Nitric oxide metabolism and breakdown

In the current Adult Treatment Panel guidelines for cardiovascular risk detection,1 the plasma-based markers recommended for use in global risk assessment or in the definition of the metabolic syndrome are low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. It is widely recognized, however, that more than half of all future vascular events occur in individuals without overt hyperlipidemia. For example, in a recent large-scale analysis of >27 000 healthy American women, 77% of all future events occurred in those with LDL-C levels <4.14 mmol/L (<160 mg/dL) and 45% of all events occurred in those with LDL-C values <3.36 mmol/L (<130 mg/dL).2 Although risk-scoring systems that additionally evaluate traditional risk factors such as smoking, hypertension, and diabetes greatly improve risk prediction, multiple studies demonstrate that 20% to 25% of all future events occur in individuals with only 1 of these factors.3 Moreover, the prevalence of traditional risk factors is almost as high in those without disease as in affected individuals.4

As our understanding of the pathobiology of atherothrombosis has improved, researchers have attempted to evaluate the activities of these biological processes by measuring markers in plasma or urine (ie, biomarkers). Indeed, a series of candidate biomarkers reflecting inflammation, hemostasis, thrombosis, and oxidative stress have been evaluated as potential clinical tools in an effort to improve risk prediction. To be useful in a clinical setting, the biomarker of interest must be shown in multiple prospective studies to predict future cardiovascular events. Retrospective studies are of limited value because they are prone to bias and cannot exclude the possibility that the particular biomarker is elevated as a result of, rather than a cause of, disease. To be used widely, the proposed biomarker should provide independent information on risk or prognosis beyond that available from global assessment algorithms such …

Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events

https://www.jidonline.org/article/S0022-202X(15)36878-0/pdf

UVA Irradiation of Human Skin Vasodilates Arterial Vasculature and Lowers Blood Pressure Independently of Nitric Oxide Synthase

Cushing's syndrome of glucocorticoid excess is named after the eminent Boston neurosurgeon Harvey W. Cushing (1869-1939). The recognition that glucocorticoid excess produces hypertension led to examination of the role of cortisol in essential hypertension, but it is only over the last decade that evidence has emerged to support the concept. Despite the widespread assumption that cortisol raises blood pressure as a consequence of renal sodium retention, there are few data consistent with the notion. Although it has a plethora of actions on brain, heart and blood vessels, kidney, and body fluid compartments, precisely how cortisol elevates blood pressure is unclear. Candidate mechanisms currently being examined include inhibition of the vasodilator nitric oxide system and increases in vasoconstrictor erythropoietin concentration.

Cushing, cortisol, and cardiovascular disease.

Detection of endothelial dysfunction with brachial artery ultrasound scanning.

BACKGROUND AND PURPOSE: Preoperative evaluation of brain AVMs is crucial for the selection of surgical candidates. Our goal was to use artificial intelligence to predict postsurgical motor defects in patients with brain AVMs involving motor-related areas. MATERIALS AND METHODS: Eighty-three patients who underwent microsurgical resection of brain AVMs involving motor-related areas were retrospectively reviewed. Four artificial intelligence–based indicators were calculated with artificial intelligence on TOF-MRA and DTI, including FN5mm/50mm (the proportion of fiber numbers within 5–50mm from the lesion border), FN10mm/50mm (the same but within 10–50mm), FP5mm/50mm (the proportion of fiber voxel points within 5–50mm from the lesion border), and FP10mm/50mm (the same but within 10–50mm). The association between the variables and long-term postsurgical motor defects was analyzed using univariate and multivariate analyses. Least absolute shrinkage and selection operator regression with the Pearson correlation coefficient was used to select the optimal features to develop the machine learning model to predict postsurgical motor defects. The area under the curve was calculated to evaluate the predictive performance. RESULTS: In patients with and without postsurgical motor defects, the mean FN5mm/50mm, FN10mm/50mm, FP5mm/50mm, and FP10mm/50mm were 0.24 (SD, 0.24) and 0.03 (SD, 0.06), 0.37 (SD, 0.27) and 0.06 (SD, 0.08), 0.06 (SD, 0.10) and 0.01 (SD, 0.02), and 0.10 (SD, 0.12) and 0.02 (SD, 0.05), respectively. Univariate and multivariate logistic analyses identified FN10mm/50mm as an independent risk factor for long-term postsurgical motor defects (P = .002). FN10mm/50mm achieved a mean area under the curve of 0.86 (SD, 0.08). The mean area under the curve of the machine learning model consisting of FN10mm/50mm, diffuseness, and the Spetzler-Martin score was 0.88 (SD, 0.07). CONCLUSIONS: The artificial intelligence–based indicator, FN10mm/50mm, can reflect the lesion-fiber spatial relationship and act as a dominant predictor for postsurgical motor defects in patients with brain AVMs involving motor-related areas.

