Nitric oxide overcomes Cd and Cu toxicity in in vitro-grown tobacco plants through increasing contents and activities of rubisco and rubisco activase

AbstractToxic heavy metals such as cadmium (Cd) and copper (Cu) are global problems that are a growing threat to the environment. Despite some heavy metals are required for plant growth and development, others are considered toxic elements and do not play any known physiological role in plant cells. Elevated doses of Cd or Cu cause toxicity in plants and generate damages due to the stress condition and eventually cause a significant reduction in quantity and quality of crop plants. The nitric oxide (NO) donor sodium nitroprusside (SNP) is reported to alleviate the toxicity of some heavy metals like Cd and Cu. In the current study, the role of NO in alleviating stresses of Cd and Cu was investigated in in vitro-grown tobacco (Nicotiana tabacum) Based on plant growth, total chlorophyll contents, contents and activities of rubisco and rubisco activase. According to the results of this study, the growth and total chlorophyll contents of Cd/Cu stressed plants were hugely decreased in the absence of SNP, while the supplementation of SNP resulted in a significant increase of both fresh weight and total chlorophyll contents. Remarkable reductions of Rubisco and rubisco activase contents and activities were observed in Cd and Cu-induced plants. SNP supplementation showed the highest contents and activities of rubisco and rubisco activase compared to the control and Cu/Cd-stressed plants. Taken together, our findings suggest that SNP could play a protective role in regulation of plant responses to abiotic stresses such as Cd and Cu by enhancing Rubisco and Rubisco activase

Pharmacokinetic Comparison of 2 Fixed-Dose Combination Tablets of Amlodipine and Valsartan in Healthy Male Korean Volunteers: A Randomized, Open-Label, 2-Period, Single-Dose, Crossover Study

AbstractBackgroundAmlodipine and valsartan have different mechanisms of action, and it is known that the combination therapy with the 2 drugs increases treatment effects compared with the monotherapy with each drug. A fixed-dose combination (FDC) drug is a formulation including fixed amounts of active drug ingredients combined in a single dosage form that is expected to improve medication compliance.ObjectiveThe goal of this study was to compare the pharmacokinetic profiles of single administration of a newly developed FDC tablet containing amlodipine orotate 10 mg and valsartan 160 mg (test formulation) with the conventional FDC tablet of amlodipine besylate 10 mg and valsartan 160 mg (reference formulation) in healthy male Korean volunteers.MethodsThis was a randomized, open-label, single-dose, 2-way crossover study. Eligible subjects were between the ages of 20 and 50 years and within 20% of their ideal weight. Each subject received a single dose of the reference and the test formulations, with a 14-day washout period between formulations. Blood samples were collected up to 144 hours after the dose, and pharmacokinetic parameters were determined for amlodipine and valsartan. Adverse events were evaluated based on subject interviews and physical examinations.ResultsForty-eight of the 50 enrolled subjects completed the study. For both amlodipine and valsartan, the primary pharmacokinetic parameters were included in the range for assumed bioequivalence, yielding 90% CI ratios of 0.9277 to 0.9903 for AUC0–last and 0.9357 to 1.0068 for Cmax in amlodipine, and 0.9784 to 1.1817 for AUC0–last and 0.9738 to 1.2145 for Cmax in valsartan. Dizziness was the most frequently noted adverse event, occurring in 4 subjects with the test formulation, followed by oropharyngeal pain occurring in 1 subject with the test formulation and 3 subjects with the reference formulation. All other adverse events occurred in <3 subjects.ConclusionsThese findings suggest that the pharmacokinetics of the newly developed FDC tablet of amlodipine and valsartan did not differ significantly from the conventional FDC tablet in these healthy Korean male subjects. Both formulations were well tolerated, with no serious adverse events observed. ClinicalTrials.gov identifier: NCT01823913

Culture supernatant of adipose stem cells can ameliorate allergic airway inflammation via recruitment of CD4+CD25+Foxp3 T cells

