Inhibition of PCSK9 with evolocumab modulates lipoproteins and monocyte activation in high-risk ASCVD subjects.

Background: Mechanistic studies suggest that proprotein convertase subtilisin/kexin type 9 inhibitors can modulate inflammation.

Methods: Double-blind, placebo-controlled trial randomized 41 ASCVD subjects with type 2 diabetes with microalbuminuria and LDL-C level >70 mg/dL on maximum tolerated statin therapy received subcutaneous evolocumab 420 mg every 4 weeks or matching placebo. The primary outcomes were change in circulating immune cell transcriptional response, lipoproteins and blood viscosity at 2 weeks and 12 weeks.

Association of blood viscosity and device-free days among hospitalized patients with COVID-19.

Background: Increased estimated whole blood viscosity (eWBV) predicts higher mortality in patients hospitalized for coronavirus disease 2019 (COVID-19). This study assesses whether eWBV is an early predictor of non-fatal outcomes among patients hospitalized for acute COVID-19 infection.

Methods: This retrospective cohort study included 9278 hospitalized COVID-19 patients diagnosed within 48 h of admission between February 27, 2020 to November 20, 2021 within the Mount Sinai Health System in New York City.

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

Background: Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19.

Blood hyperviscosity in acute and recent COVID-19 infection.

Background: Elevated estimated blood viscosity (EBV), derived from hematocrit and globulins, is associated with thrombotic complications, organ failure, and higher mortality in COVID-19 patients. Although informative, EBV does not account for cellular interactions or fibrinogen.

Objective: Investigate whether patients with acute and recent COVID-19 have altered whole blood viscosity (WBV) when measured at both high and low shear rates using in vitro blood samples from patients.

Association of total VLDL particle concentrations with elevated blood viscosity in patients with type 2 diabetes.

Microvascular disease is an important cause of morbidity in patients with T2DM. Total VLDL concentrations is associated with increased BV, a major determinant of microvascular flow in patients with T2DM. Measurement of VLDL concentration may provide insight into lipoprotein associated microvascular complications of diabetes.

Efficacy of Statin Therapy in Patients with Hospital Admission for COVID-19.

Purpose: COVID-19 is characterized by dysfunctional immune responses and metabolic derangements, which in some, lead to multi-organ failure and death. Statins are foundational lipid-lowering therapeutics for cardiovascular disease and also possess beneficial immune-modulating properties. Because of these immune-modulating properties, some have suggested their use in COVID-19.

Failure of cosegregation between a rare STAP1 missense variant and hypercholesterolemia.

Autosomal dominant familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein cholesterol levels and an increased risk for atherosclerotic cardiovascular disease. Although rare pathogenic variants in genes encoding the low-density lipoprotein receptor, apolipoprotein B, proprotein convertase subtilisin/kexin 9 are found in more than 80% of molecularly defined patients with FH, a few rare minor causative genes have been proposed, including the gene encoding signal-transducing adaptor family member 1 (STAP1). Here, we describe a patient with hypercholesterolemia and the rare heterozygous missense variant p.

Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial.

Background: Microvascular blood flow (MBF) impairment in patients with lower extremity arterial disease (LEAD) is associated with more severe major adverse limb events (MALE). The contribution of ticagrelor, a P2Y12 antagonist and an adenosine enhancer, on blood viscosity (BV) and BV-dependent MBF in LEAD is unknown. The aim of the trial is to investigate the effects of ticagrelor on BV, and explore the association of BV-dependent MBF in participants with LEAD and type 2 diabetes (T2DM).

Ticagrelor and the Prevention of Microvascular Complications in Diabetes Patients with Lower Extremity Arterial Disease; Rationale and Design of the Hema-Kinesis Trial.

Background: Lower extremity arterial disease (LEAD) occurs more common in patients with diabetes than without diabetes. Microvascular complications of diabetes contribute to higher rates of adverse limb events in patients with LEAD. Blood flow in the macrocirculation and microcirculation is reduced with increasing low-shear and high-shear blood viscosity.

Systematic Review of Methods Used for the Microvascular Assessment of Peripheral Arterial Disease.

Lower extremity peripheral arterial disease (LEAD) is increasing in prevalence in low with approximately 202 million people affected with LEAD worldwide. Certain subgroups of individuals (cigarette smokers, diabetics) that are particularly high risk for LEAD and major adverse limb events (MALE). Conventionally, the ankle-brachial index (ABI) is the recommended screening test for LEAD.

Regulation of TLR4-mediated signaling by IBP/Def6, a novel activator of Rho GTPases.

TLRs play a fundamental role in innate immune responses. Although Rho GTPases have been implicated in TLR-mediated signaling pathways, the molecules that control their activation in response to TLR engagement are largely unknown. IFN regulatory factor-4-binding protein (IBP; which is encoded by the gene Def6) is a unique type of activator for Rac that plays a crucial role in TCR-mediated signaling and adaptive immune responses.

IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor.

The T helper 17 (Th17) cell lineage is important in inflammatory and autoimmune responses, via its ability to produce interleukin-17 (IL-17) and IL-21. Given the potentially deleterious effects of Th17 cells, their generation needs to be strictly controlled. IRF-4 is a transcription factor that has recently emerged as a key regulator of Th17 cell differentiation.

Loss of IRF-4-binding protein leads to the spontaneous development of systemic autoimmunity.

IFN regulatory factor 4-binding (IRF-4-binding) protein (IBP) is a novel type of activator of Rho GTPases that is recruited to the immunological synapse upon TCR stimulation. Here we demonstrate that loss of IBP leads to the spontaneous development of a systemic autoimmune disorder characterized by the accumulation of effector/memory T cells and IgG+ B cells, profound hypergammaglobulinemia, and autoantibody production. Similar to human SLE, this syndrome primarily affects females.

Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice.

Aim: To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation.

Methods: Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki-67 labeling index (LI) were examined to evaluate the preservation of original features.

Impact of cyclooxygenase-2 gene expression on tumor invasiveness in a human renal cell carcinoma cell line.

Purpose: We have previously confirmed that cyclooxygenase-2 (COX-2) is expressed in a human renal cell carcinoma (RCC) cell line and it has an important role in cell tumorigenesis and angiogenesis. In the current study we evaluated the impact on cell adhesion and tumor invasiveness in human RCC cell lines by transfection of COX-2 sense and antisense cDNAs.

Materials And Methods: A human RCC cell line that expresses COX-2 was transfected with COX-2 sense or antisense cDNA.

Significance of COX-2 expression in human renal cell carcinoma cell lines.

Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX-2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis of human RCC.

Creation of luminal tissue covered with urothelium by implantation of cultured urothelial cells into the peritoneal cavity.

Purpose: We established the culture condition of seeding urothelial cells onto a scaffold for implantation into the peritoneal cavity and evaluated the histology of implanted urothelial cells.

Materials And Methods: In part 1 of the study cultured porcine bladder urothelial cells were seeded onto 3 types of collagen gel made on microporous membrane, including collagen gel with or without cultured porcine bladder fibroblasts, or a feeder layer. The macroscopic and microscopic appearance of the gel with urothelial cells were examined in vitro.