bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and mechanistic values of microRNA‐130a and microRNA‐203 in patients with papillary thyroid carcinoma
Authors: Zhu Jie , Zheng Xiaoyu , Yang Xi
Published: November 2019

This research was determined to unearth the diagnostic values and the effects of microRNA (miR)‐130a and miR‐203 on cell proliferation and apoptosis of papillary thyroid carcinoma (PTC). Expression of miR‐130a and miR‐203 were evaluated and were subjected to correlation analysis. The diagnostic values of miR‐130a and miR‐203 and their associations with clinicopathological characteristics of patients with PTC were measured. The expression levels of miR‐130a and miR‐203 in K1, IHH4, TPC‐1, and BCPAP cells together with Nthy‐ori 3‐1 cells were measured. Cells were transfected with miR‐130a mimics, miR‐203 mimics, and coordinate of miR‐130a mimics and miR‐203 mimics. Cell growth, colony formation, and apoptosis were detected by cell counting kit‐8 (CCK‐8) assay, colony formation assay, and flow cytometry. PTC tissues had decreased miR‐130a and miR‐203 relative to adjacent normal tissues and normal thyroid tissue (both P < .05). miR‐130a was in positive correlation with miR‐203 (r = 0.754, P < .01). miR‐130a was related with tumor infiltration and tumor stage while miR‐203 was implicated in tumor stage and lymph‐node metastasis. The area under the curve (AUC), sensitivity, as well as specificity for miR‐130 in predicting PTC was 0.839, 74.5%, and 85.0% and those for miR‐203 were 0.818, 73.7%, and 84.0%, respectively. PTC cells had lower expression of miR‐130a and miR‐203 than that in Nthy‐ori 3‐1 cells. After transfected miR‐130a and miR‐203 mimics in BCPAP and TPC‐1 cells, both cells had increased miR‐130a and miR‐203, promoted cell apoptosis rate and decreased cell growth rate, and colony formation ability. After coordinately transfected with miR‐130a mimics and miR‐203 mimics, the cell growth and colony formation ability of PTC cells were restrained, and apoptosis of PTC cells was elevated (all P < .05). This study highlights that miR‐130a and miR‐203 have satisfactory diagnostic value in PTC and upregulated miR‐130a and miR‐203 can inhibit PTC cell growth and promote cell apoptosis.
Antioxidant, hepatoprotective, genoprotective, and cytoprotective effects of quercetin in a murine model of arthritis
Authors: Saccol Renata da Silva Pereira , da Silveira Karine Lanes , Manzoni Alessandra Guedes , Abdalla Fátima Husein , de Oliveira Juliana Sorraila , Dornelles Guilherme Lopes , Barbisan Fernanda , Passos Daniela Ferreira , Casali Emerson André , de Andrade Cinthia Melazzo , da Cruz Ivana Beatrice Mânica , Leal Daniela Bitencourt Rosa
Published: November 2019

Rheumatoid arthritis is a highly debilitating inflammatory autoimmune disease which is characterized by joint destruction. The present study sought to investigate the effect of quercetin in rats with complete Freund's adjuvant‐induced arthritis. Animals were divided into control/saline, control/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg) arthritis/saline, and arthritis/quercetin (5 mg/kg, 25 mg/kg, and 50 mg/kg); the treatments were administered for 45 days. Biochemical, oxidative stress, genotoxicity, and cytotoxicity parameters were evaluated. All doses of quercetin reduced the levels of aspartate aminotransferase, thiobarbituric acid‐reactive substances, and reactive oxygen species; however, only treatment with 25 or 50 mg/kg increased catalase activity. Total thiol and reduced glutathione levels were not significantly affected by the induction nor by the treatments. Genotoxicity assessed by DNA damage, and cytotoxicity through picogreen assay, decreased after treatments with quercetin. Our results present evidence of the antioxidant, cytoprotective, genoprotective and hepatoprotective, and effects of quercetin, demonstrating its potential as a candidate for coadjuvant therapy.
Formin mDia1 contributes to migration and epithelial‐mesenchymal transition of tubular epithelial cells exposed to TGF‐β1
Authors: Li Yu‐Ying , Jiang Guo‐Tao , Chen Li‐Jie , Jiang Yan‐Hong , Jiao Jun‐Dong
Published: November 2019

