Novel phenylpiperazine derivatives as potent transient receptor potential vanilloid 1 antagonists.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, which is considered a highly validated target for pain perception. Repeated activation with agonists to desensitize receptors or use the antagonists can both exert analgesic effects. In this work, two series of novel phenylpiperazine derivatives were designed, synthesized, and evaluated for the in vitro receptor inhibitory activity and in vivo analgesic activity.

Hemodynamic Impairment of Blood Pressure and Stroke Mechanisms in Symptomatic Intracranial Atherosclerotic Stenosis.

Background: Hemodynamic impairment of blood pressure may play a crucial role in determining the mechanisms of stroke in symptomatic intracranial atherosclerotic stenosis). We aimed to elucidate this issue and assess the impacts of modifications to blood pressure on hemodynamic impairment.

Methods: From the Third China National Stroke Registry III, computed fluid dynamics modeling was performed using the Newton-Krylov-Schwarz method in 339 patients with symptomatic intracranial atherosclerotic stenosis during 2015 to 2018.

MDSC-derived S100A8/9 contributes to lupus pathogenesis by promoting TLR7-mediated activation of macrophages and dendritic cells.

Toll-like receptors (TLRs), especially TLR7, play an important role in systemic lupus erythematosus (SLE) pathogenesis. However, the regulatory mechanism underlying the abnormal activation of TLR pathways in patients with SLE has not been elucidated. Notably, accumulating evidence indicates that myeloid-derived suppressor cells (MDSCs) are important regulators of inflammation and autoimmune diseases.

ACK1 Contributes to the Pathogenesis of Inflammation and Autoimmunity by Promoting the Activation of TLR Signaling Pathways.

Toll-like receptors (TLRs) are the first line of defense in the immune system, whose activation plays a key role in the pathogenesis of inflammation and autoimmunity. TLRs can activate a variety of immune cells such as macrophages and dendritic cells, which produce proinflammatory cytokines, chemokines, and co-stimulatory molecules that lead to the development of inflammation and autoimmune diseases. As a nonreceptor tyrosine kinase, ACK1 is involved in multiple signaling pathways and physiological processes.

Arctigenin inhibits abnormal germinal center reactions and attenuates murine lupus by inhibiting IFN-I pathway.

Interferon-I (IFN-I) signaling pathway plays a vital role in the differentiation of germinal center B cells and the pathogenesis of systemic lupus erythematosus (SLE). Therefore, targeting the IFN-I signaling pathway could serve as an effective treatment strategy in SLE. Arctigenin is an active ingredient present in the seeds of Arctium lappa L.

Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation.

Toll-like receptors (TLRs) play critical roles in regulating the abnormal activation of the immune cells resulting in the pathogenesis of inflammation and autoimmune diseases. Pyruvate kinase M2 (PKM2), which governs the last step of glycolysis, is involved in multiple cellular processes and pathological conditions. However, little is known about the involvement of PKM2 in regulating TLR-mediated inflammation and autoimmunity.

Are prominent medullary veins better than prominent cortical veins as predictors of early clinical outcome in patients with acute ischemic stroke?

Purpose: The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) can be dichotomized into prominent cortical veins (PCV) and prominent medullary veins (PMV). This study was designed to compare the predictive value of PCV and PMV in the evaluation of the severity of acute ischemic stroke (AIS) in patients within the reperfusion window.

Methods: Forty-seven consecutive patients with AIS within the middle cerebral artery territory were recruited.

Comparison of three FLAIR vascular hyperintensities methodologies in patients with acute ischemic stroke.

Background: Multiple methods have been used to analyze fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) which may represent collaterals in patients with acute ischemic stroke (AIS); however, there is no consensus between methods.

Purpose: To compare three frequently used FVH methods for predicting early infarct volume and clinical outcome in patients with AIS.

Material And Methods: Patients with AIS in middle cerebral artery territory were recruited.

Nanodiamond phantoms mimicking human liver: perspective to calibration of T1 relaxation time in magnetic resonance imaging.

Phantoms of biological tissues are materials that mimic the properties of real tissues. This study shows the development of phantoms with nanodiamond particles for calibration of T1 relaxation time in magnetic resonance imaging. Magnetic resonance imaging (MRI) is a commonly used and non-invasive method of detecting pathological changes inside the human body.

Characteristics of Wall Shear Stress and Pressure of Intracranial Atherosclerosis Analyzed by a Computational Fluid Dynamics Model: A Pilot Study.

Although wall shear stress (WSS) and pressure play important roles in plaque vulnerability, characteristics of the two indices in intracranial atherosclerosis (ICAS) have not been fully investigated yet. This study aimed to elucidate this issue by means of establishing a non-invasive computational fluid dynamics method with time-of-flight magnetic resonance angiography (TOF-MRA) of the whole cerebral artery. Subjects with symptomatic ICAS in the middle cerebral artery domain were enrolled, excluding those with concomitant internal carotid artery stenosis.

Middle Cerebral Artery Atherosclerosis and Deep Subcortical Infarction: A 3T Magnetic Resonance Vessel Wall Imaging Study.

Background: Deep subcortical infarction is a major subtype of stroke in middle cerebral artery (MCA) territory. This study aims to evaluate the relationship between characteristics of MCA plaque and features of deep subcortical infarction.

Methods: Patients with recent acute ischemic stroke and deep subcortical infarction were prospectively enrolled.