SDS-PAGE of supernatant after ASC cultivation. Comparison of protein composition of con sup (concentrated medium for ASCs cultivation) and ASC sup (concentrated culture supernatant after ASC cultivation for 3 days) using SDS-PAGE. Thirty micrograms of each sample was loaded into an SDS-PAGE gel. After electrophoresis, the gel was stained by Coomassie Blue (M molecular marker, arrow indicated extra proteins compared to control). (PPT 370 kb

Prediction Forecast for Culex tritaeniorhynchus Populations in Korea

AbstractObjectivesJapanese encephalitis is considered as a secondary legal infectious disease in Korea and is transmitted by mosquitoes in the summer season. The purpose of this study was to predict the ratio of Culex tritaeniorhynchus to all the species of mosquitoes present in the study regions.MethodsFrom 1999 to 2012, black light traps were installed in 10 regions in Korea (Busan, Gyeonggi, Gangwon, Chungbuk, Chungnam, Jeonbuk, Jeonnam, Gyeongbuk, Gyeongnam, and Jeju) to capture mosquitoes for identification and classification under a dissecting microscope. The number of mosquitoes captured/week was used to calculate its daily occurrence (mosquitoes/trap/night). To predict the characteristics of the mosquito population, an autoregressive model of order p (AR(p)) was used to execute the out-of-sample prediction and the in-sample estimation after presumption.ResultsCompared with the out-of-sample method, the sample-weighted regression method's case was relatively superior for prediction, and this method predicted a decrease in the frequency of Cx. tritaeniorhynchus for 2013. However, the actual frequency of this species showed an increase in frequency. By contrast, the frequency rate of all the mosquitoes including Cx. tritaeniorhynchus gradually decreased.ConclusionThe number of patients with Japanese encephalitis has been strongly associated with the occurrence and density of vector mosquitoes, and the importance of this infectious disease has been highlighted since 2010. The 2013 prediction indicated an increase after an initial decrease, although the ratio of the two mosquito species decreased. The increase in vector density may be due to changes in temperature and the environment. Thus, continuous prevalence prediction is warranted

Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration

Retinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod degeneration. Although rd10 mice lacking Rip3 developed comparable rod degeneration to control rd10 mice, they displayed a significant preservation of cone cells. Ultrastructural analysis of rd10 mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued by Rip3 deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones in rd10 mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa

Identification of Novel Reference Genes Using Multiplatform Expression Data and Their Validation for Quantitative Gene Expression Analysis

Normalization of mRNA levels using endogenous reference genes (ERGs) is critical for an accurate comparison of gene expression between different samples. Despite the popularity of traditional ERGs (tERGs) such as GAPDH and ACTB, their expression variability in different tissues or disease status has been reported. Here, we first selected candidate housekeeping genes (HKGs) using human gene expression data from different platforms including EST, SAGE, and microarray, and 13 novel ERGs (nERGs) (ARL8B, CTBP1, CUL1, DIMT1L, FBXW2, GPBP1, LUC7L2, OAZ1, PAPOLA, SPG21, TRIM27, UBQLN1, ZNF207) were further identified from these HKGs. The mean coefficient variation (CV) values of nERGs were significantly lower than those of tERGs and the expression level of most nERGs was relatively lower than high expressing tERGs in all dataset. The higher expression stability and lower expression levels of most nERGs were validated in 108 human samples including formalin-fixed paraffin-embedded (FFPE) tissues, frozen tissues and cell lines, through quantitative real-time RT-PCR (qRT-PCR). Furthermore, the optimal number of nERGs required for accurate normalization was as few as two, while four genes were required when using tERGs in FFPE tissues. Most nERGs identified in this study should be better reference genes than tERGs, based on their higher expression stability and fewer numbers needed for normalization when multiple ERGs are required

Targeting the stress support network regulated by autophagy and senescence for cancer treatment

