Fragment-based drug design of novel inhibitors targeting lipoprotein (a) kringle domain KIV-10-mediated cardiovascular disease.

Cardiovascular diseases (CVDs) are the leading cause of death globally, attributed to a complex etiology involving metabolic, genetic, and protein-related factors. Lipoprotein(a) (Lp(a)), identified as a genetic risk factor, exhibits elevated levels linked to an increased risk of cardiovascular diseases. The lipoprotein(a) kringle domains have recently been identified as a potential target for the treatment of CVDs, in this study we utilized a fragment-based drug design approach to design a novel, potent, and safe inhibitor for lipoprotein(a) kringle domain. With the use of fragment library (61,600 fragments) screening, combined with analyses such as MM/GBSA, molecular dynamics simulation (MD), and principal component analysis, we successfully identified molecules effective against the kringle domains of Lipoprotein(a). The hybridization process (Breed) of the best fragments generated a novel 249 hybrid molecules, among them 77 exhibiting superior binding affinity (≤ -7 kcal/mol) compared to control AZ-02 (-6.9 kcal/mol), Importantly, the top ten molecules displayed high similarity to the control AZ-02. Among the top ten molecules, BR1 exhibited the best docking energy (-11.85 kcal/mol ), and higher stability within the protein LBS site, demonstrating the capability to counteract the pathophysiological effects of lipoprotein(a) [Lp(a)]. Additionally, principal component analysis (PCA) highlighted a similar trend of motion during the binding of BR1 and the control compound (AZ-02), limiting protein mobility and reducing conformational space. Moreover, ADMET analysis indicated favorable drug-like properties, with BR1 showing minimal violations of Lipinski's rules. Overall, the identified compounds hold promise as potential therapeutics, addressing a critical need in cardiovascular medicine. Further preclinical and clinical evaluations are needed to validate their efficacy and safety, potentially ushering in a new era of targeted therapies for CVDs.

A simple clinical risk score (ABCDMP) for predicting mortality in patients with AECOPD and cardiovascular diseases.

BACKGROUND: The morbidity and mortality among hospital inpatients with AECOPD and CVDs remains unacceptably high. Currently, no risk score for predicting mortality has been specifically developed in patients with AECOPD and CVDs. We therefore aimed to derive and validate a simple clinical risk score to assess individuals' risk of poor prognosis. STUDY DESIGN AND METHODS: We evaluated inpatients with AECOPD and CVDs in a prospective, noninterventional, multicenter cohort study. We used multivariable logistic regression analysis to identify the independent prognostic risk factors and created a risk score model according to patients' data from a derivation cohort. Discrimination was evaluated by the area under the receiver-operating characteristic curve (AUC), and calibration was assessed by the Hosmer-Lemeshow goodness-of-fit test. The model was validated and compared with the BAP-65, CURB-65, DECAF and NIVO models in a validation cohort. RESULTS: We derived a combined risk score, the ABCDMP score, that included the following variables: age > 75 years, BUN > 7 mmol/L, consolidation, diastolic blood pressure ≤ 60 mmHg, mental status altered, and pulse > 109 beats/min. Discrimination (AUC 0.847, 95% CI, 0.805-0.890) and calibration (Hosmer‒Lemeshow statistic, P = 0.142) were good in the derivation cohort and similar in the validation cohort (AUC 0.811, 95% CI, 0.755-0.868). The ABCDMP score had significantly better predictivity for in-hospital mortality than the BAP-65, CURB-65, DECAF, and NIVO scores (all P < 0.001). Additionally, the new score also had moderate predictive performance for 3-year mortality and can be used to stratify patients into different management groups. CONCLUSIONS: The ABCDMP risk score could help predict mortality in AECOPD and CVDs patients and guide further clinical research on risk-based treatment. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trail Registry NO.:ChiCTR2100044625; URL: http://www.chictr.org.cn/showproj.aspx?proj=121626 .