Combined diagnosis of breast cancer in the early stage by MRI and detection of gene expression.

Breast cancer is one of the most common cancer types in humans. Magnetic resonance imaging (MRI) is an efficient method for the detection of human breast cancer. However, the efficacy of MRI in detecting breast cancer in the early stage requires to be improved.

NPR-9 regulates the innate immune response in Caenorhabditis elegans by antagonizing the activity of AIB interneurons.

npr-9 encodes a homologue of the gastrin-releasing peptide receptor (GRPR) and is expressed in AIB interneurons. In this study, we investigated the role of NPR-9 in the neuronal control of innate immunity using the model system Caenorhabditis elegans. After exposure to Pseudomonas aeruginosa PA14, npr-9(tm1652) mutants showed resistance to infection, decreased PA14 colonization and increased expression of immunity-related genes.

Subject-Specific Fully-Coupled and One-Way Fluid-Structure Interaction Models for Modeling of Carotid Atherosclerotic Plaques in Humans.

Background: Hemodynamics play an important role in the development and progression of carotid atherosclerosis, and may be important in the assessment of plaque vulnerability. The aim of this study was to develop a system to assess the hemodynamics of carotid atherosclerotic plaques using subject-specific fluid-structure interaction (FSI) models based on magnetic resonance imaging (MRI).

Material And Methods: Models of carotid bifurcations (n=86 with plaques from 52 patients, n=14 normal carotids from 12 participants) were obtained at the Department of Radiology, Beijing Tian Tan Hospital between 2010 and 2013.

Distribution and features of middle cerebral artery atherosclerotic plaques in symptomatic patients: a 3.0 T high-resolution MRI study.

Objectives: To investigate the distribution and features of middle cerebral artery (MCA) atherosclerotic plaques in patients with acute ischaemic strokes using high-resolution magnetic resonance (MR) imaging.

Methods: Forty-six plaques from 44 MCAs (18 right and 26 left) in patients with acute symptomatic ischaemic strokes were studied. High-resolution MR imaging including tb1 weighted imaging (T1WI), tb2 weighted imaging (T2WI), PD weighted imaging (PDWI) and three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) sequences were used to visualise the plaques.

Hemodynamic parameters distribution of upstream, stenosis center, and downstream sides of plaques in carotid artery with different stenosis: a MRI and CFD study.

Background: Histopathological studies have shown significant differences in plaque components and surface conditions between upstream and downstream of the stenosis. It can be deduced that the flow status near the plaques is different from the flow status at the upstream side, stenosis center, or downstream side of the plaque.

Purpose: To study the hemodynamic parameter distribution in different locations near atherosclerotic plaques in the carotid arteries with different stenosis degrees.

Association of plaque compositions and stenosis patterns in carotid bifurcation using MR imaging.

Objectives: To investigate the relationship between plaque compositions and stenosis patterns in patients with atherosclerotic plaques at the carotid bifurcation using magnetic resonance (MR) imaging.

Methods: One hundred and four carotid arteries with stenosis over 50% from 75 symptomatic stroke patients (64 male and 11 female; mean age 58·2±13·3 years) were studied. Plaque compositions were analyzed by high-resolution MR imaging using a 3·0T MR with a surface coil.

Association between cerebral microbleeds and the first onset of intracerebral hemorrhage - a 3.0 T MR study.

Background: Cerebral microbleeds (CMBs) detected by gradient-echo MRI have been proven to be a potential risk factor for further bleeding, while the association between CMBs and the first onset of intracerebral hemorrhage has not been well investigated.

Purpose: To analyze the association between CMBs and the first onset of primary intracerebral hemorrhage (pICH).

Material And Methods: Two hundred and two consecutive inpatients with ICH and 234 consecutive outpatients without ICH as control group were enrolled in this study.

Distribution of wall shear stress in carotid plaques using magnetic resonance imaging and computational fluid dynamics analysis: a preliminary study.

Background: Wall shear stress is an important factor in the destabilization of atherosclerotic plaques. The purpose of this study was to assess the distribution of wall shear stress in advanced carotid plaques using high resolution magnetic resonance imaging and computational fluid dynamics.

Methods: Eight diseased internal carotid arteries in seven patients were evaluated.

Effect of baseline magnetic resonance imaging (MRI) apparent diffusion coefficient lesion volume on functional outcome in ischemic stroke.

Objective: We explored the relationship between predicted infarct core, predicted ischemic penumbras and predicted final infarct volumes obtained though apparent diffusion coefficient (ADC)-based method, as well as other clinical variables, and functional outcome.

Methods: Patients with acute cerebral ischemic stroke were retrospectively recruited. The National Institutes of Health Stroke Scale score was evaluated at baseline and the modified Rankin Scale (mRS) at day 90.

Prediction of infarct core and salvageable ischemic tissue volumes by analyzing apparent diffusion coefficient without intravenous contrast material.

Rationale And Objectives: To investigate whether baseline apparent diffusion coefficient (ADC) maps can be employed to predict both infarct core and salvageable ischemic tissue volumes in acute ischemic stroke.

Materials And Methods: An automated image analysis system based on baseline ADC maps was tested against 30 patients with acute ischemic stroke of anterior circulation to predict both infarct core and salvageable ischemic tissue volumes. The predicted infarct core and predicted salvageable ischemic tissue were quantitatively and qualitatively compared with follow-up imaging data in recanalization and no recanalization groups, respectively.