Current Pharmaceutical Design - Volume 27, Issue 18, 2021

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.

Cardiac and vascular diseases are often associated with increased oxidative stress and inflammation, and both may contribute to the disease progression. However, successful applications of antioxidants in the clinical setting are very rare and specific anti-inflammatory therapeutics only emerged recently. Reasons for this rely on the great diversity of oxidative stress and inflammatory cells that can either act as cardioprotective or cause tissue damage in the heart. Recent large-scale clinical trials found that highly specific anti-inflammatory therapies using monoclonal antibodies against cytokines resulted in lower cardiovascular mortality in patients with pre-existing atherosclerotic disease. In addition, unspecific antiinflammatory medication and established cardiovascular drugs with pleiotropic immunomodulatory properties such as angiotensin converting enzyme (ACE) inhibitors or statins have proven beneficial cardiovascular effects. Normalization of oxidative stress seems to be a common feature of these therapies, which can be explained by a close interaction/crosstalk of the cellular redox state and inflammatory processes. In this review, we give an overview of cardiac reactive oxygen species (ROS) sources and processes of cardiac inflammation as well as the connection of ROS and inflammation in ischemic cardiomyopathy in order to shed light on possible cardioprotective interventions.

Patients with rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that is characterized by articular and extra-articular manifestations and a pro-inflammatory and pro-oxidant state, suffer from premature atherosclerosis and excessive cardiovascular disease burden. A key step in the pathogenesis of atherosclerosis is impaired synthesis of the endogenous messenger nitric oxide (NO) by endothelial cells which, in turn, alters local homeostatic mechanisms and favors vascular damage and plaque deposition. While the exact mechanisms of endothelial dysfunction in RA remain to be established, there is good evidence that RA patients have relatively high circulating concentrations of the methylated arginine asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of endothelial NO synthase (eNOS). This review discusses the biological and pathophysiological role of ADMA, the interplay between ADMA, inflammation and oxidative stress, and the available evidence on the adverse impact of ADMA on endothelial function and atherosclerosis and potential ADMA-lowering therapies in RA patients.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Chronic atherosclerosis induced vascular inflammation and perturbation of lipid metabolism is believed to be a major cause of CVD. Interplay of innate and adaptive Immune system has been interwined with various risk factors associated with the initiation and progression of atherosclerosis in CVD. A large body of evidence indicates a correlation between immunity and atherosclerosis. Retention of plasma lipoproteins in arterial subendothelial wall triggers the T helper type 1 (Th1) cells and monocyte-derived macrophages to form atherosclerotic plaques. In the present review, we will discuss the pathogenesis of CVD in relation to atherosclerosis with a particular focus on pro-atherogenic role of immune cells. Recent findings have also suggested anti-atherogenic roles of different B cell subsets. Therapeutic approaches to target atherosclerosis risk factors have reduced the mortality, but a need exists for the novel therapies to treat arterial vascular inflammation. These insights into the immune pathogenesis of atherosclerosis can lead to new targeted therapeutics to abate cardiovascular mortality and morbidity.

Vascular inflammation is responsible for many cardiovascular diseases and endothelial dysfunction is often the first trigger. Many factors can contribute to altering vascular homeostasis and despite that some risk factors cannot be changed, some lifestyle changes might dramatically improve vascular function. In this regard, physical activity has been identified as one of the most important interventions that can positively affect endothelial dysfunction. In recent years, the discovery of irisin, a novel myokine with pleiotropic effects, has caught the attention of many researchers. This review summarizes the most relevant intervention trials, evaluating irisin modifications in subjects with or without cardiovascular risk factors assigned to physical activity programs, to improve cardiovascular risk markers.

Long-lasting subclinical inflammation is associated with a wide range of human diseases, particularly at a middle and older age. Recent reports showed that there is a direct causal link between inflammation and cancer development, as several cancers were found to be associated with chronic inflammatory conditions. In patients with cancer, healthy endothelial cells regulate vascular homeostasis, and it is believed that they can limit tumor growth, invasiveness, and metastasis. Conversely, dysfunctional endothelial cells that have been exposed to the inflammatory tumor microenvironment can support cancer progression and metastasis. Dysfunctional endothelial cells can exert these effects via diverse mechanisms, including dysregulated adhesion, permeability, and activation of NF-ΚB and STAT3 signaling. In this review, we highlight the role of vascular inflammation in predisposition to cancer within the context of two common disease risk factors: obesity and smoking. In addition, we discuss the molecular triggers, pathophysiological mechanisms, and the biological consequences of vascular inflammation during cancer development and metastasis. Finally, we summarize the current therapies and pharmacological agents that target vascular inflammation and endothelial dysfunction.

