Role of macrophage autophagy in atherosclerosis: modulation by bioactive compounds

2021 ◽  
Vol 478 (7) ◽  
pp. 1359-1375
Author(s):  
MD Khurshidul Zahid ◽  
Hazera Binte Sufian ◽  
Mahua Choudhury ◽  
Masao Yamasaki ◽  
Ahmed Al-Harrasi ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Antibacterial Properties ◽  
Chronic Inflammatory Disease ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
Atherosclerosis Development ◽  
Dietary Bioactive Compounds

Atherosclerosis is a chronic inflammatory disease associated with lipid metabolism disorder. Autophagy is a catabolic process and contributes to maintaining cellular homeostasis. Substantial evidence suggests that defective autophagy is implicated in several diseases, including atherosclerosis, while increased autophagy mitigates atherosclerosis development. Thus, understanding the mechanisms of autophagy regulation and its association with atherosclerosis is vital to develop new therapies against atherosclerosis. Dietary bioactive compounds are non-nutrient natural compounds that include phenolics, flavonoids, and carotenoids. Importantly, these bioactive compounds possess anti-inflammatory, antioxidant, and antibacterial properties that may alleviate various chronic diseases. Recently, examining the effects of bioactive compounds on autophagy activity in atherogenesis has drawn considerable attention. The current review discusses the role of macrophage autophagy in the development and progression of atherosclerosis. We also summarize our current knowledge of the therapeutic potential of bioactive compounds on atherosclerosis and autophagy.

scholarly journals The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3219 ◽  
Author(s):  
Balbina García-Reyes ◽  
Anna-Laura Kretz ◽  
Jan-Philipp Ruff ◽  
Silvia von Karstedt ◽  
Andreas Hillenbrand ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Transcriptional Elongation ◽  
Cyclin Dependent Kinases ◽  
Dismal Prognosis ◽  
The Family ◽  
Cycle Regulation

The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC’s resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

scholarly journals The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signaling Cascades ◽  
Cell Functions ◽  
Regulatory Circuits ◽  
Complex Functions ◽  
Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

scholarly journals The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1887 ◽  
Author(s):  
Francesco Bonollo ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Sofia Karkampouna
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Progression ◽  
Normal Prostate ◽  
Prostate Tumorigenesis

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.

scholarly journals Atypical Chemokine Receptors in Cardiovascular Disease

2019 ◽  
Vol 119 (04) ◽  
pp. 534-541 ◽  
Author(s):  
Selin Gencer ◽  
Emiel van der Vorst ◽  
Maria Aslani ◽  
Christian Weber ◽  
Yvonne Döring ◽  
...  
Keyword(s):  
G Protein ◽  
Chemokine Receptors ◽  
Cellular Response ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Signalling Pathways ◽  
Atherosclerosis Development ◽  
G Protein Coupled ◽  
Precise Role

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

scholarly journals Dietary Bioactive Compounds and Human Health and Disease

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 348 ◽  
Author(s):  
Sonia González
Keyword(s):  
Human Health ◽  
Bioactive Compounds ◽  
Scientific Evidence ◽  
Health And Disease ◽  
Nutritional Compounds ◽  
Dietary Bioactive Compounds

In the last century, solid scientific evidence has demonstrated the role of nutritional compounds in the maintenance of health [...]

scholarly journals The role of miR-320 in glucose and lipid metabolism disorder-associated diseases

2021 ◽  
Vol 17 (2) ◽  
pp. 402-416
Author(s):  
Hengzhi Du ◽  
Yanru Zhao ◽  
Zhongwei Yin ◽  
Dao Wen Wang ◽  
Chen Chen
Keyword(s):  
Lipid Metabolism ◽  
Lipid Metabolism Disorder ◽  
Associated Diseases ◽  
Metabolism Disorder ◽  
Glucose And Lipid Metabolism

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehran Pashirzad ◽  
Reihaneh Khorasanian ◽  
Maryam Mahmoudi Fard ◽  
Mohammad-Hassan Arjmand ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Erk Signaling ◽  
Clinical Settings ◽  
Cancer Cell Proliferation ◽  
Resistance Mutations ◽  
Clinical Value

