bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature and storage time strongly affect the germination success of perennial Euphorbia species in Mediterranean regions
Authors: Cristaudo Antonia , Catara Stefania , Mingo Antonio , Restuccia Alessia , Onofri Andrea 
Published: September 2019

AbstractThis study aims to explore the effect of environmental factors (temperature, light, storage time) on germination response and dormancy patterns in eight Mediterranean native wildplants, belonging to the Euphorbia L. genus. In detail, we considered E. amygdaloides subsp. arbuscula, E. bivonae subsp. bivonae, E. ceratocarpa, E. characias, E. dendroides, E. melapetala, E. myrsinites, and E. rigida. We collected seeds from natural plant populations and performed germination assays in climatic chambers at seven constant temperatures (from 5 to 35°C, with 5°C increments), and four fluctuating temperature regimes (8/15, 8/20, 8/25, and 8/30°C, with a 12/12 hr thermoperiod). Germination assays were set up both in dark (D) and in light/dark conditions (L/D, 12/12 hr photoperiod), after short and long seed storage (SS around 30 days and LS around 150 days). For all these species, except E. amygdaloides subsp. arbuscula, results show that the final germinated proportions were improved by a long storage period (>150 days), which supports the existence of nondeep physiological dormancy. Optimal temperature levels ranged from 14.3 to 21.3°C and base temperatures ranged from 5.6 to 12.1°C, while ceiling temperatures from 25.6 to 34.7°C. For none of these species, germinations were favored by an alternating daily temperature regime, while in several instances, germinations were quicker and more complete in darkness, than in an alternating light/dark regime. In some instances, extreme temperature levels (5 and 30°C) induced dormancy and germinations did not resume when seeds were exposed at optimal temperature levels. Results are discussed in terms of the dynamics of emergences and how this might be affected by climate changes.
Host plant use of a polyphagous mirid, Apolygus lucorum: Molecular evidence from migratory individuals
Authors: Wang Qian , Bao Weifang , Zhang Qian , Fu Xiaowei , Yang Yizhong , Lu Yanhui 
Published: September 2019

AbstractWhile the host plant use of insect herbivores is important for understanding their interactions and coevolution, field evidence of these preferences is limited for generalist species. Molecular diet analysis provides an effective option for gaining such information, but data from field‐sampled individuals are often greatly affected by the local composition of their host plants. The polyphagous mirid bug Apolygus lucorum (Meyer‐Dür) seasonally migrates across the Bohai Sea, and molecular analysis of migrant bugs collected on crop‐free islands can be used to estimate the host plant use of A. lucorum across the large area (northern China) from where these individuals come. In this study, the host plant use of A. lucorum adults was determined by identifying plant DNA using a three‐locus DNA barcode (rbcL, trnH‐psbA, and ITS) in the gut of migrant individuals collected on Beihuang Island. We successfully identified the host plant families of A. lucorum adults, and the results indicated that captured bugs fed on at least 17 plant families. In addition, gut analyses revealed that 35.9% of A. lucorum individuals fed on multiple host plants but that most individuals (64.1%) fed on only one plant species. Cotton, Gossypium hirsutum L., DNA was found in 35.8% of the A. lucorum bugs examined, which was much higher than the percentage of bugs in which other host plants were found. Our work provides a new understanding of multiple host plant use by A. lucorum under natural conditions, and these findings are available for developing effective management strategies against this polyphagous pest species.
RPB5‐Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding
Authors: Wan Zheng‐Hua , Jiang Tian‐Yi , Shi Yuan‐Yuan , Pan Yu‐Fei , Lin Yun‐Kai , Ma Yun‐Han , Yang Chun , Feng Xiao‐Fan , Huang Li‐Feng , Kong Xiao‐Ni , Ding Zhi‐Wen , Tan Ye‐Xiong , Dong Li‐Wei , Wang Hong‐Yang 
Published: September 2019

Background and Aims
Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5‐mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression.

Approach and Results
RMP‐overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch‐like ECH‐associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP‐KEAP1‐NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis.

