bluuebunny/crossref_metadata_2025 huggingface dataset:
A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway
Authors: Wu Chia‐Lun , Chen Chun‐Liang , Huang Hsu‐Shan , Yu Dah‐Shyong
Published: June 2018

The incidence and mortality rate of urological cancers is increasing yearly. Niclosamide has been repurposed as an anti‐cancer drug in recent years. Synthesized derivative of niclosamide was testified for its anti‐cancer activity in urological cancers. MTT assay was used to measure the cytotoxicity effect of niclosamide and its derivatives in urological cancer cell lines. Migratory ability was monitored by scratch migration assay. Apoptosis and cell cycle changes were analyzed by annexin V and PI staining. The apoptosis‐related signal proteins were evaluated by western blotting. T24 had the best drug sensitivity with the lowest IC50 in niclosamide and B17 treatment than DU145 and Caki‐1 cells. After niclosamide and B17 treatment, the mitotic cells were decreased, but apoptotic bodies and morphology changes were not prominent in T24, Caki‐1, and DU145 cells. The migratory ability was inhibited in niclosamide treatment than control group on Caki‐1 cells and niclosamide and B17 treatment than control group on DU145 cells. Early apoptosis cells were increased after niclosamide and B17 treatment than control group without cell cycle changes in T24, Caki‐1, and DU145 cells. Programmed cell death was activated majorly through PAPR and bcl‐2 in T24 and caspase‐3 in Caki‐1 cells, respectively. Niclosamide and B17 derivative had good ability in inhibition proliferation and migratory ability in T24, Caki‐1, and DU145 cells without prominent morphology and apoptotic body changes. UCC cells are more sensitive to niclosamide and B17 treatment. Early apoptosis was induced after niclosamide and B17 treatment through different mechanisms in T24, Caki‐1, and DU145 cells.
Effects of cultivar and aging on parboiled rice properties
Authors: Lii Eric , Mauromoustakos Andy , Wang Ya‐Jane
Published: June 2018

Background and objectives

Parboiled rice is an important commodity, and its properties are affected by parboiling conditions and feedstock properties. This study investigated the impact of cultivar and aging on parboiled rice properties under different parboiling conditions.

Findings

Regardless of parboiling conditions, cultivar with greater protein content had greater milling yields and cooked rice hardness, and lower deformed kernels and water absorption than low protein content cultivar. Deformed kernel had shown that aging effect was more significant on low protein content cultivar. Cultivar was the most important factor affecting parboiled rice properties and followed closely by soaking and steaming temperatures. Aging accounted for more than 10% of the total variance, and aging generally resulted in increased cooked rice hardness, and decreased deformed kernels, whiteness, pasting viscosities, and soluble solids.

Conclusions

Parboiled rice prepared from freshly harvested and aged rice displayed different properties. Cultivar with a greater protein content showed to have better protection against severe parboiling condition while preserving desired properties. Aging effect was more evident for rice of a low protein content. Even under different parboiling conditions, parboiled fresh‐harvested and aged rice still resulted in different properties.

Significance and novelty

The present study suggests the importance of protein content in the cultivar effect and its impact on aging effect.
Eculizumab application during pregnancy in a patient with paroxysmal nocturnal hemoglobinuria: A case report with review of the literature
Authors: Lauritsch‐Hernandez Lisa Sophie , Kraehenmann Franziska , Balabanov Stefan , Kimmich Nina
Published: June 2018

Key Clinical Message

Eculizumab is highly effective in inhibiting complement activation and has successfully shown to prevent complications and to improve quality of life in patients with paroxysmal nocturnal hemoglobinuria (PNH). Its application during pregnancy showed favorable fetal and maternal outcome in the presented case and has proven to be effective without raising safety concerns.
Solvent‐Free Synthesis of Bismuth Oxychloride Microflower/Nanosheet Homojunctions for Photoactivity Enhancement
Authors: Yao Hanyu , Li Haiping , Hu Tingxia , Hou Wanguo
Published: June 2018

Solvent‐free synthesis of bismuth‐based photocatalysts with hierarchical architectures has been rarely reported yet. Herein, BiOCl hierarchical microflowers (MFs) were prepared via a solvent‐free route for the first time, using chlorobutanol as the chlorine source. The reaction temperature (T) plays a key role for formation of MFs. The MFs were formed at T >120 °C and some MFs merged into large nanosheets (LNs). MF/LN homojunctions were constructed because considerable differences in sizes and exposed facets between the MFs and the LNs cause differences in their energy band levels. The sample prepared at 120 °C possesses the highest contents of MFs and homojunctions, specific surface area (SBET, 13 m2 g−1), and photoactivity, indicating the high photoactivity of the sample arises from fabrication of homojunctions as well as the high SBET. This work provides a solvent‐free way to simultaneously synthesize BiOCl MFs and homojunctions, which paves an avenue for solvent‐free synthesis of other photocatalysts.
Synthesis of N,O,B‐Chelated Dipyrromethenes through an Unexpected Intramolecular Cyclisation: Enhanced Near‐Infrared Emission in the Aggregate/Solid State
Authors: Liu Yang , Niu Li‐Ya , Liu Xue‐Liang , Chen Peng‐Zhong , Yao Yi‐Shan , Chen Yu‐Zhe , Yang Qing‐Zheng
Published: June 2018

