The role of natural products as PCSK9 modulators: A review.

A variety of mechanisms and drugs have been shown to attenuate cardiovascular disease (CVD) onset and/or progression. Recent researchers have identified a potential role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in modulating lipid metabolism and reducing plasma low density lipoprotein (LDL) levels. PCSK9 is the central protein in the metabolism of LDL cholesterol (LDL-C) owing to its major function in LDL receptor (LDLR) degradation. Due to the close correlation of cardiovascular disease with lipid levels, many in vivo and in vitro investigations are currently underway studying the physiological role of PCSK9. Furthermore, many studies are actively investigating the mechanisms of various compounds that influence lipid associated-disorders and their associated cardiovascular diseases. PCSK9 inhibitors have been shown to have significant impact in the prevention of emerging cardiovascular diseases. Natural products can effectively be used as PCSK9 inhibitors to control lipid levels through various mechanisms. In this review, we evaluate the role of phytochemicals and natural products in the regulation of PCSK9, and their ability to prevent cardiovascular diseases. Moreover, we describe their mechanisms of action, which have not to date been delineated.

Protective Effects of Plant-Derived Compounds Against Traumatic Brain Injury.

Inflammation in the nervous system is one of the key features of many neurodegenerative diseases. It is increasingly being identified as a critical pathophysiological primitive mechanism associated with chronic neurodegenerative diseases following traumatic brain injury (TBI). Phytochemicals have a wide range of clinical properties due to their antioxidant and anti-inflammatory effects. Currently, there are few drugs available for the treatment of neurodegenerative diseases other than symptomatic relief. Numerous studies have shown that plant-derived compounds, in particular polyphenols, protect against various neurodegenerative diseases and are safe for consumption. Polyphenols exert protective effects on TBI via restoration of nuclear factor kappa B (NF-κB), toll-like receptor-4 (TLR4), and Nod-like receptor family proteins (NLRPs) pathways. In addition, these phytochemicals and their derivatives upregulate the phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/AKT) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, which have critical functions in modulating TBI symptoms. There is supporting evidence that medicinal plants and phytochemicals are protective in different TBI models, though future clinical trials are needed to clarify the precise mechanisms and functions of different polyphenolic compounds in TBI.

Universal control of a bosonic mode via drive-activated native cubic interactions.

Linear bosonic modes offer a hardware-efficient alternative for quantum information processing but require access to some nonlinearity for universal control. The lack of nonlinearity in photonics has led to encoded measurement-based quantum computing, which relies on linear operations but requires access to resourceful ('nonlinear') quantum states, such as cubic phase states. In contrast, superconducting microwave circuits offer engineerable nonlinearities but suffer from static Kerr nonlinearity. Here, we demonstrate universal control of a bosonic mode composed of a superconducting nonlinear asymmetric inductive element (SNAIL) resonator, enabled by native nonlinearities in the SNAIL element. We suppress static nonlinearities by operating the SNAIL in the vicinity of its Kerr-free point and dynamically activate nonlinearities up to third order by fast flux pulses. We experimentally realize a universal set of generalized squeezing operations, as well as the cubic phase gate, and exploit them to deterministically prepare a cubic phase state in 60 ns. Our results initiate the experimental field of polynomial quantum computing, in the continuous-variables notion originally introduced by Lloyd and Braunstein.

The Relationship Between Psoriasis, COVID-19 Infection and Vaccination During Treatment of Patients.

Since the outbreak of the COVID-19 pandemic in December 2019, scientists worldwide have been looking for a way to control this global threat. One of the most successful and practical solutions has been the development and worldwide distribution of the COVID-19 vaccines. However, in a small percentage of cases, vaccination can lead to de novo development or exacerbation of immune or inflammatory conditions such as psoriasis. Due to the immunomodulatory nature of this disease, people affected by psoriasis and other related skin conditions have been encouraged to receive COVID-19 vaccines, which are immunomodulatory by nature. As such, dermatological reactions are possible in these patients, and cases of onset, exacerbation or change in the type of psoriasis have been observed in patients administered with COVID-19 vaccines. Considering the rarity and minor nature of some of these cutaneous reactions to COVID-19 vaccination, there is a general consensus that the benefits of vaccination outweigh the potential risks of experiencing such side effects. Nevertheless, healthcare workers who administer vaccines should be made aware of the potential risks and advise recipients accordingly. Furthermore, we suggest careful monitoring for potentially deleterious autoimmune and hyperinflammatory responses using point-of-care biomarker monitoring.

Regulatory Effects of Statins on SIRT1 and Other Sirtuins in Cardiovascular Diseases.

Adverse cardiovascular disease (CVD) outcomes, such as sudden cardiac death, acute myocardial infarction, and stroke, are often catastrophic. Statins are frequently used to attenuate the risk of CVD-associated morbidity and mortality through their impact on lipids and they may also have anti-inflammatory and other plaque-stabilization effects via different signaling pathways. Different statins, including atorvastatin, rosuvastatin, pravastatin, pitavastatin, and simvastatin, are administered to manage circulatory lipid levels. In addition, statins are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase via modulating sirtuins (SIRTs). During the last two decades, SIRTs have been investigated in mammals and categorized as a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs) with significant oxidative stress regulatory function in cells-a key factor in extending cell lifespan. Recent work has demonstrated that statins upregulate SIRT1 and SIRT2 and downregulate SIRT6 in both in vitro and in vivo experiments and clinical trials. As statins show modulatory properties, especially in CVDs, future investigations are needed to delineate the role of SIRT family members in disease and to expand knowledge about the effects of statins on SIRTs. Here, we review what is currently known about the impact of statins on SIRTs and how these changes correlate with disease, particularly CVDs.