bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating misreporting in condom use and its determinants among sex workers: Evidence from the list randomisation method
Authors: Treibich Carole , Lépine Aurélia
Published: October 2018

Social desirability bias, which is the tendency to underreport socially undesirable health behaviours, significantly distorts information on sensitive behaviours gained from self‐reports. We applied the list randomisation method to indirectly elicit condom use among female sex workers and tested it among 651 female sex workers in Senegal, a country where sex workers face high social stigma and where the AIDS epidemic is mainly concentrated among this population. On the basis of our list randomisation, we found that the condom use rate in the last sexual intercourse with a client was 78%, which is significantly lower than the 97% obtained when asked directly in the survey. When estimating condom use among the subgroups, we found that female sex workers who are at a higher risk of infection are less likely to use condoms.
The effect of patient satisfaction with academic hospitals on their loyalty
Authors: Rostami Mina , Ahmadian Leila , Jahani Yunes , Niknafs Aliakbar
Published: October 2018

Objectives

Patients' loyalty to a health care institution can lead to the aggregation of patients' medical history in an institution and facilitating access to records by health care providers. Considering the increase of the competition between providers, it is important to gain patients' satisfaction, which leads to their return and loyalty. Therefore, this study evaluated the effect of patients' satisfaction with service quality on their loyalty.

Methods

A cross‐sectional descriptive and analytical study was carried out in academic hospitals. A sample of 260 patients admitted to these hospitals was recruited. The data gathering tool was an expert‐validated questionnaire which its reliability was confirmed by Cronbach's alpha. Data were analyzed using descriptive statistics, correlation coefficient, and multivariate regression analysis in SPSS20.

Results

The mean score of service quality was calculated 74.23 out of 100. Among the quality dimensions, “physician visit” had the highest score with 84.01 ± 20, and the “waiting time” dimension had the lowest score with the mean score of 62.45 ± 27.53. The mean score of patients' loyalty was 67.88 ± 29.79. Satisfaction with the six dimensions of service quality: “cost of services,” “hospital environment,” “delivered services,” “access to physicians and health care institutions,” “provision of information to patients,” and “acquaintance with hospitals” were identified as the most influencing factors on loyalty.

Conclusions

The results showed that patient satisfaction with service quality affects their hospital choices and increases loyalty. In order to increase patient loyalty to academic hospitals, improving the services quality along with delivering cost‐effective cares, improving hospital environment, and providing useful information to patients are recommended.
Climate change and its impact on water availability of large international rivers over the mainland Southeast Asia
Authors: Liu Zhaofei , Wang Rui , Yao Zhijun
Published: October 2018

Changes in climate and the resulting hydrologic variability are of great concern in international river basins. Based on observed station data, climate change and its impact on water availability in large international rivers across mainland Southeast Asia (MSA) were investigated by a combined method of trend detection and hydrologic budget balance analysis. This method can be applied easily to other studies to evaluate impacts of climate change on run‐off and water resources at the basin scale. Precipitation showed a decreasing trend in the MSA during 1960–2016, especially in the dry season. Decreasing precipitation and increasing evapotranspiration were the main reasons for severe droughts during recent years. Climate change was the main reason for run‐off changes over the MSA. The presence of dams in the upstream region was not enough to change the annual variability of natural run‐off in the Mekong River. Run‐off and precipitation changes showed significant variances in different basins and regions, and in different periods. The overall trend of precipitation and run‐off showed a periodicity of about 35 years. Nonprecipitation effects were also significant in some regions, including increasing irrigation water demand in the Red River and increasing glacial melt in the Brahmaputra River basin. Melt increased at least 75.2 × 108 m3/10a during 1960–2003, representing 1.2% of mean annual run‐off in the Brahmaputra River. The positive effect of glacial meltwater was almost equal to the negative effect of evapotranspiration on run‐off change in the Lancang River. Increasing evapotranspiration played a dominant effect on run‐off changes in the Yarlung Zangbo River basin during 1960–2010.
CLDN18.1 attenuates malignancy and related signaling pathways of lung adenocarcinoma in vivo and in vitro
Authors: Luo Jiao , Chimge Nyam‐Osor , Zhou Beiyun , Flodby Per , Castaldi Alessandra , Firth Amy L. , Liu Yixin , Wang Hongjun , Yang Chenchen , Marconett Crystal N. , Crandall Edward D. , Offringa Ite A. , Frenkel Baruch , Borok Zea
Published: October 2018