Conclusion
These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.
Twenty‐five years after its publication, innovative solutions to the three delays model are essential
Authors: Harrison Margo S. , Yarinbab Teklemariam , Liyew Tewodros , Kirub Ephrem , Teshome Biruk , Muldrow Margaret 
Published: September 2019

Twenty‐five years after its publication, the Three Delays Model still appears to be a relevant model for rural southwest Ethiopia.
Analysis of differential expression profile of miRNA in peripheral blood of patients with lung cancer
Authors: He Qingfang , Fang Yirong , Lu Feng , Pan Jin , Wang Lixin , Gong Weiwei , Fei Fangrong , Cui Jingjie , Zhong Jieming , Hu Ruying , Liang Mingbin , Fang Le , Wang Hao , Yu Min , Zhang Zuo‐Feng 
Published: September 2019

AbstractPurposeTo identify potential molecular targets for lung cancer intervention and diagnosis, we analyzed the differential miRNA expression of peripheral blood between lung cancer patients and healthy controls.MethodsThree pairs of cases’ and controls’ peripheral blood samples were evaluated for miRNA expression by microarray. 12 miRNAs were selected for RT‐PCR validation and target genes prediction. In addition, 4 miRNAs were selected for future validation by RT‐PCR in a large sample of 145 cases and 55 frequency‐matched healthy controls.ResultsA total of 338 differentially expressed miRNAs were screened and identified by microarray. According to the fold changes, the top ten upregulated miRNAs were hsa‐miR‐124‐3p, hsa‐miR‐379‐5p, hsa‐miR‐3655, hsa‐miR‐450b‐5p, hsa‐miR‐29a‐5p, hsa‐miR‐200a‐3p, hsa‐miR‐542‐3p, hsa‐miR‐138‐5p, hsa‐miR‐219a‐2‐3p, and hsa‐miR‐4701‐3p, and the top ten downregulated miRNAs were hsa‐miR‐34c‐5p, hsa‐miR‐135a‐5p, hsa‐miR‐132‐3p, hsa‐miR‐3178, hsa‐miR‐4449, hsa‐miR‐4999‐3p, hsa‐miR‐1246, hsa‐miR‐4424, hsa‐miR‐1252‐5p, and hsa‐miR‐24‐2‐5p. RT‐PCR verification of the 12 miRNAs revealed that 5 of 8 upregulated miRNAs, 2 of 4 downregulated miRNAs showed a significant difference between the cases and controls (P < .05). A large number of target genes and their functional set showed overlapping among the 453 predicted target genes of the 12 miRNAs (P < .01). RT‐PCR in the large sample confirmed the significant differential expression level of hsa‐miR‐29a‐5p, hsa‐miR‐135a‐5p, hsa‐miR‐542‐3p, and hsa‐miR‐4491 between cases and controls (P < .05), and three of these microRNA, except hsa‐miR‐29a‐5p, were significant after Bonferroni correction for adjustment of multiple comparisons.ConclusionThere was a significant difference in miRNAs expression in the peripheral blood between lung cancer patients and healthy controls, and 4 miRNAs were validated by a large‐size sample.
Emergence and transmission of New Delhi metallo‐beta‐lactamase‐5‐producing Escherichia coli Sequence Type 361 in a Tertiary Hospital in South Korea
Authors: Park Yumi , Choi Qute , Kwon Gye Cheol , Koo Sun Hoe 
Published: September 2019

AbstractBackgroundThe emergence of carbapenem‐resistant Escherichia coli (E coli) is a serious global health threat, but little is known about carbapenemase‐producing E coli in Daejeon, South Korea. The aim of this study was to investigate characteristics of thirteen carbapenem‐resistant E coli isolates in a tertiary hospital.MethodsThirteen non‐duplicate carbapenem‐resistant E coli strains were collected from October 2017 to January 2018. Antimicrobial susceptibility was determined with the E test or disk diffusion method. The carbapenem minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The colistin and tigecycline MICs were determined by broth microdilution. The resistance genes, including carbapenemase genes, were evaluated by polymerase chain reaction, and DNA sequencing was performed to characterize the genes. Pulsed‐field gel electrophoresis and multilocus sequence typing (MLST) were performed to evaluate the clonal relatedness of isolates. The clinical data of patients were retrospectively reviewed.ResultsAll the E coli isolates harbored blaNDM‐5 gene and were resistant to most of the antimicrobial agents, such as carbapenem, cephalosporins, ciprofloxacin, and chloramphenicol, excluding amikacin and colistin. Other resistant genes, such as blaTEM‐1, blaCTX‐M‐15, blaCMY‐2, aac(6')‐Ib‐cr, and qepA, were detected. The E coli isolates harboring blaNDM‐5 belonged to ST361 (n = 11), ST12 (n = 1), ST410 (n = 1), and PFGE types A (n = 11), B (n = 1), and C (n = 1).ConclusionsThis study reports on an outbreak of a predominant epidemic clone, the NDM‐5 producing, multidrug‐resistant E coli ST361 isolate. These findings suggest that we should pay attention to infection control measures to limit the spread of NDM‐5‐producing pathogens.
Linc‐ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR‐204‐5p/MDM2
Authors: Gao Han , Wang Tian , Zhang Peng , Shang Muhe , Gao Zhikui , Yang Fei , Liu Ran 
Published: September 2019

