Malignant peripheral nerve sheath tumors (MPNST) represent a group of highly heterogeneous human malignancies often with multiple histological origins, divergent differentiation patterns, and diverse immunohistochemical presentations. The differential diagnosis of MPNST from other spindle cell neoplasms poses great challenges for pathologists. This report provides a mini-review of these unique features associated with MPNST and also presents the first cases of MPNST with six differentiation patterns.

Oxidative stress plays a critical role in the pathophysiology of contrast-induced nephropathy (CIN). Since the specific treatment of CIN remains an unmet medical need, it is imperative to find an effective strategy against the clinical management of CIN. The transcription factor Nrf2 is known to regulate antioxidative stress response. The aim of the present study was to assess the effects of tert-butylhydroquinone (t-BHQ), an activator of Nrf2, in the prevention of CIN and elucidate the underlying mechanism of its action in vitro and in vivo. We established a rat model of CIN and treated the animals with t-BHQ (25 mg/kg). The effects of t-BHQ treatment on CIN rats were elucidated by assessing renal function, HE staining, immunohistochemistry, and western blotting. We also studied the activity of oxidative stress-related markers, such as intracellular ROS level, MDA level, SOD2 activity, and GSH/GSSG ratio. We validated our results by siRNA-mediated silencing of Nrf2 in HK-2 cells exposed to the radiocontrast agent. Treatment with t-BHQ significantly ameliorated the renal function and the histopathological lesions in CIN rats. Further, pretreatment with t-BHQ significantly increased the SOD2 activity and GSH/GSSG ratio and decreased the levels of ROS and MDA in animals subjected to ioversol exposure. In addition, t-BHQ treatment increased the expression of Nrf2, Sirt3, and SOD2 and concomitantly decreased the expression of acetylated-SOD2. When Nrf2-silenced HK-2 cells were exposed to radiocontrast agent, they suffered severe cell oxidative stress, exhibited lower expression of Sirt3 and SOD2, and expressed higher levels of acetylated-SOD2; however, t-BHQ treatment did not affect the protein expression of these indicators in si-Nrf2 HK-2 cells. Our findings suggested that Nrf2 plays an important role in the regulation of the Sirt3/SOD2 antioxidative pathway, and t-BHQ may be a potential agent to ameliorate radiocontrast-induced nephropathy via activating the Nrf2/Sirt3/SOD2 signaling pathway in vitro and in vivo.

Background Renal impairment (RI) is associated with poor survival in newly diagnosed multiple myeloma (MM) patients. Renal function recovery has been one of the main therapeutic goals in those patients. Methods The records from 393 newly diagnosed MM patients in our hospital between January 2012 and December 2016 were retrospectively analyzed. RI was defined as an eGFR < 40 mL/min according to the novel IMWG criteria. RI patients were categorized based on their renal function at diagnosis: severe RI: eGFR < 30 mL/min, and mild RI: 30 mL/min ≤ eGFR <40 mL/min. We explored whether RI, and particularly severe RI, was an adverse prognostic factor for survival, and investigated the impact of renal function recovery on survival. Results Severe RI, hemoglobin <100 g/L, LDH ≥ 245 U/L, hyperuricemia, 1q21 amplification, and lack of novel agent treatment were associated with decreased overall survival (OS). Severe RI patients with renal response had a median OS of 27 months compared with 18 months for those patients without renal response (P = .030), but their median OS was still significantly lower than that for patients without severe RI, which was 51 months. In severe RI patients, the overall renal response rate in bortezomib‐based regimens was significantly higher than that in nonbortezomib‐based regimens. Conclusion Our results suggest that severe RI is an adverse prognostic factor for survival in newly diagnosed MM patients, restoration of renal function may improve survival, and bortezomib‐based regimens may be the preferred treatment in patients with severe RI.

BackgroundA great number of studies reported that 12/15-lipoxygenase (12/15-LO) played an important role in atherosclerosis. And its arachidonic acid(AA) metabolite, 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15(S)-HETE), is demonstrated to mediate endothelial dysfunction. 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) was formed from 15-hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-HETE. However, relatively little is known about the biological effects of 15-oxo-ETE in cardiovascular disease. Here, we explore the likely role of 15-lipoxygenase (LO)-1-mediated AA metabolism,15-oxo-ETE, in the early pathogenesis of atherosclerosis.MethodsThe 15-oxo-ETE level in serum was detected by means of liquid chromatography and online tandem mass spectrometry (LC-MS/MS). And the underlying mechanisms were illuminated by molecular techniques, including immunoblotting, MTT assay, immunocytochemistry and Immunohistochemistry. ResultsIncreased 15-oxo-ETE level is found in in patients with acute myocardial infarction (AMI). After 15-oxo-ETE treatment, Human umbilical vein endothelial cells (HUVECs) showed more attractive to monocytes, whereas monocyte adhesion is suppressed when treated with PKC inhibitor. In ex vivo study, exposure of arteries from C57 mice and ApoE−/−mice to 15-oxo-ETE led to significantly increased E-selectin expression and monocyte adhesion.ConclusionsThis is the first report that 15-oxo-ETE promotes early pathological process of atherosclerosis by accelerating E-selectin expression and monocyte adhesion. 15-oxo-ETE -induced monocyte adhesion is partly attributable to activation of PKC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0518-2) contains supplementary material, which is available to authorized users.

Ischemia/reperfusion may induce inflammation and cell death through the nuclear factor (NF)‑κB signaling pathway. As a negative regulator of NF‑κB, zinc finger A20 exhibits anti-apoptotic and anti‑inflammatory effects in vitro. The present study was designed to upregulate A20 expression using an A20 transfection approach to investigate the in vivo protective effects of the A20 gene on renal ischemia reperfusion injury. The A20 gene was cloned into a pcDNA3.1 vector to construct the expression plasmid pcDNA3.1‑A20. The plasmid was wrapped with a liposome and injected intravenously into rats 48 h prior to establishing the models of renal ischemia reperfusion injury. Saline and the empty plasmid pcDNA3.1 were used as controls. Following 24 h post‑operation, A20 expression was determined using reverse transcription‑quantitative polymerase chain reaction and western blotting. The renal function and structure were assessed by analyzing the concentrations of serum creatinine (Scr), blood urea nitrogen (BUN) and histological features. Renal tissues were additionally examined for renal tubular cell apoptosis and NF‑κB activity. The results demonstrated that in vivo transfection of pcDNA3.1‑A20 induced renal A20 expression in rats. A20 overexpression in vivo significantly reduced renal injury as demonstrated by the improved levels of Scr and BUN and the reduction in histological damage. These improvements were accompanied by a suppression of renal proximal tubular epithelial cell apoptosis and an inhibition of NF‑κB activity. These results indicated that transfection of the A20 gene upregulates the expression of A20 in vivo and protects the kidneys from ischemia reperfusion injury via inhibition of the NF‑κB signal transduction pathway.