Carotid artery disease is commonly encountered in clinical practice and accounts for approximately 30% of ischemic strokes in the general population. Numerous biomarkers have been investigated as predictors of the onset and progression of carotid disease, the occurrence of cerebrovascular complications, and overall prognosis. Among them, blood cell count (BCC) indexes of systemic inflammation might be particularly useful, from a pathophysiological and clinical point of view, given the inflammatory nature of the atherosclerotic process. The aim of this review is to discuss the available evidence regarding the role of common BCC indexes, such as the neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW), in the diagnosis and risk stratification of carotid artery disease, and their potential clinical applications.

In light of the growing resistance toward current antiviral drugs, efforts to discover novel and effective antiviral therapeutic agents remain a pressing scientific effort. Antiviral peptides (AVPs) represent promising therapeutic agents due to their extraordinary advantages in terms of potency, efficacy and pharmacokinetic properties. The growing volume of newly discovered peptide sequences in the post-genomic era requires computational approaches for timely and accurate identification of AVPs. Machine learning (ML) methods such as random forest and support vector machine represent robust learning algorithms that are instrumental in successful peptide-based drug discovery. Therefore, this review summarizes the current state-of-the-art application of ML methods for identifying AVPs directly from the sequence information. We compare the efficiency of these methods in terms of the underlying characteristics of the dataset used along with feature encoding methods, ML algorithms, cross-validation methods and prediction performance. Finally, guidelines for the development of robust AVP models are also discussed. It is anticipated that this review will serve as a useful guide for the design and development of robust AVP and related therapeutic peptide predictors in the future.

Protein palmitoylation is a fundamental and reversible post-translational lipid modification that involves a series of biological processes. Although a large number of experimental studies have explored the molecular mechanism behind the palmitoylation process, the computational methods has attracted much attention for its good performance in predicting palmitoylation sites compared with expensive and time-consuming biochemical experiments. The prediction of protein palmitoylation sites is helpful to reveal its biological mechanism. Therefore, the research on the application of machine learning methods to predict palmitoylation sites has become a hot topic in bioinformatics and promoted the development in the related fields. In this review, we briefly introduced the recent development in predicting protein palmitoylation sites by using machine learningbased methods and discussed their benefits and drawbacks. The perspective of machine learning-based methods in predicting palmitoylation sites was also provided. We hope the review could provide a guide in related fields.

Background/Aim: Papillary Thyroid Cancer (PTC) is the most common type of endocrine malignancy. Although PTC has an excellent prognosis, the recurrent or metastatic disease could affect patients' survival. Recent studies show that Histone Deacetylase Inhibitors (HDACIs) might be promising anticancer agents against PTC. The aim of this review is to evaluate the role of HDACIs as an additional modality in PTC treatment and to depict the latest trends of current research on this field. Materials and Methods: This literature review was performed using the MEDLINE database. The search strategy included terms: “thyroid cancer”, “papillary”, “HDAC”, “histone”, and “deacetylase”. Results: Agents, such as Suberoyl Anilide Hydroxamic Acid, Trichostatin A, Valproic Acid, Sodium butyrate, Panobinostat, Belinostat, Romidepsin, CUDC907 and N-Hydroxy-7-(2-naphthylthio)-Hepanomide have shown promising anti-cancer effects on PTC cell lines but fail to trigger a major response in clinical trials. Conclusion: HDACIs have no significant effect as monotherapy against PTC, but further research needs to be conducted in order to investigate their potential effect when used as an additional modality.

Aspirin has emerged as a promising intervention in cancer in the past decade. However, there are existing controversies regarding the anticancer properties of aspirin as its mechanism of action has not been clearly defined. In addition, the risk of bleeding in the gastrointestinal tract from aspirin is another consideration that requires medical and pharmaceutical scientists to work together to develop more potent and safe aspirin therapy in cancer. This review presents the most recent studies of aspirin with regard to its role in cancer prevention and treatment demonstrated by highlighted clinical trials, mechanisms of action as well as approaches to develop aspirin therapy best beneficial to cancer patients. Hence, this review provides readers with an overview of aspirin research in cancer that covers not only the unique features of aspirin, which differentiate aspirin from other non-steroidal anti-inflammatory drugs (NSAIDs), but also strategies that can be used in the development of drug delivery systems carrying aspirin for cancer management. These studies convey optimistic messages on the continuing efforts of the scientist on the way of developing an effective therapy for patients with a low response to current cancer treatments.