AbstractThe long intergenic noncoding RNA, regulator of reprogramming (linc‐ROR) has been reported to participate in tumorigenesis, while its functions and fundamental mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, gain‐of‐function assays showed that linc‐ROR upregulation enhanced cell viability, promoted cell proliferation, and inhibited apoptosis. Mechanistically, the regulatory network of linc‐ROR/miR‐204‐5p/MDM2 was established with bioinformatics analysis and online databases, then validated via dual‐luciferase reporter assays, RNA immunoprecipitation assays in ESCC cells. Linc‐ROR positively regulates the expression of MDM2 as a molecular sponge of miR‐204‐5p. Moreover, results of western blot and coimmunoprecipitation indicated that linc‐ROR overexpression enhanced the ubiquitination level of p53, and its downstream apoptosis‐related genes have showed higher bcl‐2 expression, lower bax, and cleaved caspase‐3 expressions, while miR‐204‐5p could counteract with this effect. Finally, small interfering RNAs tailored to linc‐ROR were established to further evaluate its effects on ESCC comprehensively. In summary, this study revealed that linc‐ROR modulated cell apoptosis and regulated p53 ubiquitination via targeting miR‐204‐5p/MDM2 axis, which provides a novel therapeutic insight into treatments for ESCC.
MicroRNA‐188‐5p promotes apoptosis and inhibits cell proliferation of breast cancer cells via the MAPK signaling pathway by targeting Rap2c
Authors: Zhu Xinying , Qiu Jinxia , Zhang Tao , Yang Yaping , Guo Shuai , Li Tianshun , Jiang Kangfeng , Zahoor Arshad , Deng Ganzhen , Qiu Changwei 
Published: September 2019

AbstractBreast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA‐188‐5p (miR‐188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR‐188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR‐188 in 4T1 and MCF‐7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR‐188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR‐188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual‐luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen‐activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR‐188 is a cancer progression suppressor and a promising future target for breast cancer therapy.
JNK‐IN‐8, a c‐Jun N‐terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
Authors: Zheng Jianjian , Dai Qinxue , Han Kunyuan , Hong Wandong , Jia Danyun , Mo Yunchang , Lv Ya , Tang Hongli , Fu Hongxing , Geng Wujun 
Published: September 2019

AbstractC‐Jun N‐terminal kinase (JNK) is a pivotal MAPK (mitogen‐activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK‐IN‐8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK‐IN‐8 in ischemic stroke and the mechanisms underlying of JNK‐IN‐8 about neuroprotection are not well understood. In this work, male rats were treated with JNK‐IN‐8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot‐fault test (FFT), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) levels were assessed. We found that JNK‐IN‐8‐treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK‐IN‐8 also played anti‐inflammatory roles as indicated through decreased activation of microglia and decreased IL‐6, IL‐1β, and TNF‐α expression. Furthermore, JNK‐IN‐8 suppressed the activation of JNK and nuclear factor‐κB (NF‐κB) signaling as indicated by the decreased level of phosphorylated‐JNK and p65. All data demonstrate that JNK‐IN‐8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF‐κB and is a promising agent for the prevention of ischemic brain injury.
miR‐122‐5p promotes aggression and epithelial‐mesenchymal transition in triple‐negative breast cancer by suppressing charged multivesicular body protein 3 through mitogen‐activated protein kinase signaling
Authors: Wang Zheng , Wang Xiangyu 
Published: September 2019

AbstractTriple‐negative breast cancer (TNBC) is highly metastatic and frequently has a poor prognosis. The lack of comprehension of TNBC and gene therapy targets has led to limitedly effective treatment for TNBC. This study was conducted to better understand the molecular mechanism behind TNBC progression, and to find out promising gene therapy targets for TNBC. Herein the influence of miR‐122‐5p's binding charged multivesicular body protein 3 (CHMP3) 3′‐untranslated region (3′‐UTR) on in TNBC cells was investigated. in vitro experiments quantitative real‐time polymerase chain reaction, immunoblot analysis, dual‐luciferase reporter gene assay, cell counting assay, transwell invasion assay, and flow cytometry‐determined cell apoptosis assay were employed. We also used TargetScan Human 7.2 database to find out the target relationship between miR‐122‐5p and CHMP3 3′‐UTR. TImer algorithm was used to provide an overview of the expression of CHMP3 gene across human pan‐cancer, to predict the survival outcome of breast cancer patients, and to predict the correlation between CHMP3 gene expression and epithelial‐mesenchymal transition (EMT) and mitogen‐activated protein kinase (MAPK)‐related gene expression. CHMP3 gene was significantly downregulated across a wide range of human cancers including breast cancer (BRCA). A higher level of CHMP3 gene predicted a better 3‐ and 5‐year survival outcome of patients with BRCA. In our experiments, miR‐122‐5p was significantly upregulated and CHMP3 gene was significantly downregulated in TNBC cells compared with normal cell line. miR‐122‐5p mimics enhanced TNBC cell viability, proliferation, and invasion whereas the upregulation of CHMP3 gene led to an opposite outcome. Forced expression of miR‐122‐5p suppressed cell apoptosis, compelled EMT and MAPK signaling whereas forced expression of CHMP3 did the opposite. We then conclude that miR‐122‐5p promotes aggression and EMT in TNBC by suppressing CHMP3 through MAPK signaling.
Exploiting yoeB‐yefM toxin‐antitoxin system of Streptococcus pneumoniae on the selective killing of miR‐21 overexpressing breast cancer cell line (MCF‐7)
Authors: Houri Hamidreza , Ghalavand Zohreh , Faghihloo Ebrahim , Fallah Fatemeh , Mohammadi‐Yeganeh Samira 
Published: September 2019

AbstractToxin‐antitoxin (TA) systems are two‐component genetic modules widespread in bacterial and archaeal genomes, in which the toxin module is rendered inactive under resting conditions by its antitoxin counterpart. Under stress conditions, however, the antitoxin is degraded, freeing the toxin to exert its lethal effects. Although not evolved to function in eukaryotes, some studies have established the lethal activity of these bacterial toxins by inducing apoptosis in mammalian cells, an effect that can be neutralized by its cognate antitoxin. Inspired by the way the toxin can become active in eukaryotes cells, we produced an engrained yoeB‐yefM TA system to selectively kill human breast cancer cells expressing a high level of miR‐21. Accordingly, we generated an engineered yefM antitoxin gene with eight miR‐21 target sites placed in its 3′untranslated region. The resulting TA system acts autonomously in human cells, distinguishing those that overexpress miR‐21, killed by YoeB, from those that do not, remaining protected by YefM. Thus, we indicated that microRNA‐control of the antitoxin protein of bacterial TA systems constitutes a novel strategy to enhance the selective killing of human cancer cells by the toxin module. The present study provides significant insights for developing novel anticancer strategies avoiding off‐target effects, a challenge that has been pursued by many investigators over the years.
Chitooligosaccharide inhibits RANKL‐induced osteoclastogenesis and ligation‐induced periodontitis by suppressing MAPK/ c‐fos/NFATC1 signaling
Authors: Xu Weifeng , Chen Xinwei , Wang Yexin , Fan Baoting , Guo Ke , Yang Chi , Yu Shiqi , Pang Yichuan , Zhang Shanyong 
Published: September 2019

