TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination

Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)–deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur.     

The Effect of Regular Colchicine Treatment on Biomarkers Related with Vascular Injury in Newly Diagnosed Patients with Familial Mediterranean Fever

We aimed to evaluate some of the vascular biomarkers in newly diagnosed, colchicine naive familial Mediterranean fever (FMF) patients. Our primary aim was to investigate the effect of regular colchicine treatment on these variables. Twenty-four (12 males [M] and 12 females [F], 33.3?±?13.4?years) newly diagnosed FMF patients were included in the study. These patients were started on colchicine treatment following the initial assessment and were studied again no earlier than 2?months. Five patients were lost to follow-up, and assessment of the on-treatment patients was performed on the remaining 19 patients (8 M and 11 F, 33.6?±?11.8?years). There were 19 healthy subjects (11 M and 8 F, 32.2?±?7.2?years) who served as a control group. Cellular adhesion molecules (CAMs; soluble intercellular adhesion molecule-1 [sICAM-1] and soluble CD146 [sCD146]), plasminogen activator inhibitor-1 (PAI-1), fetuin-A and hs-CRP were studied. Examinations were performed on attack-free periods. The levels of hs-CRP, fetuin-A, sICAM-1, and PAI-1 were significantly higher in newly diagnosed patients compared to those of controls (P??0.05). On-treatment sCD146 was found significantly lower than the controls (P??0.05). Administration of therapeutic doses of colchicine markedly reduces vascular injury parameters and normalizes the values in FMF.     

Transarterial Embolization of Liver Cancer in a Transgenic Pig Model

PurposeTo develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies.Materials and MethodsLiver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53^R167H and KRAS^G12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40–120 μm (4 pigs) or 100–300 μm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy.ResultsLiver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3–4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40–120 μm or 100–300 μm Embosphere microspheres, while untreated tumors showed continued growth.ConclusionsLiver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.     

The association between methylation levels of targeted genes and albuminuria in patients with early diabetic kidney disease

Objective: The incidence of diabetes and its complications are greatly increasing world-wide. Diabeticnephropathy (DN) is the main cause of end-stage renal disease and is associated with high morbidity and mortality. It is important to predict patients with high risk for DN in the early stage. We selected the genes which have an important role on diabetic kidney disease. We aimed to investigate the association between DNA methylation levels of targeted genes and albuminuria in patients with early DN.

Methods: We collected the clinical data of patients with type 2 diabetes mellitus. We measured spot urine albumin creatinine ratio to calculate albuminuria level. We divided patients into two groups based on albumin excretion as patients with (n?=?69) and without DN (n?=?27). We performed methylation profiling after bisulfite conversion by pyrosequencing method. The mean value of percent methylation level of each gene was calculated.

Results: We compared targeted genes (TIMP-2, AKR1B1, MMP-2, MMP-9, MYL9, SCL2A4, SCL2A1, SCL4A3) methylation levels and albuminuria. We found significant negative correlation between TIMP-2 and AKR1B1 gene methylation levels and albuminuria levels.

Conclusions: The present study provided evidence that hypomethylation of TIMP-2 and AKR1B1 genes can be associated with albuminuria in patients with early DN. We may speculate that the hypomethylation of TIMP-2 and AKR1B1 genes may be an early surrogate marker of DN.     

Is it possible using handgrip strength instead of body mass index in MNA-SF test to assess the nutritional status of geriatric patients?

Introduction

In Mini-Nutritional Assessment-Short Form (MNA-SF) test, a practical and reliable alternative parameter is still necessary for patients with difficult body mass index evaluation. We aimed to show whether or not handgrip strength may be used instead of body mass index (BMI) in MNA-SF test.

Materials and Methods

MNA-SF test scores, calf circumferences (CC), handgrip strength (HGS), and BMI of 191 patients were evaluated. The first one of calculated MNA-SF tests was with BMI, the second one with CC, and the last one with HGS. Zero point was given if CC was <31 cm and 3 points were given if CC was ≥31 cm. Zero, 1, 2, and 3 points were given if the loss of HGS when compared to expected HGS were ≥%60, from ≥%30 to <%60, from ≥%10 to <%30, and <%10 or greater than expected HGS, respectively. MNA-SF scores and nutritional status according to these three measures were compared.

Results

Mean age and median MNA-SF scores of the patients were 75±7.6 years and 12 points (min-max: 0-14) respectively. There were strongly positive correlations between MNA-SF scores with BMI and CC, with BMI and HGS, and with CC and HGS (r=0.938 p<0.001, r=0.938 p<0.001, r=0.914 p<0.001, respectively). Substantial agreement in nutritional status of the patients were seen between MNA-SF groups with BMI and CC, with CC and HGS, and with BMI and HGS (kappa: 0.795 p<0.001, kappa: 0.709 p<0.001, and kappa: 0.760 p<0.001, respectively).

Conclusions

HGS might be considered instead of BMI in MNA-SF test to assess nutritional status of geriatric patients.

     

Monocyte/high-density lipoprotein ratio predicts the mortality in ischemic stroke patients

Objective

The inflammatory process is a very important stage in the development and prognosis of acute ischemic stroke (AIS). The monocyte to high-density lipoprotein (HDL) ratio (MHR) is accepted as a novel marker for demonstrating inflammation. However, the role of MHR as a predictor of mortality in patients with AIS remains unclear.