Stretch-activated channels in heart valve cells

The aortic valve is a sophisticated structure that performs complex functions to preserve the unidirectional flow of blood and maintenance of myocardial function. Valve endothelial cells (VECs) cover the two surfaces of aortic valve cusps in a continuous layer consisting of the endocardium and the sinus wall endothelium. Valve interstitial cells (VICs) are a heterogeneous and dynamic population of cells that form the body of valve cusps and are located within the extracellular matrix. VECs experience continuous and different mechanical forces in both side and VICs are experience continuous and varying mechanical forces, including stretch. These mechanical forces are translated to the cells via electrochemical or biochemical signals through mechanotransduction pathways, which may include stretch-activated ion channels (SACs) which are membrane proteins capable of responding to mechanical force and activate intracellular signalling pathways that mediate the functional response of the cells. The overall aim of this study was to investigate SACs presence and their functional roles in VECs and VICs. The presence of stretch-activated ion channels was studied electrophysiologically and biochemically in VECs from each side of the valve and different phenotypes of VICs. The role of SAC on alignment of and proliferation VECs, migration and collagen production in VICs were assessed. Stretch-activated ion channels receptors including (KCNK2, KCNJ8, TRPM4, TRPV4 and TRPC6) were present in VECs and VICs. SACs have the same channel activity in VECs from aortic and ventricular sides, but the expression level of some SACs are significantly more in VECs isolated from the ventricular side. Additionally, functional roles of SACs in VECs was demonstrated where blocking of SACs significantly reduced VECs alignment under shear stress. SACs activity and expression varied in VICs of a fibroblast, myofibroblast and osteoblast phenotype, which correlated with changes in fibroblast and osteoblast markers. SACs blockers significantly reduced migration and collagen production of VICs in response to mechanical stretch. Also, SACs activators regulated VICs proliferation in static condition. In conclusion, SACs are present in VECs and VICs and have regulatory roles in some mechanically-mediated cells responses or function. This study shows a role for SACs in the mechanobiology of valve cells, and information provides a new insight towards understanding valve cell function in health and disease.Open Acces

High prevalence of lack of knowledge and unhealthy lifestyle practices regarding premature coronary artery disease and its risk factors among the Saudi population

Abstract Objective Literature regarding coronary artery disease (CAD) and awareness of its risk factors is available in Saudi Arabia (SA). However, it is lacking with respect to premature coronary artery disease (PCAD). Therefore, it is necessary to evaluate the lack of knowledge of this underrepresented critical issue and to devise a well-constructed strategy for PCAD. This study aimed to assess the knowledge of PCAD and its risk factors in SA. Methods A cross-sectional questionnaire-based study was performed in the Department of Physiology, College of Medicine, King Saud University (KSU), Riyadh, SA between July 01, 2022, and October 25, 2022. A validated proforma was sent to the Saudi population. The sample size was 1046 participants. Results Proforma results indicated that 46.1% (n = 484) of participants believed that CAD could occur in people under the age of 45, whereas 18.6% (n = 196) did not believe, and 34.8% (n = 366) did not know. There was a highly statistically significant association present between sex and the belief that CAD can affect people who are under the age of 45 (p < 0.001), with 355 (73.3%) females believing that CAD can affect people below the age of 45 compared to 129 (26.7%) males. The results also showed a highly statistically significant relationship between educational status and the belief that CAD can affect people who are under the age of 45 (bachelor’s degree, 392 participants, representing 81.1%; p < 0.001). Furthermore, having employment was notably positively associated with that belief (p = 0.049) as was having a health specialty (p < 0.001). In addition, 62.3% (n = 655) of participants were not aware of their lipid profile, 49.1% (n = 516) preferred using vehicles to get to nearby places, 70.1% (n = 737) did not undergo regular medical checkups, 36.3% (n = 382) took medications without consultations, 55.9% (n = 588) did not exercise weekly, 69.5% (n = 112) were E-cigarette smokers, and 77.5% (n = 810) consumed fast food weekly. Conclusions Individuals from SA have an evident lack of public knowledge and poor lifestyle practices regarding PCAD, which demonstrates the need for health authorities to take a more targeted and attentive approach toward PCAD awareness. In addition, extensive media involvement is required to highlight the severity of PCAD and its risk factors in the population

Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022

Stress, Anxiety, and Depression in Pre-Clinical Medical Students: Prevalence and Association with Sleep Disorders

Our aim was to assess sleep quality in different subgroups of preclinical medical students, and then to identify specific lifestyle factors, academic and social factors as well as Corona virus related factors that were associated with poor sleeping quality and poor psychological health. Study participants were all medical students at King Saud University of Medical Sciences in the first and second years (648 students), and the study was conducted from December 2021 to January 2022. We administered the survey on paper as well as online. We used three types of questionnaires in this study. The first was a self-administered questionnaire, the second was a validated Insomnia Severity Index (ISI) for finding sleeping problems, and the third was a validated DASS 10 for determining Depression, Anxiety, and Stress. A total of 361 pre-clinical medical students consisted of 146 (40.4%) males and 215 (59.5%) females. The majority of the students, 246 (68.1%), were in their second year. Furthermore, in the current study, students who had poor academic performance (15.8%), satisfactory academic performance (21.3%), or good academic performance (30.7%) had significant sleeping problems found (&chi;2 = 19.4; p = 0.001), among them poor academic performance students 21.6%, satisfactory academic performance students (29.3%), and good academic performance students (29.3%) had moderate to severe levelled sleeping problems. Similarly, poor, satisfactory, and good academic performers experienced the highest levels of anxiety (poor = 21.5%; satisfactory = 22.1%; and good = 22.8%); stress (poor = 22.4%; satisfactory = 25.2%; and good = 22.4%); and depression (poor = 40.5%; satisfactory = 40.5%; and good = 11.9%). The majority of students (64.8%) reported that during the pandemic crisis their anxiety levels were high. Additionally, students reported significantly high sleeping issues (&chi;2 = 10.6; p = 0.001) and also serious psychological issues (Anxiety = 34.9 (0.000); Stress = 32.5 (0.000); and Depression = 5.42 (0.01)). There was a high prevalence of sleep issues, anxiety, stress, and depression among the pre-clinical medical students, with significantly higher sleeping disorders, anxiety, stress, and depression levels among those medical students who struggle with their academic performances, poor lifestyle factor, and poor Social and COVID management