The expression of HER-2/neu (c-erbB2), survivin and cycline D1 in serous ovarian neoplasms: their correlation with clinicopathological variables

Ovarian cancer is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of HER-2/neu (c-erbB2), survivin and cycline D1 biomarkers in serous ovarian neoplasms and their correlations with clinicopathological variables in serous ovarian cancers. We analyzed pathological specimens of 62 patients with benign (n = 25), borderline (n = 14) and malignant (n = 23) serous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Significantly more immunoreactivity with HER-2/neu was detected in malignant tumors (100 %) compared to borderline (78.6 %) and benign tumors (48 %) (P < 0.01). Survivin expression was significantly higher in malignant tumors (91.3 %) than those found in borderline (71.4 %) and benign tumors (24 %) (P < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (95.6 %) compared to borderline (85.7 %) and benign tumors (48 %) (P < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant serous tumors. In terms of clinicopathological variables, only tumor grade was associated with the expression of all biomarkers others exhibited different correlations in serous ovarian cancers. The expressions of HER-2/neu (c-erbB2), survivin and cycline D1 are positively correlated with the malignant potential of serous ovarian neoplasms.     

The production of recombinant cationic α‐helical antimicrobial peptides in plant cells induces the formation of protein bodies derived from the endoplasmic reticulum

Synthetic linear antimicrobial peptides with cationic α‐helical structures, such as BP100, are valuable as novel therapeutics and preservatives. However, they tend to be toxic when expressed at high levels as recombinant peptides in plants, and they can be difficult to detect and isolate from complex plant tissues because they are strongly cationic and display low extinction coefficient and extremely limited immunogenicity. We therefore expressed BP100 with a C‐terminal tag which preserved its antimicrobial activity and demonstrated significant accumulation in plant cells. We used a fluorescent tag to trace BP100 following transiently expression in Nicotiana benthamiana leaves and showed that it accumulated in large vesicles derived from the endoplasmic reticulum (ER) along with typical ER luminal proteins. Interestingly, the formation of these vesicles was induced by BP100. Similar vesicles formed in stably transformed Arabidopsis thaliana seedlings, but the recombinant peptide was toxic to the host during latter developmental stages. This was avoided by selecting active BP100 derivatives based on their low haemolytic activity even though the selected peptides remained toxic to plant cells when applied exogenously at high doses. Using this strategy, we generated transgenic rice lines producing active BP100 derivatives with a yield of up to 0.5% total soluble protein.     

A SGLT2 inhibitor dapagliflozin suppresses prolonged ventricular-repolarization through augmentation of mitochondrial function in insulin-resistant metabolic syndrome rats

Background

Metabolic syndrome (MetS) is a prevalent risk factor for cardiac dysfunction. Although SGLT2-inhibitors have important cardioprotective effects in hyperglycemia, their underlying mechanisms are complex and not completely understood. Therefore, we examined mechanisms of a SGLT2-inhibitor dapagliflozin (DAPA)-related cardioprotection in overweight insulin-resistant MetS-rats comparison with insulin (INSU), behind its glucose-lowering effect.

Methods

A 28-week high-carbohydrate diet-induced MetS-rats received DAPA (5 mg/kg), INSU (0.15 mg/kg) or vehicle for 2 weeks. To validate MetS-induction, we monitored all animals weekly by measuring body weight, blood glucose and HOMO-IR index, electrocardiograms, heart rate, systolic and diastolic pressures.

Results

DAPA-treatment of MetS-rats significantly augmented the increased blood pressure, prolonged Q–R interval, and low heart rate with depressed left ventricular function and relaxation of the aorta. Prolonged-action potentials were preserved with DAPA-treatment, more prominently than INSU-treatment, at most, through the augmentation in depressed voltage-gated K⁺-channel currents. DAPA, more prominently than INSU-treatment, preserved the depolarized mitochondrial membrane potential, and altered mitochondrial protein levels such as Mfn-1, Mfn-2, and Fis-1 as well as provided significant augmentation in cytosolic Ca²⁺-homeostasis. Furthermore, DAPA also induced significant augmentation in voltage-gated Na⁺-currents and intracellular pH, and the cellular levels of increased oxidative stress, protein-thiol oxidation and ADP/ATP ratio in cardiomyocytes from MetS rats. Moreover, DAPA-treatment normalized the increases in the mRNA level of SGLT2 in MetS-rat heart.