The function and therapeutic potential of transfer RNA-derived small RNAs in cardiovascular diseases: A review.

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

Circulating perturbation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is associated to cardiac remodeling and NLRP3 inflammasome in cardiovascular patients with insulin resistance risk.

Lipidome perturbation occurring during meta-inflammation is associated to left ventricle (LV) remodeling though the activation of the NLRP3 inflammasome, a key regulator of chronic inflammation in obesity-related disorders. Little is known about phosphatidylcholine (PC) and phosphatidylethanolamine (PE) as DAMP-induced NLRP3 inflammasome. Our study is aimed to evaluate if a systemic reduction of PC/PE molar ratio can affect NLRP3 plasma levels in cardiovascular disease (CVD) patients with insulin resistance (IR) risk. Forty patients from IRCCS Policlinico San Donato were enrolled, and their blood samples were drawn before heart surgery. LV geometry measurements were evaluated by echocardiography and clinical data associated to IR risk were collected. PC and PE were quantified by ESI-MS/MS. Circulating NLRP3 was quantified by an ELISA assay. Our results have shown that CVD patients with IR risk presented systemic lipid impairment of PC and PE species and their ratio in plasma was inversely associated to NLRP3 levels. Interestingly, CVD patients with IR risk presented LV changes directly associated to increased levels of NLRP3 and a decrease in PC/PE ratio in plasma, highlighting the systemic effect of meta-inflammation in cardiac response. In summary, PC and PE can be considered bioactive mediators associated to both the NLRP3 and LV changes in CVD patients with IR risk.

Unravelling the role of cathepsins in cardiovascular diseases.

Lysosomal cathepsins as a regulatory medium have been assessed as potential therapeutic targets for the treatment of various cardiac diseases such as abdominal aortic aneurysm, hypertension, cardiomyopathy, coronary heart disease, atherosclerosis, etc. They are ubiquitous lysosomal proteases with papain-like folded protein structures that are involved in a variety of physiological processes, such as the digestion of proteins, activation of pro-inflammatory molecules, degradation of extracellular matrix components, and maturation of peptide hormones. Cathepsins are classified into three major groups: cysteine cathepsins, aspartic cathepsins, and serine-threonine cathepsins. Each of these groups is further divided into subgroups based on their substrate specificity, structural characteristics, and biochemical properties. Several studies suggest that cathepsins control the degradation of ECM components such as collagen and elastin fibres. These enzymes are highly expressed in macrophages and inflammatory cells, and their upregulation has been demonstrated to be critical in the progression of atherosclerotic lesions. Additionally, increased cathepsin activity has been linked to increased vascular inflammation and oxidative stress, both of which are associated with CVDs. Specifically, the inhibition of cathepsins may reduce the release of pro-apoptotic mediators such as caspase-3 and PARP-1, which are thought to contribute to plaque instability. The potential of cathepsins as biomarkers and therapeutic targets has also been supported by the identification of potential cathepsin inhibitors, which could be used to modulate the activities of cathepsins in a range of diseases. This review shall familiarise the readers with the role of cysteinyl cathepsins and their inhibitors in the pathogenesis of cardiovascular diseases.

Spatial analysis of the impact of urban built environment on cardiovascular diseases: a case study in Xixiangtang, China.

