bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tributyltin oxide exposure impairs mouse oocyte maturation and its possible mechanisms
Authors: Yang Lei‐Lei , Cui Ying‐Xue , Ma Jun‐Yu , Ge Zhao‐Jia , Shen Wei , Yin Shen 
Published: September 2018

AbstractTributyltin oxide (TBTO) has been widely used as marine antifouling composition, preservative, biocide, and a stabilizer in plastic industry. Previous studies have indicated that TBTO can cause immunotoxicity as an environmental pollutant. However, little is known about its reproductive toxicity, especially on female oocyte maturation and the underlying mechanisms. In this study, mouse oocytes were cultured with different concentrations of TBTO in vitro, and several crucial events during meiotic maturation were evaluated. We found that the first polar body extrusion rate was significantly reduced, which reflected the disruption of meiotic maturation. The rate of abnormal spindle organization increased significantly, accompanied with a higher rate of chromosome misalignment. In addition, TBTO treatment increased reactive oxygen species generation markedly, which also accelerated the early‐stage apoptosis. Moreover, heterogeneous mitochondrial distribution, mitochondrial dysfunction, and higher rate of aneuploidy were detected, which consequently disrupted in vitro fertilization. In conclusion, our results indicated that TBTO exposure could impair mouse oocyte maturation by affecting spindle organization, chromosome alignment, mitochondria functions, oxidative stress, and apoptosis.
MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors
Authors: Pereira Sofia S , Monteiro Mariana P , Costa Madalena M , Ferreira Jorge , Alves Marco G , Oliveira Pedro F , Jarak Ivana , Pignatelli Duarte 
Published: September 2018

AbstractUnraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen‐activated protein kinase (MAPK) signaling pathways (extracellular signal‐regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK‐MAPK‐ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho‐p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK‐MAPK‐ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.
Negative regulation of the RLR‐mediated IFN signaling pathway by duck ubiquitin‐specific protease 18 (USP18)
Authors: Gu Tiantian , Lu Lu , An Chen , Zhang Yu , Wu Xinsheng , Xu Qi , Chen Guohong 
Published: September 2018

AbstractUbiquitin‐specific protease 18 (USP18) plays an important role in regulating type I interferon (IFN) signaling in innate immunity, and has a crucial impact on the IFN therapeutic effect. Although significant progress has been made in elucidating USP18 function in mammals, the role of USP18 in ducks (duUSP18) remains poorly understood. In this study, we cloned the USP18 gene from white crested ducks by reverse transcription polymerase chain reaction (RT‐PCR) and rapid amplification of complementary DNA (cDNA) ends. We determined that duUSP18 cDNA contains a 52‐bp 5′UTR, a 1,131‐bp open reading frame and a 356‐bp 3′UTR, and encodes a 376‐amino acid protein. Multiple sequence alignments showed that duUSP18 shares high similarity with USP18 from other vertebrates. Overexpression of duUSP18 inhibited nuclear factor‐κB (NF‐κB) and interferon regulatory factor 1 (IRF1) activity, and reduced IFN‐β production following 5′ triphosphate double‐stranded RNA (5′ppp dsRNA) or lipopolysaccharide (LPS) stimulation. duUSP18 knockdown significantly activated 5′ppp dsRNA‐induced and LPS‐induced NF‐κB and IRF1 activation, and induced IFN‐β expression in duck embryo fibroblasts. Furthermore, Quantitative real‐time PCR (qRT‐PCR) revealed that overexpression or knockdown of duUSP18 could alter the expression of genes related to the RLR‐mediated IFN signaling pathway following the treatment with 5′ppp dsRNA. In addition, site‐directed mutation analysis revealed that cysteine 66 (C66), histidine 313 (H313), and histidine 321 (H321) of duUSP18 were critical for inhibiting IFN‐β activity. Taken together, these results suggest that duck USP18 plays an important role in innate immune responses against double‐stranded RNA viruses in the RLR‐mediated IFN signaling pathway, and that further studies are warranted to elucidate its underlying mechanisms, which could provide molecular insights into the effect of the treatment of duck diseases.
Streptozotocin‐induced type II diabetic rat administered with nonobesogenic high‐fat diet is highly susceptible to myocardial ischemia–reperfusion injury: An insight into the function of mitochondria
Authors: Ansari Mahalakshmi , Gopalakrishnan Senthilkumar , Kurian Gino A. 
Published: September 2018

AbstractRationaleOur recent study suggested that ischemia–reperfusion (I/R) induced oxidative stress was minimal in the rat heart during initial stage of diabetes and the one that progressed to diabetic cardiomyopathy (DCM), despite having higher infarct and low cardiac performance. Mitochondrial dysfunction is an important mediator for adverse outcome in rat heart affected with diabetes, which is also a potential contributor for the cardiac reperfusion injury.ObjectiveThe current study aims to evaluate the susceptibility of diabetes heart with or without myopathy to I/R injury and its influence on cardiac mitochondrial function.Methods and ResultsMale Wistar rats (3 weeks old) were fed with high‐fat diet for 8 weeks followed by diabetes mellitus (DM) induction via streptozotocin (35 mg/kg body weight) and maintained for further 4 weeks. The animal displayed cardiomyopathy characteristics like hypertrophy, fibrosis, and insulin resistance‐termed diabetic cardiomyopathy (DCM). To study the specific effect of DCM on I/R, we included diabetic rats without cardiomyopathy. Induction of I/R in different groups suggested higher vulnerability to injury in DCM rat hearts than DM and normal (measured via hemodynamics, triphenyltetrazolium chloride stain, and apoptotic markers). Mitochondrial function at the subpopulation level was evaluated with respect to adenosine triphosphate (ATP) concentration, membrane potential, swelling behavior, and oxidative stress, wherein the results confirmed I/R‐induced mitochondrial dysfunction. Unlike normal heart, DM, and DCM heart challenged to I/R exhibited altered ATP producing capacity among subsarcolemmal and interfibrillar mitochondria.ConclusionThe above results suggest that mitochondrial changes associated with diabetes and cardiomyopathy significantly contribute to the adverse outcome of I/R injury.
Matrix metalloproteinase‐13 is a target gene of high‐mobility group box‐containing protein 1 in modulating oral cancer cell invasion
Authors: Chan Chien‐Yi , Lin Tzu‐Yuan , Sheu Jim Jinn‐Chyuan , Wu Wen‐Chieh , Huang Chun‐Yin 
Published: September 2018

AbstractTranscription factor high‐mobility group box‐containing protein 1 (HBP1) may function as a tumor suppressor in various types of cancer. In a previous study, we demonstrated that HBP1 suppressed cell invasion in oral cancer. To further understand the underlying mechanism, the current study is aimed at investigating how HBP1 exerts its antimetastatic potential in oral cancer. In a cell model, ectopic expression of HBP1 potently suppressed epithelial–mesenchymal transition, cellular migration, and invasion; conversely, HBP1 knockdown promoted these malignant phenotypes. The matrix metalloproteinase (MMP) family is highly implicated in tumor metastasis. Therefore, we examined the effect of HBP1 on the activation of the MMP members, MMP‐2, ‐9, and ‐13 that are highly associated with the aggressiveness of oral cancer. Ectopic expression of HBP1 resulted in a mild reduction in the expression and activity of MMP‐2 and ‐9, yet it had a potent inhibitory effect on MMP‐13. In contrast, HBP1 knockdown strongly enhanced the activation of MMP‐13. Further, we demonstrated that MMP‐13 is a target of HBP1 transcription repression as evidenced by the identification of an HBP1 binding site in the cis proximal region of the MMP‐13 promoter. More important, MMP‐13 knockdown significantly alleviated HBP1 small interfering RNA‐mediated promotion in cell invasion. Analysis of oral tumor specimens revealed that the low HBP1 (<0.3‐fold)/high MMP‐13 (>3‐fold) status was associated with metastatic potential. All told, our study provides evidence supporting the idea that the HBP1–MMP‐13 axis is a key regulator of the aggressiveness in oral cancer.
Upregulation of long noncoding RNA MEG3 inhibits the osteogenic differentiation of periodontal ligament cells
Authors: Liu Yi , Zeng Xuemin , Miao Jie , Liu Chunpeng , Wei Fulan , Liu Dongxu , Zheng Zhong , Ting Kang , Wang Chunling , Guo Jie 
Published: September 2018

AbstractObjectiveThis study aims to discuss long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) function of regulating osteogenesis in human periodontal ligament cells (hPDLCs).MethodsFirst, use of a mineralizing solution induced osteogenic differentiation of hPDLCs to establish a differentiated cell model. Through microarray analysis, we selected a lncRNA MEG3 with marked changes between differentiated and undifferentiated cells. The quantitative polymerase chain reaction was used to detect the
MEG3 content and an enzyme‐linked immunosorbent assay was used to detect changes in related proteins. Cell viability was determined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and apoptosis was measured by flow cytometry. Alizarin red staining was also used to evaluate cells’ osteogenic level. Finally, RNA‐binding protein immunoprecipitation assays were conducted to further clarify the endogenous relationship between
MEG3 and bone morphogenetic protein 2 (
BMP2) in hPDLCs.ResultsMEG3 was downregulated in osteogenic differentiation hPDLCs induced by mineralizing solution. Overexpression of
MEG3 inhibited cell viability and increased cell apoptosis.
MEG3 overexpression can reverse osteogenic differentiation induced by mineralizing solution.
MEG3 can suppress
BMP2 through interaction with heterogeneous nuclear ribonucleoprotein I.ConclusionUpregulation of MEG3 inhibits the osteogenic differentiation of periodontal ligament cells by downregulating
BMP2 expression.
Structural basis of urea‐induced unfolding of Fasciola gigantica glutathione S‐transferase
Authors: Kalita Jupitara , Shukla Rohit , Tripathi Timir 
Published: September 2018

AbstractGlutathione S‐transferases (GSTs) are enzymes that are involved in the detoxification of harmful electrophilic endogenous and exogenous compounds by conjugating with glutathione (GSH). The liver fluke GSTs have multifunctional roles in the host–parasite interaction, such as general detoxification and bile acid sequestration to synthase activity. The GSTs have been highlighted as vaccine candidates towards parasitic flukes. In this study, we have thoroughly examined the urea‐induced unfolding of a mu‐class Fasciola gigantica GST1
(FgGST1) using spectroscopic techniques and molecular dynamic simulations. FgGST1 is a highly cooperative molecule, because during urea‐induced equilibrium unfolding, a concurrent unfolding of the protein without stabilization of any folded intermediate was observed. The protein was stabilized with conformational free energy of about ~12.36 kcal/mol. The protein loses its activity with increasing urea concentration, as the GSH molecule is not able to bind to the protein. We also studied the fluorescence quenching of Trp residues and the obtained
K
SV data that provided additional information on the unfolding of FgGST1. Molecular dynamic trajectories simulated in different urea concentrations and temperatures indicated that urea destabilizes FgGST1 structure by weakening hydrophobic interactions and the hydrogen bond network. We observed a precise correlation between the in vitro and in silico studies.
Circulating miR‐22‐5p and miR‐122‐5p are promising novel biomarkers for diagnosis of acute myocardial infarction
Authors: Wang Yu , Chang Wenguang , Zhang Yuan , Zhang Lei , Ding Han , Qi Hongzhao , Xue Sheng , Yu Hua , Hu Longgang , Liu Dacheng , Zhu Wenjie , Wang Yin , Li Peifeng 
Published: September 2018

AbstractBackground/AimsThis study sought to evaluate the potential of circulating microRNAs (miRNAs) as novel indicators for acute myocardial infarction (AMI).MethodsPlasma samples were collected from each participant, and total RNA was extracted. Quantitative real‐time polymerase chain reaction were used to investigate the expression of circulating miRNAs. We measured circulating levels of six individual miRNAs, which are known to be relevant to AMI, in the plasma samples from 66 AMI patients and 70 non‐AMI healthy comparisons.ResultsFive small RNAs were specifically expressed in AMI patients, plasma miR‐122‐5p levels is significantly elevated (p < 0.0001) in AMI patients, while plasma miR‐22‐5p (
p < 0.05) levels were significantly decreased. In addition, significant correlations between miR‐22‐5p and miR‐122‐5p (
R = 0.773), miR‐122‐5p and creatine kinase isoenzyme (CK‐MB;
R = 0.6296) were detected. Further, receiver operating characteristic (ROC) analysis indicated that miR‐22‐5p showed considerable diagnostic efficiency for predicting AMI (area under the curve [AUC] = 0.975). Combining miR‐22‐5p and miR‐122‐5p in a panel increased the sensitivity (98.6%) of distinguishing between patients with AMI and healthy comparisons.ConclusionCirculating miR‐22‐5p and miR‐122‐5p could be considered promising novel diagnostic biomarkers for AMI.
No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV‐1–Infected Subjects
Authors: Vourvahis Manoli , McFadyen Lynn , Nepal Sunil , Valluri Srinivas Rao , Fang Annie , Fate Gwendolyn D. , Wood Linda S. , Marshall Jean‐Claude , Chan Phylinda L. S. , Nedderman Angus , Haynes Julian , Savage Mark E. , Clark Andrew , Smith Kimberly Y. , Heera Jayvant 
Published: September 2018

AbstractMaraviroc is a C‐C chemokine receptor type‐5 antagonist approved for the treatment of HIV‐1. Previous studies show that cytochrome P450 3A5 (CYP3A5) plays a role in maraviroc metabolism. CYP3A5 is subject to a genetic polymorphism. The presence of 2 functional alleles (CYP3A5*1/*1) confers the extensive metabolism phenotype, which is rare in whites but common in blacks. The effect of CYP3A5 genotype on maraviroc and/or metabolite pharmacokinetics was evaluated in 2 clinical studies: a post hoc analysis from a phase 2b/3 study (NCT00098293) conducted in 494 HIV‐1–infected subjects (study 1) in which the impact on maraviroc efficacy in 303 subjects was also assessed, and a study conducted in 47 healthy volunteers (study 2). In study 2 (NCT02625207), extensive metabolizers had 26% to 37% lower mean area under the concentration‐time curve compared with poor metabolizers (no CYP3A5*1 alleles). This effect diminished to 17% in the presence of potent CYP3A inhibition. The effect of CYP3A5 genotype was greatest in the formation of the metabolite (1S,2S)‐2‐hydroxymaraviroc. In study 1, the CYP3A5*1/*1 genotype unexpectedly had higher maraviroc area under the curve predictions (20%) compared with those with no CYP3A5*1 alleles. The reason for this disparity remains unclear. The proportions of subjects with viral loads <50 and <400 copies/mL for maraviroc were comparable among all 3 CYP3A5 genotypes. In both studies maraviroc exposures were in the range of near‐maximal viral inhibition in the majority of subjects. These results demonstrate that although CYP3A5 contributes to the metabolism of maraviroc, CYP3A5 genotype does not affect the clinical response to maraviroc in combination treatment of HIV‐1 infection at approved doses.
Environmentally induced phenotypic plasticity explains hatching synchrony in the freshwater turtleChrysemys picta
Authors: McGlashan Jessica K. , Thompson Michael B. , Janzen Fredric J. , Spencer Ricky‐John 
Published: September 2018

AbstractEnvironmentally cued hatching allows embryos to alter the time of hatching in relation to environment through phenotypic plasticity. Spatially variable temperatures within shallow nests of many freshwater turtles cause asynchronous development of embryos within clutches, yet neonates still hatch synchronously either by hatching early or via metabolic compensation. Metabolic compensation and changes in circadian rhythms presumably enable embryos to adjust their developmental rates to catch up to more advanced embryos within the nest. Hatchlings of the North American freshwater turtleChrysemys pictausually overwinter within the nest and emerge the following spring, but still hatch synchronously via hatching early. Here, we used rates of oxygen consumption and heart rate profiles to investigate the metabolic rates of clutches ofC. pictadeveloping in conditions that result in asynchronous development to determine if compensatory changes in metabolism occur during incubation. Embryos hatched synchronously and displayed circadian rhythms throughout incubation, but exhibited no evidence of metabolic compensation. Phenotypic traits of hatchlings, including body size and righting performance, were also not affected by asynchronous development. We conclude that less developed embryos ofC. pictahatch synchronously with their clutch‐mates by hatching early, which does not appear to inflict a fitness cost to individuals. The ultimate mechanism for synchronous hatching inC. pictacould be for hatchlings to ensure an optimal overwintering position within the center of the nest. Consequently, immediate fitness costs will not hinder hatchling survival. The geographic location, as well as environmental and genetic factors unique to populations, can all influence hatching behavior in turtles through phenotypic plasticity. Hence, synchronous hatching is an adaptive bet‐hedging strategy in turtles, but the mechanisms to achieve it are diverse.
IL-20 receptor cytokines in autoimmune diseases
Authors: Chen Jun , Caspi Rachel R , Chong Wai Po 
Published: September 2018

