Adverse Cardiovascular Event ◽  
Matricellular Protein ◽  
Pathological State ◽  
Adverse Cardiovascular Event ◽  
Anti Inflammatory

Unprecedented advances in secondary prevention have greatly improved the prognosis of cardiovascular diseases (CVDs); however, CVDs remain a leading cause of death globally. These findings suggest the need to reconsider cardiovascular risk and optimal medical therapy. Numerous studies have shown that inflammation, pro-thrombotic factors, and gene mutations are focused not only on cardiovascular residual risk but also as the next therapeutic target for CVDs. Furthermore, recent clinical trials, such as the Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial, showed the possibility of anti-inflammatory therapy for patients with CVDs. Osteopontin (OPN) is a matricellular protein that mediates diverse biological functions and is involved in a number of pathological states in CVDs. OPN has a two-faced phenotype that is dependent on the pathological state. Acute increases in OPN have protective roles, including wound healing, neovascularization, and amelioration of vascular calcification. By contrast, chronic increases in OPN predict poor prognosis of a major adverse cardiovascular event independent of conventional cardiovascular risk factors. Thus, OPN can be a therapeutic target for CVDs but is not clinically available. In this review, we discuss the role of OPN in the development of CVDs and its potential as a therapeutic target.

scholarly journals Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities

2021 ◽  
Author(s):  
Richard Radun ◽  
Michael Trauner
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Therapeutic Potential ◽  
Farnesoid X Receptor ◽  
Metabolic Homeostasis ◽  
Nonalcoholic Fatty Liver ◽  
Metabolic Dysregulation ◽  
Attractive Therapeutic Target

AbstractNonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, increasingly contributing to the burden of liver transplantation. In search for effective treatments, novel strategies addressing metabolic dysregulation, inflammation, and fibrosis are continuously emerging. Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.

scholarly journals The Role of IGF/IGF-IR-Signaling and Extracellular Matrix Effectors in Bone Sarcoma Pathogenesis

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2478
Author(s):  
George N. Tzanakakis ◽  
Eirini-Maria Giatagana ◽  
Aikaterini Berdiaki ◽  
Ioanna Spyridaki ◽  
Kyoko Hida ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Bone Sarcoma ◽  
Response To Therapy ◽  
Targeted Therapeutics ◽  
Attractive Therapeutic Target ◽  
Bone Sarcomas ◽  
Agent Development ◽  
Insulin Like Growth Factors ◽  
Igf Signaling

Bone sarcomas, mesenchymal origin tumors, represent a substantial group of varying neoplasms of a distinct entity. Bone sarcoma patients show a limited response or do not respond to chemotherapy. Notably, developing efficient chemotherapy approaches, dealing with chemoresistance, and preventing metastasis pose unmet challenges in sarcoma therapy. Insulin-like growth factors 1 and 2 (IGF-1 and -2) and their respective receptors are a multifactorial system that significantly contributes to bone sarcoma pathogenesis. Whereas failures have been registered in creating novel targeted therapeutics aiming at the IGF pathway, new agent development should continue, evaluating combinatorial strategies for enhancing antitumor responses and better classifying the patients that could best benefit from these therapies. A plausible approach for developing a combinatorial strategy is to focus on the tumor microenvironment (TME) and processes executed therein. Herewith, we will discuss how the interplay between IGF-signaling and the TME constituents affects sarcomas’ basal functions and their response to therapy. This review highlights key studies focusing on IGF signaling in bone sarcomas, specifically studies underscoring novel properties that make this system an attractive therapeutic target and identifies new relationships that may be exploited. Potential direct and adjunct therapeutical implications of the extracellular matrix (ECM) effectors will also be summarized.

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