Protective effects of curcumin on antioxidant status, body weight gain, and reproductive parameters in male rats exposed to subchronic 2,3,7,8-tetrachlorodibenzo-p-dioxin

The aim of this study was to investigate the effects of curcumin (CUR) on antioxidant status, body weight (BW) gains, and some reproductive parameters in male rats exposed to subchronic doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Thirtytwo rats were divided into four groups. The first group was kept as control. The second group (TCDD group) was given TCDD at a dose of 50 ng kg 1 BW per day; the third group (CUR group) was treated with CUR at a dose of 80 mg kg 1 BW per day. The fourth group (TCDD þ CUR group) was given TCDD and CUR at the same doses simultaneously. Malondialdehyde (MDA) levels were significantly increased in the TCDD group. In addition, TCDD exposure decreased liver superoxide dismutase (SOD) activity, catalase (CAT) activities of kidney and brain, glutathione peroxidase (GSH-Px) activities of liver, kidney, and brain, and glutathione levels of liver, kidney, and heart. However, CUR treatment with TCDD exposure decreased MDA levels in all tissues and increased SOD activities of liver, kidney, and brain, CAT activity of heart, and GSH-Px activities of heart and brain. TCDD caused a decrease in BW gain, and CUR partially eliminated this effect of TCDD. In addition, while reproductive organ weights, sperm concentration, and sperm motility tended to decrease with TCDD exposure, these effects tended to be close to normal levels by CUR treatment. In conclusion, CUR was seen to be effective in the treatment and prevention of toxicity induced by subchronic TCDD exposure

Antiperoxidative and anti-apoptotic effects of lycopene and ellagic acid on cyclophosphamide-induced testicular lipid peroxidation and apoptosis

The present study was conducted to investigate the possible protective effects of lycopene (LC) and ellagic acid (EA) on cyclophosphamide (CP)-induced testicular and spermatozoal toxicity associated with the oxidative stress and apoptosis in male rats. Forty-eight healthy adult male Sprague-Dawley rats were divided into six groups of eight rats each. The control group was treated with placebo; the LC, EA and CP groups were given LC (10 mg kg−1), EA (2 mg kg−1) and CP (15 mg kg−1), respectively, alone; the CP+LC group was treated with a combination of CP (15 mg kg−1) and LC (10 mg kg−1); and the CP+EA group was treated with a combination of CP (15 mg kg−1) and EA (2 mg kg−1). All treatments were maintained for 8 weeks. At the end of the treatment period, bodyweight and the weight of the reproductive organs, sperm concentration and motility, testicular tissue lipid peroxidation, anti-oxidant enzyme activity and apoptosis (i.e. Bax and Bcl-2 proteins) were determined. Administration of CP resulted in significant decreases in epididymal sperm concentration and motility and significant increases in malondialdehyde levels. Although CP significantly increased the number of Bax-positive (apoptotic) cells, it had no effect on the number of Bcl-2-positive (anti-apoptotic) cells compared with the control group. However, combined treatment of rats with LC or EA in addition to CP prevented the development of CP-induced lipid peroxidation and sperm and testicular damage. In conclusion, CP-induced lipid peroxidation leads to structural and functional damage, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protect against the development of these detrimental effects

Attenuating effect of lycopene and ellagic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced spermiotoxicity and testicular apoptosis

This study was conducted to investigate the prophylactic effects of lycopene (LC) and ellagic acid (EA) on 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)-induced testicular and spermatozoal toxicity. These toxicological changes are associated with the oxidative stress and apoptosis in male rats. Forty-eight male rats were allocated to one of six groups of 8 rats each: control, LC, EA, TCDD, TCDD+LC, and TCDD+EA. The control group was treated with 0.5 mL/ rat slightly alkaline solution+0.5 mL/rat corn oil every other day. The LC group was treated with 0.5 mL/rat slightly alkaline solution+0.5 mL/rat corn oil containing 10 mg/kg of LC every other day. The EA group received 0.5 mL/rat corn oil+0.5 mL/rat slightly alkaline solution containing 2 mg/kg of EA every other day. The TCDD group received 0.5 mL/rat corn oil containing 100 ng/kg/day of TCDD+0.5 mL/rat slightly alkaline solution. The TCDD+LC group was treated with 0.5 mL/rat TCDD+0.5 mL/rat LC. The TCDD+EA group was treated with 0.5 mL/rat TCDD+0.5 mL/rat EA. All treatments were made by gavage, and the experimental period was maintained during 8 weeks. Sperm motility, concentration, and abnormal sperm rate in epididymal tissue, testicular tissue lipid peroxidation (LPO), antioxidant enzyme activity, histopathological changes, and apoptosis (i.e., Bax and Bcl-2 proteins) were determined. TCDD exposure resulted in significant decreases in sperm motility, concentration, testicular superoxide dismutase activity, germinal cell-layer thickness, Johnsen’s testicular score, and significant increases in abnormal sperm rate, testicular malondialdehyde, glutathione levels, Bax-positive staining, and Bax-positive apoptotic cell score, along with some testicular histopathological lesions. TCDD treatment did not affect significantly catalase activity. However, combined treatment with LC or EA, in addition to TCDD, prevented the development of TCDD-induced damages in sperm quality, testicular histology, and LPO. Improvements in testicular apoptosis after the administration of LC and EA to TCDD-treated rats were minimal, but not statistically significant. TCDD-induced lipid peroxidation leads to functional and structural damages, as well as apoptosis, in spermatogenic cells of rats. Both LC and EA protected against the development of these effect

