Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted ...attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy.
MicroRNAs in Cardiac Hypertrophy Wehbe, Nadine; Nasser, Suzanne Awani; Pintus, Gianfranco ...
International journal of molecular sciences,
09/2019, Letnik:
20, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac ...remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy.
Visfatin/NAMPT (nicotinamide phosphoribosyltransferase) is an adipocytokine with several intriguing properties. It was first identified as pre-B-cell colony-enhancing factor but turned out to possess ...enzymatic functions in nicotinamide adenine dinucleotide biosynthesis, with ubiquitous expression in skeletal muscles, liver, cardiomyocytes, and brain cells. Visfatin exists in an intracellular (iNAMPT) and extracellular (eNAMPT) form. Intracellularly, visfatin/iNAMPT plays a regulatory role in NAD
biosynthesis and thereby affects many NAD-dependent proteins such as sirtuins, PARPs, MARTs and CD38/157. Extracellularly, visfatin is associated with many hormone-like signaling pathways and activates some intracellular signaling cascades. Importantly, eNAMPT has been associated with several metabolic disorders including obesity and type 1 and 2 diabetes. In this review, a brief overview about visfatin is presented with special emphasis on its relevance to metabolic diseases. Visfatin/NAMPT appears to be a unique molecule with clinical significance with a prospective promising diagnostic, prognostic, and therapeutic applications in many cardiovasculo-metabolic disorders.
Sex-related differences in pain and opioids has been the focus of many researches. It is demonstrated that women experience greater clinical pain, lower pain threshold and tolerance, more sensitivity ...and distress to experimentally induced pain compared to men. Sex differences in response to opioid treatment revealed inconsistent results. However, the etiology of these disparities is not fully elucidated. It is, therefore, conceivable now that this literature merits to be revisited comprehensively. Possible multifaceted factors seem to be associated. These include neuroanatomical, hormonal, neuroimmunological, psychological, social and cultural aspects and comorbidities. This review aims at providing an overview of the substantial literature documenting the sex differences in pain and analgesic response to opioids from animal and human studies within the context of the modulatory effects of the aforementioned factors. A detailed and critical discussion of the cellular and molecular signaling pathways underlying the modulatory actions of gonadal hormones in the sexual dimorphism in pain processing and opioid analgesia is extensively presented. It is indicated that sexual dimorphic activation of certain brain regions contributes to differential pain sensitivity between females and males. Plausible crosstalk between sex hormones and neuroimmunological signaling pertinent to toll-like and purinergic receptors is uncovered as causal cues underlying sexually dimorphic pain and opioid analgesia. Conceivably, a thorough understanding of these factors may aid in sex-related advancement in pain therapeutic management.
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Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative ...stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.
Hypertension remains a major contributor to cardiovascular disease (CVD), a leading cause of global death. One of the major insults that drive increased blood pressure is inflammation. While it is ...the body's defensive response against some homeostatic imbalances, inflammation, when dysregulated, can be very deleterious. In this review, we highlight and discuss the causative relationship between inflammation and hypertension. We critically discuss how the interplay between inflammation and reactive oxygen species evokes endothelial damage and dysfunction, ultimately leading to narrowing and stiffness of blood vessels. This, along with phenotypic switching of the vascular smooth muscle cells and the abnormal increase in extracellular matrix deposition further exacerbates arterial stiffness and noncompliance. We also discuss how hyperhomocysteinemia and microRNA act as links between inflammation and hypertension. The premises we discuss suggest that the blue‐sky scenarios for targeting the underlying mechanisms of hypertension necessitate further research.