BACKGROUND: The built environment, as a critical factor influencing residents' cardiovascular health, has a significant potential impact on the incidence of cardiovascular diseases (CVDs). METHODS: Taking Xixiangtang District in Nanning City, Guangxi Zhuang Autonomous Region of China as a case study, we utilized the geographic location information of CVD patients, detailed road network data, and urban points of interest (POI) data. Kernel density estimation (KDE) and spatial autocorrelation analysis were specifically employed to identify the spatial distribution patterns, spatial clustering, and spatial correlations of built environment elements and diseases. The GeoDetector method (GDM) was used to assess the impact of environmental factors on diseases, and geographically weighted regression (GWR) analysis was adopted to reveal the spatial heterogeneity effect of environmental factors on CVD risk. RESULTS: The results indicate that the built environment elements and CVDs samples exhibit significant clustering characteristics in their spatial distribution, with a positive correlation between the distribution density of environmental elements and the incidence of CVDs (Moran's I > 0, p < 0.01). Further factor detection revealed that the distribution of healthcare facilities had the most significant impact on CVDs (q = 0.532, p < 0.01), followed by shopping and consumption (q = 0.493, p < 0.01), dining (q = 0.433, p < 0.01), and transportation facilities (q = 0.423, p < 0.01), while the impact of parks and squares (q = 0.174, p < 0.01) and road networks (q = 0.159, p < 0.01) was relatively smaller. Additionally, the interaction between different built environment elements exhibited a bi-factor enhancement effect on CVDs. In the local analysis, the spatial heterogeneity of different built environment elements on CVDs further revealed the regional differences and complexities. CONCLUSIONS: The spatial distribution of built environment elements is significantly correlated with CVDs to varying degrees and impacts differently across regions, underscoring the importance of the built environment on cardiovascular health. When planning and improving urban environments, elements and areas that have a more significant impact on CVDs should be given priority consideration.

Association of second-hand smoking with sleep quality among adults in Ibadan, Nigeria: a cross-sectional evaluation of data from the COMBAT-CVDs study.

PURPOSE: Sleep quality (SQ) is essential in the overall well-being and quality of life, but little is known about the association of secondhand smoking (SHS) with SQ. This study assessed the relationship between SHS and SQ among adults who had never smoked in Ibadan, Nigeria. METHODS: We identified 3193 respondents who had never smoked or used any form of tobacco product in the Community-based Investigation of the Risk Factors for Cardiovascular Diseases in the Ibadan and suburbs (COMBAT-CVDs) study. SHS was self-reported, SQ assessed using a sleep quality scale, and SQ scores were classified by the quartile distributions of SQ scores in this sample as good (< 7), moderate (7-13), fair (14-20), and poor (≥ 21), and logistic regression models were used to estimate the multivariable-adjusted odds ratio and 95% confidence interval (CI) of the association between SHS and SQ in a two-sided test at P < 0.05. RESULTS: The mean (SD) of age in this sample was 34.8 ± 15.1 years; 1621 (50.8%) were females, and 848 (26.6%) experienced SHS. The multivariable-adjusted odds by categories of SQ scores (using good SQ as reference) in the light of SHS were OR: 1.64 (95%CI 1.28, 2.12) for moderate SQ, OR: 1.88 (95%CI 1.46, 2.42) for fair SQ and OR: 2.14 (95%CI 1.66, 2.75) for poor SQ; P < 0.0001 after adjusting for relevant covariates. The sex- and age groups- stratified analyses revealed similar trends. CONCLUSION: SHS is associated with higher odds of poor SQ in this study. Culturally relevant interventions for mitigating exposure to SHS might improve SQ and overall quality of life, particularly among vulnerable populations.

Risk factors for cardio-cerebrovascular events among patients undergoing continuous ambulatory peritoneal dialysis and their association with serum magnesium.

