bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-21 promotes bevacizumab induced epithelial-mesenchymal transition in retinal pigment epithelial cells by regulating Snail expression via TGFβ1/smad2/3 signaling pathway
Authors: Yang Lingling , Hua Yingbin , Zhou Li , Song Shan , Xu Haifeng 
Published: May 2019

Abstract
Background

The purpose of this study was to investigate the role of microRNA-21 (miR-21) on bevacizumab (BEV)-induced Epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells in vitro.

Methods

Human retinal pigment epithelial cells line (ARPE-19) were exposed to clinical dosage of BEV and miR-21 expression was measured by qRT-PCR assay. The effects of miR-21 on BEV-induced EMT were examined through gain- or loss- expression of miR-21 using miR-21 mimic or inhibitor. The expression of α-smooth muscle actin (α-SMA), E-cadherin, Snail, TGFβ1 and smad2/3 were detected by western blot. TGFβ1/smad2/3 signaling was inhibited by using SB431542 and SIS3.

Results

Clinical dosage of BEV caused EMT and enhanced miR-21 expression in ARPE-19 cells. The inhibition of miR-21 attenuated the EMT effect of BEV, while over-expression of miR-21 promoted this activity. Snail was up-regulated by BEV and the promotion was partially suppressed by miR-21 inhibitor and aggravated by miR-21 mimic. miR-21 regulated BEV-induced TGFβ1 increasing and smad2/3 phosphorylation. The EMT and Snail expression promoted by BEV and miR-21 mimic in ARPE-19 cells was impaired by inhibition of TGFβ1/smad2/3 signaling.

Conclusions

miR-21 promoted BEV-induced EMT in ARPE cells through up-regulating of Snail expression via regulation of TGFβ1/smad2/3 signaling pathway. miR-21 might be a potential miRNA-based therapeutic target in reducing BEV-induced subretinal fibrosis.
Water reuse in the production of non-reinforced concrete elements: An alternative for decentralized wastewater management
Authors: Duarte Natalia Cangussu , Amaral Ana Elitha dos Santos , Gomes Bianca Graziella Lento Araujo , Siqueira Gustavo Henrique , Tonetti Adriano Luiz 
Published: May 2019

Abstract
Replacement of water by treated wastewater in concrete production, totally or in part, could lead to great water economy. Therefore, this experiment evaluated compressive strength from non-reinforced concrete samples produced with a combination of potable water (PW) and treated domestic wastewater (TW) at four different proportions: 0, 50, 75, and 100% of TW in the mixture. Ten samples were prepared for each proportion and the samples were tested for axial compression on the 28th day after concrete preparation. The data were statistically evaluated to analyze the influence of TW in concrete quality. It was possible to note that there was no significant difference between concretes produced using only PW and those produced with 50 and 75% TW, but when only TW was used, the concrete compressive strength increased on average 17.7%, which indicates the good potential of water reuse in the production of non-reinforced concrete elements.
Electrodialysis-based zero liquid discharge in industrial wastewater treatment
Authors: Havelka Jan , Fárová Hana , Jiříček Tomáš , Kotala Tomáš , Kroupa Jan 
Published: May 2019

Abstract
Over the past few decades, reverse osmosis (RO) has been the dominant technology employed in zero liquid discharge (ZLD) systems for industrial wastewater treatment (WWT). However, RO is limited to a maximum operating salinity of about 75 g kg−1. Electrodialysis (ED) is a potentially attractive option as it can achieve much higher concentrations, thereby reducing the capacity and energy demand of the subsequent evaporation step. Feed-and-bleed experiments were undertaken on a laboratory-scale ED stack using a series of model solutions based on the most common inorganic salts with the aim of determining maximum achievable concentrations. The maximum salt concentration achievable via ED ranged between 104.2 and 267.6 g kg−1, with levels predominantly limited by water transport. In addition, a straightforward review of how ED incorporation can affect ZLD process economics is presented. The operational cost of an ED-based ZLD system for processing RO retentate was almost 20% lower than comparable processes employing high-efficiency RO and disc tubular RO. As the ED-based ZLD system appears economically preferable, and as maximum achievable concentrations greatly exceeded RO operating limits, it would appear to be a promising approach for bridging the gap between RO and evaporation, and may even eliminate the evaporation step altogether.
Perioperative use of levosimendan in cardiac surgery
Authors: Lomivorotov V. V. , Yeremenko A. A. , Boboshko V. A. , Abubakirov M. N. 
Published: May 2019

<div data-canvas-width="623.7918644546122">It is known that low cardiac output in patients undergoing cardiac surgery is associated with organ dysfunction and mortality in the postoperative period. Catecholamines have been the standard therapy for many years, although they carry substantial risks for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve the cardiac function with</div><div data-canvas-width="623.8018800588713">no imbalance in oxygen consumption, and to have protective effects in other organs. Several clinical trials have found beneficial effects of cardiogenic and non-cardiogenic perioperative use of levosimendan. The aim of this article was to describe the mechanism of levosimendan action, as well as to overview the current data regarding its clinical application.</div><div data-canvas-width="623.8018800588713"><span><br /></span></div><div data-canvas-width="623.8018800588713"><span>Received 22 April 2015. Accepted 18 June 2015.</span></div><div data-canvas-width="311.3250427845475"> </div><div data-canvas-width="311.3250427845475"> </div>
Endothelin Receptor Antagonism: A New Era in the Treatment of Pulmonary Arterial Hypertension
Authors: Channick Richard N. , Rubin Lewis J. 
Published: May 2019

Abstract
The endothelin system has been extensively studied over the last several years. It is clear that endothelin-1 (ET-1) is a key mediator in pulmonary vascular biology and physiology. Abnormal increases in ET-1 production and decreased pulmonary clearance appear to play a major pathogenetic and perpetuating role in the pulmonary hypertensive process, through their vasconstrictive, smooth muscle cell proliferative and profibrotic effects. The degree of overexpression of ET-1 may correlate with the severity of pulmonary hypertension (PH). Advances in understanding the role of ET-1 in pulmonary hypertension have driven the development of endothelin receptor antagonists. One such agent, bosentan (Tracleer), is FDA approved for pulmonary arterial hypertension. Bosentan was approved following two randomized, placebo-controlled, double-blind studies that both showed marked improvement in exercise capacity after treatment with bosentan. The beneficial effects of bosentan appear to be sustained in most patients followed for as long as 22 months. Other uses for endothelin receptor antagonists are being examined, such as in combination with epoprostenol (Flolan) or in pediatric PH patients.
Insight into Mechanistic Action of Thymoquinone Induced Melanogenesis in Cultured Melanocytes
Authors: Zaidi Kamal U. , Khan Firoz N. , Ali Sharique A. , Khan Kausar P. 
Published: May 2019

Background:
Melanin plays a crucial role in camouflage, social communication and
protection against harmful ultraviolet radiations. Melanin is synthesized by melanocytes through
melanogenesis and several intrinsic and extrinsic factors are involved during the process. Any
change occuring in the normal melanogenesis process can cause severe pigmentation problems of
hypopigmentation or hyperpigmentation.

Objective:
The present study is based on the evaluation of the effect of thymoquinone on
melanogenesis and their possible mechanism of action using the B16F10 melanoma cell line for the
production via blocking signaling pathways.

Methods:
Phase contrast microscopy, cell viability, tyrosinase activity, melanin content and
western blot analysis were used in the present study.

Results:
In the present investigation, cultured melanocytes exhibit that the stimulation of melanin
synthesis when treated with thymoquinone. Tyrosinase activity and melanin production in B16F10
melanoma cell line was increased in doze-dependent manner. In western blot, we investigated the
involvement of the cAMP/PKA pathway in thymoquinone induced melanogenesis. It was observed
protein kinase inhibitors PKA, PKC, PKB and MEK1 decreased the stimulatory effects of
thymoquinone from 11.45- fold value to 8.312, 6.631, 4.51, and 7.211-fold value, respectively.
However, the results also prove that thymoquinone may partially induce tyrosinase expression via
PKA, PKB, PKC and MEK1 signaling pathways.