The first example of the synthesis of mono‐N,O‐B‐chelated dipyrromethene (BODIPY) derivatives through an unexpected intramolecular nucleophilic displacement of the fluorine by alkenols in the presence of boron trifluoride as Lewis acid is reported. The chlorine in the indacene core allowed for further structural modifications through nucleophilic substitutions or palladium‐catalysed coupling reactions to afford new fluorophores with tuneable photophysical properties. Their expanded conjugation structure resulted in distinct red‐shifted absorption and emission spectra in organic solutions. Furthermore, the twisted steric hindrance of the benzene substitution patterns suppressed aggregation‐induced quenching, leading to an enhanced NIR emission in the aggregate/solid state, which was rarely observed for BODIPY dyes. Nanoparticles of the fluorophores formed by the assembly with the polymeric surfactant F127 were successfully used for bioimaging of living cells and for tumour‐targeted imaging in a tumour‐bearing mouse model.
Randomized Phase I Healthy Volunteer Study of UTTR1147A (IL‐22Fc): A Potential Therapy for Epithelial Injury
Authors: Rothenberg Michael E. , Wang Yehong , Lekkerkerker Annemarie , Danilenko Dimitry M. , Maciuca Romeo , Erickson Rich , Herman Ann , Stefanich Eric , Lu Timothy T.
Published: June 2018

Most treatments for epithelial injury target hematopoietic mechanisms, possibly causing immunosuppression. Interleukin (IL)‐22 promotes tissue regeneration, acting directly on epithelial cells. UTTR1147A, a human IL‐22Fc (immunoglobulin G (IgG)4) fusion protein, activates IL‐22 signaling. This phase I placebo‐controlled trial of single, ascending, i.v. (1–120 μg/kg) and s.c (3–120 μg/kg) doses of UTTR1147A analyzed its effects on safety, tolerability, pharmacokinetics, and pharmacodynamic biomarkers in healthy volunteers. Most adverse events (AEs) were mild or moderate. The maximum tolerated i.v. dose in healthy volunteers was 90 μg/kg. Predominant AEs were dose‐dependent reversible skin effects consistent with IL‐22 pharmacology. UTTR1147A exposure increased approximately dose‐proportionally, with a half‐life of ~1 week. IL‐22 biomarkers (regenerating islet protein 3A (REG3A), serum amyloid A (SAA), and C‐reactive protein (CRP)) increased dose‐dependently. Neither inflammatory symptoms and signs nor cytokines increased with CRP elevations. UTTR1147A demonstrated acceptable safety, pharmacokinetics, and IL‐22R engagement, supporting further clinical development.
Structure‐Guided Engineering of α‐Keto Acid Decarboxylase for the Production of Higher Alcohols at Elevated Temperature
Authors: Sutiono Samuel , Carsten Jörg , Sieber Volker
Published: June 2018

Branched‐chain keto acid decarboxylases (KDCs) are a class of enzymes that catalyze the decarboxylation of α‐keto acids. They are key enzymes for production of higher alcohols in vivo and in vitro. However, the two most active KDCs (KivD and KdcA) have only moderate thermostability (<55 °C), which hinders the production of alcohols at high temperatures. Herein, structure‐guided engineering toward improved thermostability of KdcA is outlined. Strategies such as stabilization of the catalytic center, surface engineering, and optimization of dimer interactions were applied. With seven amino acid substitutions, variant 7M.D showed an increase of the temperature at which 50 % of activity remains after one‐hour incubation
by 14.8 °C without compromising its substrate specificity. 7M.D exhibited greater than 400‐fold improvement of half‐life at 70 °C and greater than 600‐fold increase in process stability in the presence of 4 % isobutanol at 50 °C. 7M.D is more promising for the production of higher alcohols in thermophiles (>65 °C) and in cell‐free applications.
Centralized spectrum leasing via cooperative SU assignment in cognitive radio networks
Authors: Deng Hou , Huang Liusheng , Yang Chenkai , Xu Hongli
Published: June 2018

As the increasing demand of the radio spectrum, the researchers pay more attention to the technology of cognitive radio networks to improve the use of the scarce spectrum resources. Recently, cooperative communications combining with cognitive radio have been proposed in many literatures to improve the channel capacity. The primary users with poor transmission environment transmit their packets with the assistance of the secondary users (SUs) by offering them spectrum resources. This paper first raises issues in existing works, such as non‐optimal selection, selection collision, and transmission interruption. Aiming at these issues, we design a centralized system model and a cooperative relaying protocol for multiple primary user pairs to dynamically lease spectrum in exchange for the transmission assistance of SUs. Then we define 2 problems of the cooperative SU assignment to maximize total rate and maximize number of assigned SUs. We prove they are NP‐hard and propose a local search algorithm for the objective of maximize total rate and a
‐approximation algorithm for another objective. Our simulation results show that our system and algorithms can effectively improve the performance of the wireless networks.
Spatial analyses of two color polymorphisms in an alpine grasshopper reveal a role of small‐scale heterogeneity
Authors: Dieker Petra , Beckmann Luisa , Teckentrup Julia , Schielzeth Holger
Published: June 2018