Autophagy and cellular senescence are two potent tumor suppressive mechanisms activated by various cellular stresses, including the expression of activated oncogenes. However, emerging evidence has also indicated their pro-tumorigenic activities, strengthening the case for the complexity of tumorigenesis. More specifically, tumorigenesis is a systemic process emanating from the combined accumulation of changes in the tumor support pathways, many of which cannot cause cancer on their own but might still provide excellent therapeutic targets for cancer treatment. In this review, we discuss the dual roles of autophagy and senescence during tumorigenesis, with a specific focus on the stress support networks in cancer cells modulated by these processes. A deeper understanding of such context-dependent roles may help to enhance the effectiveness of cancer therapies targeting autophagy and senescence, while limiting their potential side effects. This will steer and accelerate the pace of research and drug development for cancer treatment.N

Folliculosebaceous Cystic Hamartoma in a Patient with Neurofibromatosis Type I

Folliculosebaceous cystic hamartoma (FSCH) is a rare cutaneous hamartoma composed of dilated folliculosebaceous units and mesenchymal elements. It presents as a papule or nodule usually on the face and scalp, rarely on the genital or trunk area. Histologically, FSCH shares several similar features to sebaceous trichofolliculoma. We report one case of FSCH misdiagnosed as a neurofibroma. He was a 38-year-old man with a neurofibromatosis type I and a nodule on his left earlobe was excised under the impression of neurofibroma. Pathological examination revealed FSCH. Although FSCH is clinically not distinctive, awareness of the lesion is important to differentiate papulonodular or cyst-like cutaneous lesions

Increase of Ceftazidime- and Fluoroquinolone-Resistant Klebsiella pneumoniae and Imipenem-Resistant Acinetobacter spp. in Korea: Analysis of KONSAR Study Data from 2005 and 2007

PURPOSE: Antimicrobial resistance monitoring could be a useful source of information for treating and controlling nosocomial infections. We analyzed antimicrobial resistance data generated by Korean Hospitals and by a commercial laboratory in 2005 and 2007. MATERIALS AND METHODS: Susceptibility data for 2005 and 2007 were collected from 37 and 41 hospitals, respectively, and from one commercial laboratory. Intermediate susceptibility was not included in the calculation of resistance rates. RESULTS: Methicillin-resistant Staphylococcus aureus (MRSA) (64%), third-generation cephalosporin-resistant Klebsiella pneumoniae (29%), fluoroquinolone-resistant Escherichia coli (27%), Pseudomonas aeruginosa (33%), and Acinetobacter spp. (48%), and amikacin-resistant P. aeruginosa (19%) and Acinetobacter spp. (37%) were prevalent in hospitals in 2007. A gradual increase of vancomycin-resistant Enterococcus faecium and imipenem-resistant Acinetobacter spp. was observed. Higher incidences of thirdgeneration cephalosporin-resistant E. coli and K. pneumoniae and imipenemresistant P. aeruginosa were found in the commercial laboratory than in the hospitals. CONCLUSION: Methicillin-resistant S. aureus, third-generation cephalosporin- resistant K. pneumoniae, and fluoroquinolone-resistant E. coli, P. aeruginosa and Acinetobacter spp. remain prevalent in Korea, while the incidence of vancomycin-resistant E. faecium and imipenem-resistant Acinetobacter spp. has increased gradually. The higher prevalences of third-generation cephalosporinresistant E. coli and K. pneumoniae, and imipenem-resistant P. aeruginosa in the commercial laboratory are a new concern.ope

Cutaneous melanoma in women☆☆☆

Background: Gender disparity in melanoma outcome is consistently observed, suggesting that gender is as an important prognostic factor. However, the source of this gender disparity in melanoma remains unclear. Objective: This article reviews advances in our understanding of gender differences in melanoma and how such differences may contribute to outcomes. Methods: A broad literature search was conducted using the PubMed database, with search terms such as ‘gender differences in melanoma’ and ‘sex differences in melanoma.’ Additional articles were identified from cited references. Results: Herein, we address the gender-linked physiologic differences in skin and melanoma. We discuss the influence of estrogen on a woman’s risk for melanoma and melanoma outcomes with regard to pregnancy, oral contraceptives, hormone replacement therapy, and UV tanning. Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients