Descriptive analysis of MC4R gene variants associated with obesity listed on ClinVar.

Objectives: The most recent version of ClinVar was utilized to filter variants of the MC4R gene based on location, condition, and clinical significance with the goal of obtaining benign and disease-associated variants of the MC4R gene. MC4R gene variants can lead to dysregulation of energy expenditure and appetite control, which prompted this study to delineate the distinctive features of MC4R gene variants submitted to the ClinVar repository regarding their association with obesity and related phenotypes.

Method: A thorough search was conducted in the ClinVar repository for clinically significant MC4R variants through the utilization of the gene name MC4R[gene] and MeSH terms "MC4R[gene]" and "single gene"[properties]" in the search box.

Positive impact of nutrition in the prevention of peripheral vascular disease and severe acute respiratory syndrome coronavirus 2: review.

Recent research has shown that there is a link between the trend of cardiovascular disease (CVD), chronic symptoms of SARS-CoV-2 (COVID-19), and medical nutrition therapy. Making positive changes to an individual's lifestyle can help to reduce the symptoms that follow exposure to CVD and COVID-19. Sustainable nutrition and lifestyle changes can positively impact an individual's health.

Validation of plasma neutrophil gelatinase-associated lipocalin as a biomarker for diabetes-related acute kidney injury.

Objective: This retrospective study aimed to investigate the correlation between neutrophil gelatinase-associated lipocalin (NGAL) levels and the clinical progression and severity of diabetes-related acute kidney injury (AKI). The quantitative determination of NGAL in plasma on the Beckman Coulter AU480 analyzer was measured using the Bioporto NGAL Test, a particle-enhanced turbidimetric immunoassay with hospitalized patients at an East Central Georgia Medical Center.

Methods: The clinical determination of plasma NGAL included a retrospective cohort study where 45 adult patients were selectively recruited.

Review of the limitations of current biomarkers in acute kidney injury clinical practices.

Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging.

The G-protein βγ subunits regulate platelet function.

Aims: G-protein coupled receptors (GPCRs) tightly regulate platelet function by interacting with various physiological agonists. An essential mediator of GPCR signaling is the G protein αβγ heterotrimers, in which the βγ subunits are central players in downstream signaling. Herein, we investigated the role of Gβγ subunits in platelet function, hemostasis and thrombogenesis.

The JUUL E-Cigarette Elevates the Risk of Thrombosis and Potentiates Platelet Activation.

Background: Smoking is the main preventable cause of death in the United States and worldwide and is associated with serious cardiovascular health consequences, including thrombotic diseases. Recently, electronic cigarettes (e-cigarettes) and, in particular JUUL, have attained wide popularity among smokers, nonsmokers, pregnant females, and even the youth, which is alarming. Interestingly, there is/are no information/studies regarding the effect of JUUL on cardiovascular diseases, specifically in the context of modulation of platelet activation.

Short-Term Exposure to Waterpipe/Hookah Smoke Triggers a Hyperactive Platelet Activation State and Increases the Risk of Thrombogenesis.

Objective: Cardiovascular disease is a major public health problem. Among cardiovascular disease's risk factors, tobacco smoking is considered the single most preventable cause of death, with thrombosis being the main mechanism of cardiovascular disease mortality in smokers. While tobacco smoking has been on the decline, the use of waterpipes/hookah has been rising, mainly due to the perception that they are less harmful than regular cigarettes.

The effects of hookah/waterpipe smoking on general health and the cardiovascular system.

Hookah or waterpipe smoking or use is an emerging trend in the US population, especially among the youth. The misperception of hookah being less harmful than cigarettes and the availability of different but "appealing" flavors are considered among the main reasons for this trend. Hookah users however are exposed to many of the same toxic compounds/by-products as cigarette users, but at dramatically higher levels, which might lead to more severe negative health effects.

Mouse transient receptor potential channel type 6 selectively regulates agonist-induced platelet function.

While changes in intracellular calcium levels is a central step in platelet activation and thrombus formation, the contribution and mechanism of receptor-operated calcium entry (ROCE) via transient receptor potential channels (TRPCs) in platelets remains poorly defined. In previous studies, we have shown that TRPC6 regulates hemostasis and thrombosis, in mice. In the present studies, we employed a knockout mouse model system to characterize the role of TRPC6 in ROCE and platelet activation.

Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis.

Background Platelets are the cellular mediators of hemostasis and thrombosis, and their function is regulated by a number of molecular mediators, such as small GTP ases. These small GTP ases are themselves regulated by guanine nucleotide exchange factors such as Arhgefs, several of which are found in platelets, including the highly expressed Arhgef1. However, the role of Arhgef1 in platelets has not yet been investigated.

Regulator of G-Protein Signaling 16 Is a Negative Modulator of Platelet Function and Thrombosis.

Background Members of the regulator of G-protein signaling ( RGS ) family inhibit G-protein coupled receptor signaling by modulating G-protein activity. In platelets, there are 3 different RGS isoforms that are expressed at the protein level, including RGS 16. Recently, we have shown that CXCL 12 regulates platelet function via RGS 16.

Author Correction: Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling HS biomedicine.

