bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rac1 is necessary for capacitation and acrosome reaction in guinea pig spermatozoa
Authors: Ramírez‐Ramírez Danelia , Salgado‐Lucio Monica L. , Roa‐Espitia Ana L. , Fierro Reyna , González‐Márquez Humberto , Cordero‐Martínez Joaquín , Hernández‐González Enrique O. 
Published: November 2019

AbstractActin cytoskeleton remodeling is a critical process for the acquisition of fertilizing capacity by spermatozoa during capacitation. However, the molecular mechanism that regulates this process has not been fully elucidated. In somatic cells, Ras‐related C3 botulinum toxin substrate 1 protein (Rac1) promotes the polymerization of actin by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane. Rac1 is expressed in mammalian spermatozoa; however, the role of Rac1 in sperm physiology is unknown. This study aimed to elucidate the participation of Rac1 in capacitation and acrosome reaction (AR). Rac1 was found to be dispersed throughout the acrosome and without changes in the middle piece. After 60 minutes of capacitation, Rac1 was found in the apical region of the acrosome only, which concurred with an increase in Rac1‐GTP. Rac1 inhibition prevented such changes. In the middle piece, Rac1 localization remained unchanged. Besides, Rac1 inhibition blocked capacitation and AR. The present study demonstrates that Rac1 participates only in the actin cytoskeleton remodeling that occurs in the acrosomal apical region during capacitation, a region where a large amount of actin is polymerized and shaped in a diadem‐like structure. Our data also show that this actin cytoskeleton organized by Rac1 interacts with filamin‐1, and such interaction was blocked by the inhibition of Rac1, which led to a different organization of the actin cytoskeleton. All these outcomes imply that the formation of an F‐actin cytoskeleton in the acrosomal apical region is a necessary event for capacitation and AR, and which is Rac1 driven.
Snx10 and PIKfyve are required for lysosome formation in osteoclasts
Authors: Sultana Farhath , Morse Leslie R. , Picotto Gabriela , Liu Weimin , Jha Prakash K. , Odgren Paul R. , Battaglino Ricardo A. 
Published: November 2019

AbstractBone resorption and organelle homeostasis in osteoclasts require specialized intracellular trafficking. Sorting nexin 10 (Snx10) is a member of the sorting nexin family of proteins that plays crucial roles in cargo sorting in the endosomal pathway by its binding to phosphoinositide(3)phosphate (PI3P) localized in early endosomes. We and others have shown previously that the gene encoding sorting Snx10 is required for osteoclast morphogenesis and function, as osteoclasts from humans and mice lacking functional Snx10 are dysfunctional. To better understand the role and mechanisms by which Snx10 regulates vesicular transport, the aim of the present work was to study PIKfyve, another PI3P‐binding protein, which phosphorylates PI3P to PI(3,5)P2. PI(3,5)P2 is known to be required for endosome/lysosome maturation, and the inhibition of PIKfyve causes endosome enlargement. Overexpression of Snx10 also induces accumulation of early endosomes suggesting that both Snx10 and PIKfyve are required for normal endosome/lysosome transition. Apilimod is a small molecule with specific, nanomolar inhibitory activity on PIKfyve but only in the presence of key osteoclast factors CLCN7, OSTM1, and Snx10. This observation suggests that apilimod's inhibitory effects are mediated by endosome/lysosome disruption. Here we show that both Snx10 and PIKfyve colocalize to early endosomes in osteoclasts and coimmunoprecipitate in vesicle fractions. Treatment with 10 nM apilimod or genetic deletion of PIKfyve in cells resulted in the accumulation of early endosomes, and in the inhibition of osteoclast differentiation, lysosome formation, and secretion of TRAP from differentiated osteoclasts. Snx10 and PIKfyve also colocalized in gastric zymogenic cells, another cell type impacted by Snx10 mutations. Apilimod‐specific inhibition of PIKfyve required Snx10 expression, as it did not inhibit lysosome biogenesis in Snx10‐deficient osteoclasts. These findings suggest that Snx10 and PIKfyve are involved in the regulation of endosome/lysosome homeostasis via the synthesis of PI(3,5)P2 and may point to a new strategy to prevent bone loss.
Upregulated calcium‐binding tyrosine phosphorylation‐regulated protein‐a/b regulates cell proliferation and apoptosis and predicts poor prognosis in hepatocellular carcinoma
Authors: Yu Xiang‐Nan , Guo Hong‐Ying , Liu Tao‐Tao , Zhang Guang‐Cong , Zhu Hai‐Rong , Shi Xuan , Song Guang‐Qi , Jiang Xue‐Mei , Huang Xiao‐Xi , Weng Shu‐Qiang , Dong Ling , Shen Xi‐Zhong , Huang Yang‐Qing , Zhu Ji‐Min 
Published: November 2019

AbstractBackgroundCalcium‐binding tyrosine phosphorylation‐regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR‐a/b (combined CABYR‐a and CABYR‐b), in HCC remain to be established.MethodsCABYR‐a/b expression was detected in HCC tissues and cell lines by quantitative real‐time polymerase chain reaction and Western blot analysis. The correlation of CABYR‐a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR‐a/b were also investigated using molecular biology approaches.ResultsThe present research found that CABYR‐a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR‐a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR‐a/b level had poorer overall survival (OS) and disease‐free survival (DFS) than those with reduced CABYR‐a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR‐a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR‐a/b downregulation suppressed cell proliferation and induced G1‐phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B‐cell lymphoma 2 (Bcl‐2) and increasing Bcl‐2‐associated death promoter.ConclusionOur research indicates that CABYR‐a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.
MiR‐92a regulates brown adipocytes differentiation, mitochondrial oxidative respiration, and heat generation by targeting SMAD7
Authors: Zhang Zhipin , Jiang Huixin , Li Xiang , Chen Xiaomin , Huang Yihua 
Published: November 2019

AbstractBrown adipocytes are rich in mitochondria and linked to the body's blood fat levels and obesity. MiR‐92a is negatively correlated with the activity of brown adipocytes. This study aimed to explore the mechanism of miR‐92a on brown adipocytes. The expression of miR‐92a in C2C12 cell was detected by a quantitative real‐time‐polymerase chain reaction (qRT‐PCR). C2C12 cells were induced to brown adipocytes. The direct target gene of miR‐92a was determined using the dual‐luciferase reporter assay. Brown adipocytes were treated with isoprenaline (Iso) and transfected by miR‐92a inhibitor and siSMAD7. The expression of heat‐producing genes and adipose differentiation genes related to brown adipocytes were detected by qRT‐PCR and Western blot analysis. The expression of SMAD7, p‐SMAD2, and p‐SMAD3 were detected using Western blot analysis. The mitochondrial content was measured by mitotracker fluorescent staining. MiR‐92a inhibitor significantly decreased the expression of miR‐92a in C2C12 cells. MiR‐92a inhibitor could upregulate the expression of Ucp1, Cox7a1, Elovl3, Ppargc1α, PPARγ, and FABP4, and its effect on Ucp1 was increased after the treatment of isoprenaline. Moreover, miR‐92a inhibitor increased mitochondrial content, oxygen consumption rate (OCR) and the expression of SMAD7 and suppressed the expressions of p‐SMAD2 and p‐SMAD3, whereas miR‐92a directly targeted SMAD7 to exert its inhibitory effects. SiSMAD7 reversed the effects of the inhibitor on heat‐producing genes, mitochondrial content, OCR and the expressions of SMAD7, p‐SMAD2, and p‐SMAD3 in brown adipocytes. Blocking miR‐92a might promote brown adipocytes differentiation, mitochondrial oxidative respiration, and thermogenesis by targeting SMAD7 to inhibit the expressions of p‐SMAD2 and p‐SMAD3.
Knockdown of lncRNA ZFAS1‐suppressed non–small cell lung cancer progression via targeting the miR‐150‐5p/HMGA2 signaling
Authors: Zeng Zhaolong , Zhao Guofang , Rao Chuangzhou , Hua Gang , Yang Minglei , Miao Xiaobo , Ying Jingjing , Nie Liangqin 
Published: November 2019