Conclusion:
The present finding proposed that thymoquinone is a protective challenger for
melanogenesis and it might be useful for the treatment of hypopigmentary disorders.
Brain Cancer-Activated Microglia: A Potential Role for Sphingolipids
Authors: Bottai Daniele , Adami Raffaella , Paroni Rita , Ghidoni Riccardo 
Published: May 2019

:Almost no neurological disease exists without microglial activation. Microglia has exert a pivotal role in the maintenance of the central nervous system and its response to external and internal insults. Microglia have traditionally been classified as, in the healthy central nervous system, “resting”, with branched morphology system and, as a response to disease, “activated”, with amoeboid morphology; as a response to diseases but this distinction is now outmoded. The most devastating disease that hits the brain is cancer, in particular glioblastoma. Glioblastoma multiforme is the most aggressive glioma with high invasiveness and little chance of being surgically removed. During tumor onset, many brain alterations are present and microglia have a major role because the tumor itself changes microglia from the pro-inflammatory state to the anti-inflammatory and protects the tumor from an immune intervention.:What are the determinants of these changes in the behavior of the microglia? In this review, we survey and discuss the role of sphingolipids in microglia activation in the progression of brain tumors, with a particular focus on glioblastoma.
Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency
Authors: Henriques Bárbara J. , Lucas Tânia G. , Martins Esmeralda , Gaspar Ana , Bandeira Anabela , Nogueira Célia , Brandão Otilia , Rocha Hugo , Vilarinho Laura , Gomes Cláudio M. 
Published: May 2019

Background:
Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a congenital rare
metabolic disease with broad clinical phenotypes and variable evolution. This inborn error of
metabolism is caused by mutations in the ETFA, ETFB or ETFDH genes, which encode for the
mitochondrial ETF and ETF:QO proteins. A considerable group of patients has been described to
respond positively to riboflavin oral supplementation, which constitutes the prototypic treatment for
the pathology.

Objectives:
To report mutations in ETFA, ETFB and ETFDH genes identified in Portuguese
patients, correlating, whenever possible, biochemical and clinical outcomes with the effects of
mutations on the structure and stability of the affected proteins, to better understand MADD
pathogenesis at the molecular level.

Methods:
MADD patients were identified based on the characteristic urinary profile of organic acids
and/or acylcarnitine profiles in blood spots during newborn screening. Genotypic, clinical and
biochemical data were collected for all patients. In silico structural analysis was employed using
bioinformatic tools carried out in an ETF:QO molecular model for the identified missense mutations.

Results:
A survey describing clinical and biochemical features of eight Portuguese MADD patients
was made. Genotype analysis identified five ETFDH mutations, including one extension
(p.X618QextX*14), two splice mutations (c.34+5G>C and c.405+3A>T) and two missense
mutations (ETF:QO-p.Arg155Gly and ETF:QO-p.Pro534Leu), and one ETFB mutation (ETFβ-
p.Arg191Cys). Homozygous patients containing the ETFDH mutations p.X618QextX*14,
c.34+5G>C and ETF:QO-p.Arg155Gly, all presented severe (lethal) MADD phenotypes. However,
when any of these mutations are in heterozygosity with the known ETF:QO-p.Pro534Leu mild
variant, the severe clinical effects are partly and temporarily attenuated. Indeed, the latter
destabilizes an ETF-interacting loop, with no major functional consequences. However, the position
155 in ETF:QO is localized at the ubiquinone binding and membrane interacting domain, and is
thus expected to perturb protein structure and membrane insertion, with severe functional effects.
Structural analysis of molecular models is therefore demonstrated to be a valuable tool to
rationalize the effects of mutations in the context of the clinical phenotype severity.

Conclusion:
Advanced molecular diagnosis, structural analysis and clinical correlations reveal that
MADD patients harboring a severe prognosis mutation in one allele can actually revert to a milder
phenotype by complementation with a milder mutation in the other allele. However, such patients
are nevertheless in a precarious metabolic balance which can revert to severe fatal outcomes
during catabolic stress or secondary pathology, thus requiring strict clinical follow-up.
Postprandial Hypertriglyceridaemia Revisited in the Era of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement, Main Text
Authors: Kolovou Genovefa D. , Watts Gerald F. , Mikhailidis Dimitri P. , Pérez-Martínez Pablo , Mora Samia , Bilianou Helen , Panotopoulos George , Katsiki Niki , Ooi Teik C. , Lopez-Miranda José , Tybjærg-Hansen Anne , Tentolouris Nicholas , Nordestgaard Børge G. 
Published: May 2019

:Residual vascular risk exists despite the aggressive lowering of Low-Density Lipoprotein Cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of Triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whethe a standardised Oral Fat Tolerance Test (OFTT) can improve atherosclerotic Cardiovascular (CV) Disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile.:An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no strict endpoint trials have been performed.:Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or nonfasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL).:Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample.
Antinuclear Antibodies and Lupus-like Manifestations in Rheumatoid Arthritis and Ankylosing Spondylitis Patients at 4 Months' Follow-up After Treatment with Infliximab and Etanercept
Authors: Aghdashi Mir Amir , Khadir Mohsen , Dinparasti-Saleh Roshan 
Published: May 2019

Background:
Up to 44% of patients treated with infliximab and 7% of patients treated
with etanercept reported to have anti-drug antibodies within the first 6 months of treatment. Recently,
anti-TNF-α therapies have been reported to be employed in the induction of the druginduced
lupus erythematous.

Objective:
The aim of the present study was to investigate the relationship between anti-TNFα antibodies
and various manifestations of lupus erythematous.

Methods:
We enrolled a total of 56 cases divided into 28 known cases of rheumatoid arthritis and
28 cases of ankylosing spondylitis patients and 56 controls. The case group was divided into 4
groups according to the underlying disease (RA or AS) and treatment regimen (infliximab or etanercept).
ANA and anti-dsDNA levels and lupus criteria were assessed at the beginning of the study
and 4 months after the initiation of anti-TNFα.

Results:
36% and 21% of RA patients treated with infliximab, were ANA and anti-dsDNA positive
after 4 months (P=0.003, P=0.025). 28% and 7% of RA patients treated with etanercept, were ANA
and anti-dsDNA positive after 4 months (P=0.009, P=0.15). 21% and 7% of AS patients treated
with infliximab, were ANA and anti-dsDNA positive, respectively (P=0.025, P=0.15). 14% and 7%
of AS patients treated with etanercept, were ANA and anti-dsDNA positive, respectively (P=0.63,
P=0.15). Three patients who were positive for auto-antibodies developed three criteria for SLE.

Conclusions:
Infliximab potentially may increase both ANA and anti-dsDNA levels in rheumatoid
arthritis, but only ANA in ankylosing spondylitis patients. In general, clinicians should consider
different clinical symptoms of ATIL, which may be present as a lupus-like syndrome similar to
idiopathic SLE or classical DIL.
STK33-dependent transcriptional regulation of SFTA3 induces Cisplatin-resistance in lung adenocarcinoma
Authors: Zhou Kuilong , Dong Runzhi , Wang Zhiheng , Tang Zhian , Gao Xuezhen , Du Yaqing , Zhang Xiaoli , Li Xiangying , Xie Qingfan 
Published: May 2019

:
Drug-resistance has become a major obstacle for Cisplatin usage in non-small cell lung cancer. In this study, we identified a poorly-studied kinase Serine/Threonine Kinase 33 (STK33) as the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma. Additionally, STK33-dependent Cisplatin-resistance promotes tumor growth of lung adenocarcinoma both in vitro and in vivo. Clinically, STK33 expression was enriched in lung adenocarcinoma and was correlated to poor prognosis of lung cancer patients. Mechanically, STK33 promoted cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of surfactant associated 3 (SFTA3), indicating that STK33-SFTA3 signaling axis could be a potential therapeutic target for Cisplatin-resistant lung adenocarcinoma.
Edukasi dan Sosialisasi Gerakan masyarakat Cerdas Menggunakan Obat (Gema Cermat)
Authors: Nining Nining , Yeni Yeni 
Published: May 2019

Health problems are so complex today. It encourages the people to look for effective treatment alternatives and also efficient in terms of cost. Self medication is being an alternative that has been taken by the the people. Irrational self medication management could lead to disadvantages such as medication errors due to misdiagnosis, inappropriate drugs use due to bias of information from drug advertisements and unwanted drug reactions. Education and Socialization of Gema Cermat was conducted by UHAMKA pharmacist lecturers on December 24th, 2017 in cooperation with PCPM Setu and pharmacists PC IAI Bekasi district as an effort in order to improve the concern, awareness, understanding and skill of people in using drugs properly and correctly. The methods used are CBIA, giving the brochure of Gema Cermat, the pocket books of drugs use and drugs classification, pre-test, post-test and materials about Gema Cermat through oral presentation by a pharmacist. The results of education and socialization of Gema Cermat are improving the values of the community regarding the proper and correct use of drugs. It could be seen from the increasing of average pre-test score, 72.5 to 89.7 on post-test. People could analyze and record data that they need to be considered on the drugs use so that the proper and correct use of drugs can be achieved.
Estrategias para aumentar el interés y disminuir el temor a aprender Física y Matemáticas
Authors: Rentería Servín Beatriz Olivia 
Published: May 2019

<p>La Física y las Matemáticas representan un reto para la enseñanza. Un considerable número de estudiantes expresan tener grandes dificultades con estas dos asignaturas; uno de los primeros obstáculos a vencer para lograr un óptimo aprendizaje de dichas asignaturas son las ideas negativas adquiridas previamente; por ejemplo: “La asignatura es muy difícil”, “La asignatura es aburrida”, “Nunca me ha ido bien en esas materias”, etcétera.</p> <p>En este trabajo se presentan algunas actitudes y estrategias que se recomienda poner en práctica a los asesores de Bachillerato a Distancia, pues han resultado favorables al aplicarlas en algunos cursos de la asignatura de Física y Matemáticas en el Bachillerato a Distancia de la UNAM.</p>
PİŞMİŞ SERAMİK ATIKLARIN ARTİSTİK YÜZEYLERDE GERİ DÖNÜŞÜMÜ VE ÇAĞDAŞ SERAMİK SANATÇISI DAVİD BİNNS
Authors: POYRAZ Mine 
Published: May 2019

Pişmiş seramik malzeme, bünyesi gereği yeniden kullanılamayan, depolanması, yok edilmesi ya da geri dönüştürülmesi zor, geri dönüşüm uygulamaları arasında yer almaktadır. Seramik kaplama bünyelerine pişmiş katı atıkların öğütülerek geri dönüşüm amaçlı kullanıldığı uygulamalara Dünyada rastlanmakla birlikte, ülkemiz seramik sektöründe firmaların pişmiş atık geri dönüşüm uygulamalarına çok az rastlanmaktadır. Özellikle atıkların tane boyutu daha iri olarak kullanıldığı artistik uygulamalara ise daha nadir rastlanmaktadır. Bu alanda David Binns ve Alexander Brenner tarafından yapılan atık malzemelerin geri dönüşümü çalışmaları daha artistik uygulamalar olarak karşımıza çıkmaktadır. Çağdaş seramik sanatçısı David Binns farklı kaynaklardan ilham alarak seramik, cam ve agregadan oluşan malzemelere alternatif kullanım alanları araştırarak, yüksek oranda geri dönüşümlü üretimler yapmaktadır. Bu çalışmada artistik pişmiş atık geri dönüşüm uygulamalarının çok az rastlanır olması nedeni ile farklı bünyelerde pişmiş atıklarının kullanıldığı artistik uygulamalar gerçekleştirilmiştir.