Abstract
IL-19, IL-20, and IL-24 are the members of IL-10 family. They are also known as IL-20 receptor (IL-20R) cytokines as they all signal through the IL-20RA/IL-20RB receptor complex; IL-20 and IL-24 (but not IL-19) also signal through the IL-20RB/IL22RA1 receptor complex. Despite their protein structure homology and shared use of receptor complexes, they display distinct biological functions in immune regulation, tissue homeostasis, host defense, and oncogenesis. IL-20R cytokines can be expressed by both immune cells and epithelial cells, and are important for their interaction. In general, these cytokines are considered to be associated with pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. However, a number of studies also highlighted their suppressive functions in regulating both innate and adaptive T cell responses and other immune cells, suggesting that the role of IL-20R cytokines in autoimmunity may be complex. In this review, we will discuss the immunobiological functions of IL-20R cytokines and how they are involved in regulating autoimmune diseases.
This review outlines the current view of the biological effects of IL-20 receptor cytokines and the roles of these cytokines in autoimmune diseases.
Functional anatomy of the male reproductive system of the American lobster (Homarus americanus)
Authors: Comeau Michel , Benhalima Kadra 
Published: September 2018

AbstractDespite supporting a valuable fishery, the reproductive system of the male American lobster (Homarus americanus) is poorly understood. The elongated H‐shaped testis is responsible for spermatogenesis and is composed of follicles, a common collecting duct with interlaced scattered striated muscles, and a serosa as an external wall. Sertoli cells are associated with the spermatogenesis that produces spermatozoa, which are transferred to the collecting duct through a temporary passageway. Spermatogenesis is asynchronous between follicles and occurs on a continuous basis. The anterior and posterior lobes of the testes are independent and connect to the vasa deferentia through the Y‐shaped collecting tubules that have a different cell anatomy and function than the two organs they connect. The vas deferens is divided into four regions. Spermatophores, produced in the proximal vas deferens, are packets of spermatozoa encapsulated in a single layer—the spermatophoric wall, which is composed of mucopolysaccharide acid. Large dense ovoid granules and the seminal fluid, composed of acidic sulfated mucosubstances, are secreted in the median vas deferens. Spermatophores within these secreted substances (i.e., semen) are stored in the distal vas deferens that, with the spermiduct (last region of the vas deferens), is responsible for the extrusion of the semen by striated muscle contractions. Smooth muscles suggest a peristaltic movement of the spermatophores within the vas deferens. Finally, the gonopores and the first pair of pleopods (i.e., gonopod) move the semen to the female seminal receptacle during copulation.
Respiratory viral infections in infants with possible sepsis
Authors: Aykac Kubra , Karadag‐Oncel Eda , Tanır Basaranoglu Sevgen , Alp Alpaslan , Cengiz Ali Bulent , Ceyhan Mehmet , Kara Ates 
Published: September 2018

BackgroundKnowledge of infections leading to sepsis is needed to develop comprehensive infection prevention and sepsis, as well as early recognition and treatment strategies.The aim of this study was to investigate the etiology of sepsis and evaluate the proportion of respiratory viral pathogens in infants under two years of age with possible sepsis.MethodsThe prospective study was performed in two years. Multiplex reverse transcriptase polymerase chain reaction (RT‐PCR) was performed to detect viral pathogens. All patients who were included in this study had sepsis symptoms as defined by the Surviving Sepsis Campaign.ResultsWe compared 90 patients with sepsis into three groups as patients (n = 33) who had only viral positivity in nasopharyngeal swab, patients (17) had proven bacterial infection with or without viral infection, and patients (40) without the pathogen detection. Human rhinovirus (16.7%) and influenza (7.8%) were the most commonly seen viruses. A cough was more common in the viral infection group than other groups (
P = 0.02) and median thrombocyte count was lower in the bacterial infection group than the others (
P = 0.01). Patients having bacterial sepsis had the longest duration of hospitalization than the other groups (
P = 0.04). During winter and spring seaons, patients with sepsis had more viral infection; however, in summer and autumn period, patients were mostly in a state that we could not prove infection agents (
P = 0.02).ConclusionsOur results suggest that respiratory tract viruses may play an important role in patients with sepsis and they should be kept in mind, especially during winter and spring seasons. In overall infection, viral respiratory viruses as a single pathogen with a detection rate of 36.6% in sepsis etiology.