Discrete color polymorphisms represent a fascinating aspect of intraspecific diversity. Color morph ratios often vary clinally, but in some cases, there are no marked clines and mixes of different morphs occur at appreciable frequencies in most populations. This poses the questions of how polymorphisms are maintained. We here study the spatial and temporal distribution of a very conspicuous color polymorphism in the club‐legged grasshopperGomphocerus sibiricus. The species occurs in a green and a nongreen (predominately brown) morph, a green–brown polymorphism that is common among Orthopteran insects. We sampled color morph ratios at 42 sites across the alpine range of the species and related color morph ratios to local habitat parameters and climatic conditions. Green morphs occurred in both sexes, and their morph ratios were highly correlated among sites, suggesting shared control of the polymorphism in females and males. We found that in at least 40 of 42 sites green and brown morphs co‐occurred with proportions of green ranging from 0% to 70% with significant spatial heterogeneity. The proportion of green individuals tended to increase with decreasing summer and winter precipitations. Nongreen individuals can be further distinguished into brown and pied individuals, and again, this polymorphism is shared with other grasshopper species. We found pied individuals at all sites with proportions ranging from 3% to 75%, with slight, but significant variation between years. Pied morphs show a clinal increase in frequency from east to west and decreased with altitude and lower temperatures and were more common on grazed sites. The results suggest that both small‐scale and large‐scale spatial heterogeneity affects color morph ratios. The almost universal co‐occurrence of all three color morphs argues against strong effects of genetic drift. Instead, the data suggest that small‐scale migration–selection balance and/or local balancing selection maintain populations polymorphic.
Subtle foodscape displacement of a native ungulate by free‐ranging livestock in a forest agroecosystem
Authors: Wam Hilde Karine , Herfindal Ivar
Published: June 2018

The prevalence of livestock grazing in wildlife areas is increasing. This transformation of ecosystems into agroecosystems is concerning because the introduction of new species may cause niche displacement of the functionally related native species. We used a large‐scale fence scheme and fecal analyses to study the influence of free‐ranging livestock on moose diet on three boreal forest ranges. We found low interspecific diet overlap between moose and livestock (mean Pianka's O across ranges = 0.21, SD = 0.104), and the diet overlap with livestock did not differ between moose in areas with livestock and in adjacent control areas without livestock. Still, moose sympatric with livestock had less fecal nitrogen (a proxy for diet quality) than moose in the control areas. Our findings suggest that interspecific interactions other than direct food competition contributed to reduce the moose’ foraging opportunities, such as altered forage abundance and composition, or behavioral avoidance of livestock. We caution that displacement in the foodscape (i.e., spatiotemporal use of food) can occur through pathways not evident in niche indices based on composition of plant species in the diet.
Queuing, takeovers, and becoming a fat cat: Long‐term data reveal two distinct male spatial tactics at different life‐history stages in Namibian cheetahs
Authors: Melzheimer Joerg , Streif Sabrina , Wasiolka Bernd , Fischer Manuela , Thalwitzer Susanne , Heinrich Sonja K. , Weigold Annika , Hofer Heribert , Wachter Bettina
Published: June 2018

In mammals, male spatial tactics and sociality can be predicted from the size, degree of overlap and ease of defense of female individual or group home ranges (HRs). An exception is apparently the cheetah (Acinonyx jubatus) for which studies from East Africa describe a socio‐spatial organization where resident males defend small territories, which cover a portion of large ranges of solitary females, and non‐territorial males (floaters) roam over vast areas whilst queuing for access to territories. Most studies from southern Africa did not report the existence of territorial males and floaters, but a system with both males and females roaming over vast areas with overlapping HRs. Here, we derive and test predictions from previously described spatial tactics in felids by studying the movements, behavior, and/or physical characteristics of 164 radio‐collared Namibian cheetahs on commercial farmland from 2002 to 2014. The results demonstrate the existence of male territory holders and floaters and a, by mammalian standards, unique sociality in that commonly groups of males, sometimes solitary males defended small areas partially overlapping with large ranges of solitary females. When a solitary male or a group of males switched between both tactics, floating usually preceded territory holding, suggesting that both spatial phases are equivalent to distinct life‐history stages. Switching from roaming as a floater to holding a territory was also associated with an increase in body mass index (BMI) and a change in the observed behavior of animals captured in traps when approached by humans. Both BMI and this behavior are therefore reliable, quick biomarkers of an individual's space use tactic and life‐history stage. We elaborate the implications of this socio‐spatial organization for models of ecological movements and on conflict mitigation measures such as translocations or the planning of future protected areas. We suggest that such implications also apply to other species where one sex exhibits two space use tactics and two sets of range sizes.
An Alkyne Rod to Constrain a Peptide Backbone in an Extended Conformation
Authors: Přibylka Adam , Krchňák Viktor
Published: June 2018

An N,N′‐bound rod‐shaped diyne bridge was introduced into a peptide to constrain the peptide backbone in an extended conformation. Linear precursors were achieved via solid‐phase synthesis using simple commercially available building blocks. Subsequently, 13‐ to 15‐membered peptide macrocycles were obtained in excellent crude purity via in solution copper‐catalyzed cyclization. Density functional theory calculations of the lowest energy conformers suggested that the strain inside the macrocycle caused only slight deformation of the binding angles of the butadiyne moiety.
An immersed boundary method for solving compressible flow with arbitrarily irregular and moving geometry
Authors: Mo Huangrui , Lien Fue‐Sang , Zhang Fan , Cronin Duane S.
Published: June 2018

