The Nrf2/ARE Pathway: A Promising Target to Counteract Mitochondrial Dysfunction in Parkinson's Disease

Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases as strict regulation of integrated mitochondrial functions is essential for neuronal signaling, plasticity, and transmitter release. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD). Several PD-associated genes interface with mitochondrial dynamics regulating the structure and function of the mitochondrial network. Mitochondrial dysfunction can induce neuron death through a plethora of mechanisms. Both mitochondrial dysfunction and neuroinflammation, a common denominator of PD, lead to an increased production of reactive oxygen species, which are detrimental to neurons. The transcription factor nuclear factor E2-related factor 2 (Nrf2, NFE2L2) is an emerging target to counteract mitochondrial dysfunction and its consequences in PD. Nrf2 activates the antioxidant response element (ARE) pathway, including a battery of cytoprotective genes such as antioxidants and anti-inflammatory genes and several transcription factors involved in mitochondrial biogenesis. Here, the current knowledge about the role of mitochondrial dysfunction in PD, Nrf2/ARE stress-response mechanisms, and the evidence for specific links between this pathway and PD are summarized. The neuroprotection of nigral dopaminergic neurons by the activation of Nrf2 through several inducers in PD is also emphasized as a promising therapeutic approach

Optimization of PERC fabrication based on loss analysis in an industrially relevant environment: First results from GUNAM photovoltaic line (GPVL)

Passivated emitter and rear cell (PERC) concept with an already developed roadmap for 24% efficiency will be leading the photovoltaics industry in the upcoming years. In a few industrial pilot lines, efficiencies above 22% have already been attained. Pilot lines have important roles in bridging lab scale proven concepts with the products which are ready for mass production. Therefore, GUNAM Photovoltaic Line which is specialized on PERC concepts has been established to overcome the barriers that hinder the performance of c-Si solar cells in PERC concepts in a relevant environment. The aim of this article is to show how a loss analysis can be employed in a practical way in an industrially relevant environment. The analysis depends on the first results of the studies from 6 months ramp up period of GPVL A batch of standard PERC type solar cells with p-type base and atomic layer deposited Al2O3 rear passivation have been fabricated during the ramp up of the line. A detailed gain-loss analysis was performed to address the optical, electrical and recombination losses in order to increase the cell efficiency

Mesenchymal Stem Cells Combined With IFN gamma Induce Apoptosis of Breast Cancer Cells Partially Through TRAIL

Background: Mesenchymal stem cells (MSCs) have gained remarkable attention because of their ability to dualistically regulate tumor growth. The main objective of this study was to evaluate the apoptotic effects of human bone marrow-derived (hBM) MSCs in combination with interferon gamma (IFN-gamma) on MCF-7 breast cancer cells, and to determine the cytokines involved in the apoptotic process. Materials and Methods: hBM-MSCs were co-cultured with MCF-7 cells either directly and indirectly for 72 h in-vitro. Levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), apoptosis and cytokines were analyzed. Results: hBM-MSCs increased the apoptosis of MCF-7 cells partially through TRAIL in vitro. IFN-gamma enhanced the apoptotic effect of hBM-MSCs (p<0.001). Conclusion: hBM-MSCs in combination with IFN-gamma might be a suitable therapy for breast cancer

APJ receptor A445C gene polymorphism in Turkish patients with coronary artery disease

Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (chi(2) = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (chi(2) = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P <= 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD

Cutaneous manifestations in pediatric oncology patients

Background/Objectives Oncology patients present with various skin manifestations related to primary disease and treatments. Although these skin toxicities are well described in adults, studies of pediatric oncology patients are limited. The objective of this study was to evaluate the cutaneous findings in pediatric oncology patients receiving chemotherapy

Laser induced periodic surface structured c-Si solar cell with more than 16% efficiency

Crystalline-Si (c-Si) based solar cells (SC) efficiency remains one of the most challenging part in photovoltaic industry. Besides of the thermodynamical limits, the optical losses due to indirect band-gap structure of the material require additional treatment which known as a photonic design of the SC surface [1]. Numerous manipulations are performed to increase the efficiency of commercial solar cells. In most of these methods, the main concept is increasing light interaction by the cell through chemical modification of the morphology of the surface. Creation of pyramid-like structure on SC surface through the chemical etching by KOH solution is the most common industrial method nowadays. Recently we proposed Nonlinear Laser Lithography (NLL) as an alternative method for the traditional chemical etching [2]. The method is based on the well known phenomenon Laser Induced Periodic Surface Structuring (LIPSS), allowing creation of wellordered, periodic ablation and/or oxidation lines on the material surface with subwavelength period under ultrashort pulse laser illumination. In comparison with the traditional chemical treatment, the method is cheap, single-step and chemically free. However, the damage of the crystalline structure of the SC surface during ablation limiting the final efficiency of the device. In the current work, we demonstrate the new achievement in the efficiency of c-Si solar cell based on NLL treated surface. By proper design of the laser parameters and the scanning geometry during the NLL process, as well as proper post-passivation of the SC surface, we demonstrate more than 16% efficiency of the final device. To the best of our knowledge, this is the highest efficiency demonstrated so far on a laser treated c-Si solar cell without any chemical texturing

Laser Induced Periodic Surface Structured c-Si Solar Cell with more than 16% efficiency

Crystalline-Si (c-Si) based solar cells (SC) efficiency remains one of the most challenging part in photovoltaic industry. Besides of the thermodynamical limits, the optical losses due to indirect band-gap structure of the material require additional treatment which known as a photonic design of the SC surface [1]. Numerous manipulations are performed to increase the efficiency of commercial solar cells. In most of these methods, the main concept is increasing light interaction by the cell through chemical modification of the morphology of the surface. Creation of pyramid-like structure on SC surface through the chemical etching by KOH solution is the most common industrial method nowadays. Recently we proposed Nonlinear Laser Lithography (NLL) as an alternative method for the traditional chemical etching [2]. The method is based on the well known phenomenon Laser Induced Periodic Surface Structuring (LIPSS), allowing creation of wellordered, periodic ablation and/or oxidation lines on the material surface with subwavelength period under ultrashort pulse laser illumination. In comparison with the traditional chemical treatment, the method is cheap, single-step and chemically free. However, the damage of the crystalline structure of the SC surface during ablation limiting the final efficiency of the device. In the current work, we demonstrate the new achievement in the efficiency of c-Si solar cell based on NLL treated surface. By proper design of the laser parameters and the scanning geometry during the NLL process, as well as proper post-passivation of the SC surface, we demonstrate more than 16% efficiency of the final device. To the best of our knowledge, this is the highest efficiency demonstrated so far on a laser treated c-Si solar cell without any chemical texturing

K-RAS and N-RAS mutations in testicular germ cell tumors

Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5 non-seminoma cases (26%) [p = 0.55]. AK-RAS mutation was present in 4 pure seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: One with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors