MerTK is a mediator of alpha-synuclein fibril uptake by human microglia.

Mer tyrosine kinase (MerTK) is a receptor tyrosine kinase that mediates non-inflammatory, homeostatic phagocytosis of diverse types of cellular debris. Highly expressed on the surface of microglial cells, MerTK is of importance in brain development, homeostasis, plasticity and disease. Yet, involvement of this receptor in the clearance of protein aggregates that accumulate with ageing and in neurodegenerative diseases has yet to be defined.

Analysis of the microglia transcriptome across the human lifespan using single cell RNA sequencing.

Background: Microglia are tissue resident macrophages with a wide range of critically important functions in central nervous system development and homeostasis.

Method: In this study, we aimed to characterize the transcriptional landscape of ex vivo human microglia across different developmental ages using cells derived from pre-natal, pediatric, adolescent, and adult brain samples. We further confirmed our transcriptional observations using ELISA and RNAscope.

MicroRNA-210 regulates the metabolic and inflammatory status of primary human astrocytes.

Background: Astrocytes are the most numerous glial cell type with important roles in maintaining homeostasis and responding to diseases in the brain. Astrocyte function is subject to modulation by microRNAs (miRs), which are short nucleotide strands that regulate protein expression in a post-transcriptional manner. Understanding the miR expression profile of astrocytes in disease settings provides insight into the cellular stresses present in the microenvironment and may uncover pathways of therapeutic interest.

Unraveling molecular mechanism underlying biomaterial and stem cells interaction during cell fate commitment using high throughput data analysis.

Stem cell differentiation towards various somatic cells and body organs has proven to be an effective technique in the understanding and progression of regenerative medicine. Despite the advances made, concerns regarding the low efficiency of differentiation and the remaining differences between stem cell products and their in vivo counterparts must be addressed. Biomaterials that mimic endogenous growth conditions represent one recent method used to improve the quality and efficiency of stem cell differentiation, though the mechanisms of this improvement remain to be completely understood.

Comparison of clinical and histopathological characteristics of short-term progressive and non-progressive blood blister-like aneurysms.

Background: Many blood blister aneurysms (BBAs) have been documented with a rapid progression history in repeated angiography. The underlying mechanism and clinical significance remained elusive. This current study aims to clarify the clinical and histopathological differences between short-term progressive BBA and non-progressive BBAs.

Lesion stage-dependent causes for impaired remyelination in MS.

Multiple sclerosis (MS) is the most frequent demyelinating disease and a leading cause for disability in young adults. Despite significant advances in immunotherapies in recent years, disease progression still cannot be prevented. Remyelination, meaning the formation of new myelin sheaths after a demyelinating event, can fail in MS lesions.

Presence of vasa vasorum in human intracranial aneurysms.

Objectives: Vasa vasorum is associated with the pathogenesis of various cerebrovascular diseases, but its presence in intracranial aneurysms (IA) and its ability to act as a predicting factor of IA rupture remain unrevealed.

Methods: Histological investigation was performed for 3 middle meningeal arteries and 25 human IAs that were sequentially collected from 2017 to 2019. Relevant medical information was collected from the hospital information and imaging system.

Intracranial Aneurysm Presenting Robust Metal Artifact.

Background: Intracranial aneurysm (IA) is a debilitating cerebrovascular degeneration. Current clinical diagnosis relies mainly on conventional angiogram except for some peculiar aneurysms. Nonetheless, there is no documentation of aneurysm showing robust intracranial artifact on computed tomography or magnetic resonance imaging.

Novel Molecular Leads for the Prevention of Damage and the Promotion of Repair in Neuroimmunological Disease.

Neuroinflammation is a prominent pathological feature of all neuroimmunological diseases, including, but not limited to, multiple sclerosis (MS), myasthenia gravis, neuromyelitis optica, and Guillain-Barré syndrome. All currently-approved therapies for the treatment of these diseases focus on controlling or modulating the immune (innate and adaptive) responses to limit demyelination and neuronal damage. The primary purpose of this review is to detail the pre-clinical data and proposed mechanism of action of novel drugs currently in clinical trial, with a focus on novel compounds that promote repair and regeneration in the central nervous system (CNS).

Multicolor Flow Cytometry and Cytokine Analysis Provides Enhanced Information on Kidney Transplant Biopsies.

Introduction: Current processing of renal biopsy samples provides limited information about immune mechanisms causing kidney injury and disease activity. We used flow cytometry with transplanted kidney biopsy samples to provide more information on the immune status of the kidney.

Methods: To enhance the information available from a biopsy, we developed a technique for reducing a fraction of a renal biopsy sample to single cells for multicolor flow cytometry and quantitation of secreted cytokines present within the biopsy sample.

Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer.

Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens.

Plasma C4d+ Endothelial Microvesicles Increase in Acute Antibody-Mediated Rejection.

Background: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. Currently, AMR diagnosis relies on biopsy which is an invasive procedure. A noninvasive biomarker of acute AMR could lead to early diagnosis and treatment of this condition and improve allograft outcome.

Novel diagnostics in renal transplantation.

Renal transplantation is the treatment of choice for many patients with end stage renal disease. While significant progress has been achieved in short-term outcomes, long-term graft survival has only marginally improved. More than 50% of transplanted kidneys from deceased donors fail within ten years; and from living donors, within 12 years.