Renal tubular epithelial cells may undergo epithelial‐mesenchymal transition (EMT) in response to stimuli, such as transforming growth factor (TGF)‐β1, leading to myofibroblast activation and renal fibrosis. The formin mDia1 is required for nucleation and polymerization of actin and the microtubule cytoskeleton. The present study sought to explore the role of mDia1 in EMT of tubular epithelial cells. A rat model of unilateral ureteral obstruction (UUO) was established. The expression of TGF‐β1, collagen I, collagen III, and mDia1 in the kidneys was examined at day 7 after surgery. The effect of mDia1 on EMT was explored in NRK‐52E cells by exposing them to TGF‐β1. Increased expression of TGF‐β1, collagen I, collagen III, and mDia1 was found in obstructive kidneys of UUO model rats. Exposing rat tubular epithelial cells to TGF‐β1 promoted collagen I and collagen III expression but had no effect on mDia1 expression. Silencing mDia1 expression impeded epithelial cell migration as well as reduced TGF‐β1, collagen, and Profilin1 expression, whereas mDia1 overexpression exerted an opposite effect. Furthermore, mDia1 regulated the expression of vimentin, α‐smooth muscle actin, and E‐cadherin and focal adhesion‐kinase (FAK)/Src activation through Profilin1. Inhibition of the mDia1 activator RhoA by fasudil reversed EMT, and FAK/Src activation induced by mDia1. In conclusion, mDia1 regulated tubular epithelial cell migration, collagen expression, and EMT in NRK‐52E cells exposed to TGF‐β1. Thus, suppression of mDia1 activation might be a strategy to counteract renal fibrosis.
MicroRNA‐7 promotes neural differentiation of trabecular meshwork mesenchymal stem cell on nanofibrous scaffold
Authors: Jedari Behrouz , Rahmani Ali , Naderi Mahmood , Nadri Samad
Published: November 2019

The purpose of this study was to investigate miR‐7 overexpression effects on neural differentiation of mesenchymal stem cells (MSCs) on both two‐dimensional (2D) and three‐dimensional (3D) culture systems. We upregulated miR‐7 through lentiviral vector in trabecular meshwork MSCs (TMMSCs) and polymers of poly l‐lactic acid/polycaprolactone fibrous scaffold were fabricated by electrospinning and characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FTIR). Neural markers expression was evaluated through quantitative‐polymerase chain reaction (q‐PCR) and immunostaining. The results showed that the high percentage of cell transduction (84.9%) and miR‐7 expression (folds: 677.93 and 556.4) was detected in TMMSCs‐miR‐7(+). SEM and FTIR established the fabrication of the hybrid scaffold. q‐PCR analysis showed that on days 14 and 21 of transduction, the expression level of Nestin and glial fibrillary acidic protein (GFAP) genes were significantly higher in the scaffold (3D) compared with tissue culture polystyrene (2D) culture. The expression of microtubule‐associated protein‐2 (MAP‐2) and GFAP genes in TMMSCs‐miR‐7(+) cells were significantly higher than those miR‐7(−) cells after 21 days of cell culture. Also, MAP‐2 and Nestin proteins were detected in TMMSCs‐miR‐7(+) cells. Our results demonstrate that miR‐7 is involved in neural differentiation of TMMSCs and scaffold can improve differentiate into glial and neural progenitor cells. These findings provided some information for future use of microRNAs and scaffold in tissue engineering and cell therapy for neurological diseases.
CDK2 destabilizes tumor suppressor C/EBPα expression through ubiquitin‐mediated proteasome degradation in acute myeloid leukemia
Authors: Thacker Gatha , Mishra Mukul , Sharma Akshay , Singh Anil Kumar , Sanyal Sabyasachi , Trivedi Arun Kumar
Published: November 2019

Deregulation and functional inhibition of CCAAT‐enhancer‐binding protein α (C/EBPα), a key transcription factor of myeloid lineage leads to development of myeloid leukemia. In this study, we show that cyclin‐dependent kinase 2 (CDK2) negatively regulates C/EBPα protein levels in myeloid leukemia cells. The overexpression of CDK2 inhibited C/EBPα both in a heterologous HEK293T and U937 myeloid leukemia cells. On the contrary, CDK2 depletion enhanced endogenous C/EBPα protein levels. CDK2 mitigated C/EBPα levels by promoting its ubiquitin‐mediated proteasome degradation. We further showed that although CDK2 interacted with C/EBPα, direct interaction of CDK2 with C/EBPα is not involved in C/EBPα downregulation. CDK2‐dependent phosphorylation of C/EBPα on its widely reported phosphorylatable amino acid residues is apparently not required for C/EBPα degradation by CDK2. Furthermore, our data demonstrate that CDK2‐driven C/EBPα inhibition mitigates its transactivation potential and cellular functions such as ability to promote myeloid differentiation and growth arrest.
MicroRNA‐326 attenuates hepatic stellate cell activation and liver fibrosis by inhibiting TLR4 signaling
Authors: Liao Xin , Zhan Wei , Tian Tian , Yu Lei , Li Rui , Yang Qin
Published: November 2019

Hepatic fibrosis is a chronic inflammatory and reversible repair reaction of the liver under the continuous action of virus or various injuries. In this study, we aimed at identifying the role of miR‐326 in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. In this study, the liver fibrosis mouse model was developed by injecting CCl4. Liver tissue morphology was observed and the expression level of α‐smooth muscle actin, collagen1α1 and miR‐326 was measured. Target gene identification was performed by loss‐of‐function and gain‐of‐function. The effect of miR‐326 on the expression level of the cytokines associated with the TLR4/MyD88/nuclear factor‐κB (NF‐κB) pathway was assessed in vitro and in vivo. We show that miR‐326 was downregulated in CCl4‐induced fibrotic mice and activated HSCs. The target gene of miR‐326 is TLR4. Moreover, miR‐326 inhibited the activation of HSCs in vitro through TLR4/MyD88/NF‐κB signaling. miR‐326 attenuated hepatic fibrosis and inflammation of CCl4‐induced mice in vivo. Our results demonstrate for the first time that miR‐326 inhibits HSC activation through TLR4/MyD88/NF‐κB signaling. Furthermore, miR‐326 plays critical roles in attenuating liver fibrosis and inflammation, suggesting the therapeutic potential of miRNAs.
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

Actin 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

Bone 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

Background

Calcium‐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.

Methods

CABYR‐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.

Results

The 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.

Conclusion

Our 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

Brown 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

Non–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

Colorectal 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

Breast 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

Background

Alpha‐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.

Methods

A 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.

Results

Compared 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%).

Conclusion

Current 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

Empowerment 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

The 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

Little 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

The 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.
The landscape of immune checkpoint inhibitor plus chemotherapy versus immunotherapy for advanced non‐small‐cell lung cancer: A systematic review and meta‐analysis
Authors: Wang Chengdi , Qiao Wenliang , Jiang Yuting , Zhu Min , Shao Jun , Wang Tao , Liu Dan , Li Weimin
Published: November 2019

Background

Lung cancer is the leading cause of cancer‐related deaths worldwide and the prognosis remains poor. The recent introduction of the immune checkpoint inhibitor (ICI), or plus chemotherapy, both resulted in the survival benefit for patients with advanced non‐small‐cell lung cancer (NSCLC), but it remains unanswered which is superior. The current study aimed to estimate the comparative efficacy and safety of ICI‐chemotherapy versus ICI‐monotherapy in advanced NSCLC.