AbstractConsidering the high rate of osteoclast‐related diseases worldwide, research targeting osteoclast formation/function is crucial. In vitro, we demonstrated that chitooligosaccharide (CS) dramatically inhibited osteoclastogenesis as well as osteoclast function dose‐dependently. CS suppressed osteoclast‐specific genes expression during osteoclastogenesis. Furthermore, we found that CS attenuated receptor activator of nuclear factor kappa B ligand (RANKL)‐mediated mitogen‐activated protein kinase (MAPK) pathway involving p38, erk1/2, and jnk, leading to the reduced expression of c‐fos and nuclear factor of activated T cells c1 (NFATc1) during osteoclast differentiation. In vivo, we found CS protected rats from periodontitis‐induced alveolar bone loss by micro‐computerized tomography and histological analysis. Overall, CS inhibited RANKL‐induced osteoclastogenesis and ligature‐induced rat periodontitis model, probably by suppressing the MAPK/c‐fos/NFATc1 signaling pathway. Therefore, CS may be a safe and promising treatment for osteoclast‐related diseases.
Acetaminophen sensitizing erastin‐induced ferroptosis via modulation of Nrf2/heme oxygenase‐1 signaling pathway in non‐small‐cell lung cancer
Authors: Gai Chengcheng , Yu Mengyu , Li Zihaoran , Wang Yonghong , Ding Dejun , Zheng Jie , Lv Shijun , Zhang Weifen , Li Wentong 
Published: September 2019

AbstractGrowing evidence confirms that ferroptosis plays an important role in tumor growth inhibition. However, some non‐small‐cell lung cancer (NSCLC) cell lines are less sensitive to erastin‐induced ferroptotic cell death. Elucidating the mechanism of resistance of cancer cells to erastin‐induced ferroptosis and increasing the sensitivity of cancer cells to erastin need to be addressed. In our experiment, erastin and acetaminophen (APAP) cotreatment inhibited NSCLC cell viability and promoted ferroptosis and apoptosis, accompanied with attenuation of glutathione and ectopic increases in lipid peroxides. Erastin and APAP promoted NSCLC cell death by regulating nucleus translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2); and the ferroptosis induced by erastin and APAP was abrogated by bardoxolone methyl (BM) with less generation of reactive oxygen species and malondialdehyde. As a downstream gene of Nrf2, heme oxygenase‐1 expression decreased significantly with the cotreatment of erastin and APAP, which could be rescued by BM. In vivo experiment showed that the combination of erastin and APAP had a synergic therapeutic effect on xenograft of lung cancer. In short, the present study develops a new effective treatment for NSCLC by synergizing erastin and APAP to induce ferroptosis.
Intact caveolae are required for proper extravillous trophoblast migration and differentiation
Authors: Reppetti Julieta , Reca Alejandra , Seyahian E. Abril  , Medina Yollyseth , Martínez Nora , Szpilbarg Natalia , Damiano Alicia E. 
Published: September 2019

AbstractCaveolae constitute membrane domains critical for the organization and synchronization of different signaling molecules related to numerous cell processes such as cell migration, invasion, and differentiation. Caveolin‐1 (Cav‐1) is the main integral membrane protein of these domains. Recently, it was found that a normal expression of aquaporin‐3 (AQP3) is required for extravillous trophoblast (EVT) cell migration. Our aim was to investigate the role of caveolae in the migration, invasion, and endovascular differentiation of human EVT cells during placentation and its interaction with AQP3. EVT cells (Swan 71 cell line) were cultured in complete Dulbecco's modified Eagle's medium–nutrient mixture F12 and treated with 5 mM methyl‐β‐cyclodextrin (MβCD) to disrupt caveolae. We found that after MβCD treatment, Cav‐1 protein was undetectable. In this condition, the ability of the cells to migrate was significantly decreased compared with the control cells, while no differences were observed in the number of invading cells and the metalloproteinases activity between control and MβCD‐treated cells. Surprisingly, the disruption of caveolae significantly enhanced EVT endovascular differentiation. On the contrary, the silencing of AQP3, negatively affected tube‐like formation. The theoretical analysis of the primary sequence of AQP3 protein revealed a putative Cav‐1‐binding site. In addition, immunoprecipitation and double immunofluorescence assays showed that AQP3 colocalized with Cav‐1. These results showed that during placentation an intact caveola in EVT cells may be necessary for AQP3 and Cav‐1 interaction and any perturbations might result in serious pregnancy disorders.