/pdf/artificial-intelligence-assisted-evaluation-of-the-spatial-30uvoxxs.pdf

Artificial Intelligence–Assisted Evaluation of the Spatial Relationship between Brain Arteriovenous Malformations and the Corticospinal Tract to Predict Postsurgical Motor Defects

OBJECTIVE
To investigate the role of long non-coding RNA ZEB1-AS1 in cerebral ischemia/reperfusion injury (CI/RI).


METHODS
We detected the temporal changes of ZEB1-AS1 and HMGB1 expression using qPCR and Western blotting in SD rats following CI/RI induced by middle cerebral artery occlusion (MCAO). The rat models of CI/RI were subjected to injections of vectors for ZEB1-AS1 overexpression or knockdown into the lateral ventricle, and the changes in cognitive function, brain water content, blood-brain barrier integrity, and IL-1β and TNF-α levels in the cerebrospinal fluid (CSF) and serum were observed. Neuronal loss and cell apoptosis in the cortex of the rat models were detected by FJC and TUNEL methods, and HMGB1 and TLR-4 expressions were analyzed with Western blotting. We also examined the effects of ZEB1-AS1 knockdown on apoptosis and expressions of HMGB1 and TLR-4 in SH-SY5Y cells with oxygen-glucose deprivation/reoxygenation (OGD/R).


RESULTS
In CI/RI rats, the expressions of ZEB1-AS1 and HMGB1 in the brain tissue increased progressively with the extension of reperfusion time, reaching the peak levels at 24 h followed by a gradual decline. ZEB1-AS1 overexpression significantly aggravated icognitive impairment and increased brain water content, albumin content in the CSF, and IL-1β and TNF-α levels in the CSF and serum in CI/RI rats (P < 0.05), while ZEB1-AS1 knockdown produced the opposite effects (P < 0.05 or 0.01). ZEB1-AS1 overexpression obviously increased the number of FJC-positive neurons in the cortex and enhanced the expressions of HMGB1 and TLR-4 in the rat models (P < 0.01); ZEB1-AS1 knockdown significantly reduced the number of FJC-positive neurons and lowered HMGB1 and TLR-4 expressions (P < 0.01). In SH-SY5Y cells with OGD/R, ZEB1-AS1 knockdown significantly suppressed cell apoptosis and lowered the expressions of HMGB1 and TLR-4 (P < 0.01).


CONCLUSION
ZEB1-AS1 overexpression aggravates CI/RI in rats through the HMGB1/TLR-4 signaling axis.

[Long noncoding RNA ZEB1-AS1 aggravates cerebral ischemia/reperfusion injury in rats through the HMGB1/TLR-4 signaling axis].

Background: Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin lymphoma (NHL) of a mature B cell malignancy, which accounts for ∼6% of NHLs. It is hallmarked with the chromosomal translocation t(11;14)(q13; q32). MCL is considered difficult to treat, with frequent relapse after effective conventional chemotherapy, contributing to a short median survival of 5–7 years and thus warranting the development of new therapeutics. Although the recent approval of Bruton tyrosine kinase inhibitor (BTKi) therapy has greatly improved the treatment of MCL, patients exhibiting primarily (intrinsically) resistance or BTKi-induced resistance, have few treatment options. 

HX301 (ON123300) shows broad antitumor activity in preclinical mantle cell lymphoma models, inclusive of those resistant to BTKi

Dynamic intervention-based biomarkers may reduce heterogeneity and motivate targeted interventions in clinical high risk for psychosis

M200 Evaluation of eight commercially available clinical chemistry assays on the ALINITY® C system

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