Diabetic cardiomyopathy (DCM) is a constellation of symptoms consisting of ventricular dysfunction and cardiomyocyte disarray in the presence of diabetes. The exact cause of this type of ...cardiomyopathy is still unknown; however, several processes involving the mitochondria, such as lipid and glucose metabolism, reactive oxygen species (ROS) production, apoptosis, autophagy and mitochondrial biogenesis have been implicated. In addition, polyphenols have been shown to improve the progression of diabetes. In this review, we discuss some of the mechanisms by which polyphenols, particularly resveratrol, play a role in slowing the progression of DCM. The most important intermediates by which polyphenols exert their protective effect include Bcl-2, UCP2, SIRT-1, AMPK and JNK1. Bcl-2 acts to attenuate apoptosis, UCP2 decreases oxidative stress, SIRT-1 increases mitochondrial biogenesis and decreases oxidative stress, AMPK increases autophagy, and JNK1 decreases apoptosis and increases autophagy. Our dissection of these molecular players aims to provide potential therapeutic targets for the treatment of DCM.
The Role of Epac in Cancer Progression Wehbe, Nadine; Slika, Hasan; Mesmar, Joelle ...
International journal of molecular sciences,
09/2020, Letnik:
21, Številka:
18
Journal Article
Recenzirano
Odprti dostop
Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular ...mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.
Atherosclerosis-related cardiovascular diseases (CVDs) are the leading cause of death globally. Several lines of evidence are supportive of the contributory role of vascular inflammation in ...atherosclerosis. Diverse immune cell types, including monocytes/macrophages, T-cells and neutrophils, as well as specialized proresolving lipid mediators, have been successfully characterized as key players in vascular inflammation. The increased prevalence of atherosclerotic CVD in men in comparison to age-matched premenopausal women and the abolition of sex differences in prevalence during menopause strongly suggest a pivotal role of sex hormones in the development of CVD. Indeed, many animal and human studies conclusively implicate sex hormones as a crucial component in driving the immune response. This is further corroborated by the effective identification of sex hormone receptors in vascular endothelial cells, vascular smooth muscle cells and immune cells. Collectively, these findings suggest a cellular communication between sex hormones and vascular or immune cells underlying the vascular inflammation in atherosclerosis. The aim of this review is to provide an overview of vascular inflammation as a causal cue underlying atherosclerotic CVDs within the context of the modulatory effects of sex hormones. Moreover, the cellular and molecular signaling pathways underlying the sex hormones- immune system interactions as potential culprits for vascular inflammation are highlighted with detailed and critical discussion. Finally, the review concludes by speculations on the potential sex-related efficacy of currently available immunotherapies in mitigating vascular inflammation. Conceivably, a deeper understanding of the immunoregulatory influence of sex hormones on vascular inflammation-mediated atherosclerosis permits sex-based management of atherosclerosis-related CVDs.
Estrogen and Bisphenol A in Hypertension Wehbe, Zena; Nasser, Suzanne A.; El-Yazbi, Ahmed ...
Current hypertension reports,
03/2020, Letnik:
22, Številka:
3
Journal Article
Recenzirano
Purpose of Review
Cardiovascular disease (CVD) is a non-subsiding disease that remains a leading cause of morbidity and mortality. CVD has been associated with endocrine disruptors, such as bisphenol ...A (BPA). This review critically summarizes existing findings on BPA and hypertension, with particular attention to genomic, non-genomic, molecular, and cellular mechanisms of action that render BPA as a cardiovascular estrogenic disruptor.
Recent Findings
Owing to its similar estrogenic structure, BPA has been shown to affect various phenotypes that are regulated by the natural hormone, estrogen. Indeed, BPA has been shown to interact with estrogen receptors, located both in the cell membrane and in the cytoplasm/nucleus. Given that estrogen plays an important role in cardiovascular physiology, a contributing role for BPA in CVD would not be unexpected. Existing literature, though limited, established BPA as a source of disruption in cardiovascular health, particularly hypertension. However, effects of BPA are largely dependent on the dose, patient gender, tissue, and developmental stage of the exposed tissue/organ.
Summary
Accumulating evidence argues for an adverse effect of BPA on blood pressure, with this effect being gender, dose, and time specific. Thus, comprehensive studies which take these factors and other parameters, like epigenetic factors, into account are warranted before a thorough understanding is at hand.
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