bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein
Authors: Batool Asiya , Aashaq Sabreena , Andrabi Khurshid I. 
Published: May 2019

AbstractEukaryotic initiation factor 4E (eIF4E), a fundamental effector and rate limiting element of protein synthesis, binds the 7‐methylguanosine cap at the 5′ end of eukaryotic messenger RNA (mRNA) specifically as a constituent of eIF4F translation initiation complex thus facilitating the recruitment of mRNA to the ribosomes. This review focusses on the engagement of signals contributing to growth factor originated maxim and their role in the activation of eIF4E to achieve a collective influence on cellular growth, with a key focus on conjuring vital processes like protein synthesis. The review invites considerable interest in elevating the appeal of eIF4E beyond its role in regulating translation viz a viz cancer genesis, attributed to its phosphorylation state that improves the prospect for the growth of the cancerous cell. This review highlights the latest studies that have envisioned to target these pathways and ultimately the translational machinery for therapeutic intervention. The review also brings forward the prospect of eIF4E to act as a converging juncture for signaling pathways like mTOR/PI3K and Mnk/MAPK to promote tumorigenesis.
Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients
Authors: Naseem Afreen , Bhat Zafar Iqbal , Kalaiarasan Ponnusamy , Kumar Bhupender , Bin Hafeez Zubair , Tiwari Raj Ranjan , Wahabi Khushnuma , Gandhi Gauri , Alam Rizvi M. Moshahid 
Published: May 2019

AbstractGenetic and epigenetic anomalies accountable for genetic dysregulation are the most common aberrations that determine the underlying heterogeneity of the tumor cells. Currently, phosphatase and tensin homolog (PTEN) incongruity has emerged as potent and persuasive malfunctioning in varied human malignancies. In this study, we have analysed the promoter hypermethylation and expression status of PTEN. We identified different mutations in the exonic region of PTEN. Functional consequences of these mutations were explored using in silico techniques. Promoter hypermethylation of PTEN was detected using methylation‐specific polymerase chain reaction (MS‐PCR), expression analysis was performed with immunohistochemistry (IHC) and mutation by direct sequencing in a total of 168 uterine cervix tumor cases. The findings were statistically correlated with the clinical parameters. In addition, the effect of nonsynonymous mutations was studied with molecular dynamics simulations. PTEN promoter hypermethylation (45.8%) was found to be significantly associated with the of PTEN loss (57.14%, P < 0.0001). Tumor stages, tumor size, lymph node (LN) were found to be significantly correlated with both PTEN promoter hypermethylation and PTEN loss. Histological grade, however, showed a significant association with only PTEN loss. In total, 11.76% of tumors exhibited mutations in exon 5 and 7, out of which E150K of exon 5 showed the highest deviations in the crystal structure of PTEN by in silico analysis. This study provides valuable insights into oncology and paves the path in the development of efficient biomarker and/or imperative therapeutic tool for cervical cancer treatment.
The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial
Authors: Ahmadi Majid , Hajialilo Mehrzad , Dolati Sanam , Eghbal‐Fard Shadi , Heydarlou Hanieh , Ghaebi Mahnaz , Ghassembaglou Arezou , Aghebati‐Maleki Leili , Samadi Kafil Hossein , Kamrani Amin , Rahnama Badrossadat , Rikhtegar Reza , Yousefi Mehdi 
Published: May 2019

AbstractAimAnkylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients.MethodsTest group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR‐27, miR‐17, and miR‐146a) and cytokines including Interleukin‐10 (IL‐10), TGF‐β, and IL‐6 were assessed by real‐time polymerase chain reaction. Furthermore, enzyme‐linked immunosorbent assay was done to determine the secretion levels of cytokines.ResultsAfter treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT‐PCR data indicated that the expression of miR‐17 and miR‐27 were significantly decreased following nanocurcumin treatment while miR‐146a and FoxP3 were significantly increased. Moreover, nanocurcumin‐treated group had high levels of IL‐10 and TGF‐β and low levels of IL‐6 production than control group.ConclusionThe findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases.This study is registered with IRCT.ir, number IRCT2017052927520N7.
The association between IL‐17A and IL‐23R polymorphisms and coronary artery disease risk in a Middle Eastern Chinese population
Authors: Zhao Qiang , Jiang Huaxin , Ma Teng , Qiu Hao , Guo Ming , Zhang Xinghua 
Published: May 2019

BackgroundPolymorphisms in IL‐17A and IL‐23R may affect the expression of these genes and could contribute to a patient's susceptibility to coronary artery disease (CAD). Although this association was investigated by previous studies, the relationship remains unclear.MethodWe conducted this hospital‐based case‐control study to determine whether polymorphisms in these two genes could be associated with a risk of CAD. A total of 191 patients and 131 controls, as determined by SXscore, were enrolled in this study. The genotyping was performed with the Sequenom MassARRAY platform.ResultsThe results showed that that the FPG and HbA1C levels were higher in patients with CAD than in the controls. In addition, the HDL and ApoA1 levels were significantly higher in the controls than in the cases. In contrast, the Lp(a) level was significantly lower in the controls than in the patients. The IL‐17A rs2275913 and IL‐23R rs6682925 polymorphisms were associated with an increased risk of CAD (rs2275913: AA vs GG: crude OR = 2.16, 95% CI = 1.08‐4.30; AG/AA vs GG: crude OR = 1.81, 95% CI = 1.04‐3.15; rs6682925 CC vs TT: crude OR = 1.91, 95% CI = 1.00‐3.63). The subgroup analysis by SXscore revealed that the IL‐23R rs6682925 polymorphism (CT/CC vs TT: crude OR = 3.72, 95% CI = 1.19‐11.66) was associated with an increased risk of CAD in patients with a high SXscore.ConclusionThis study suggested that T2DM, Lp(a), HDL‐c, and ApoA1 were risk factors of CAD and that the IL‐17A rs2275913 and IL‐23R rs6682925 polymorphisms may contribute to susceptibility to CAD.
Leukocytosis in patients with favism and association with blood transfusion
Authors: Faraji‐Goodarzi Mojgan , Taee Nadereh , Bajelan Amir , Safdari Mohammad 
Published: May 2019

AbstractIntroductionLeukocytosis is a condition marked by abnormal increase in leukocyte count due to an inflammatory response as a defense against most of the infections, or bone tumors; including leukemia. The aim of this study is to analyze the effect of blood transfusion in leukocytosis patients with favism as compared to patients treated with antibiotics or combination of both. MethodsA total of 97 patients with favism who were referred to the University hospital in 2016‐2017 were studied.Key findingsThese patients experienced acute hemolysis following beans meal. These patients were either treated with blood transfusion, antibiotics or combination of both. ConclusionsThis study shows that blood transfusion is an effective therapeutic option for the treatment of leukocytosis. Antibiotics are not deemed necessary for the treatment and blood transfusion alone, can decrease leukocytes to the normal level.
Comparison of computed tomography‐guided percutaneous needle biopsy and endobronchial biopsy in the diagnosis of multifocal pulmonary lesions
Authors: Li Xiao‐Feng , Zheng Li‐Li , He Yu , Wang Mao‐Shui 
Published: May 2019

AbstractBackgroundThe retrospective study aimed to compare computed tomography (CT)‐guided percutaneous needle biopsy (PNB) and endobronchial biopsy (EB) in the diagnosis of multifocal pulmonary lesions with endobronchial involvement.MethodsBetween November 2014 and June 2017, consecutive patients who had underwent both CT‐guided PNB and EB via bronchoscopy for diagnosis of pulmonary lesions were evaluated retrospectively. Tissue samples were submitted for pathological examination, acid‐fast bacilli, TB RT‐PCR, and mycobacterial culture. Sensitivities of the two methods alone or in combination were calculated and compared using Fisher's exact test.ResultsSixty‐seven patients (46 men and 21 women) were enrolled and could be diagnosed (32 malignant, 18 TB, and 17 benign). A final diagnosis of either malignant or TB diseases was made in 34 (68.0%) patients for CT‐guided PNBs, 19 (38.0%) patients for EBs, and 42 (84.0%) patients for the combination of both methods. Further statistical analysis showed significant difference in sensitivity between CT‐guided PNBs, or the combination of both methods, and EBs (all P < 0.05), and no difference between CT‐guided PNBs and the combination (P > 0.05). However, the combination of both methods appears to have the highest sensitivity in the detection of malignancies or TB diseases.ConclusionCompared with EB, CT‐guided PNB has a high diagnostic yield for the detection of TB and malignancy in patients with multifocal pulmonary lesions with endobronchial involvement. When the two biopsies are combined, it appears to provide an incremental diagnostic value for the pulmonary lesions.
Rat sinus mucosa‐ and periosteum‐derived exosomes accelerate osteogenesis
Authors: Sun Ruinan , Xu Shuyu , Wang Zuolin 
Published: May 2019

AbstractGuided bone regeneration (GBR) is commonly used for alveolar bone augmentation. The paracrine mechanism in the field of bone tissue engineering has been emphasized in recent years and exosomes are considered to have the potential of promoting osteogenesis. We aimed to study the influence of sinus mucosa and periosteum on bone regeneration through paracrine stimulation, especially via exosomes, and compare the differences between them. Here, we report that conditioned medium (CM) from sinus mucosa‐derived cells (SMCs) and periosteum‐derived cells (PCs) and the isolated exosomes enhanced the proliferation, migration and osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BM‐MSCs) in vitro. A rat model of femoral bone defects was used to demonstrate that the exosomes derived from SMCs (SMC‐Exos) and PCs (PC‐Exos) can accelerate bone formation in vivo. Furthermore, we present a preliminary discussion of the possible functional components involved in the effects of SMC‐Exos and PC‐Exos on bone regeneration. In conclusion, these results demonstrated that the sinus mucosa and periosteum can accelerate osteogenesis through paracrine effects and the exosomes play important roles in this process.
The cationic cell‐penetrating KT2 peptide promotes cell membrane defects and apoptosis with autophagy inhibition in human HCT 116 colon cancer cells
Authors: Maraming Pornsuda , Klaynongsruang Sompong , Boonsiri Patcharee , Peng Shu‐Fen , Daduang Sakda , Leelayuwat Chanvit , Pientong Chamsai , Chung Jing‐Gung , Daduang Jureerut 
Published: May 2019

AbstractThe anticancer activity of cationic antimicrobial peptides (AMPs) has become more interesting because some AMPs have selective recognition against cancer cells. However, their antitumor properties and underlying mechanisms in cancer cells have not been clearly understood. In this study, we evaluated the effects of KT2 (lysine/tryptophan‐rich AMP) on the cellular uptake and internalization mechanism, cell viability, surface charge of the cell membrane, membrane integrity, apoptotic cell death, and autophagy in human HCT 116 colon cancer cells. We found that KT2 interacted with the cell membrane of HCT 116 cells and was internalized into HCT 116 cells via clathrin‐mediated and caveolae‐mediated endocytosis mechanisms. The interaction of KT2 with cells caused cell membrane structure change, elevated membrane permeability, and KT2 also affected the lipid component. The results of atomic force microscopy showed cellular membrane defects of KT2‐treated cells. The internalized KT2 induced nuclear condensation and apoptotic cell death. It elevated the apoptotic factor levels including those of cytochrome c and apoptosis‐inducing factor. Furthermore, KT2 inhibited autophagy by the suppression of autophagy‐related 5, autophagy‐related 7, autophagy‐related 16 like 1, and Beclin‐1 proteins. In conclusion, these results revealed the cytotoxicity of cationic KT2 against HCT 116 cells and may help to clarify the interactions between cationic AMPs and cancer cells.
Micromixing efficiency in a rotating foam stirrer reactor with various reactor configurations and liquid viscosities
Authors: Yang Yu‐Cheng , Ouyang Yi , Yu Xiao‐Hui , Yu Qing‐Jie , Liu Jing‐Dong , Yang Shi‐Ying , Arowo Moses 
Published: May 2019

AbstractBACKGROUNDThe rotating foam stirrer reactor (RFSR) has shown its high mass transfer efficiency. Nevertheless, its micromixing efficiency, which is one of the significant parameters, still needs more comprehensive study for its better application and optimization. This work therefore employed the iodide–iodate reaction system to analyze the micromixing efficiency in an RFSR, and the effects of reactor configuration and liquid viscosity on micromixing efficiency were investigated.RESULTSThe results show that high micromixing efficiency can be achieved when the feed location is at the outer edge of the rotor. Solid foam with low pores per linear inch (ppi) and equipping baffles on the reactor wall can also considerably improve the micromixing efficiency. The results further reveal that the micromixing efficiency decreased with increasing liquid viscosity. Micromixing times in an RFSR with various configurations, estimated based on the incorporation model, ranged from 2.1 × 10−4 to 2.0 × 10−2 s. The minimum value is smaller than that of many conventional reactors and is competitive with that of some novel reactors. In addition, a correlation to predict the micromixing time based on the average energy dissipation rate was developed, which agreed well with experimental values.CONCLUSIONThis study indicates that the RFSR has excellent micromixing efficiency and also provides fundamental information for optimization of the RFSR and its application in process industries. © 2019 Society of Chemical Industry
Chemoirradiated neutrophils and T cells differentially affect immune functions of APCs
Authors: Franklin Cindy , Bruderek Kirsten , Schilling Bastian , Brandau Sven 
Published: May 2019

Abstract
Extracorporeal photopheresis (ECP) is known as an immunomodulatory therapy with few side effects, which is mainly used in the treatment of cutaneous T cell lymphoma, graft-versus-host disease, and allograft rejection. During ECP, leukocytes are separated from whole blood by leukapheresis, subsequently chemoirradiated with 8-methoxypsoralen and UVA light, and re-infused into the patient. Although clinically effective, its mode of action has not been fully elucidated. In the present study, we analyzed the interaction of chemoirradiated neutrophils and CD3+ lymphocytes with APC in an in vitro model. We report that chemoirradiated CD3+ T cells induced increased expression of activation markers on dendritic cells (DC), macrophages, and monocytes. Coculture of chemoirradiated CD3+ T cells with these APC also led to significantly increased secretion of TNF-α. Although less pronounced, additional activation of APC took place when APC were stimulated with LPS or IFN-γ. In contrast, chemoirradiated neutrophils did not show activating effects on APC. The presence of chemoirradiated neutrophils during LPS and IFN-γ stimulation of DC rather diminished DC and macrophage activation. In line with these findings DC cocultured with chemoirradiated CD3+ T cells, but not neutrophils, showed significantly increased activation of CD3+ responder lymphocytes in a mixed lymphocyte reaction. With this study, we demonstrate that chemoirradiated leukocytes have differential indirect immunomodulatory effects. Whereas chemoirradiated CD3+ T cells activate APC, chemoirradiated neutrophils suppress activation of APC in the presence of other activating factors, suggesting that the composition of the ECP-treated buffy coat might be of importance for its immunomodulatory effects.
Formation of 3‐hydroxyglutaric acid in glutaric aciduria type I: in vitro participation of medium chain acyl‐CoA dehydrogenase
Authors: Peters Verena , Morath Marina , Mack Matthias , Liesert Michael , Buckel Wolfgang , Hoffmann Georg F. , Vockley Jerry , Ghisla Sandro , Zschocke Johannes 
Published: May 2019

Abstract3‐Hydroxyglutaric acid (3‐OH‐GA) in urine has been identified as the most reliable diagnostic marker for glutaric aciduria type I (GA I). We showed that hydratation of glutaconyl‐CoA to 3‐hydroxyglutaryl‐CoA, which is subsequently hydrolyzed to 3‐OH‐GA, is efficiently catalyzed by 3‐methylglutaconyl‐CoA hydratase (3‐MGH). We have now investigated whether mitochondrial acyl‐CoA‐dehydrogenases can convert glutaryl‐CoA to glutaconyl‐CoA. Short‐chain acyl‐CoA dehydrogenase (SCAD), medium‐chain acyl‐CoA dehydrogenase (MCAD), and long‐chain acyl‐CoA dehydrogenase (LCAD) accepted glutaryl‐CoA as a substrate. The highest kcat of glutaryl‐CoA was found for MCAD (0.12 ± 0.01 second−1) and was about 26‐fold and 52‐fold higher than those of LCAD and SCAD, respectively. The turnover of MCAD for glutaryl‐CoA was about 1.5% of that of its natural substrate octanoyl‐CoA. Despite high Km (above 600 μM) and low turnover rate, the oxidation of glutaryl‐CoA by MCAD in combination with 3‐MGH could explain the urinary concentration of 3‐OH‐GA in GA I patients.
The genetic and biochemical basis of trimethylaminuria in an Irish cohort
Authors: Doyle Samantha , O'Byrne James J. , Nesbitt Mandy , Murphy Daniel N. , Abidin Zaza , Byrne Niall , Pastores Gregory , Kirk Richard , Treacy Eileen P. 
Published: May 2019

