Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Disruption of Conscious Access in Psychosis Is Associated with Altered Structural Brain Connectivity

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in long-distance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis.     

Sentinel lymph node localization and staging with a low-dose of superparamagnetic iron oxide (SPIO) enhanced MRI and magnetometer in patients with cutaneous melanoma of the extremity - The MAGMEN feasibility study

BackgroundIn patients with melanoma, sentinel lymph node (SLN) status is pivotal for treatment decisions. Current routine for SLN detection combines Technetium^99m (Tc⁹⁹) lymphoscintigraphy and blue dye (BD). The primary aim of this study was to examine the feasibility of using a low dose of superparamagnetic iron oxide (SPIO) injected intracutaneously to detect and identify the SLN, and the secondary aim was to investigate if a low dose of SPIO would enable a preoperative MRI-evaluation of SLN status.MethodsPatients with melanoma of the extremities were eligible. Before surgery, a baseline MRI of the nodal basin was followed by an injection of a low dose (0.02–0.5 mL) of SPIO and then a second MRI (SPIO-MRI). Tc⁹⁹ and BD was used in parallel and all nodes with a superparamagnetic and/or radioactive signal were harvested and analyzed.ResultsFifteen patients were included and the SLNB procedure was successful in all patients (27 SLNs removed). All superparamagnetic SLNs were visualized by MRI corresponding to the same nodes on scintigraphy. Micrometastatic deposits were identified in four SLNs taken from three patients, and SPIO-MRI correctly predicted two of the metastases. There was an association between MRI artefacts in the lymph node and the dose SPIO given.DiscussionIt is feasible to detect SLN in patients with melanoma using a low dose of SPIO injected intracutaneously compared with the standard dual technique. A low dose of SPIO reduces the lymph node MRI artefacts, opening up for a non-invasive assessment of SLN status in patients with cancer.     

Interleukin-34 drives macrophage polarization to the M2 phenotype in autoimmune hepatitis

BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation.     

Lycopene and resveratrol ameliorate zinc oxide nanoparticles-induced oxidative stress in Nile tilapia,Oreochromis niloticus

Industrial products contained nano-zinc oxide (ZnONP) can gain access to the aquaculture environment causing hazardous effects on the living biota. Therefore, this work was planned to examine the ameliorative effects of dietary supplementation of lycopene (LYC) and/or resveratrol (RES) against ZnONP toxicity in Nile tilapia. Five groups with 20 fish each were used; Control, received tap water only; ZnONP group, was intoxicated with ZnONP (50 mg/L); ZnONP-LYC group, was exposed to ZnONP and LYC (500 mg/ kg of the diet); ZnONP-RES group, was exposed to ZnONP and RES (50 mg/kg of the diet); ZnONP-LYC-RES group, was exposed to ZnONP and a combination of LYC and RES. The experiment was continued for 30 days. Fish blood and tissues were then assembled for determination of liver and kidney function and oxidative stress status in liver, kidney, and gills tissue. Results revealed a considerable elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), cholesterol, urea, and creatinine with a noticeable lowering of total proteins and albumin serum levels in response to ZnONP intoxication. In addition, there were significant increase in malondialdehyde (MDA) and reduction in the reduced-glutathione (GSH) levels and superoxide dismutase (SOD) and catalase (CAT) activities. However, treatment with LYC and/or RES ameliorated the ZnONP-inflicted oxidative stress which possibly attributed to their beneficial antioxidant activities.     

Case of metastatic glioblastoma with primitive neuronal component to the lung

Glioblastoma (GBM) with primitive neuronal component (GBM‐PNC) is a rare GBM subtype recently categorized by the World Health Organization in the revised classification system of 2016. Extracranial metastases originating from GBM‐PNC are rare and metastasis to solid organs has never been reported. Herein, we present the first case of metastasis of GBM‐PNC to the lung. A 49‐year‐old man presenting with headache was diagnosed with multiple tumors adhering to the dura matter in the right temporal lobe. Despite surgery and chemoradiotherapy, 2 months after the initial therapy, the patient presented with CSF dissemination and lung metastases. The patient succumbed to the disease 12 months after the first surgery. We discuss the possibility that GBM‐PNC may constitute a subtype of glioma with particularly poor prognosis, tending to dissemination and metastasis. Our results suggest that a complementary regular inspection of the whole body via CT may be recommended for the follow‐up of patients with GBM‐ PNC.