AbstractNon–small cell lung cancer (NSCLC) is the main type of lung malignancy. Early diagnosis and treatments for NSCLC are far from satisfactory due to the limited knowledge of the molecular mechanisms regarding NSCLC progression. Long noncoding RNA (lncRNA) ZNFX1 antisense RNA1 (ZFAS1) has been implicated for its functional role in the progression of malignant tumors. This study aimed to determine the ZFAS1 expression from lung cancer clinical samples and to explore the molecular mechanisms underlying ZFAS1‐modulated NSCLC progression. Experimental assays revealed that clinical samples and cell lines of lung malignant tumors showed an upregulation of ZFSA1. ZFAS1 expression was markedly upregulated in the lung tissues from patients with advanced stage of this malignancy. The loss‐of‐function assays showed that knockdown of ZFAS1‐suppressed NSCLC cell proliferative, as well as invasive potentials, increased NSCLC cell apoptotic rates in vitro and also attenuated tumor growth of NSCLC cells in the nude mice. Further experimental evidence showed that ZFAS1 inversely affected miR‐150‐5p expression and positively affected high‐mobility group AT‐hook 2 (HMGA2) expression in NSCLC cell lines. MiR‐150‐5p inhibition or HMGA2 overexpression counteracted the effects of ZFAS1 knockdown on NSCLC cell proliferative, invasive potentials and apoptotic rates. In light of examining the clinical lung cancer samples, miR‐150‐5p expression was downregulated and the HMGA2 expression was highly expressed in the lung cancer tissues compared with normal ones; the ZFAS1 expression showed a negative correlation with miR‐150‐5p expression but a positive correlation with HMGA2 expression in lung cancer tissues. To summarize, we, for the first time, demonstrated the inhibitory effects of ZFAS1 knockdown on NSCLC cell progression, and the results from mechanistic studies indicated that ZFAS1‐mediated NSCLC progression cells via targeting miR‐150‐5p/HMGA2 signaling.
miR‐144 suppresses cell proliferation and migration in colorectal cancer by targeting NRAS
Authors: Ji Xuemei , Liu Yanqing , Kao Xiaoming , Chen Xiaorui , Zhao Yi , Zhang Shuyan , Chen Liya , Yu Mengchao , Wei Juan , Yang Zhao , Wang Fangyu 
Published: November 2019

AbstractColorectal cancer (CRC) is a type of malignant cancer that has become particularly prevalent worldwide. It is of crucial importance to CRC treatment that the underlying molecular mechanism of CRC progression is determined. The NRAS gene is an important small G protein that is involved in various biological processes, including cancers. NRAS is an oncogene in many neoplasms but its function and regulation in CRC have seldom been investigated. In this study, it was uncovered that the NRAS protein was significantly upregulated in CRC tissues. According to a bioinformatics prediction, we identified that miR‐144 may target NRAS to suppress its expression. In vitro experiments indicated that miR‐144 decreased NRAS expression in different CRC cell lines (SW480, LoVo, and Caco2). By inhibiting NRAS, miR‐144 repress SW480 cell proliferation and migration. Moreover, miR‐144 decelerated the growth of SW480 xenograft tumors in vivo by targeting NRAS. In summary, our results identified a novel miR‐144‐NRAS axis in CRC that could promote the research and treatment of CRC.
A prognostic eight‐gene expression signature for patients with breast cancer receiving adjuvant chemotherapy
Authors: Cui Qiuxia , Tang Jianing , Zhang Dan , Kong Deguang , Liao Xing , Ren Jiangbo , Gong Yan , Xie Conghua , Wu Gaosong 
Published: November 2019

AbstractBreast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi‐mRNA‐based signature model and constructed a relative nomogram in predicting distant‐recurrence‐free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high‐ and low‐risk scores. Obvious differences of distant‐recurrence‐free survival were found between these two groups. This eight‐mRNA‐based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3‐year distant‐recurrence by the eight‐mRNA signature. A nomogram that combined both the eight‐mRNA‐based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight‐mRNA signature effectively classified patients into low‐ and high‐risk of distant recurrence, we concluded that this eight‐mRNA‐based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.
Clinical value of LHPP‐associated microRNAs combined with protein induced by vitamin K deficiency or antagonist‐II in the diagnosis of alpha‐fetoprotein‐negative hepatocellular carcinoma
Authors: Tian Zeyu , Yu Tanbo , Wei Hongyan , Ning Ning 
Published: November 2019

AbstractBackgroundAlpha‐fetoprotein (AFP) has received extensive attention in the differential diagnosis of hepatocellular carcinoma (HCC), especially for AFP‐negative HCC (AFP‐NHCC). The current study aimed to explore the value of targeted regulation of LHPP expression‐related microRNAs (miRs) and protein induced by vitamin K deficiency or antagonist‐II (PIVKA‐II) in the differential diagnosis of AFP‐NHCC.MethodsA retrospective study was conducted on a testing set—including 214 AFP‐NHCC patients, 200 cirrhosis, and 210 controls, and a validation set—including 140 AFP‐NHCC patients, 134 cirrhosis, and 128 controls recruited from The First Affiliated Hospital of Hunan Normal University. Serum miRs were examined using quantitative real‐time PCR method. Serum PIVKA‐II was measured by enzyme‐linked immunosorbent assay.ResultsCompared with adjacent tissues, LHPP protein levels in cancer tissues were significantly decreased (P < .05). Predictive software and dual‐luciferase reporter assays showed that miR‐363‐5p and miR‐765 can target LHPP expression. Serum miR‐363‐5p, miR‐765, and PIVKA‐II levels were significantly higher in AFP‐HCC patients than in cirrhosis and controls. A logistic regression model combining miR‐363‐5p, miR‐765, and PIVKA‐II was performed. This model presented a high discriminating value (AUC: 0.930, sensitivity/specificity: 79.4%/95.4%) than any single indicator. In the validation set, this model still showed a high discriminating value (AUC: 0.936, sensitivity/specificity: 83.6%/94.7%).ConclusionCurrent model combining serum miR‐363‐5p, miR‐765, and PIVKA‐II has potential significance for diagnosis of AFP‐NHCC.
Developing and testing the College Student Empowerment Scales for Racial/Ethnic Minorities
Authors: Back Lindsey T. , Keys Christopher B. 
Published: November 2019

AbstractEmpowerment is defined as a process by which marginalized groups gain mastery over issues of concern to them. One such population is racial and ethnic minority college students. These students experience academic disparities while simultaneously relying on higher education to facilitate more equitable social outcomes for themselves and ultimately to strengthen U.S. society for all. Nonetheless, nearly four decades after Rappaport's introduction of the empowerment construct, we still have no core constructs or measure of them for understanding and assessing the empowerment of underrepresented students on college campuses. As an initial step to understand and evaluate empowerment for this important population, this study drew from previous qualitative research to create and field‐test a quantitative measure with racial/ethnic minority college students. Exploratory factor analyses in independent samples identified 4 factors of empowerment: Self‐Efficacy/Control, University Environment, Financial Confidence, and Student Racial/Ethnic Identity. Confirmatory factor analyses illustrated relationships between factors. Findings revealed that the measure, the College Student Empowerment Scales for Racial/Ethnic Minorities (CSES), is valid and reliable. Results emphasize internalized influences on psychological empowerment through an individual's identity within empowering university and societal contexts. Future directions are discussed, including research using this measure and opportunities for intervention in universities.
Youth anti‐racism action: Contributions of youth perceptions of school racial messages and critical consciousness
Authors: Bañales Josefina , Aldana Adriana , Richards‐Schuster Katie , Flanagan Constance A. , Diemer Matthew A. , Rowley Stephanie J. 
Published: November 2019