: The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

scholarly journals Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment

Biology ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 60 ◽  
Author(s):  
Anastasia V. Poznyak ◽  
Andrey V. Grechko ◽  
Varvara A. Orekhova ◽  
Yegor S. Chegodaev ◽  
Wei-Kai Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Current Knowledge ◽  
Chronic Inflammatory Disease ◽  
Therapeutic Properties ◽  
Atherosclerosis Development ◽  
Reactive Oxidant ◽  
Key Events ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Atherosclerosis can be regarded as chronic inflammatory disease affecting the arterial wall. Despite the recent progress in studying the pathogenesis of atherosclerosis, some of the pathogenic mechanisms remain to be fully understood. Among these mechanisms is oxidative stress, which is closely linked to foam cells formation and other key events in atherosclerosis development. Two groups of enzymes are involved in the emergence of oxidative stress: Pro-oxidant (including NADPH oxidases, xanthine oxidases, and endothelial nitric oxide synthase) and antioxidant (such as superoxide dismutase, catalases, and thioredoxins). Pro-oxidant enzymes in normal conditions produce moderate concentrations of reactive oxidant species that play an important role in cell functioning and can be fully utilized by antioxidant enzymes. Under pathological conditions, activities of both pro-oxidant and antioxidant enzymes can be modified by numerous factors that can be relevant for developing novel therapies. Recent studies have explored potential therapeutic properties of antioxidant molecules that are capable to eliminate oxidative damage. However, the results of these studies remain controversial. Other perspective approach is to inhibit the activity of pro-oxidant enzymes and thus to slow down the progression of atherosclerosis. In this review we summarized the current knowledge on oxidative stress in atherosclerosis and potential antioxidant approaches. We discuss several important antioxidant molecules of plant origin that appear to be promising for treatment of atherosclerosis.

scholarly journals Proinflammatory Role of Vascular Endothelial Growth Factor in the Pathogenesis of Rheumatoid Arthritis: Prospects for Therapeutic Intervention

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Seung-Ah Yoo ◽  
Seung-Ki Kwok ◽  
Wan-Uk Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Current Knowledge ◽  
Chronic Inflammatory Disease ◽  
Vascular Endothelial ◽  
New Therapeutic Approaches ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Recent experimental and clinical studies have placed new emphasis on the role of angiogenesis in chronic inflammatory disease. Vascular endothelial growth factor (VEGF) and its receptors are the best characterized system in the regulation of rheumatoid arthritis (RA) by angiogenesis. Furthermore, in addition to its angiogenic role, VEGF can act as a direct proinflammatory mediator during the pathogenesis of RA, and protect rheumatoid synoviocytes from apoptosis, which contributes to synovial hyperplasia. Therefore, the developments of synovial inflammation, hyperplasia, and angiogenesis in the joints of RA patients seem to be regulated by a common cue, namely, VEGF. Agents that target VEGF, such as anti-VEGF antibody and aptamer, have yielded promising clinical data in patients with cancer or macular degeneration, and in RA patients, pharmacologic modulations targeting VEGF or its receptor may offer new therapeutic approaches. In this review, the authors integrate current knowledge of VEGF signaling and information on VEGF antagonists gleaned experimentally and place emphasis on the use of synthetic anti-VEGF hexapeptide to prevent VEGF interacting with its receptor.

Therapeutic Potential of miR-494 in Thrombosis and Other Diseases: A Review

2016 ◽  
Vol 69 (10) ◽  
pp. 1078 ◽  
Author(s):  
Jasmine Tay ◽  
Jim Tiao ◽  
Quintin Hughes ◽  
Grace Gilmore ◽  
Ross Baker
Keyword(s):  
Nucleic Acids ◽  
Contraceptive Use ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Expression Profiles ◽  
Protein S ◽  
Oral Contraceptive Use ◽  
S Deficiency ◽  
Functional Nucleic Acids

Functional nucleic acids, such as microRNAs (miRNAs), have been implicated in the pathophysiology of many diseases. The miRNA expression profiles of various cancers including haematological malignancies are well defined, but the role of miRNAs in haemostasis and the regulation of coagulation is poorly understood. We identified that miR-494 is oestrogen responsive and directly targets the anticoagulant protein, Protein S, as a mechanism for acquiring Protein S deficiency under high oestrogenic conditions such as during pregnancy and oral contraceptive use. Furthermore, previous studies have also characterised miR-494 to be involved in many biological processes. This paper reviews the current knowledge in the role of miRNAs in regulating haemostatic proteins and the known biological functions of miR-494, highlighting miR-494 as an emerging therapeutic target, with an overview of the strategy we have employed in identifying functional nucleic acids such as miRNAs that target haemostatic factors and the therapeutic potential of miR-494-directed therapy for the treatment of thrombotic disorders.

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