Serum magnesium levels exceeding 0.9 mmol/L are associated with increased survival rates in patients with CKD. This retrospective study aimed to identify risk factors for cardio-cerebrovascular events among patients receiving continuous ambulatory peritoneal dialysis (CAPD) and to examine their correlations with serum magnesium levels. Sociodemographic data, clinical physiological and biochemical indexes, and cardio-cerebrovascular event data were collected from 189 patients undergoing CAPD. Risk factors associated with cardio-cerebrovascular events were identified by univariate binary logistic regression analysis. Correlations between the risk factors and serum magnesium levels were determined by correlation analysis. Univariate regression analysis identified age, C-reactive protein (CRP), red cell volume distribution width standard deviation, red cell volume distribution width corpuscular volume, serum albumin, serum potassium, serum sodium, serum chlorine, serum magnesium, and serum uric acid as risk factors for cardio-cerebrovascular events. Among them, serum magnesium ≤0.8 mmol/L had the highest odds ratio (3.996). Multivariate regression analysis revealed that serum magnesium was an independent risk factor, while serum UA (<440 µmol/L) was an independent protective factor for cardio-cerebrovascular events. The incidence of cardio-cerebrovascular events differed significantly among patients with different grades of serum magnesium (χ2 = 12.023, p = 0.002), with the highest incidence observed in patients with a serum magnesium concentration <0.8 mmol/L. High serum magnesium levels were correlated with high levels of serum albumin (r = 0.399, p < 0.001), serum potassium (r = 0.423, p < 0.001), and serum uric acid (r = 0.411, p < 0.001), and low levels of CRP (r = -0.279, p < 0.001). In conclusion, low serum magnesium may predict cardio-cerebrovascular events in patients receiving CAPD.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Crosstalk of NLRP3 inflammasome and noncoding RNAs in cardiomyopathies.

Cardiovascular diseases (CVDs) identified as a serious public health problem. Although there is a lot of evidence that inflammatory processes play a significant role in the progression of CVDs, however, the precise mechanism is not fully understood. Nevertheless, recent studies have focused on inflammation and its related agents. Nucleotide oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) is a type of pattern recognition receptor (PRR) that can recognize pathogen-associated molecular patterns and trigger innate immune response. NLRP3 is a component of the NOD-like receptor (NLR) family and have a pivotal role in detecting damage to cardiovascular tissue. It is suggested that activation of NLRP3 inflammasome leads to initiating and propagating the inflammatory response in cardiomyopathy. So, late investigations have highlighted the NLRP3 inflammasome activation in various forms of cardiomyopathy. On the other side, it was shown that noncoding RNAs (ncRNAs), particularly, microRNAs, lncRNAs, and circRNAs possess a regulatory function in the immune system's inflammatory response, implicating their involvement in various inflammatory disorders. In addition, their role in different cardiomyopathies was indicated in recent studies. This review article provides a summary of recent advancements focusing on the function of the NLRP3 inflammasome in common CVDs, especially cardiomyopathy, while also discussing the therapeutic potential of inhibiting the NLRP3 inflammasome regulated by ncRNAs.

Marine-Derived Compounds Applied in Cardiovascular Diseases: Submerged Medicinal Industry.

Cardiovascular diseases (CVDs) are among the most impactful illnesses globally. Currently, the available therapeutic option has several side effects, including hypotension, bradycardia, arrhythmia, and alteration in different ion concentrations. Recently, bioactive compounds from natural sources, including plants, microorganisms, and marine creatures, have gained a lot of interest. Marine sources serve as reservoirs for new bioactive metabolites with various pharmacological activities. The marine-derived compound such as omega-3 acid ethyl esters, xyloketal B, asperlin, and saringosterol showed promising results in several CVDs. The present review focuses on marine-derived compounds' cardioprotective potential for hypertension, ischemic heart disease, myocardial infarction, and atherosclerosis. In addition to therapeutic alternatives, the current use of marine-derived components, the future trajectory, and restrictions are also reviewed.

The Scope of Practice for Primary Cardiovascular Disease Prevention Expanded to Advanced Practice Providers: What Does the Data Show?