Methods

Studies were identified by searching PubMed, Embase, and Cochrane library. The randomized controlled trials (RCTs) that ICI monotherapy or ICI plus chemotherapy compared with chemotherapy in NSCLC were included with available primary endpoints of progression‐free survival (PFS), overall survival (OS), objective response rate, or treatment‐related adverse events. A fixed‐effect or random‐effects model was adopted depending on between‐study heterogeneity.

Results

A total of 20 RCTs involving 12,025 patients with NSCLC were included. Both ICI‐monotherapy and ICI‐chemotherapy resulted in significantly prolonged survival compared to chemotherapy and the former led to significantly longer PFS. The magnitude of survival benefits appeared to be greatest among those treated with pembrolizumab plus platinum‐based chemotherapy (OS, 0.56; PFS, 0.54). Additionally, OS and PFS advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD‐L1) expression level, but not in intermediate PD‐L1 TPS.

Conclusions

Pembrolizumab plus platinum‐based chemotherapy was recommended as the optimal first‐line therapy for advanced patients with NSCLC. Additionally, PD‐L1 alone is not recommended as an adequate molecular biomarker to identify eligible patients for routine clinical practice in immunotherapy.
Signatures of altered DNA methylation gene expression after central and peripheral nerve injury
Authors: Shi Guidong , Zhou Xianhu , Wang Xu , Zhang Xiaolei , Zhang Ping , Feng Shiqing
Published: November 2019

Nerve damage can lead to movement and sensory dysfunction, with high morbidity and disability rates causing severe burdens on patients, families, and society. DNA methylation is a kind of epigenetics, and a great number of previous studies have demonstrated that DNA methylation plays an important role in the process of nerve regeneration and remodeling. However, compared with the central nervous system, the peripheral nervous system shows stronger recovery after injury, which is related to the complex microenvironment and epigenetic changes occurring at the site of injury. Therefore, what common epigenetic changes between the central and peripheral nervous systems remain to be elucidated. We first screened differential methylation genes after spinal cord injury and sciatic nerve injury using whole‐genome bisulfite sequencing and methylated DNA immunoprecipitation sequencing, respectively. Subsequently, a total of 16 genes had the same epigenetic changes after spinal cord injury and sciatic nerve injury. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. Furthermore, a protein−protein interaction network analysis indicated that Dnm3, Ntrk3, Smurf1, Dpysl2, Kalrn, Shank1, Dlg2, Arsb, Reln, Bmp5, Numbl, Prickle2, Map6, and Htr7 were the core genes. These outcomes may provide novel insights into the molecular mechanism of the subacute phase of nerve injury. These verified genes can offer potential diagnostic and therapeutic targets for nerve injury.
Biohydrogen production from winery effluents: control of the homoacetogenesis through the headspace gas recirculation
Authors: Buitrón Germán , Muñoz‐Páez Karla M , Quijano Guillermo , Carrillo‐Reyes Julián , Albarrán‐Contreras Blanca A
Published: November 2019

BACKGROUND

Fermentative hydrogen production has an inherent limitation caused by hydrogen‐consuming metabolic pathways such as homoacetogenesis related to high hydrogen partial pressures. In this study, a strategy based on recirculating the headspace gas was applied to increase the hydrogen release from the liquid to the gas phase in an upflow anaerobic sludge blanket(UASB) reactor fed with winery effluents. The influence of the gas upflow recirculation velocity on hydrogen production, hydrogen consumption by homoacetogenesis, and microbial community structure was evaluated.

RESULTS

Under the control condition (only liquid recirculation), the hydrogen productivity was as much as 22 mL H2 L−1 h−1. Conversely, the hydrogen productivity increased up to 62 mL H2 L−1 h−1 when the reactor was operated with an upflow gas recirculation velocity of 28.6 m d−1. The increase in mass transfer, due to the gas recirculation, produces a decrease (up to 70%) in the hydrogen consumption rate associated with homoacetogenesis. High‐throughput 16s rDNA sequencing characterization showed that the gas recirculation strategy promoted the development of hydrogen‐producing microorganisms related to Megasphaera elsdenii and decreased the abundance of hydrogen‐consuming bacteria related to Clostridium carboxidivorans and C. ljungdahlii.