AbstractBackgroundInherited trimethylaminuria (TMAU), a rare genetic disorder of hepatic metabolism of trimethylamine (TMA) causing excessive accumulation of malodorous trimethylamine (TMA), is a socially distressing disorder. Diagnosis is made by biochemical analysis of urine, with the calculation of flavin monooxygenase trimethylamine conversion capacity. Genetic testing, sequencing the entire coding region of the FMO3 gene has been recommended for affected individuals who convert less than 90% of the total TMA load to TMAO.MethodsGenetic analysis was undertaken for 13 Irish patients with TMAU of varying phenotypic severity (three severe, six moderate, and four mild).ResultsA genetic diagnosis was made for seven patients, including for five of the nine moderate to severely affected cases. We noted the c.913G>T;p.(Glu305*) and c.458C>T;p.(Pro153Leu) mutations in this Irish population with severe TMAU which is consistent with our earlier findings in Australian and North American families of Irish and British descent.Three individuals were noted to be homozygous for the common variant haplotype c.472G>A;923A>G;p.(Glu158Lys);(Glu308Gly). We also identified three novel variants in this population, which are likely to be pathogenic: c.682G>A;p(Gly228Ser), c.694G>T:p(Asp232Tyr), and c.989G>A;p.(Gly330Glu).ConclusionUrinary biochemical analysis probably remains the first line diagnostic approach to classify the various types of TMAU. FMO3 gene analysis is likely only to be informative for certain presentations of TMAU.
A novel missense variant in SLC18A2 causes recessive brain monoamine vesicular transport disease and absent serotonin in platelets
Authors: Padmakumar Manisha , Jaeken Jaak , Ramaekers Vincent , Lagae Lieven , Greene Daniel , Thys Chantal , Van Geet Chris , BioResource NIHR , Stirrups Kathleen , Downes Kate , Turro Ernest , Freson Kathleen 
Published: May 2019

AbstractBackgroundBrain monoamine vesicular transport disease is an infantile onset neurodevelopmental disorder caused by variants in SLC18A2, which codes for the vesicular monoamine transporter 2 (VMAT2) protein, involved in the transport of monoamines into synaptic vesicles and of serotonin into platelet dense granules.Case presentationThe presented case is of a child, born of healthy consanguineous parents, who exhibited hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems. A trial treatment with L‐DOPA proved unsuccessful and the exact neurological involvement could not be discerned due to normal metabolic and brain magnetic resonance imaging results.Platelet studies and whole genome sequencing were performed. At age 4, the child's platelets showed a mild aggregation and adenosine triphosphate secretion defect that could be explained by dysmorphic dense granules observed by electron microscopy. Interestingly, the dense granules were almost completely depleted of serotonin. A novel homozygous p.P316A missense variant in VMAT2 was detected in the patient and the consanguineous parents were found to be heterozygous for this variant. Although the presence of VMAT2 on platelet dense granules has been demonstrated before, this is the first report of defective platelet dense granule function related to absent serotonin storage in a patient with VMAT2 deficiency but without obvious clinical bleeding problems.ConclusionsThis study illustrates the homology between serotonin metabolism in brain and platelets, suggesting that these blood cells can be model cells for some pathways relevant for neurological diseases. The literature on VMAT2 deficiency is reviewed.
Atmospheric heat sinks over the western Tibetan Plateau associated with snow depth in late spring
Authors: Xiao Zhixiang , Duan Anmin , Wang Ziqian 
Published: May 2019

AbstractThe atmospheric heat source/sink (AHS) and snow cover/depth over the Tibetan Plateau (TP) in late spring play important roles in modulating the evolution of Asian summer monsoons. However, quantitative estimation of the AHS over the TP is still a large challenge because of limited observational data. In this work, both data analyses and numerical simulations from the Weather Research and Forecasting model with an updated daily snow‐depth data set are conducted to explore the intrinsic connection between the AHS and snow depth over the TP in May. Data analyses indicate that only a weak negative relationship exists between snow depth and the AHS over the western TP. On the other hand, despite the overall consistency in the spatial pattern of the AHS between the reanalysis data sets and the Weather Research and Forecasting model, a strong cooling effect (about −14.4 W/m2) appears over the western TP (32°–40°N, 70°–78°E) and the Nyenchen Tanglha Mountains in the simulation, where the altitude is above 4,000 m with thick snow cover. This characteristic is opposite to that observed in reanalysis data sets. Further analysis indicates that the underestimated atmospheric net longwave radiative cooling effect that is associated with snow depth may exaggerate the atmospheric heat source in current reanalysis data sets. Large uncertainties in the AHS still exist in current state‐of‐the‐art reanalysis data sets, especially over the regions of the TP covered by snow.