Renal microangiopathies and membranoproliferative GN (MPGN) can manifest similar clinical presentations and histology, suggesting the possibility of a common underlying mechanism in some cases. Here, we performed homozygosity mapping and whole exome sequencing in a Turkish consanguineous family and identified DGKE gene variants as the cause of a membranoproliferative-like glomerular microangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN. This gene encodes the diacylglycerol kinase DGK«, which is an intracellular lipid kinase that phosphorylates diacylglycerol to phosphatidic acid. Immunofluorescence confocal microscopy demonstrated that mouse and rat Dgk« colocalizes with the podocyte marker WT1 but not with the endothelial marker CD31. Patch-clamp experiments in human embryonic kidney (HEK293) cells showed that DGK« variants affect the intracellular concentration of diacylglycerol. Taken together, these results not only identify a genetic cause of a glomerular microangiopathy but also suggest that the phosphatidylinositol cycle, which requires DGKE, is critical to the normal function of podocytes.

Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic ‘crown-like structure (CLS)’ around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte–macrophage–breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1–TSC2 complex–mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte–macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin–estrogen–macrophage axis, and sirtuin 1 (SIRT1)–adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines.

Topical CsA treatment appears to improve the signs and symptoms of dry eye and inhibits apoptosis and MMP-9 expression in conjunctival epithelial cells in TO-related dry eye patients after 2 months of treatment.

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BackgroundBreast carcinomas can be classified into five subtypes based on gene expression profiling or immunohistochemical characteristics. Among these subtypes, basal-like breast carcinomas (BLBCs) are one of the most studied group, due to their poor prognosis. The aim of this study was to investigate the prevalance, morphological and immunohistochemical features of BLBCs, in Turkish population.MethodsFive hundred invasive breast carcinomas were reviewed for several morphological features and immunostained for oestrogen and progesterone receptors, c-ERB-B2, cytokeratin5/6, cytokeratin14, vimentin and epidermal growth factor receptor (EGFR). Basal-like breast carcinoma was defined as a triple negative tumor with cytokeratin5/6 and/or EGFR positive.ResultsThe prevalance of BLBC was 9.6%. All medullary carcinomas and 55.6% of metaplastic carcinomas showed basal-like immunophenotype. Patients with BLBC were younger (p=0.04) and had higher-grade tumors (p<0.0001). Morphologic features associated with BLBC included increased mitosis, nuclear pleomorphism, presence of geographic and/or central necrosis, pushing margin of invasion and stromal lymphocytic response (p<0.0001). Presence of prominent nucleoli and vesicular nuclear chromatin were the cytological features correlated with basal-like phenotype (p<0.0001). On multivariate analyses, BLBCs were associated with high mitotic number (p<0.0001), the presence of vesicular chromatin (p=0.004), high tubular grade (p=0.011), lymphocytic response (p=0.031) and the absence of carcinoma insitu (p=0.039). Vimentin was positive in 53.2% of BLBCs, while cytokeratin14 was less frequently expressed (27.7%).ConclusionsBLBCs have some distinctive, but not pathognomonical, morphological features. Paying attention to these features and adding cytokeratin14 and vimentin to the immunohistochemical panel can help the definitive diagnosis of BLBCs.Virtual slideHttp://www.diagnosticpathology.diagnomx.eu/vs/5962175467857400

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Mycophenolate mofetil (MMF) is considered to be a promising therapeutic agent in primary glomerulonephritis but there are no data on the use of MMF in Henoch-Schönlein nephritis (HSN). Herein we report the first adult crescentic HSN patient in whom long-term complete remission was achieved after MMF therapy.

AIM: Topical hemostatic agents are widely used in brain surgery but they have some disadvantages such as foreign body reaction, being a focus for infection and causing artifacts in radiological examinations. The purpose of this study is to compare the effectiveness and safety of microporous polysaccharide hemospheres (MPH) with a well known agent, oxidized regenerated cellulose (ORC), histopathologically and radiologically. MATeRIAL and MeTHodS: Standard brain lesions (4x1mm) were created in 24 hemispheres in 12 New-Zealand rabbits. Animals were divided into three groups; control, ORC and MPH. Twenty-four hours later, all rabbits magnetic resonance brain imaging. After imaging, the animals were sacrificed and the brains were removed for histopathological analysis. ReSULTS: Histopathological analysis showed no significant difference between the groups. Radiological examination showed no significant difference between the MPH and ORC groups in terms of edema but the edema in control group was significantly prominent than MPH and ORC groups (p<0.001). CoNCLUSIoN: A new agent (MPH) provides safe and effective hemostasis in the brain in this study. The most important advantage of microporous polysaccharide hemospheres is their rapid clearance from the surgical field and therefore having the potential of causing less imaging artifacts.