PURPOSE OF REVIEW: The review aims to explore the available literature on the role of advance practice providers (APPs) in the primary prevention of cardiovascular diseases (CVD). RECENT FINDINGS: CVD are the major cause of death and disease with the growing burden of direct and indirect costs. Globally, one out of every three deaths is due to CVD. A total of 90% of CVD cases are due to modifiable risk factors which are preventable; however, challenges are faced by the already overburdened healthcare systems where the shortage of workforce is a common constraint. Different CVD preventive programs are working but, in a silo, and with different approaches except in few of the high-income countries where specialized workforce such as advance practice providers (APPs) is trained and employed in practice. Such initiatives are already proven more effective in terms of health and economic outcomes. Through an extensive literature search of APPs' role in the primary prevention of CVD, we identified very few high-income countries where APPs' role has already been integrated into the primary healthcare system. However, in low- and middle-income countries (LMICs), no such roles are defined. In these countries, either the overburdened physicians or any other health professionals (not trained in primary prevention of CVD) sometimes provide brief advice on CVD risk factors. Hence, prompt attention is appealed by the current scenario of CVD prevention specifically in LMICs.

Efficient Classification of ECG Images Using a Lightweight CNN with Attention Module and IoT.

Cardiac disorders are a leading cause of global casualties, emphasizing the need for the initial diagnosis and prevention of cardiovascular diseases (CVDs). Electrocardiogram (ECG) procedures are highly recommended as they provide crucial cardiology information. Telemedicine offers an opportunity to provide low-cost tools and widespread availability for CVD management. In this research, we proposed an IoT-based monitoring and detection system for cardiac patients, employing a two-stage approach. In the initial stage, we used a routing protocol that combines routing by energy and link quality (REL) with dynamic source routing (DSR) to efficiently collect data on an IoT healthcare platform. The second stage involves the classification of ECG images using hybrid-based deep features. Our classification system utilizes the "ECG Images dataset of Cardiac Patients", comprising 12-lead ECG images with four distinct categories: abnormal heartbeat, myocardial infarction (MI), previous history of MI, and normal ECG. For feature extraction, we employed a lightweight CNN, which automatically extracts relevant ECG features. These features were further optimized through an attention module, which is the method's main focus. The model achieved a remarkable accuracy of 98.39%. Our findings suggest that this system can effectively aid in the identification of cardiac disorders. The proposed approach combines IoT, deep learning, and efficient routing protocols, showcasing its potential for improving CVD diagnosis and management.

Heart Sound Classification Network Based on Convolution and Transformer.

Electronic auscultation is vital for doctors to detect symptoms and signs of cardiovascular diseases (CVDs), significantly impacting human health. Although progress has been made in heart sound classification, most existing methods require precise segmentation and feature extraction of heart sound signals before classification. To address this, we introduce an innovative approach for heart sound classification. Our method, named Convolution and Transformer Encoder Neural Network (CTENN), simplifies preprocessing, automatically extracting features using a combination of a one-dimensional convolution (1D-Conv) module and a Transformer encoder. Experimental results showcase the superiority of our proposed method in both binary and multi-class tasks, achieving remarkable accuracies of 96.4%, 99.7%, and 95.7% across three distinct datasets compared with that of similar approaches. This advancement holds promise for enhancing CVD diagnosis and treatment.

Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review.

One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis. A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders.

The Drp1-Mediated Mitochondrial Fission Protein Interactome as an Emerging Core Player in Mitochondrial Dynamics and Cardiovascular Disease Therapy.