CONCLUSION

The results indicated that headspace recirculation at gas upflow velocities higher than 17.8 m d−1 increased the hydrogen production rate concomitantly with the reduction of both the homoacetogenic activity and the abundance of H2‐consuming bacteria. The study demonstrated that headspace recirculation could be a promising way to control homoacetogenesis, and therefore, to increase the biohydrogen productivity from complex substrates such as winery effluents. © 2019 Society of Chemical Industry
Review of pervaporation and vapor permeation process factors affecting the removal of water from industrial solvents
Authors: Vane Leland M
Published: November 2019

A recent review article (Journal of Chemical Technology & Biotechnology 94: 343–365 (2019)) identified several commercially‐available permselective materials for drying organic solvents with pervaporation (PV) and vapor permeation (V·P) separation processes. The membrane materials included polymeric and inorganic substances exhibiting a range in the performance characteristics: water permeance, water/solvent selectivity, and maximum use temperature. This article provides an overview of the factors affecting the design of PV/V·P processes utilizing these membranes to remove water from common organic solvents. Properties of the specific membrane and of the solvent substantially affect the PV/V·P separation. Equally important is the impact of operating parameters on the overall separation. To study these impacts, simplified process performance equations and detailed spreadsheet calculations were developed for single‐pass and recirculating batch PV systems and for single‐pass V·P systems. Estimates of membrane area, permeate concentration, solvent recovery, permeate condenser temperatures, and heating requirements were calculated. Process variables included: solvent type, water permeance, water/solvent selectivity, initial and final water concentrations, operating temperature (PV) or feed pressure (V·P), temperature drop due to evaporation (PV) or feed‐side pressure drop (V·P), and permeate pressure. The target solvents considered were: acetonitrile, 1‐butanol, N,N‐dimethyl formamide, ethanol, methanol, methyl isobutyl ketone, methyl tert‐butyl ether, tetrahydrofuran, acetone, and 2‐propanol. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.
Malic acid production from renewables: a review
Authors: Kövilein Aline , Kubisch Christin , Cai Liyin , Ochsenreither Katrin
Published: November 2019

Malic acid derived from fossil resources is currently applied in the food and beverage industries with a medium global production capacity. However, in the transition from a fossil‐based to a bio‐based economy, biotechnologically produced l‐malic acid may become an important platform chemical with many new applications, especially in the field of biopolymers. In this review, currently used petrochemical production routes to dl‐malic acid are outlined and insights into possible bio‐based alternatives for microbial l‐malic acid production are provided. Besides ecological reasons, the possibility to produce enantiopure l‐malic acid by microbial fermentation is the biggest advantage over chemical synthesis. State‐of‐the‐art and open challenges concerning production host engineering, substrate choice and downstream processing are addressed. With regard to production hosts, a literature overview is given covering the leading natural production strains of Aspergillus, Ustilago and Aureobasidium, as well as Escherichia coli as the most important engineered recombinant host. The utilization of renewable substrates as an alternative to glucose is emphasized in particular as a key aspect for a competitive bio‐based production. Out of the alternative substrates discussed in this review, the industrial side‐streams crude glycerol and molasses seem to be most promising for large‐scale l‐malic acid production. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Dual anti‐inflammatory and antiglycation propensities of a potentially novel class of functionalized fluoroquinolones
Authors: Hamdan Alaa , Kasabri Violet , Al‐Hiari Yusuf , Arabiyat Shereen , AlAlawi Sundus , Bustanji Yasser
Published: November 2019