Claudins are a family of transmembrane proteins integral to the structure and function of tight junctions (TJ). Disruption of TJ and alterations in claudin expression are important features of invasive and metastatic cancer cells. Expression of CLDN18.1, the lung‐specific isoform of CLDN18, is markedly decreased in lung adenocarcinoma (LuAd). Furthermore, we recently observed that aged Cldn18
−/− mice have increased propensity to develop LuAd. We now demonstrate that CLDN18.1 expression correlates inversely with promoter methylation and with LuAd patient mortality. In addition, when restored in LuAd cells that have lost expression, CLDN18.1 markedly attenuates malignant properties including xenograft tumor growth in vivo as well as cell proliferation, migration, invasion and anchorage‐independent colony formation in vitro. Based on high throughput analyses of Cldn18
−/− murine lung alveolar epithelial type II cells, as well as CLDN18.1‐repleted human LuAd cells, we hypothesized and subsequently confirmed by Western analysis that CLDN18.1 inhibits insulin‐like growth factor‐1 receptor (IGF‐1R) and AKT phosphorylation. Consistent with recent data in Cldn18
−/− knockout mice, expression of CLDN18.1 in human LuAd cells also decreased expression of transcriptional co‐activator with PDZ‐binding motif (TAZ) and Yes‐associated protein (YAP) and their target genes, contributing to its tumor suppressor activity. Moreover, analysis of LuAd cells in which YAP and/or TAZ are silenced with siRNA suggests that inhibition of TAZ, and possibly YAP, is also involved in CLDN18.1‐mediated AKT inactivation. Taken together, these data indicate a tumor suppressor role for CLDN18.1 in LuAd mediated by a regulatory network that encompasses YAP/TAZ, IGF‐1R and AKT signaling.
Investigating the effects of lycopene and green tea on the metabolome of men at risk of prostate cancer: The ProDiet randomised controlled trial
Authors: Beynon Rhona A. , Richmond Rebecca C. , Santos Ferreira Diana L. , Ness Andrew R. , May Margaret , Smith George Davey , Vincent Emma E. , Adams Charleen , Ala‐Korpela Mika , Würtz Peter , Soidinsalo Sebastian , Metcalfe Christopher , Donovan Jenny L. , Lane Athene J. , Martin Richard M. ,   the ProtecT Study Group,   The PRACTICAL consortium
Published: October 2018

Lycopene and green tea consumption have been observationally associated with reduced prostate cancer risk, but the underlying mechanisms have not been fully elucidated. We investigated the effect of factorial randomisation to a 6‐month lycopene and green tea dietary advice or supplementation intervention on 159 serum metabolite measures in 128 men with raised PSA levels (but prostate cancer‐free), analysed by intention‐to‐treat. The causal effects of metabolites modified by the intervention on prostate cancer risk were then assessed by Mendelian randomisation, using summary statistics from 44,825 prostate cancer cases and 27,904 controls. The systemic effects of lycopene and green tea supplementation on serum metabolic profile were comparable to the effects of the respective dietary advice interventions (R2 = 0.65 and 0.76 for lycopene and green tea respectively). Metabolites which were altered in response to lycopene supplementation were acetate [β (standard deviation difference vs. placebo): 0.69; 95% CI = 0.24, 1.15; p = 0.003], valine (β: −0.62; −1.03, −0.02; p = 0.004), pyruvate (β: −0.56; −0.95, −0.16; p = 0.006) and docosahexaenoic acid (β: −0.50; −085, −0.14; p = 0.006). Valine and diacylglycerol were lower in the lycopene dietary advice group (β: −0.65; −1.04, −0.26; p = 0.001 and β: −0.59; −1.01, −0.18; p = 0.006). A genetically instrumented SD increase in pyruvate increased the odds of prostate cancer by 1.29 (1.03, 1.62; p = 0.027). An intervention to increase lycopene intake altered the serum metabolome of men at risk of prostate cancer. Lycopene lowered levels of pyruvate, which our Mendelian randomisation analysis suggests may be causally related to reduced prostate cancer risk.
Financial firm bankruptcies, international stock markets, and investor sentiment
Authors: Papakyriakou Panayiotis , Sakkas Athanasios , Taoushianis Zenon
Published: October 2018

We consider bankruptcy announcements of large financial institutions in the United States and examine their impact on an international sample of 66 stock market indices. Employing an event‐study methodology, we find that stock markets exhibit strong adverse reaction in the aftermath of such announcements. Further, we develop a surprise measure, based on the country‐level investor sentiment, and find that stock markets in negatively surprised countries respond quickly by sustaining significantly larger declines in the first three trading days following the announcements. Finally, we examine the reaction of stock markets, conditional on the economic classification of their home countries, and find that stock markets in developing (developed) economies are associated with substantially larger (smaller) economic losses.
Board diversity, corporate governance, corporate performance, and executive pay
Authors: Sarhan Ahmed A. , Ntim Collins G. , Al‐Najjar Basil
Published: October 2018

Departing from previous studies, this paper investigates the impact of corporate board diversity on corporate performance and executive pay within the context of Middle East and North African countries. Our sample includes a balanced panel of 600 firm‐year observations, consisting of 100 individual firms drawn from five Middle Eastern countries (Egypt, Jordan, Oman, Saudi Arabia, and United Arab of Emirates) over the 2009–2014 period. The findings are three‐fold. First, board diversity, as measured by director gender and nationality, has a positive effect on corporate financial performance. Second, the relationship between board diversity and corporate performance is stronger in better governed firms than their poorly governed counterparts. Finally, board diversity, as measured by director gender, ethnicity, and nationality, enhances the pay‐for‐performance sensitivity but not the actual executive pay. Our results suggest that decisions about board diversity are not merely influenced by moral values; they arise because of the cost–benefit considerations of what diversity can bring to the firm. The findings are robust to controlling for different alternatives of board diversity measures, corporate governance proxies, corporate outcomes, and types of endogeneities.
In chemico assessment of potential sensitizers: Stability and direct peptide reactivity of 24 fragrance ingredients
Authors: Avonto Cristina , Wang Yan‐Hong , Chittiboyina Amar G. , Vukmanovic Stanislav , Khan Ikhlas A.
Published: October 2018