In this paper, a novel immersed boundary method is developed, validated, and applied. Through devising a second‐order three‐step flow reconstruction scheme, the proposed method is able to enforce the Dirichlet, Neumann, Robin, and Cauchy boundary conditions in a straightforward and consistent manner. Equipped with a fluid‐solid coupling framework that integrates high‐order temporal and spatial discretization schemes, numerical experiments concerning flow involving stationary and moving objects, convex and concave geometries, no‐slip and slip wall boundary conditions, as well as subsonic and supersonic motions are conducted to validate the method. Using analytical solutions, experimental observations, published numerical results, and Galilean transformations, it is demonstrated that the proposed method can provide efficient, accurate, and robust boundary treatment for solving flow with arbitrarily irregular and moving geometries on Cartesian grids. On the basis of the proposed method, the development of a solver that unifies one‐, two‐, and three‐dimensional computations and the generation of complex geometric objects via simply positioning components are described. In addition, a surface‐normalized absolute flux is proposed for interface sharpness measurement, and an analytically solvable modified vortex preservation problem is developed for a convergence study concerning smooth flow with irregular geometries.
Pressure‐based unified solver for gas‐liquid two‐phase flows where compressible and incompressible flows coexist
Authors: Yamamoto Tetsuya , Takatani Kouji
Published: June 2018

We propose a pressure‐based unified solver for gas‐liquid two‐phase flows where compressible and incompressible flows coexist. Unlike the original thermo–Cubic Interpolated Propagation Combined Unified Procedure (CIP‐CUP) method proposed by Himeno et al (Transactions of the Japan Society of Mechanical Engineers, Series B, 2003), we split the advection term of the governing equations into a conservation part and into the rest. The splitting of advection term has two advantages. One is the high degree of freedom in choosing discretization schemes such as central‐difference schemes, upwind schemes, and Total Variation Diminishing (TVD) schemes. The other is the ease of implementation on unstructured grids. The advantages enable the analyses of various flows such as turbulent and supersonic ones in actual complicated boundaries. Therefore, the solver is useful for practical analyses. The solver was validated on the following test cases: subsonic single‐phase flows, incompressible single‐phase turbulent flows, and incompressible gas‐liquid two‐phase flows. With unstructured grids, we obtained the equivalent results as the ones with structured grids. After the validations, subsonic jet impinging on a water pool was calculated and compared with experimental results. It was confirmed that the calculated results were consistent with the experimental ones.
Modeling of starter cultures growth for improved Thai sausage fermentation and cost estimating for sausage preparation and transportation
Authors: Sriphochanart Wiramsri , Skolpap Wanwisa
Published: June 2018

The purpose of this study was to improve Thai fermented sausage flavor by adding starter cultures (i.e., Pediococcus pentosaceus, Pediococcus acidilactici, Weissella cibaria, Lactobacillus plantarum, Lactobacillus pentosus, and Lactobacillus sakei) as compared with naturally fermented sausage. The predictive mathematical models for growth of P. acidilactici and natural lactic acid bacteria (LAB) in Thai fermented sausage were developed to obtain specific prepared sausage quality. Furthermore, comparisons of sausage preparation and transportation cost between nonrefrigerated and refrigerated trucks were studied. The concentration of 3‐methyl‐butanoic acid synthesized from LAB inoculated sausage was higher than in the control sample which contributed to the flavor forming. Moreover, the proposed unstructured kinetic models of Thai fermented sausage substrates and products describing the consumption of total protein and glucose, and the production of nonprotein nitrogen responsible for flavor enhancer, lactic acid and formic acid concentration were successfully fitted with two selected experimental data sets of the in situ fermentation of Thai fermented sausage. Finally, the transportation of inoculated sausages in a nonrefrigerated truck by combining fermentation process and transportation was more cost efficient for delivering sausages in a long distance.
Nuclear nonmetastatic protein 23‐H1 expression and epithelial‐mesenchymal transition in laryngeal carcinoma: A pilot investigation
Authors: Marioni Gino , Cappellesso Rocco , Ottaviano Giancarlo , Fasanaro Elena , Marchese‐Ragona Rosario , Favaretto Niccolò , Giacomelli Luciano , Guzzardo Vincenza , Martini Alessandro , Fassina Ambrogio , Blandamura Stella
Published: June 2018

Background

In epithelial‐to‐mesenchymal transition, epithelial cells lose their features, acquiring a mesenchymal‐like phenotype. Nm23‐H1 protein relates to tumor cells' metastatic potential, its low expression in carcinomas often meaning a poor prognosis. This study newly investigated the role of nuclear nm23‐H1 in laryngeal squamous cell carcinoma epithelial‐to‐mesenchymal transition.

Methods

Immunohistochemical analyses of nuclear nm23‐H1, E‐cadherin, N‐cadherin, Snail, Zinc finger E‐box binding homeobox (ZEB)1, and ZEB2 were performed in 33 consecutive patients with laryngeal SCC.

Results

Mean nuclear nm23‐H1 expression was lower in patients whose disease recurred (P = .0046). Disease‐free survival (DFS) was longer for patients whose nuclear nm23‐H1 expression was ≥10% (P = .0083). Nuclear nm23‐H1 and E‐cadherin expressions correlated directly (P = .018). Mean E‐cadherin expression was lower in patients whose disease recurred (P = .03). The DFS was shorter in patients with ZEB2 expression ≥5% (P = .006).

Conclusions

Nuclear nm23‐H1 expression warrants further investigation in laryngeal SCC as a prognostic marker identifying patients at higher risk of recurrence. nm23‐H1 targeted treatments may be capable of regulating epithelial‐to‐mesenchymal transition.
Positive correlation between vitamin D receptor gene FokI polymorphism and colorectal cancer susceptibility in South‐Khorasan of Iran
Authors: Moossavi Maryam , Parsamanesh Negin , Mohammadoo‐Khorasani Milad , Moosavi Mahsa , Tavakkoli Tahmineh , Fakharian Tahereh , Naseri Mohsen
Published: June 2018

Colorectal cancer (CRC) is a global public health problem. Despite the major milestone in early diagnosis and treatment of colorectal cancer, the prevalence of CRC rates is still rising. The etiology of CRC is still unknown but we know CRC is influenced by both of environment and genetic factors. In this study, we aimed to elucidate the role of vitamin D receptor gene polymorphic regions; FokI and TaqI single nucleotide polymorphisms, in increasing the risk of colorectal cancer in Birjand population. One hundred patients with CRC and 100 healthy controls recruited to the study. Genotyping was performed by PCR‐RFLP (restriction fragment length polymorphism) method technique for all individuals. There were statistically significant differences between ff genotype and f allele of FokI SNP in case and control groups. Our results manifested positive correlation between ff genotype and f allele of FokI SNP with colorectal cancer predisposition (P = 0.035, P = 0.0001 respectively) in South Khorasan population. The present study showed that FokI polymorphism but not TaqI polymorphism may contribute to CRC susceptibility. In addition, ff genotype of FokI polymorphism was associated with CRC risk.
Diazoxide ameliorates severity of experimental osteoarthritis by activating autophagy via modulation of the osteoarthritis‐related biomarkers
Authors: Meng ZhuLong , Shen BiXin , Gu YunTao , Wu ZiQuan , Yao JiangLing , Bian YangYang , Zeng DeLu , Chen KeWei , Cheng ShaoWen , Fu Jian , Peng Lei , Zhao YingZheng
Published: June 2018

Accumulating evidence suggests that autophagy plays a protective role in chondrocytes and prevents cartilage degeneration in osteoarthritis (OA). The objective of this study was to investigate the effect of diazoxide on chondrocyte death and cartilage degeneration and to determine whether these effects are correlated to autophagy in experimental OA. In this study, a cellular OA model was established by stimulating SW1353 cells with interleukin 1β. A rat OA model was generated by transecting the anterior cruciate ligament combined with the resection of the medial menisci, followed by treatment with diazoxide or diazoxide combination with 3‐methyladenine. The percentage of viable cells was evaluated using calcein‐acetoxymethyl/propidium iodide double staining. The messenger RNA expression levels of collagen type II alpha 1 chain (COL2A1), matrix metalloproteinase 13 (MMP‐13), TIMP metallopeptidase inhibitor 1 (TIMP‐1), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) were determined using quantitative real‐time polymerase chain reaction. The cartilage thickness and joint space were evaluated using ultrasound. SW1353 cell degeneration and autophagosomes were observed using transmission electron microscopy. The expression levels of microtubule‐associated protein 1 light chain 3 (LC3), beclin‐1, P62, COL2A1, and MMP‐13 were evaluated using immunofluorescence staining and Western blot analysis. Diazoxide significantly attenuated articular cartilage degeneration and SW1353 cell death in experimental OA. The restoration of autophagy was observed in the diazoxide‐treated group. The beneficial effects of diazoxide were markedly blocked by 3‐methyladenine. Diazoxide treatment also modulated the expression levels of OA‐related biomarkers. These results demonstrated that diazoxide exerted a chondroprotective effect and attenuated cartilage degeneration by restoring autophagy via modulation of OA‐related biomarkers in experimental OA. Diazoxide treatment might be a promising therapeutic approach to prevent the development of OA.
Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function
Authors: Zhao Xiaoqin , Rong Can , Pan Fenghui , Xiang Lizhi , Wang Xinlei , Hu Yun
Published: June 2018

Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose‐stimulated insulin secretion, and enzyme‐linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full‐length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196‐122893419 (GRCH37/hg19) within the SRY‐related HMG‐box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet β‐cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes.
Downregulation of IL‐22 can be considered as a risk factor for onset of type 2 diabetes
Authors: Asadikaram Gholamreza , Akbari Hamed , Safi Zohreh , Shadkam Mitra , Khaksari Mohammad , Shahrokhi Nader , Najafipour Hamid , Sanjari Mojgan , Arababadi Mohammad Kazemi
Published: June 2018

There is some controversy as for the roles played by tumor growth factor‐β (TGF‐β), interleukin‐1β (IL‐1β), and IL‐22 in the onset process of type 2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF‐β, IL‐1β, and IL‐22 in the new cases and long period T2D patients as well as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D patients who have suffered from the disease more than 2 years (group 2), and 104 healthy controls have been selected from 6240 (3619 females) patients who were under study population from Kerman Coronary Artery Disease Risk Factor Study. Serum levels of TGF‐β, IL‐1β, and IL‐22 have been evaluated using commercial kits. Serum levels of TGF‐β and IL‐1β significantly increased, while IL‐22 decreased in 2 groups in comparison to healthy controls. Serum levels of IL‐22, but not TGF‐β and IL‐1β, were significantly decreased in group 1 in comparison to healthy controls. There were no significant differences between groups 1 and 2 as for the cytokine levels. Serum levels of IL‐22 increased in the females in group 2 when compared to females in group 1. It appears that TGF‐β and IL‐1β participate in the induction of inflammation after establishment of T2D, while decrease in IL‐22 may be considered as a key factor for onset of the disease. Gender can also be considered as the main risk factor for variation in cytokine levels.
MicroRNA‐19 restores vascular endothelial cell function in lower limb ischemia‐reperfusion injury through the KLF10‐dependent TGF‐β1/Smad signaling pathway in rats
Authors: Xu Yong‐Le , Zhang Min‐Hong , Guo Wei , Xue Yan , Du Xin , Zhang Tao , Wu Na , Wu Ye
Published: June 2018