Mitochondria, the membrane-bound cell organelles that supply most of the energy needed for cell function, are highly regulated, dynamic organelles bearing the ability to alter both form and functionality rapidly to maintain normal physiological events and challenge stress to the cell. This amazingly vibrant movement and distribution of mitochondria within cells is controlled by the highly coordinated interplay between mitochondrial dynamic processes and fission and fusion events, as well as mitochondrial quality-control processes, mainly mitochondrial autophagy (also known as mitophagy). Fusion connects and unites neighboring depolarized mitochondria to derive a healthy and distinct mitochondrion. In contrast, fission segregates damaged mitochondria from intact and healthy counterparts and is followed by selective clearance of the damaged mitochondria via mitochondrial specific autophagy, i.e., mitophagy. Hence, the mitochondrial processes encompass all coordinated events of fusion, fission, mitophagy, and biogenesis for sustaining mitochondrial homeostasis. Accumulated evidence strongly suggests that mitochondrial impairment has already emerged as a core player in the pathogenesis, progression, and development of various human diseases, including cardiovascular ailments, the leading causes of death globally, which take an estimated 17.9 million lives each year. The crucial factor governing the fission process is the recruitment of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, from the cytosol to the outer mitochondrial membrane in a guanosine triphosphate (GTP)-dependent manner, where it is oligomerized and self-assembles into spiral structures. In this review, we first aim to describe the structural elements, functionality, and regulatory mechanisms of the key mitochondrial fission protein, Drp1, and other mitochondrial fission adaptor proteins, including mitochondrial fission 1 (Fis1), mitochondrial fission factor (Mff), mitochondrial dynamics 49 (Mid49), and mitochondrial dynamics 51 (Mid51). The core area of the review focuses on the recent advances in understanding the role of the Drp1-mediated mitochondrial fission adaptor protein interactome to unravel the missing links of mitochondrial fission events. Lastly, we discuss the promising mitochondria-targeted therapeutic approaches that involve fission, as well as current evidence on Drp1-mediated fission protein interactions and their critical roles in the pathogeneses of cardiovascular diseases (CVDs).

Exosomes in cardiovascular diseases: a blessing or a sin for the mankind.

Cardiovascular diseases (CVDs) comprises disorders of blood vessels and heart. Multiple cells in the heart suggests that hetero-cellular communication, which is an important aspect in heart functioning and there is a need to elucidate the way in which this inter-cellular communication occurs. Now a days, exosomal research has gained much attention. Exosomes, nano-shuttles, are EVs with diameters ranging from 40 to 160 nm (average 100 nm), secreted by body cells. These vesicles act as cell-to-cell communicators and are carriers of important biomolecules such as RNAs, miRNAs, Proteins and lipids. Exosomes can change the gene expression of the recipient cells, thereby, changes the cellular characteristics. Exosomes have known to play an essential role in protection as well as progression of various cardiovascular diseases. In the present review, role of exosomes in various CVDs have been discussed.

An overview of the pharmacological activities of scopoletin against different chronic diseases.

Chronic diseases are considered a major public health concern worldwide, and most of these diseases like cancer, cardiovascular, metabolic, and neurological disorders occur due to atypical regulation of multiple signaling pathways. It has also been observed that most of the currently approved therapies for these diseases fail to show prolonged efficacy due to their mono-targeted nature and are associated with the development of chemoresistance, thus restricting their utility. The plant-derived compounds, on the other hand, show multi-targeted nature, and thus these phytochemicals have gained wide attention as they offer negligible side effects. The present review aims to recapitulate the potential effects of one such phytochemical, Scopoletin, which was found to have a diverse range of pharmacological activities such as anti-cancer, anti-diabetic, anti-inflammatory, cardioprotective, hepatoprotective, etc. Scopoletin modulated multiple molecular signatures in cancer, including AMPK, EGFR, MAPK/ ERK, NF-κB, PI3K/Akt/ mTOR, and STAT3; regulated the levels of critical markers of metabolic diseases such as ALT, AST, TG, and TC; inflammatory diseases such as ILs and TNFs; neurological diseases such as AChE, etc. thus relieving the symptoms and severity associated with these diseases. Further, this compound has a non-toxic nature and possesses an excellent pharmacokinetic property, which warrants further investigation in clinical settings for developing it as a potential drug.

Chronic aerobic exercise prevents high-fructose diet-induced impairment in blood pressure in healthy young adults: a double-blind, randomised clinical trial.