Integrating Human-Centred Design Approach into Sustainable-Oriented 3D Printing Systems

Modern 3D printing systems have become pervasive and widely used both in professional and in informal contexts, including sustainable-oriented ones. However, the risk to create very effective but non-sustainable solutions is very high since 3D printing systems could potentially increase the environmental emergencies and the unsustainable growth. In the transition process toward sustainable ways of production and consumption, the so-called human factor still plays an important role in the achievement of sustainable-oriented actions; it drives the adoption of proper lifestyles that directly and indirectly influence the ways through which such technologies are used. Therefore, future Sustainable 3D Printing Systems should integrate the humans in the systems’ development. This study presents two important results: (a) it presents a set of interdisciplinary ‘Sustainable 3D Printing Systems’, which compose a promising sustainable-oriented scenario useful to support the transition processes toward sustainable designs and productions, and (b) it proposes a new strategy for the integration of human-centred aspects into Sustainable 3D Printing Systems, by combining insights from human-centred design approach

Matched pairs of human prostate stromal cells display differential tropic effects on LNCaP prostate cancer cells

Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells

Pore timing:the evolutionary origins of the nucleus and nuclear pore complex

The name “eukaryote” is derived from Greek, meaning “true kernel”, and describes the domain of organisms whose cells have a nucleus. The nucleus is thus the defining feature of eukaryotes and distinguishes them from prokaryotes (Archaea and Bacteria), whose cells lack nuclei. Despite this, we discuss the intriguing possibility that organisms on the path from the first eukaryotic common ancestor to the last common ancestor of all eukaryotes did not possess a nucleus at all—at least not in a form we would recognize today—and that the nucleus in fact arrived relatively late in the evolution of eukaryotes. The clues to this alternative evolutionary path lie, most of all, in recent discoveries concerning the structure of the nuclear pore complex. We discuss the evidence for such a possibility and how this impacts our views of eukaryote origins and how eukaryotes have diversified subsequent to their last common ancestor

TMPRSS2/ERG Promotes Epithelial to Mesenchymal Transition through the ZEB1/ZEB2 Axis in a Prostate Cancer Model

Prostate cancer is the most common non-dermatologic malignancy in men in the Western world. Recently, a frequent chromosomal aberration fusing androgen regulated TMPRSS2 promoter and the ERG gene (TMPRSS2/ERG) was discovered in prostate cancer. Several studies demonstrated cooperation between TMPRSS2/ERG and other defective pathways in cancer progression. However, the unveiling of more specific pathways in which TMPRSS2/ERG takes part, requires further investigation. Using immortalized prostate epithelial cells we were able to show that TMPRSS2/ERG over-expressing cells undergo an Epithelial to Mesenchymal Transition (EMT), manifested by acquisition of mesenchymal morphology and markers as well as migration and invasion capabilities. These findings were corroborated in vivo, where the control cells gave rise to discrete nodules while the TMPRSS2/ERG-expressing cells formed malignant tumors, which expressed EMT markers. To further investigate the general transcription scheme induced by TMPRSS2/ERG, cells were subjected to a microarray analysis that revealed a distinct EMT expression program, including up-regulation of the EMT facilitators, ZEB1 and ZEB2, and down-regulation of the epithelial marker CDH1(E-Cadherin). A chromatin immunoprecipitation assay revealed direct binding of TMPRSS2/ERG to the promoter of ZEB1 but not ZEB2. However, TMPRSS2/ERG was able to bind the promoters of the ZEB2 modulators, IL1R2 and SPINT1. This set of experiments further illuminates the mechanism by which the TMPRSS2/ERG fusion affects prostate cancer progression and might assist in targeting TMPRSS2/ERG and its downstream targets in future drug design efforts

Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease

Microbial diversity and biogeochemical cycling in soda lakes

Soda lakes contain high concentrations of sodium carbonates resulting in a stable elevated pH, which provide a unique habitat to a rich diversity of haloalkaliphilic bacteria and archaea. Both cultivation-dependent and -independent methods have aided the identification of key processes and genes in the microbially mediated carbon, nitrogen, and sulfur biogeochemical cycles in soda lakes. In order to survive in this extreme environment, haloalkaliphiles have developed various bioenergetic and structural adaptations to maintain pH homeostasis and intracellular osmotic pressure. The cultivation of a handful of strains has led to the isolation of a number of extremozymes, which allow the cell to perform enzymatic reactions at these extreme conditions. These enzymes potentially contribute to biotechnological applications. In addition, microbial species active in the sulfur cycle can be used for sulfur remediation purposes. Future research should combine both innovative culture methods and state-of-the-art ‘meta-omic’ techniques to gain a comprehensive understanding of the microbes that flourish in these extreme environments and the processes they mediate. Coupling the biogeochemical C, N, and S cycles and identifying where each process takes place on a spatial and temporal scale could unravel the interspecies relationships and thereby reveal more about the ecosystem dynamics of these enigmatic extreme environments