The original version of this Article contained an error in the spelling of the author Bin Geng, which was incorrectly given as Bing Geng. This has been corrected in both the PDF and HTML versions of the Article.

Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling HS biomedicine.

Hydrogen sulfide has emerged as a critical endogenous signaling transmitter and a potentially versatile therapeutic agent. The key challenges in this field include the lack of approved hydrogen sulfide-releasing probes for in human exploration and the lack of controllable hydrogen sulfide promoieties that can be flexibly installed for therapeutics development. Here we report the identification of the widely used antithrombotic drug clopidogrel as a clinical hydrogen sulfide donor.

Short-Term E-Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice.

Background: Cardiovascular disease is the main cause of death in the United States, with smoking being the primary preventable cause of premature death, and thrombosis being the main mechanism of cardiovascular mortality in smokers. Due to the perception that electronic/e-cigarettes are "safer/less harmful" than conventional cigarettes, their usage-among a variety of ages-has increased tremendously during the past decade. Notably, there are limited studies regarding the negative effects of e-cigarettes on the cardiovascular system, which is also the subject of significant debate.

Investigation of a Thromboxane A Receptor-Based Vaccine for Managing Thrombogenesis.

Background: Despite the well-established role for the thromboxane A receptor (TPR) in the development of thrombotic disorders, none of the antagonists developed to date has been approved for clinical use. To this end, we have previously shown that an antibody targeted against TPR's ligand-binding domain inhibits platelet activation and thrombus formation, without exerting any effects on hemostasis. Thus, the goal of the present studies is to design a novel TPR-based vaccine, demonstrate its ability to trigger an immune response, and characterize its antiplatelet and antithrombotic activity.

Role of IκB kinase β in regulating the remodeling of the CARMA1-Bcl10-MALT1 complex.

The current work investigates the notion that inducible clustering of signaling mediators of the IKK pathway is important for platelet activation. Thus, while the CARMA1, Bcl10, and MALT1 (CBM) complex is essential for triggering IKK/NF-κB activation upon platelet stimulation, the signals that elicit its formation and downstream effector activation remain elusive. We demonstrate herein that IKKβ is involved in membrane fusion, and serves as a critical protein kinase required for initial formation and the regulation of the CARMA1/MALT1/Bcl10/CBM complex in platelets.

P2Y antibody inhibits platelet activity and protects against thrombogenesis.

Given that platelet hyperactivity is known to give rise to thrombotic disorders, new and/or novel antiplatelet therapies are constantly being developed to add to, or to complement the current arsenal of agents. To this end, adenosine diphosphate (ADP) is an important platelet activator that acts by binding to the G-protein coupled P2Y and P2Y receptors. Although the contribution of the P2Y receptor to the genesis of thrombosis is well established, the parenteral arsenal of drugs targeting this receptor in clinical use is limited to cangrelor.

RGS10 Negatively Regulates Platelet Activation and Thrombogenesis.

Regulators of G protein signaling (RGS) proteins act as GTPase activating proteins to negatively regulate G protein-coupled receptor (GPCR) signaling. Although several RGS proteins including RGS2, RGS16, RGS10, and RGS18 are expressed in human and mouse platelets, the respective unique function(s) of each have not been fully delineated. RGS10 is a member of the D/R12 subfamily of RGS proteins and is expressed in microglia, macrophages, megakaryocytes, and platelets.

Platelet Hyperactivity in Knockout Mouse Model of Impaired Healing.

Impaired and chronic wounds occur due to defects in one or more of the overlapping stages of healing. However, problems related to the vascular system are critical for nonhealing, and chronic wounds in humans often show the presence of fibrin cuffs/clots. We hypothesized that these clots are due to alterations in platelet function; hence, we have investigated whether alterations in platelet function are present during impaired healing.

CXCL12 regulates platelet activation via the regulator of G-protein signaling 16.

The regulators of G protein signaling (RGS) protein superfamily negatively controls G protein-coupled receptor signal transduction pathways. One of the members of this family, RGS16, is highly expressed in megakaryocytes and platelets. Studies of its function in platelet and megakaryocyte biology have been limited, in part, due to lack of pharmacological inhibitors.

Arachidonic acid-derived signaling lipids and functions in impaired healing.

Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT(-/-) mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs.

The regulator of G-protein signaling 18 regulates platelet aggregation, hemostasis and thrombosis.

Regulators of G protein signaling (RGS) proteins are known to interact with and negatively regulate/turn-off G protein activation. RGS18 is identified as an R4 subfamily member of this family with specific expression in hematopoietic progenitors, myeloerythroid cells, megakaryocytes and platelets. Studies focused on understanding its function in platelet biology have been limited, in part, due to lack of pharmacological inhibitors.

A critical role for the transient receptor potential channel type 6 in human platelet activation.

While calcium signaling is known to play vital roles in platelet function, the mechanisms underlying its receptor-operated calcium entry component (ROCE) remain poorly understood. It has been proposed, but never proven in platelets, that the canonical transient receptor potential channel-6 (TRPC6) mediates ROCE. Nonetheless, we have previously shown that the mouse TRPC6 regulates hemostasis, thrombogenesis by regulating platelet aggregation.