Twenty‐four pure fragrance ingredients of concern as potential skin sensitizers were previously subjected to degradation studies and evaluated using the high throughput with dansyl cysteamine (HTS‐DCYA) method. The experimental results showed that two‐thirds of the 24 fragrance ingredients underwent chemical degradation. In some cases, such degradation was accompanied by an increase in thio‐reactivity. These results prompted us to investigate the reactivity of the same ingredients using the direct peptide reactivity assay (DPRA). In the present work, the 24 chemicals were subjected to forced degradation for 150 days, and evaluated with both DPRA and HTS‐DCYA methods. At the end of the study, four and eight compounds remained non‐reactive in the DPRA and DCYA assay, respectively. Coumarin, benzyl salicylate, benzyl cinnamate and hexyl cinnamal were found unreactive in both assays, while cinnamal, cinnamyl alcohol, hydroxycitronellal and lilial were found negative in the DCYA but positive in the DPRA method. The incongruity in reactivity of these four compounds was attributed to a possible role of pro‐oxidants formed upon degradation, resulting in depletion of peptide without formation of apparent covalent adducts with the test chemical. To validate this hypothesis, the effect of hydrogen peroxide as model pro‐oxidant on both lysine‐ and cysteine‐heptapeptide depletion in the DPRA method was thus investigated. The obtained results showed little effect of oxidative conditions on lysine depletion, while cysteine depletion was significantly affected by concentrations above 1.1 mg/L of hydrogen peroxide. Overall, both in chemico methods confirmed chemical instability should be considered when assessing the skin sensitization potential of (un)known chemicals with alternative methods.
Prediction of clinically relevant drug‐induced liver injury from structure using machine learning
Authors: Hammann Felix , Schöning Verena , Drewe Jürgen
Published: October 2018

Drug‐induced liver injury (DILI) is the most common cause of acute liver failure and often responsible for drug withdrawals from the market. Clinical manifestations vary, and toxicity may or may not appear dose‐dependent. We present several machine‐learning models (decision tree induction, k‐nearest neighbor, support vector machines, artificial neural networks) for the prediction of clinically relevant DILI based solely on drug structure, with data taken from published DILI cases. Our models achieved corrected classification rates of up to 89%. We also studied the association of a drug's interaction with carriers, enzymes and transporters, and the relationship of defined daily doses with hepatotoxicity. The results presented here are useful as a screening tool both in a clinical setting in the assessment of DILI as well as in the early stages of drug development to rule out potentially hepatotoxic candidates.
Analysis of polyvinyl alcohol release from commercially available daily disposable contact lenses using an in vitro eye model
Authors: Phan Chau‐Minh , Walther Hendrik , Riederer Donald , Lau Charis , Lorenz Kathrine Osborn , Subbaraman Lakshman Nagapatnam , Jones Lyndon
Published: October 2018

The purpose of this work was to determine the release of polyvinyl alcohol (PVA) from etafilcon A, omafilcon A, and nelfilcon A daily disposable hydrogel contact lenses using a novel in vitro model. PVA is an ocular lubricant that can be found in multiple formulations of artificial tears. Nelfilcon A innately contains PVA, so only the release of PVA from this lens was evaluated. Etafilcon A and omafilcon A lenses were incubated in a PBS solution containing PVA. The release of PVA was evaluated using a novel in vitro blink platform with Milli‐Q water and PBS under various blink conditions and flow rates. Nelfilcon A lenses significantly released more PVA than other lenses at 0.5 and 1.5 h in both PBS and Milli‐Q water (p < 0.001). For nelfilcon A, there was no statistical significance between the release profiles of PVA between the blink and no‐blink conditions, or for the various flow rates (p > 0.05). All tested groups and lenses showed a burst release within the first 4.5 h and rapidly plateaued thereafter. The current study demonstrates that releasable PVA (whether through uptake or through being inherently available from the material) is loosely bound on hydrogel lenses, and the majority is released within 4.5 h. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1662–1668, 2019.
Circulating microRNA signatures serve as potential diagnostic biomarkers for Helicobacter pylori infection
Authors: Yu Jie , Xu Qiaoxia , Zhang Xiaoyu , Zhu Miao
Published: October 2018

Helicobacter pylor (H pylori), a Gram‐negative, microaerobic human pathogen, has been found to be involved in many gastroduodenal diseases. Accurate diagnosis of H pylori infection is a vital part of the effective management of gastroduodenal diseases. Circulating microRNAs (miRNAs) have shown the potential to be used as noninvasive biomarkers for the diagnosis of infectious diseases. The aim of this study was to explore plasma miRNAs as noninvasive biomarkers for H pylori infection. We performed a plasma miRNA expression profile using Illumina high‐throughput sequencing and validated the levels of differentially expressed miRNAs in the plasma of 63 H pylori‐infected patients and 41 healthy volunteers by quantitative real‐time polymerase chain reaction (qRT‐PCR). The sequencing results showed that 37 miRNAs were upregulated in the H pylori‐infected patients compared with that in the healthy volunteers, while six miRNAs were downregulated. qRT‐PCR and receiver operator characteristic analysis suggested that the expression of miR‐28‐3p, miR‐143‐3p, miR‐151a‐3p, and miR‐148a‐3p were closely associated with H pylori infection. Therefore, the four plasma miRNA panels mentioned above could serve as promising noninvasive biomarkers of H pylori infection.
Evaluation of STAT1 and Wnt5a gene expression in gingival tissues of patients with periodontal disease
Authors: Haftcheshmeh Saeed Mohammadian , Mohammadi Asadollah , Soltani Arash , Momtazi‐Borojeni Amir Abbas , Sattari Mandana
Published: October 2018

Periodontal disease is a common chronic inflammatory disease of the oral cavity. This disease occurs as a consequence of uncontrolled inflammatory immune responses against periodontopathic bacteria. Several studies have documented the proinflammatory roles of the Signal Transducer and Activator of Transcription 1 (STAT1) and Wnt5a in inflammatory diseases. However, there has been no detailed investigation of STAT1 and Wnt5a genes expression in periodontal disease. So, we aimed to evaluate the expressions of STAT1 and Wnt5a in patients with chronic and aggressive periodontitis and determine their correlation with clinical parameters. Three groups of subjects were enrolled including control (20 healthy individuals), chronic (25 patients), and aggressive periodontitis patients (25 patients). The expressions of STAT1 and Wnt5a were evaluated in gingival tissue samples using a Real‐time polymerase chain reactions assay. The expressions of STAT1 and Wnt5a were significantly upregulated in chronic and aggressive periodontitis compared with the healthy control. We also found that the expressions of STAT1 and Wnt5a increased in aggressive periodontitis compared with chronic periodontitis. In addition, there was the linear relationship between the expression of STAT1 and Wnt5a and the clinical parameters, including clinical attachment loss and periodontal pocket depth. A linear relationship between the expressions of Wnt5a and the clinical parameters was also identified. Taken together, our findings highlight the roles of STAT1 and Wnt5a in the pathogenesis of the periodontal inflammation, suggesting these molecules as valuable therapeutic targets.
Retracted: Advanced glycation end‐products induce oxidative stress through the Sirt1/Nrf2 axis by interacting with the receptor of AGEs under diabetic conditions
Authors: Chen Xiao‐Jun , Wu Wen‐Jun , Zhou Qi , Jie Jin‐Ping , Chen Xiong , Wang Fang , Gong Xiao‐Hua
Published: October 2018

Despite the administration of exogenous insulin and other medications used to control many aspects of diabetes mellitus (DM), increased oxidative stress has been increasingly acknowledged in DM development and complications. Therefore, this study aims to investigate the role of advanced glycation end‐products (AGEs) in oxidative stress (OS) of thyroid cells in patients with DM. Patients with DM with or without thyroid dysfunction (TD) were enrolled. Thyroid toxic damage was induced by adding AGE‐modified bovine serum albumin (AGE‐BSA) to normal human thyroid follicular epithelial cells. The cell viability, cell cycle, and cell apoptosis, as well as the content of reactive oxygen species (ROS), catalase (CAT), and malondialdehyde (MDA) in cells were measured. Thyroid hormones, T3, T4, FT3, and FT4 levels were measured by enzyme‐linked immunosorbent assay. Receptor for advanced glycation end products (RAGE), sirtuin1 ( Sirt1), and NF‐E2‐related factor 2 ( Nrf2) expressions were detected, and the mitochondrial membrane potential was measured. We found increased AGEs in the serum of DM patients with TD. By increasing AGE‐BSA concentration, cell viability; the thyroid hormones T3, T4, FT3, and FT4 levels; and mitochondrial membrane potential all significantly decreased. However, the increase in AGE‐BSA concentration led to an increase in cell apoptosis, RAGE, and nuclear factor‐κB expressions but produced the opposite effect on Sirt1, Nrf2, and heme oxygenase‐1 expressions, as well as a decrease in antioxidant response element protein levels. The AGE‐BSA increased ROS and MDA levels and reduced CAT level in normal human thyroid follicular epithelial cells on a dose independence basis. Our results demonstrated that AGEs‐mediated direct increase of RAGE produced OS in thyroid cells of DM by inactivating the Sirt1/Nrf2 axis.
Retracted: Inhibition of microRNA‐940 suppresses the migration and invasion of human osteosarcoma cells through the secreted frizzled‐related protein 1–mediated Wnt/β‐catenin signaling pathway
Authors: Lin Zun‐Wen , Zhang Wei , Jiang Si‐Ding , Wei Wen‐Bo , Li Xiao‐Feng
Published: October 2018

Osteosarcoma (OS) is the most common malignant tumor of bone with a high potential for metastasis. This study intends to explore whether microRNA‐940 (miR‐940) affects the development of OS cells and the underlying mechanism. OS and adjacent normal tissues were collected from OS patients; the OS cell line with the highest expression of miR‐940 was selected, which was then subjected to transfection of miR‐940 mimic, miR‐940 inhibitor, siRNA‐secreted frizzled‐related protein 1 (SFRP1) or LiCl (agonists of Wnt/β‐catenin pathway) to identify regulation of miR‐940 to OS cells through SFRP1. The targeting relationship between miR‐940 and SFRP1 was verified using dual‐luciferase reporter gene assay. Reverse‐transcription quantitative polymerase chain reaction and Western blot assay were performed to determine miR‐940, SFRP1, β‐catenin, and cyclinD1 and apoptosis‐related genes Fas, Bax, and Bcl‐2. MTT (3‐(4, 5‐dimethylthiazol‐2‐Yl)‐2, 5‐diphenyltetrazolium bromide) assay, scratch test, transwell assay, and flow cytometry were carried out to detect proliferation, migration, invasion, and apoptosis, respectively. Nude mice models were established to observe the tumor formation. Higher expression of miR‐940, β‐catenin, and cyclinD1 and lower SFRP1 expression were identified in OS tissues. miR‐940 targeted and negatively regulated SFRP1 expression. Furthermore, upregulated miR‐940 expression activated the Wnt/β‐catenin signaling pathway in OS. With the treatment of miR‐940 mimic, LiCL, or siRNA‐SFRP1, OS cells showed promoted proliferation, migration, invasion, tumor formation, and impeded apoptosis (further reflected by elevated Bcl‐2 expression and reduced Fas and Bax expression). The study demonstrates that miR‐940 can promote the proliferation, migration, and invasion but suppress the apoptosis of human OS cells by downregulating SFRP1 through activating Wnt/β‐catenin signaling pathway.
In silico identification and in vitro validation of nogalamycin N‐oxide (NSC116555) as a potent anticancer compound against non–small‐cell lung cancer cells
Authors: Obounchoey Phongphat , Tabtimmai Lueacha , Suphakun Praphasri , Thongkhao Kannika , Eurtivong Chatchakorn , Gleeson Matthew Paul , Choowongkomon Kiattawee
Published: October 2018

The epidermal growth factor receptor (EGFR) was found to be overexpressed in several cancers, especially in lung cancers. Finding new effective drug against EGFR is the key to cancer treatment. In this study, the GOLD docking algorithm was used to virtually screen for novel human EGFR inhibitors from the NCI database. Thirty‐four hit compounds were tested for EGFR‐tyrosine kinase (TK) inhibition. Two potent compounds, 1‐amino‐4‐(4‐[4‐amino‐2‐sulfophenyl]anilino)‐9,10‐dioxoanthracene‐2‐sulfonic acid (NSC125910), and nogalamycin N‐oxide (NSC116555) were identified with IC50 values against EGFR‐TK comparable to gefitinib; 16.14 and 37.71 nM, respectively. However, only NSC116555 demonstrated cytotoxic effects against non–small‐cell lung cancer, A549, shown in the cell cytotoxicity assay with an IC50 of 0.19 + 0.01 µM, which was more potent than gefitinib. Furthermore, NSC116555 showed cytotoxicity against A549 via apoptosis in a dose‐dependent manner.
Intravenous immunoglobulin G treatment increases live birth rate in women with recurrent miscarriage and modulates regulatory and exhausted regulatory T cells frequency and function
Authors: Jafarzadeh Sara , Ahmadi Majid , Dolati Sanam , Aghebati‐Maleki Leili , Eghbal‐Fard Shadi , Kamrani Amin , Behrad Behboud , Roshangar Leila , Jadidi‐Niaragh Farhad , Yousefi Bahman , Mehdipour Mahdi , Farzadi Laya , Yousefi Mehdi
Published: October 2018

Exhausted T cells and regulatory T (Treg) cells have been recently proposed to be new risk factors for recurrent miscarriage (RM). Intravenous immunoglobulin G (IVIG) treatment reported to modulate various immune cells. In this study, the effects of IVIG on the frequency and function of exhausted T cells, exhausted Tregs, and Treg cells, as well as pregnancy outcome in women with unexplained RM (URM), were investigated. Ninety‐four pregnant women with RM were enrolled. At the time of positive pregnancy, blood samples were drawn. Forty‐four patients with URM were included as IVIG receiving treated group and received 400 mg/kg of IVIG and the rest fifty patients were considered as a control group and received no IVIG administration. IVIG was given intravenously every 4 weeks during 32 weeks of gestation. Blood samples of patients were collected after the latest administration. Exhausted T cells, exhausted Tregs, and Treg cells were evaluated pre‐ and posttreatment in both groups. IVIG induced a significant decrease in the frequency of exhausted Tregs population and function as well as a significant increase in Treg cells population, however, IVIG failed to affect population and the function of exhausted T cells. Pregnancy outcome was successful in IVIG treated women (86.3%) and were significantly different (P = 0.0006) in compared with the untreated URM subjects (42%). Therefore, employing of IVIG increases Treg cells and diminishes exhausted Tregs responses in RM patients with cellular immune anomalies throughout the pregnancy. Immunemodulatory effects of IVIG are probably associated with successful pregnancy outcome.
Nicotine stimulates IL‐6 expression by activating the AP‐1 and STAT‐3 pathways in human endothelial EA.hy926 cells
Authors: Ung Trong Thuan , Nguyen Thi Thinh , Lian Sen , Li Shinan , Xia Yong , Kim Nam Ho , Jung Young Do
Published: October 2018

Interleukin‐6 (IL‐6), a pleiotropic cytokine, plays a key role in endothelial injury and atherosclerosis. In this study, we investigated the effects of nicotine, a major psychoactive compound in cigarette smoke, on IL‐6 expression and EA.hy926 endothelial cell invasion. Nicotine stimulated IL‐6 expression via the activator protein 1 (AP‐1) transcription factor. Pharmacological inhibition and mutagenesis studies indicated that p38 mitogen‐activated protein kinase (MAPK) mediated the IL‐6‐induced upregulation of nicotine in EA.hy926 cells. Furthermore, the antioxidant compound N‐acetyl‐cysteine eliminated the nicotine‐activated production of reactive oxygen species (ROS) and inhibited signal transducer and activator of transcription 3 (STAT‐3) phosphorylation; these two mechanisms mediated the upregulation of IL‐6 expression by nicotine. In addition, the EA.hy926 cells treated with nicotine displayed markedly enhanced invasiveness due to IL‐6 upregulation. Our data demonstrate that nicotine induced IL‐6 expression, which, in turn, enhanced the invasiveness of endothelial EA.hy926 cells, via activation of the p38 MAPK/AP‐1 and ROS/STAT‐3 signaling pathways.
Flavopiridol's effects on metastasis in KRAS mutant lung adenocarcinoma cells
Authors: Dogan Turacli Irem , Demirtas Korkmaz Funda , Candar Tuba , Ekmekci Abdullah
Published: October 2018

Background

There is still no clinically approved agent for mutant KRAS, which is the most common alteration in non–small‐cell lung cancer (NSCLC). Flavopiridol is a semisynthetic flavonoid that inhibits cell growth through cyclin‐dependent kinases in G1/S or G2/M of the cell cycle and induces apoptosis. In this study, we evaluated its effect on cellular apoptosis, survival, and metastasis mechanisms on KRAS mutant A549, Calu‐1, and H2009 cell lines.

Methods

The cytotoxic effects of flavopiridol on NSCLC cells were determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide cell viability test. The cells were treated with 200 and 400 nM flavopiridol, and, then, apoptosis, survival, and metastasis‐related protein expressions were determined by Western blot analysis. The antimetastatic effects of flavopiridol were assessed by wound healing and Galectin‐3 activity assay.

Results

Flavopiridol drastically affected toxicity in all KRAS mutant NSCLC cells at nanomolar concentrations. Also, it could efficiently inhibit wound healing and Galectin‐3 activity in all the cells tested. However, the metastasis‐related protein expressions did not reflect these obvious effects on blotting. p‐Erk was activated as a cellular survival mechanism to escape apoptosis in all the cells tested.

Conclusion

Although there are many mechanisms that still need to be elucidated, flavopiridol can be used as a metastasis inhibitor and an apoptosis inducer in KRAS mutant NSCLC.
Protective effects and mechanism of curcumin on myocardial injury induced by coronary microembolization
Authors: Liu Yang , Liu Yuanhang , Huang Xuecheng , Zhang Jingchang , Yang Lihui
Published: October 2018

Objective

Coronary microembolization (CME) is a common complication during the percutaneous coronary intervention (PCI). CME‐induced local myocardial inflammation and myocardial apoptosis are the primary causes of progressive cardiac dysfunction. Curcumin exerts a protective role in various cardiovascular diseases; however, its effects in CME are yet to be clarified. Therefore, the current study investigated the effects of curcumin on myocardial inflammatory responses, myocardial apoptosis, and cardiac dysfunctions induced by CME in rats.

Methods

A total of 40 Sprague–Dawley rats were randomly divided into the following groups: Sham operation (sham group), CME group, curcumin, and control with 10 rats in each group. The ascending aortas were clamped, and the CME‐model group was established by injecting microspheres into the apex of the left ventricle. An equivalent amount of normal saline was injected to establish the sham group. The cardiac functions, serum c‐troponin I level, and apoptotic index was examined. Also, the levels of Toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MYD88), nuclear factor κB (NF‐κB) p65, BCL2‐associated X protein (Bax), B‐cell lymphoma 2 (Bcl‐2), cleaved caspase‐3, tumor necrosis factor α (TNF‐α), and interleukin‐1β (IL‐1β) were detected.

Results

Myocardial dysfunction enhanced serum c‐troponin I, and apoptotic index were induced following CME. Moreover, CME elevated the expression of TLR4, MyD88, NF‐κB p65, cleaved caspase‐3, TNF‐α, and IL‐1β, while the Bcl‐2/Bax ratio decreased. Curcumin reversed these effects by CME, while the gastric lavage control did not exert any effect.

Conclusion

Curcumin was responsible for the anti‐CME‐induced myocardial injury. The effector mechanism might be related to the reduction of cardiomyocyte apoptosis and inhibition of myocardial inflammatory responses mediated by TLR4/MyD88/NF‐κB signaling pathway.
Integrated bioinformatic analysis reveals YWHAB as a novel diagnostic biomarker for idiopathic pulmonary arterial hypertension
Authors: Wang Tao , Zheng Xuan , Li Ruidong , Liu Xintian , Wu Jinhua , Zhong Xiaodan , Zhang Wenjun , Liu Yujian , He Xingwei , Liu Wanjun , Wang Hongjie , Zeng Hesong
Published: October 2018

Idiopathic pulmonary arterial hypertension (IPAH) is a severe cardiovascular disease that is a serious threat to human life. However, the specific diagnostic biomarkers have not been fully clarified and candidate regulatory targets for IPAH have not been identified. The aim of this study was to explore the potential diagnostic biomarkers and possible regulatory targets of IPAH. We performed a weighted gene coexpression network analysis and calculated module‐trait correlations based on a public microarray data set (GSE703) and six modules were found to be related to IPAH. Two modules which have the strongest correlation with IPAH were further analyzed and the top 10 hub genes in the two modules were identified. Furthermore, we validated the data by quantitative real‐time polymerase chain reaction (qRT‐PCR) in an independent sample set originated from our study center. Overall, the qRT‐PCR results were consistent with most of the results of the microarray analysis. Intriguingly, the highest change was found for YWHAB, a gene encodes a protein belonging to the 14‐3‐3 family of proteins, members of which mediate signal transduction by binding to phosphoserine‐containing proteins. Thus,
YWHAB was subsequently selected for validation. In congruent with the gene expression analysis, plasma 14‐3‐3β concentrations were significantly increased in patients with IPAH compared with healthy controls, and 14‐3‐3β expression was also positively correlated with mean pulmonary artery pressure (
R
2 = 0.8783;
p < 0.001). Taken together, using weighted gene coexpression analysis,
YWHAB was identified and validated in association with IPAH progression, which might serve as a biomarker and/or therapeutic target for IPAH.
Curcumin as an anti‐inflammatory agent: Implications to radiotherapy and chemotherapy
Authors: Farhood Bagher , Mortezaee Keywan , Goradel Nasser Hashemi , Khanlarkhani Neda , Salehi Ensieh , Nashtaei Maryam Shabani , Najafi Masoud , Sahebkar Amirhossein
Published: October 2018

Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti‐inflammatory drugs such as nonsteroidal anti‐inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well‐documented herbal anti‐inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase‐2, inducible nitric oxide synthase, and nuclear factor κB (NF‐κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF‐κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.
Effects of intracerebroventricular administration of irisin on the hypothalamus–pituitary–gonadal axis in male rats
Authors: Tekin Suat , Beytur Ali , Erden Yavuz , Beytur Asiye , Cigremis Yilmaz , Vardi Nigar , Turkoz Yusuf , Tekedereli Ibrahim , Sandal Suleyman
Published: October 2018

Irisin is a product of fibronectin type III domain‐containing protein 5 (FNDC5) and plays an important role in energy homeostasis. In this study, we aimed to determine effects of intracerebroventricular administration of irisin on the hypothalamus–pituitary–gonadal axis by molecular, biochemical, and morphological findings.

Fourty male Wistar‐Albino rats were used and divided into four groups including control, sham (vehicle), 10, and 100 nM irisin infused groups (n = 10). Hypothalamic gonadotropin releasing hormone (GnRH) level and serum luteinizing hormone (LH), follicle‐stimulating hormone (FSH), and testosterone levels were determined. Testicular tissue histology and spermiogram analysis were also performed.

Both irisin concentrations significantly reduced hypothalamic GnRH messenger RNA (mRNA) and protein levels (p < 0.05). It was found that serum LH, FSH, and testosterone levels and Sertoli and Leydig cell numbers were decreased by irisin administration (p < 0.05). In addition, irisin administration reduced sperm density and mobility (p < 0.05). However, it did not cause any change in testicular and epididymis weights and tubular diameter.

Our results reveal that irisin can play a role in the central regulation of reproductive behavior and also reduces testosterone levels by suppressing LH and FSH secretion. These results suggest that the discovery of irisin receptor antagonists may be beneficial in the treatment of infertility.
Isolation, cultivation, and characterization of primary bovine cochlear pericytes: A new in vitro model of stria vascularis
Authors: Giurdanella Giovanni , Montalbano Giuseppe , Gennuso Florinda , Brancati Serena , Lo Furno Debora , Augello Antonio , Bucolo Claudio , Drago Filippo , Salomone Salvatore
Published: October 2018

The study of strial pericytes has gained great interest as they are pivotal for the physiology of stria vascularis. To provide an easily accessible in vitro model, here we described a growth medium‐based approach to obtain and cultivate primary bovine cochlear pericytes (BCP) from the stria vascularis of explanted bovine cochleae. We obtained high‐quality pericytes in 8–10 days with a > 90% purity after the second passage. Immunocytochemical analysis showed a homogeneous population of cells expressing typical pericyte markers, such as neural/glial antigen 2 (NG2), platelet‐derived growth factor receptorβ (PDGFRβ), α‐smooth muscle actin (α‐SMA), and negative for the endothelial marker von Willebrand factor. When challenged with tumor necrosis factor or lipopolysaccharide, BCP changed their shape, similarly to human retinal pericytes (HRPC). The sensitivity of BCP to ototoxic drugs was evaluated by challenging with cisplatin or gentamicin for 48 hr. Compared to human retinal endothelial cells and HRPC, cell viability of BCP was significantly lower (
p < 0.05) after the treatment with gentamicin or cisplatin. These data indicate that our protocol provides a simple and reliable method to obtain highly pure strial BCP. Furthermore, BCP are suitable to assess the safety profile of molecules which supposedly exert ototoxic activity, and may represent a valid alternative to in vivo tests.
Contribution of regulatory T cells to cancer: A review
Authors: Najafi Masoud , Farhood Bagher , Mortezaee Keywan
Published: October 2018

