Parkinson's disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GLUD2 mutation in MPTP-induced PD mice exacerbates movement deficits and nigral dopaminergic neuron death and reduces glutamate transporters expression and function. Using GC-Q-TOF/MS-based metabolomics, we determined that GLUD2 mutation damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the tricarboxylic acid cycle in the SN of MPTP-induced PD mice. Accordingly, GLUD2 mutant mice had reduced energy metabolism and increased apoptosis, possibly due to downregulation of brain-derived neurotrophic factor/nuclear factor E2-related factor 2 signaling in in vitro and in vivo PD models. Collectively, our findings verify the function of GLUD2 in PD and unravel a mechanism by which a genetic variant in human GLUD2 may contribute to disease onset.BACKGROUND Cardiac lymphomas can lead to heart block through tumor disruption of the cardiac conduction system. It is reported that with cardiac tumor treatment, conduction abnormalities can resolve. We present a case of cardiac lymphoma resulting in complete heart block requiring a pacemaker, followed by reduction of the pacing burden after chemotherapy. CASE REPORT A 72-year-old woman with a medical history of hypertension, hypothyroidism, and persistent atrial fibrillation presented with dyspnea on exertion and fatigue for 2 weeks. Electrocardiography revealed complete heart block with junctional bradycardia of 48 beats per min. Transthoracic echocardiography demonstrated preserved left ventricular systolic function along with a large mass (3.6×3.7 cm). An endomyocardial biopsy was consistent with diffuse large B cell lymphoma, and the cardiac involvement was thought to be secondary based on positron emission tomography scan findings. Her clinical course was complicated by an episode of syncope deemed to be due to transient asystole, and an urgent single-chamber permanent pacemaker was implanted. Chemotherapy was initiated with R-CHOP, and, following the second cycle of chemotherapy, a positron emission tomography scan revealed no increased radiotracer uptake and thus resolution of all tumors. An echocardiogram 6 weeks after chemotherapy showed complete resolution of the cardiac mass. Subsequent serial pacemaker checks demonstrated improvement of atrioventricular nodal function as manifested by reduced pacing burden. CONCLUSIONS Lymphoma with cardiac involvement can lead to conduction abnormalities, including CHB, and heart block in the setting of these tumors may be reversible with appropriate therapy; however, implantation of a pacemaker remains inevitable is some cases.BACKGROUND Preeclampsia (PE) remains one of the primary causes of maternal morbidity and mortality worldwide. This study was designed to investigate the relevance of long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) and downstream molecules in trophoblast cell proliferation and apoptosis.  https://www.selleckchem.com/products/BIBF1120.html  MATERIAL AND METHODS NEAT1 expression in the placental tissues of rats with PE was analyzed by reverse transcriptionquantitative polymerase chain reaction. The role of NEAT in trophoblast cell proliferation, migration, invasion, and apoptosis was assessed by transfecting pcDNA-NEAT1 and siRNA-NEAT1 into trophoblast cells. The microRNA (miRNA) binding to NEAT1 and the genes targeted by the screened miRNAs were predicted by Starbase, and the mechanism of action of NEAT1 in PE was further investigated. RESULTS The expression of NEAT1 lncRNA was markedly higher in placental samples of PE than control rats. Ectopic expression of NEAT1 repressed trophoblast cell proliferation, migration, invasion, and colony formation, but facilitated cell apoptosis, whereas NEAT1 downregulation resulted in the opposite effects. NEAT1 was found to act as a molecular sponge for miR-373, regulating Fms-like tyrosine kinase-1 (FLT-1) to modulate PE development. CONCLUSIONS NEAT1 may contribute to PE development by regulating trophoblast cell proliferation and apoptosis. These findings may provide a new perspective for understanding the etiology and pathogenesis of PE.BACKGROUND The treatment of complex tumors in non-functioning renal transplants requiring surgical extirpation is challenging. Here, we report the largest series of patients who underwent transplant radical nephrectomy for renal cell carcinoma (RCC) and transplant radical nephroureterectomy for urothelial cell carcinoma (UCC) in their transplanted kidneys. MATERIAL AND METHODS From 2004 to 2018, 10 patients underwent transplant radical nephrectomy (7 patients) and nephroureterectomy (3 patients). Retrospective analyses, in terms of complications, oncological recurrence, and survival, of peri-operative and long-term outcomes, were performed. RESULTS Out of the 10 patients, 7 had RCC and 3 had UCC. No intraoperative mortality occurred. Three patients presented with Clavien-Dindo grade IIIa or greater within 30 days of surgery. Two patients died within 60 days of surgery, both due to vascular events one due to myocardial infarction and one due to stroke. Two other patients died one after 2.9 years, due to myocardial infarction, and the other after 6 years, due to unknown reasons. At the 7-year follow-up, there was a 60% overall survival rate. For all patients, average survival post-nephrectomy was approximately 4.5 years, including the 6 living patients and 4 deceased patients. Importantly, there was no observed cancer recurrence. CONCLUSIONS This study reports outcomes of the largest series of transplant radical nephrectomy and nephroureterectomy for malignancies of renal allografts. In the optimized setting, extirpative surgeries appear safe, with favorable long-term oncological and survival outcomes.