Ischemia‐reperfusion injury (IRI) is a severe problem patients diagnosed with acute limb ischemia. Recently, microRNAs (miR) have emerged as regulators of IRI as well as ischemic preconditioning and ischemic postconditioning. Therefore, using rat models, this study aims to explore all of the possible mechanisms that miR‐19 exhibits with its relation to the transforming growth factor beta (TGF‐β1)/Smad signaling pathway in the lower limb IRI. An immunofluorescence staining method was used to identify the Krueppel‐like factor 10 (KLF10) positive expression and the location of KLF10 expression. The targeting relationship that miR‐19 has with KLF10 was verified by the dual‐luciferase reporter gene assay. Vascular endothelial cells (VECs) were treated with elevated or suppressed miR‐19 or KLF10 knockdown. A 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide assay was used to test cell proliferation, and flow cytometry was employed to detect both cell cycle and apoptosis. The KLF10‐positive expression in the VECs (both in cytoplasm and nucleus) was found to be elevated in the IRI rats. We found that miR‐19 was downregulated, KLF10 upregulated, and the TGF‐β1/Smad signaling pathway activated in the vascular epithelial tissues of IRI rats. KLF10 is a target gene of miR‐19. Overexpression of miR‐19 decreased the expression of KLF10, TGF‐β1, and Smad2/3. Decreased miR‐19 inhibited VEC proliferation, arrested VECs at the G1 phase, and promoted the apoptosis of VECs following their lower limb I/R injury. These results indicate miR‐19 as being an inhibitor in the VEC injury of IRI via the TGF‐β1/Smad signaling pathway by suppression of KLF10.
RUMI is a novel negative prognostic marker and therapeutic target in non–small‐cell lung cancer
Authors: Chammaa May , Malysa Agnes , Redondo Carlos , Jang Hyejeong , Chen Wei , Bepler Gerold , Fernandez‐Valdivia Rodrigo
Published: June 2018

Recent comprehensive next‐generation genome and transcriptome analyses in lung cancer patients, several clinical observations, and compelling evidence from mouse models of lung cancer have uncovered a critical role for Notch signaling in the initiation and progression of non–small‐cell lung cancer (NSCLC). Notably, Rumi is a “protein O‐glucosyltransferase” that regulates Notch signaling through O‐glucosylation of Notch receptors, and is the only enzymatic regulator whose activity is required for both ligand‐dependent and ligand‐independent activation of Notch. We have conducted a detailed study on RUMI’s involvement in NSCLC development and progression, and have further explored the therapeutic potential of its targeting in NSCLC. We have determined that Rumi is highly expressed in the alveolar and bronchiolar epithelia, including club cells and alveolar type II cells. Remarkably, RUMI maps to the region of chromosome 3q that corresponds to the major signature of neoplastic transformation in NSCLC, and is markedly amplified and overexpressed in NSCLC tumors. Notably, RUMI expression levels are predictive of poor prognosis and survival in NSCLC patients. Our data indicates that RUMI modulates Notch activity in NSCLC cells, and that its silencing dramatically decreases cell proliferation, migration, and survival. RUMI downregulation causes severe cell cycle S‐phase arrest, increases genome instability, and induces late apoptotic–nonapoptotic cell death. Our studies demonstrate that RUMI is a novel negative prognostic factor with significant therapeutic potential in NSCLC, which embodies particular relevance especially when considering that, while current Notch inhibitory strategies target only ligand‐dependent Notch activation, a large number of NSCLCs are driven by ligand‐independent Notch activity.
HOXA11‐AS promotes the growth and invasion of renal cancer by sponging miR‐146b‐5p to upregulate MMP16 expression
Authors: Yang Feng‐Qiang , Zhang Jian‐Qiu , Jin Jiang‐Jiang , Yang Chong‐Yi , Zhang Wei‐Jie , Zhang Hai‐Ming , Zheng Jun‐Hua , Weng Ze‐Ming
Published: June 2018

Recently, increasing studies showed that long noncoding RNAs (lncRNAs) play critical roles in tumor progression. However, the function and underlying mechanism of HOMEOBOX A11 antisense RNA (HOXA11‐AS) on renal cancer remain unclear. In the current study, our data showed that the expression of HOXA11‐AS was significantly upregulated in clear cell renal cell carcinoma (ccRCC) tissues and cell lines. High HOXA11‐AS expression was associated with the advanced clinical stage, tumor stage, and lymph node metastasis. Function assays showed that HOXA11‐AS inhibition significantly suppressed renal cancer cells growth, invasion, and ETM phenotype. In addition, underlying mechanism revealed that HOXA11‐AS could act as a competing endogenous RNA (ceRNA) that repressed miR‐146b‐5p expression, which regulated its downstream target MMP16 in renal cancer. Taken together, our findings suggested that HOXA11‐AS could promote renal cancer cells growth and invasion by modulating miR‐146b‐5p–MMP16 axis. Thus, our findings suggested that HOXA11‐AS could serve as potential therapeutic target for the treatment of renal cancer.
Aerobic exercise, but not metformin, prevents reduction of muscular performance by AMPk activation in mice on doxorubicin chemotherapy
Authors: de Lima Edson A. , de Sousa Luís G. O. , de S. Teixeira Alexandre Abilio , Marshall Andrea G. , Zanchi Nelo E. , Neto José C. Rosa
Published: June 2018

Doxorubicin (DOX) is a chemotherapy agent widely used in clinical practice, and it is very efficient in tumor suppression, but the use of DOX is limited by a strong association with the development of severe muscle atrophy and cardiotoxicity effects. Reversion or neutralization of the muscular atrophy can lead to a better prognosis. Recent studies have proposed that the negative effect of DOX on skeletal muscle is linked to its inhibition of AMP‐activated protein kinase (AMPk), a key mediator of cellular metabolism. On the basis of this, our goal was to evaluate if aerobic exercise or metformin treatment, activators of AMPk, would be able to attenuate the deleterious effects on skeletal muscle induced by the DOX treatment. C57BL6 mice received either saline (control) or DOX (2.5 mg/kg body weight) intraperitoneally, twice a week. The animals on DOX were further divided into groups that received adjuvant treatment in the form of moderate aerobic physical exercise (DOX+T) or metformin gavage (300 mg/body weight/day). Body weight, metabolism, distance run, muscle fiber cross‐sectional area (CSA), and protein synthesis and degradation were assessed. We demonstrated that aerobic training, but not metformin, associated with DOX increased the maximal aerobic capacity without changing muscle mass or fiber CSA, rescuing the muscle fatigue observed with DOX treatment alone. This improvement was associated with AMPk activation, thus surpassing the negative effects of DOX on muscle performance and bioenergetics. In conclusion, aerobic exercise increases AMPk activation and improved the skeletal muscle function, reducing the side effects of DOX.
Work and Family Identities and Engineering Identity
Authors: Koul Ravinder
Published: June 2018

Background

Women are underrepresented in engineering. Furthermore, those who enter engineering fields are less likely than men to persist. Although conflict between work and family roles has been a major explanation for this gender gap, there has been little examination of how work and family identities fit with the engineering identity of undergraduate students preparing for careers in engineering.

Purpose

The purpose of this study was to examine the associations between direct and indirect measures of work and family identities and engineering identity among undergraduate students in Thailand.

Design/Method

A survey methodology was used to assess work‐ and family‐focused hoped‐for and feared possible selves, anticipated conflict between work and family roles, engineering self‐concept, and intention to pursue engineering professionally. Regression analyses were used to find relationships among these measures.

Results

Findings indicate that women with balanced hoped‐for and feared possible selves in both life domains of work and family reported significantly higher engineering self‐concept than other women in the study. In addition, the salience of work identity and family identity was significantly and more positively related with engineering identity for women than for men.

Conclusion

The findings indicate strong compatibility of family, work, and engineering identities for women who intended to pursue the profession. Theoretical and practical implications of these findings for gender‐based equity are discussed.
The state of nanomedicine in Sri Lanka: challenges and opportunities
Authors: Manatunga Danushika C. , de Silva Rohini M. , de Silva K.M. Nalin
Published: June 2018

Nanomedicine is rapidly expanding in the world due to its potential impact in alleviating various critical problems related to health. In this short review, we highlight the developments in nanomedicine in Sri Lanka through the work carried out by various scientists within the country. Potential challenges in the field and obstacles for conversion to clinical products will also be discussed. Even though there are limited contributions in relation to nano‐drug carriers, antibacterial agents, and bone prostheses, the research focused on vaccine development, diagnosis, and imaging tools, and high‐throughput screening platforms have not been developed. The main emphasis has been on therapeutic applications and anticancer drug delivery. Many hybrid biocompatible materials have been developed for drug delivery applications; however, work has been limited to in vitro studies due to various reasons. These findings can be extended to in vivo studies by strengthening the collaboration between nanotechnologists and health‐related scientists, whose contribution at the clinical stages is paramount. Because of the slow pace of infrastructure development and related policies for clinical trials, many discoveries are terminated at the publication stage. Therefore, product development and commercialization are very challenging in the Sri Lankan context. The attraction of venture capitalists, investors, and government commitment represent current challenges for the product development and implementation of nanomedicine applications within the country.
Time and cell‐dependent effects of endocytosis inhibitors on the internalization of biomolecule markers and nanomaterials
Authors: Sasso Luana , Purdie Laura , Grabowska Anna , Jones Arwyn Tomos , Alexander Cameron
Published: June 2018

Endocytosis is an essential function of cells, with key roles in the internalisation of nutrients, signal molecules and also drugs. Endocytic processes are therefore widely investigated in the context of drug delivery, and inhibitors of endocytic pathways have been used to provide information regarding uptake mechanisms of drug carrier materials. Here we describe studies in which two established inhibitors of clathrin dependent and independent endocytosis, chlorpromazine and methyl‐β‐cyclodextrin respectively, were employed to probe endocytic pathways of three cell lines chosen to represent tumour‐relevant or associated phenotypes: 3 T3 (fibroblasts), HCT 116 (colon cancer) and MGLVA‐1 (gastric cancer). For clathrin mediated endocytosis the data highlight that chlorpromazine inhibition of transferrin internalization, via clathrin dependent endocytosis, is cell and time dependent. We also show that inhibition of uptake is transient with a resumption of transferrin internalization after a maximal inhibition period. The same endocytosis inhibitors were used to probe the internalization of 50 and 100 nm carboxylated polystyrene nanoparticles (C‐PS‐NPs) as model drug delivery carriers. Flow cytometry data indicated that internalisation of C‐PS‐NPs varied considerably with the incubation time of cells with chlorpromazine or methyl‐β‐cyclodextrin, and that the effects were also markedly cell‐line dependent. These data highlight that the effects of endocytosis inhibitors on the internalisation pathways even of relatively simple nanoparticles are complex and interdependent. We suggest that mechanistic investigations of the endocytic processes which govern practical applications of nanoparticles for diagnostic and therapeutic applications should be considered on a cell, time and concentration basis.
Novel nanosuspension‐based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug
Authors: Vora Lalit K. , Vavia Pradeep R. , Larrañeta Eneko , Bell Steven E.J. , Donnelly Ryan F.
Published: June 2018

A nanosuspension (NS) was formulated from the lipophilic molecule cholecalciferol (CL) for enhanced transdermal delivery by embedding this NS into hydrophilic polymer‐based dissolving microneedles (DMNs). First, the NS was prepared by sonoprecpitation with different molecular weights of poly (vinyl alcohol) and poly (vinyl pyrrolidone) as stabilizers and using two different solvents for particle size and zeta potential optimization. DMN arrays were then prepared by centrifugation‐assisted micromoulding and subsequently dried. Poly (vinyl alcohol) (10 kDa) produced a NS with the lowest particle size ( ̴ 300 nm). These particles yielded DMN with good mechanical properties when combined with aqueous blends of high molecular weight poly (vinyl pyrrolidone) (360 kDa). The particle size remained similar before and after MN preparation, as confirmed by scanning electron microscope. The CL was in the amorphous state in the free particles as well as in the DMN and, hence, no characteristic CL peak was observed in differential scanning calorimetry or X‐ray diffraction. DMN arrays were found to be strong enough to bear a 32 N force, showed efficient skin insertion, and penetrated down to the third layer (depth ≈ 375 μm) of the validated skin model Parafilm M®. An ex vivo porcine skin permeation study using Franz diffusion cells compared the permeation of CL from CL‐NS‐loaded DMN arrays and MN‐free CL‐NS patches. It was observed that CL‐NS‐loaded DMN arrays showed significantly higher (498.19 μg ± 89.3 μg) ex vivo skin permeation compared with MN‐free CL‐NS patches (73.2 μg ± 26.5 μg) over 24 h. This is the first time a NS of a hydrophobic drug has been successfully incorporated into dissolving MN and suggest that NS‐containing DMN systems could be a promising strategy for transdermal delivery of hydrophobic drugs.
Dietary betaine improves meat quality and oxidative status of broilers under heat stress
Authors: Wen Chao , Chen Yueping , Leng Zhixian , Ding Liren , Wang Tian , Zhou Yanmin
Published: June 2018

BACKGROUND

In order to investigate the effects of dietary betaine on meat quality and oxidative status of broilers under heat stress (HS), a total of 144 Arbor Acres male broilers were randomly allocated to three groups with six replicates of eight broilers per replicate from 21 to 42 days of age. The broilers in the control group were raised at 22 °C and received a basal diet, and the broilers in the other two groups were raised at 34 °C from 9:00 to 17:00 and at 22 °C for the rest of the time and fed a basal diet with or without 1000 mg kg−1 betaine.

RESULTS

Dietary betaine supplementation tended (P < 0.1) to reverse the decreased body weight gain and feed intake of broilers induced by HS. The decreased redness (a* value) of breast muscle in broilers under HS was restored (P < 0.05) by betaine, which tended (P < 0.1) to decrease drip loss of breast muscle. The broilers fed betaine‐supplemented diets had a tendency (P < 0.1) to increase moisture content but decrease crude protein content of breast muscle in broilers under HS. Moreover, betaine resulted in higher (P < 0.05) glutathione content and activities of superoxide dismutase and glutathione peroxidase but lower (P < 0.05) malondialdehyde content in breast muscle of broilers exposed to HS.

CONCLUSION

Dietary betaine supplementation alleviated the negative effects of HS on some traits of meat quality and oxidative status of broilers. © 2018 Society of Chemical Industry
The solution with internal transition layer of the reaction‐diffusion equation in case of discontinuous reactive and diffusive terms
Authors: Levashova Natalia T. , Nefedov Nikolay N. , Nikolaeva Olga A. , Orlov Andrey O. , Panin Alexander A.
Published: June 2018

In this paper, we use the asymptotical analysis to construct the asymptotic approximation of the solution with internal transition layer of the boundary value problem for a reaction‐diffusion equation on the segment in case of discontinuous reactive and diffusive terms. The internal layer is located in the vicinity of a single point of discontinuity of the mentioned terms. We also investigate the existence and stability of such solution. For the last purpose, we use the asymptotical method of differential inequalities.