AbstractThe current study examined whether youth perceptions of school racial messages that acknowledged the reality of racism (critical consciousness [CC] messages) or denied racism (color‐blind messages) predicted youth anti‐racism action through interpersonal and communal/political means. We further tested whether youths’ critical reflection of perceived inequality and anger toward social injustice—psychological aspects of CC development—mediated relations between school messages and youth actions. These questions were explored using structural equation modeling with 372 racially/ethnically diverse adolescents (Mage = 17.00; standard deviation = 1.29; female = 51.0%). Results indicated that youth perceptions of CC messages predicted their involvement in both interpersonal and communal/political anti‐racism action. Youths’ anger toward social injustice mediated links between school racial messages and anti‐racism action, albeit in unique ways. These findings underscore the power of schools in prompting youth anti‐racism action. Implications of the importance of partnerships between schools and youth community organizing groups to stimulate youth anti‐racism action were discussed.
Predictors of natural mentoring relationships and students’ adjustment to college
Authors: Berardi Luciano , Sanchez Bernadette , Kuperminc Gabriel 
Published: November 2019

AbstractLittle research exists that examines natural mentoring relationships (NMRs) during the college transition. We examine the role of parental attachment and help‐seeking behaviors in students’ development of new NMRs and the role NMRs have on students’ outcomes. Included in the study were 215 first‐year students at a large, urban, private university. Participants completed surveys at the beginning (Time 1) and at the end (Time 2) of the school year. We used structural equation modeling to test a hypothesized model that included predictors (i.e., attachment to parents and help‐seeking behaviors) of NMRs and social and academic adjustment in college. Findings show a path relationship connecting the attachment to parents to help‐seeking behaviors, and then to the number of reported NMRs. Help‐seeking behaviors mediated the association between attachment and NMRs. The number of NMRs is associated with higher social adjustment, but not academic adjustment by the end of students’ first year of college. Based on these results, we discuss the theoretical implications of newly formed NMRs and provide guidance for institutional interventions targeting first‐year college students to assist with transition challenges.
PCBP2 promotes the development of glioma by regulating FHL3/TGF‐β/Smad signaling pathway
Authors: Mao Jianhui , Sun Zhaosheng , Cui Yongjian , Du Naiyi , Guo Hong , Wei Jianhui , Hao Zhenmin , Zheng Lei 
Published: November 2019

AbstractThe purpose of this study was to investigate the role of Poly (C)‐binding protein 2 (PCBP2) and the related signaling pathway in glioma progression. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemistry (IHC) were performed to measure PCBP2 messenger RNA and protein expression in glioma tissues or cells. Cell transfection was completed using Lipofectamine 2000. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, Transwell assay and flow cytometry assay were used to explore the effects of PCBP2 expression on biological behaviors of glioma cells. Western blot assay was used for the detection of pathway related proteins. Expression of PCBP2 in glioma tissues and cells were higher than that in paracancerous tissues and normal cells (both p < .01). Moreover, the elevated expression of PCBP2 was significantly correlated with tumor size (p = .001) and WHO stage (p = .010). Knockdown of PCBP2 could suppress proliferation, migration and invasion of glioma cells and promote apoptosis. Besides, the expression of transforming growth factor‐β (TGF‐β) pathway related proteins TGF‐β1, p‐Smad2 and p‐Smad7 were decreased following the downregulation of PCBP2. PCBP2 also inhibited FHL3 expression by binding to FHL3‐3′UTR. The inhibition of FHL3 could reverse the antitumor action caused by PCBP2 silencing. In vivo assay, PCBP2 was also found to inhibit the tumor growth of glioma. PCBP2 activates TGF‐β/Smad signaling pathway by inhibiting FHL3 expression, thus promoting the development and progression of glioma.