Conclusions

Overall, our data provided a new insight into DAPA-associated cardioprotection in MetS rats, including suppression of prolonged ventricular-repolarization through augmentation of mitochondrial function and oxidative stress followed by improvement of fusion–fission proteins, out of its glucose-lowering effect.

     

The effect of astaxanthin and cadmium on rat erythrocyte G6PD, 6PGD,GR, and TrxR enzymes activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro

In this study, the effects of astaxanthin (AST) that belongs to carotenoid family and cadmium (Cd), which is an important heavy metal, on rat erythrocyte G6PD, 6PGD, GR, and TrxR enzyme activities in vivo and on rat erythrocyte 6PGD enzyme activity in vitro were studied. In in vitro studies, 6PGD enzyme was purified from rat erythrocytes with 2′,5′‐ADP Sepharose4B affinity chromatography. Results showed inhibition of enzyme by Cd at IC₅₀; 346.5 μM value and increase of 6PGD enzyme activity by AST. In vivo studies showed an increase in G6PD, 6PGD, and GR enzyme activities (P ? 0.05) and no chance in TrxR enzyme activity by AST. Cd ion inhibited G6PD, 6PGD, and GR enzyme activities (P ? 0.05) and also decreased TrxR enzyme activity (P ? 0.05). AST + Cd group G6PD enzyme activity was statistically low compared with control group (P ? 0.05). 6PGD and TrxR enzyme activities decreased without statistical significance (P ? 0.05); however, GR enzyme activity increased statistically significantly (P ? 0.05).     

A new species of Petroleuciscus (Teleostei: Cyprinidae) from the Büyük Menderes River,southwestern Anatolia,Turkey

Petroleuciscus ninae sp. nov. is described from the Büyük Menderes River drainage. The new species is distinguished by having a black lateral stripe from head to base of caudal fin, stripe distinct anteriorly and posteriorly, wider than eye diameter; numerous black pigments on anal‐fin rays; body depth at dorsal‐fin origin 27–30% standard length (L_S); head width at posterior margin of eye 16–19% L_S; and eye diameter smaller than snout length. Petroleuciscus ninae is also distinguished from other species in adjacent waters by having six fixed diagnostic nucleotide substitutions in the mitochondrial DNA coI barcode region.     

Investigation of Heavy Metal Level and Mineral Nutrient Status in Widely Used Medicinal Plants’ Leaves in Turkey: Insights into Health Implications

The use of plants in treatments has been as old as humanity and it has preserved its popularity for centuries til now because of their availability, affordability and safeness. However, despite their widespread use, safety and quality issues have been major concerns in the world due to industrial- and anthropogenic-based heavy metal contamination risks. Thus, this study was attempted to analyze the heavy metal levels and mineral nutrient status of widely used medicinal plants in Turkey to have insights about their health implications on humans. The plant concentrations of B, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb and Zn were analyzed by ICP-OES in the leaves of 44 medical plants purchased from herbal markets of three different districts of Istanbul/Turkey. The measured lowest to highest concentrations were 0.065–79.749 mg kg⁻¹ B, 921.802–12,854.410 mg kg⁻¹ Ca, 0.020–0.558 mg kg⁻¹ Cd, 0.015–4.978 mg kg⁻¹ Cr, 0.042–8.489 mg kg⁻¹ Cu, 34.356–858.446 mg kg⁻¹ Fe, 791.323–15,569.349 mg kg⁻¹ K, 102.236–2837.836 mg kg⁻¹ Mg, 4.915–91.519 mg kg⁻¹ Mn, 10.224–3213.703 mg kg⁻¹ Na, 0.001–5.589 mg kg⁻¹ Ni, 0.003–3.636 mg kg⁻¹ Pb and 2.601–36.102 mg kg⁻¹ Zn. Those levels in plants were in acceptable limits though some elements in some plants have high limits which were not harmful. Variations (above acceptable limits) in element concentrations also indicated that these plants could be contaminated with other metals and that genetic variations may influence accumulation of these elements at different contents. Overall, analyzed medicinal plants are expected not to pose any serious threat to human health.