Promoted by elevated blood glucose concentrations in diabetes, glycation involves the nonenzymatic addition of reducing sugars and/or their reactive degradation products to amine groups on proteins. New synthetic approaches to 18 fluoroquinolones (FQs) have been developed on the basis of a promising antiglycation activity using 400μM methylglyoxal as the choice glucocytotoxicity concentration. Their anti‐inflammatory and radical scavenging properties were elucidated in vitro. Intriguingly, FQs could exhibit an exceedingly more superior than or substantially comparable cytoprotection against methylglyoxal‐induced carbonyl toxicity in RAW264.7 macrophages and antiglycation activity to aminoguanidine, as the reference compound. This kind of activity can suggestively be associated with the chelating properties possessed by the synthesized FQs as their DPPH radical scavenging activities proved to be significantly inferior to those of the reference compound, the ascorbic acid. The inhibitory bioactivities using the Griess assay were examined of the compounds against lipopolysaccharide (LPS)‐induced nitric oxide (NO) production in RAW 264.7 macrophages. Selectively, compounds R‐2TCBA, R‐4FACBA, R‐3TCBA, and R‐4CLACBA exerted an exceedingly remarkable and superior anti‐inflammatory effects (P < .001 vs indomethacin IC50 value of 101.07 ± 2.2 μM) while R‐4TCBA and T‐4BrACBA were moderately more efficacious than indomethacin. Compounds T‐4CLACBA and R‐4BrACBA displayed comparable activity with indomethacin. None of the tested compounds and indomethacin exerted any cytotoxicity against RAW 264.7 mouse macrophages. FQs possess potent duality of antiglycation–anti‐inflammatory capacities and are devoid of undesirable side effects. FQs can, therefore, serve as scaffolds for the development and designing of new clinical deglycation and antiglycation therapeutic agents.
Political Communication Apprehension: Toward Productive Political Discourse Online and Face‐to‐Face
Authors: Jones‐Carmack Joy
Published: November 2019

Based on the theoretical framework of Byrne's similarity attraction paradigm and the spiral of silence theory, the current paper conceptually defines political communication apprehension as the fear or anxiety associated with real or anticipated communication about politics with another person or persons. Although communication apprehension research has encompassed numerous topics and contexts known to increase anxiety, including religion, race, and death, researchers have failed to examine the relation between political discourse and anxiety. Politics is a well‐known anxiety provoking discussion topic, and political communication apprehension is an important and timely topic that needs further investigation. Political deliberation and discussion are essential to the growth and development of a democratic society. Furthermore, the need to process beliefs, feelings, and thoughts is a natural part of human communication and relationship building. For leaders, the ability to listen and connect with empathy and respect to all people, regardless of ideological differences, is a vital component of impactful leadership. Therefore, the purpose of the review is to begin the discussion regarding political communication apprehension (PCA) and to set the stage for future studies examining the validity and reliability of a PCA measure. The current paper not only introduces PCA but also argues that PCA is a relevant construct that may hold the key to more productive political conversations for leaders and followers, online, face‐to‐face, and inside and outside the classroom.
The impact of hepatitis B virus infection status on the prevalence of nonalcoholic fatty liver disease: A population‐based study
Authors: Huang Jiaofeng , Jing Mengli , Wang Ciyang , Wang Mingfang , You Shunjie , Lin Su , Zhu Yueyong
Published: November 2019

Background

We aimed to explore the impact of hepatitis B virus (HBV) infection on the prevalence of nonalcoholic fatty liver disease (NAFLD) based on clinical big data.

Methods

Data were collected from the health examination center of the First Affiliated Hospital of Fujian Medical University. Univariate and multivariate analysis were applied to investigate the relationship between HBV and NAFLD.

Results

A total of 14 452 patients were included, with an average age of 43.84 ± 13.03 years. Cases of HBV current infection, past infection, and noninfection were 21 102 110 (14.6%), 90 039 003 (62.3%), and 33 393 339 (23.1%), respectively. The prevalence of NAFLD was significantly lower in the current infection group (29.9%) than in the past infection group (35.8%) and noninfection group (31.9%) (P < .001). After adjusting for age, the prevalence of NAFLD in the current infection group remained the lowest across all of the age groups. Multivariate analysis showed that current infection was at a lower risk of NAFLD (odds ratio [OR] = 0.717, 95% CI: 0.608‐0.846), whereas past infection had no effect on NAFLD.

Conclusions

Current HBV infection may lower the risk of NAFLD. This effect becomes insignificant when the patient is no longer infected.