The purpose of the study was to verify the effect of 4 weeks of a high-fructose diet (HFD) associated with aerobic training on the risk factors for cardiometabolic diseases. Twenty-one young adults were randomised into three groups: HFD (HFD: 1 g/kg body weight of fructose/day), high-glucose diet (HGD: 1 g/kg body weight of glucose/day) and high-fructose diet and exercise (HFDE: 1 g/kg body weight of fructose/day + 3 weekly 60-minute sessions of aerobic exercise). Before and after the 4 weeks of the intervention, blood samples were taken and flow-mediated dilatation, insulin resistance index, pancreatic beta cell functional capacity index, insulin sensitivity index and 24-h blood pressure were evaluated. HFD showed an increase in uric acid concentrations (P = 0·040), and HGD and HFDE groups showed no changes in this outcome between pre- and post-intervention; however, the HFDE group showed increased uric acid concentrations from the middle to the end of the intervention (P = 0·013). In addition, the HFD group showed increases in nocturnal systolic blood pressure (SBP) (P = 0·022) and nocturnal diastolic blood pressure (DBP) (P = 0·009). The HGD group exhibited decreases in nocturnal SBP (P = 0·028) and nocturnal DBP (P = 0·031), and the HFDE group showed a decrease in 24-h SBP (P = 0·018). The consumption of 1 g/kg of fructose per day may increase uric acid concentrations and blood pressure in adults. Additionally, aerobic exercises along with fructose consumption attenuate changes in uric acid concentrations and prevent impairment in nocturnal blood pressure.

Prevalence of cardiovascular diseases and associated factors among adults from southwest Iran: Baseline data from Hoveyzeh Cohort Study.

BACKGROUND: Cardiovascular diseases (CVDs) were the number one cause of death in Iran. The main risk factors of CVDs include unhealthy lifestyles, insulin resistance, hypertension (HTN), and hyperlipidemia. Given that there are modifiable risk factors for CVDs, this cross-sectional study aimed to evaluate the prevalence of CVDs and their risk factors among adults. METHODS: The present cross-sectional study was conducted on 9828 adults 35-70 years (both sexes). The demographic data, lifestyle habits, anthropometric data, and clinical and biochemical parameters were collected from the baseline data of the Hoveyzeh Cohort Study. The odds ratio (OR) of CVDs was assessed by multivariable logistic regression. RESULTS: The prevalence of CVDs was higher in females than males (16.2 vs. 12.6, p ≤ 0.001). The prevalence of CVDs was related to age, gender, marital status, lifestyle, anthropometric measurements, cholesterol, high-density lipoprotein, HTN, and fasting plasma glucose (FPG) (p ≤ 0.05). The participants aged 65-70 y showed the highest odds of CVDs (OR: 3.97, 95% CI: (3.14, 5.01), (p ≤ 0.001)). Males (OR: 1.76, 95% CI: (1.51, 2.05), p ≤ 0.001), married status (OR: 1.63, 95% CI: (1.08, 2.47), p = 0.021), more using a mobile phone (OR: 1.26, 95% CI: (1.09, 1.46), p ≤ 0.002), and smoking cigarettes (OR: 1.44, 95% CI: (1.24, 1.68), p ≤ 0.001) associated with CVDs. Higher odds of CVDs were related to low physical activity (PA) (OR: 1.56, 95% CI: (1.34, 1.8), p ≤ 0.001), body mass index > 30 (OR: 1.68, 95% CI: (1.01, 2.8), p ≤ 0.047). Moreover, odds of CVDs were related to systolic blood pressure (SBP) ≥ 140 mm Hg (OR: 1.25, 95% CI: (1.04, 1.51), p = 0.017), FPG = 100-126 mg/dl (OR: 1.24, 95% CI: (1.07, 1.43), p = 0.003), and FPG > 126 mg/dl (OR: 1.71, 95% CI: (1.47, 1. 98), p ≤ 0.001). CONCLUSION: The present study showed the main risk factors of CVDs were older age, married status, using a mobile phone, low PA, smoking, obesity, and abnormal FPG and SBP. The lower odds of CVDs were found in the participants with normal cholesterol.