Regulatory T cells (Tregs) represent a low number of T‐cell population under normal conditions, and they play key roles for maintaining immune system in homeostasis. The number of these cells is extensively increased in nearly all cancers, which is for dampening responses from immune system against cancer cells, metastasis, tumor recurrence, and treatment resistance. The interesting point is that apoptotic Tregs are stronger than their live counterparts for suppressing responses from immune system. Tregs within the tumor microenvironment have extensive positive cross‐talks with other immunosuppressive cells including cancer‐associated fibroblasts, cancer cells, macrophage type 2 cells, and myeloid‐derived suppressor cells, and they have negative interactions with immunostimulatory cells including cytotoxic T lymphocytes (CTL) and natural killer cells. A wide variety of markers are expressed in Tregs, among them forkhead box P3 (FOXP3) is the most specific marker and the master regulator of these cells. Multiple signals are activated by Tregs including transforming growth factor‐β, signal transducer and activator of transcription, and mTORC1. Treg reprogramming from an immunosuppressive to immunostimulatory proinflammatory phenotype is critical for increasing the efficacy of immunotherapy. This would be applicable through selective suppression of tumor‐bearing receptors in Tregs, including FOXP3, programmed death‐1, T‐cell immunoglobulin mucin‐3, and CTL‐associated antigen‐4, among others. Intratumoral Tregs can also be targeted by increasing the ratio for CTL/Treg.
Exosomes in tuberculosis: Still terra incognita?
Authors: Hadifar Shima , Fateh Abolfazl , Yousefi Mohammad Hadi , Siadat Seyed Davar , Vaziri Farzam
Published: October 2018

Today, diagnosis, vaccination, and treatment of tuberculosis (TB) remain major clinical challenges. Therefore, an introduction of new diagnostic measures and biomarkers is necessary to improve infection control. The ideal biomarker for TB infection can be defined as a host or pathogen‐derived biomolecule, which is potent for identifying infection and determining its clinical stage. Exosomes, defined as cell‐derived nanovesicles released into biological fluids, are involved in cell–cell communication and immune modulation. These vesicles have emerged as a new platform for improving the clinical diagnosis and prognosis of different infectious diseases and cancers. The role of these nanovehicles, as alternative biomarkers for the improvement of TB diagnosis and treatment, has been demonstrated in a significant body of literature. In this review, we summarized recent progress in the clinical application of exosome‐based biomarkers in TB infection.
Probiotics importance and their immunomodulatory properties
Authors: Yousefi Bahman , Eslami Majid , Ghasemian Abdolmajid , Kokhaei Parviz , Salek Farrokhi Amir , Darabi Narges
Published: October 2018

Mammalian intestine contains a large diversity of commensal microbiota, which is far more than the number of host cells. Probiotics play an insecure and protective role against the colonization of intestinal pathogenic microbes and increase mucosal integrity by stimulating epithelial cells. Probiotics have innate capabilities in many ways, including receptor antagonism, receptor expression, binding and expression of adapter proteins, expression of negative regulatory signal molecules, induction of microRNAs, endotoxin tolerance, and ultimately secretion of immunomodulatory proteins, lipids, and metabolites to modulate the immune system. Probiotic bacteria can affect homeostasis, inflammation, and immunopathology through direct or indirect effects on signaling pathways as immunosuppressant or activators. Probiotics suppress inflammation by inhibiting various signaling pathways such as the nuclear factor‐κB (NF‐κβ) pathway, possibly related to alterations in mitogen‐activated protein kinases and pattern recognition receptors pathways. Probiotics can also inhibit the binding of lipopolysaccharides to the CD14 receptor, thereby reducing the overall activation of NF‐κβ and producing proinflammatory cytokines. Some effects of modulation by probiotics include cytokine production by epithelial cells, increased mucin secretion, increased activity of phagocytosis, and activation of T and natural killer T cells, stimulation of immunoglobulin A production and decreased T cell proliferation. Intestinal microbiota has a major impact on the systemic immune system. Specific microbiota controls the differentiation of cells in lamina propria, in which Th17 cells secrete interleukin 17. The presence of Th17 and Treg cells in the small intestine is associated with intestinal microbiota, with the preferential Treg differentiation and the absence of Th17 cells, possibly reflecting alterations in the lamina propria cytokines and the intestinal gut microbiota.
The most reliable surface marker for the identification of colorectal cancer stem‐like cells: A systematic review and meta‐analysis
Authors: Abbasian Mahdi , Mousavi Elham , Arab‐Bafrani Zahra , Sahebkar Amirhossein
Published: October 2018

Several surface markers have been proposed for the identification and characterization of colorectal cancer stem‐like cells (CR‐CSLCs). However, their reliability in CR‐CSLCs identification remains controversial. This study evaluated the correlation between all candidate surface marker's expression and CSLCs properties (tumorigenicity) through monitoring in vivo tumor incidence and final tumor volume. PubMed, Web of Science, and Scopus databases were systematically searched until November 2017. A total of 27 studies were found that met the inclusion criteria for cluster of differentiation 133 (CD133) and CD44 markers. Results indicated that either CD133 or CD44 positive cells caused about twofold increase in tumor volume compared with the negative cells (p < 0.05). In two groups of cells derived from primary tumors and cell lines, CD133
+ cells had 25 and 1.45 times higher tumor incidence potential than CD133
− cells, respectively (
p < 0.05). Also, cohort evaluation showed that CD133 overexpression at protein level is a marker of poor overall survival in colorectal cancer (CRC) patients. While CD44
+ cells displayed twofold tumorigenicity compared with the negative cells (
p < 0.05), combination of CD44 and CD133 showed about sevenfold tumorigenicity potential (
p < 0.05). In conclusion, the present meta‐analysis suggests that CD133 is a robust biomarker to identify primary tumor CSLCs and can be proposed as a prognostic marker of CRC patient whereas it should be used with caution in cell lines. It seems to be more reliable to use CD133 in combination with CD44 as target biomarkers for the isolation of CR‐CSLCs in both cell line and primary tumor cells populations.