     

Dietary selenium- and vitamin E-induced alterations in some rabbit tissues

The present study was designed to investigate and compare the effects of dietary selenium (Se) and vitamin E on some physiological parameters and histological changes in liver, heart, and skin tissues, as well as the blood parameters and the related enzymes. Both sex young rabbits were fed with deficient (9.8 μg/kg diet), adequate (225 μg/kg diet), and rich (4.2 mg/kg diet) Se and vitamin E diets for 12–15 wk for this purpose. As the plasma Se levels and the erythrocyte glutathione (GSH) peroxidase activity decreased (79.8±9.4 ng/ml and 2.0±0.3 U/g Hb, respectively) in the deficient group, these values increased (100.4±2.7 ng/mL and 14.5±4.3 U/g Hb) in the rich group significantly with respect to the control group. The other antioxidant enzyme activities and the related element levels did not change significantly in either one of the experimental groups. Although the platelet counts of the two experimental groups were not different from the control values, the collagen and the adenosine diphosphate (ADP) stimulated platelet aggregation rate and intensity increased in the deficient group (p<0.05) and decreased very significantly (p<0.001) in the rich group. In both of the experimental groups, as the percentage values of the neutrophils decreased, the lymphocytes and the eosinophils increased significantly. According to the light microscopic investigations, the observed lesions of considerable intensity within the tissues that elicit cell degenerations were more pronounced in the animals fed with the rich diet than in those fed with the deficient diet. The deficiency as well as toxicity of Se and the deficiency of vitamin E caused several alterations in the physiological functions of the tissues, and these alterations were supported by the histological lesions within these tissues.     

Integration of system dynamics approach toward deepening and broadening the life cycle sustainability assessment framework: a case for electric vehicles

Purpose

Quantitative life cycle sustainable assessment requires a complex and multidimensional understanding, which cannot be fully covered by the current portfolio of reductionist-oriented tools. Therefore, there is a dire need on a new generation of modeling tools and approaches that can quantitatively assess the economic, social, and environmental dimensions of sustainability in an integrated way. To this end, this research aims to present a practical and novel approach for (1) broadening the existing life cycle sustainability assessment (LCSA) framework by considering macrolevel environmental, economic, and social impacts (termed as the triple bottom line), simultaneously, (2) deepening the existing LCSA framework by capturing the complex dynamic relationships between social, environmental, and economic indicators through causal loop modeling, (3) understanding the dynamic complexity of transportation sustainability for the triple bottom line impacts of alternative vehicles, and finally (4) investigating the impacts of various vehicle-specific scenarios as a novel approach for selection of a macrolevel functional unit considering all of the complex interactions in the environmental, social, and economic aspects.

Methods

To alleviate these research objectives, we presented a novel methodology to quantify macrolevel social, economic, and environmental impacts of passenger vehicles from an integrated system analysis perspective. An integrated dynamic LCSA model is utilized to analyze the environmental, economic, and social life cycle impact as well as life cycle cost of alternative vehicles in the USA. System dynamics modeling is developed to simulate the US passenger transportation system and its interactions with economy, the environment, and society. Analysis covers manufacturing and operation phase impacts of internal combustion vehicles (ICVs), hybrid electric vehicles (HEVs), plug-in hybrid electric vehicles (PHEVs), and battery electric vehicles (BEVs). In total, seven macrolevel indicators are selected; global warming potential, particulate matter formation, photochemical oxidant formation, vehicle ownership cost, contribution to gross domestic product, employment generation, and human health impacts. Additionally, contribution of vehicle choices to global atmospheric temperature rise and public welfare is investigated.

Results and discussion

BEVs are found to be a better alternative for most of sustainability impact categories. While some of the benefits such as contribution to employment and GDP, CO₂ emission reduction potential of BEVs become greater toward 2050, other sustainability indicators including vehicle ownership cost and human health impacts of BEVs are higher than the other vehicle types on 2010s and 2020s. While the impact shares of manufacturing and operation phases are similar in the early years of 2010s, the contribution of manufacturing phase becomes higher as the vehicle performances increase toward 2050. Analysis results revealed that the US transportation sector, alone, cannot reduce the rapidly increasing atmospheric temperature and the negative impacts of the global climate change, even though the entire fleet is replaced with BEVs. Reducing the atmospheric climate change requires much more ambitious targets and international collaborative efforts. The use of different vehicle types has a small impact on public welfare, which is a function of income, education, and life expectancy indexes.

Conclusions

The authors strongly recommend that the dynamic complex and mutual interactions between sustainability indicators should be considered for the future LCSA framework. This approach will be critical to deepen the existing LCSA framework and to go beyond the current LCSA understanding, which provide a snapshot analysis with an isolated view of all pillars of sustainability. Overall, this research is a first empirical study and an important attempt toward developing integrated and dynamic LCSA framework for sustainable transportation research.