Chronic social defeat downregulates the 5-HT1A receptor but not Freud-1 or NUDR in the rat prefrontal cortex.

The serotonin 1A receptor (5-HT1A) and its associated transcriptional regulators, five prime repressor element under dual repression (Freud-1) and nuclear-deformed epidermal autoregulatory factor (NUDR/Deaf-1) have been previously found to be the repressors for 5-HT1A in the serotonergic raphe neurons, and are also altered in postmortem brains of individuals with major depressive disorder (MDD) and in rats exposed to chronic restraint stress. We sought to find out if rats exposed to chronic social defeat (CSD) stress also show altered expression of these genes. Adult male Wistar rats were exposed to CSD stress for four consecutive weeks following which they were sacrificed and gene expression assessed in the prefrontal cortex (PFC) by quantitative real-time polymerase chain reaction.

Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups.

Differential regulation of the serotonin 1 A transcriptional modulators five prime repressor element under dual repression-1 and nuclear-deformed epidermal autoregulatory factor by chronic stress.

Chronic stress is known to affect brain areas involved in learning and emotional responses. These changes, thought to be related to the development of cognitive deficits are evident in major depressive disorder and other stress-related pathophysiologies. The serotonin-related transcription factors (Freud-1/CC2D1A; five prime repressor element under dual repression/coiled-coil C2 domain 1a, and NUDR/Deaf-1; nuclear-deformed epidermal autoregulatory factor) are two important regulators of the 5-HT1A receptor.

Effects of transcription factors Phox2 on expression of norepinephrine transporter and dopamine beta-hydroxylase in SK-N-BE(2)C cells.

Phox2a and Phox2b are two homeodomain proteins that control the differentiation of noradrenergic neurons during embryogenesis. In the present study, we examined the possible effect of Phox2a/2b on the in vitro expression of the norepinephrine transporter (NET) and dopamine beta-hydroxylase (DBH), two important markers of the noradrenergic system. SK-N-BE(2)C cells were transfected with cDNAs or short hairpin RNAs specific to the human Phox2a and Phox2b genes.

Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies.

Left ventricular hypertrophy (LVH), a common consequence of systemic hypertension associated with poor clinical outcome, is also a potentially reversible condition. Here, we probed the molecular pathways that underpin the development of LVH and their modulation by antihypertensive regimens that reversed LVH. Spontaneously hypertensive rats were studied at 12 (early LVH) and 48 weeks (late LVH), respectively, with normotensive Wistar-Kyoto rats as age-matched controls.

MDRD-estimated GFR at one year post-renal transplant is a predictor of long-term graft function.

Renal transplantation is the optimal mode of renal replacement. Improvements in graft survival and acute rejection rates have made these outcomes less useful for prognostication and as end-points in clinical trials; accurate surrogate markers of long-term graft outcome are therefore increasingly important. This study examines the relationship between both serum creatinine (SCr(1 yr)) and MDRD estimated glomerular filtration rate measured at one year (eGFR(MDRD)(1 yr)) as predictors of graft survival.

Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury.

Tissue reoxygenation following hypoxia is associated with ischemia-reperfusion injury (IRI) and may signal the development of ischemic preconditioning, an adaptive state that is protective against subsequent IRI. Here we used microarray RNA analysis of in vivo and in vitro models of IRI to delineate the underlying molecular mechanisms. Microarray analysis of renal tissue after ischemia-reperfusion revealed a number of highly up-regulated antioxidant genes including aldehyde dehydrogenases (ALDH1A1 and ALDH1A7), glutathione S-transferases (GSTM5, GSTA2 and GSTP1), and NAD(P)H quinone oxidoreductase (NQO1).

Hypoxia induces epithelial amphiregulin gene expression in a CREB-dependent manner.

Hypoxia occurs during a number of conditions in which altered epithelial proliferation is critical, including tumor development. Microarray analysis of colon-derived epithelial cells revealed a hypoxia-dependent increase in the expression of amphiregulin, an EGF receptor (EGFR) ligand that activates epithelial proliferation and has been associated with the development of colonic tumors. Amphiregulin expression was also induced in tissues from mice exposed to whole animal hypoxia.

Immune responses in kidney preservation and reperfusion injury.

Organ preservation and reperfusion injury have significant detrimental effects on both short- and long-term organ function. Ischemia reperfusion injury (IRI) underlies organ transplant dysfunction, myocardial infarction, stroke, and shock. Multiple molecular pathways are engaged in reactive oxygen production, apoptosis, signaling, and tissue regeneration.

Lipoxins: potential anti-inflammatory, proresolution, and antifibrotic mediators in renal disease.

Lipoxins are lipoxygenase-derived lipid mediators with both anti-inflammatory and proresolution properties that have been demonstrated in vivo and in vitro. The bioactivity profile of lipoxins in vitro suggests that they have therapeutic potential in acute renal failure and glomerulonephritis; predictions that have been borne out to date in experimental models of renal disease. We review recent developments on the molecular basis of lipoxin bioactions mediated through receptor crosstalk and the accumulating evidence that lipoxins may have potential as novel anti-inflammatory agents.