bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic syndrome, Mediterranean diet, and polyphenols: Evidence and perspectives
Authors: Finicelli Mauro , Squillaro Tiziana , Di Cristo Francesca , Di Salle Anna , Melone Mariarosa Anna Beatrice , Galderisi Umberto , Peluso Gianfranco 
Published: October 2018

AbstractMetabolic syndrome (MetS) is defined as the co‐occurrence of metabolic risk factors that includes insulin resistance, hyperinsulinemia, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and visceral obesity. The clinical significance of MetS consists of identifying a subgroup of patients sharing a common physiopathological state predisposing to chronic diseases. Clinical and scientific studies pinpoint lifestyle modification as an effective strategy aiming to reduce several features accountable for the risk of MetS onset. Among the healthy dietary patterns, the Mediterranean diet (MedDiet) emerges in terms of beneficial properties associated with longevity. Current evidence highlights the protective effect exerted by MedDiet on the different components of MetS. Interestingly, the effect exerted by polyphenols contained within the representative MedDiet components (i.e., olive oil, red wine, and nuts) seems to be accountable for the beneficial properties associated to this dietary pattern. In this review, we aim to summarize the principal evidence regarding the effectiveness of MedDiet–polyphenols in preventing or delaying the physiopathological components accountable for MetS onset. These findings may provide useful insights concerning the health properties of MedDiet–polyphenols as well as the novel targets destined to a tailored approach to MetS.
Crucial role of poly (ADP‐ribose) polymerase (PARP‐1) in cellular proliferation of Dictyostelium discoideum
Authors: Jubin Tina , Kadam Ashlesha , Saran Shweta , Begum Rasheedunnisa 
Published: October 2018

AbstractThe unicellular, as well as multicellular stages of Dictyostelium discoideum’s life cycle, make it an excellent model system for cell type determination, differentiation, development, and cell death studies. Our preliminary results show the involvement of poly (ADP‐ribose) polymerase‐1 (PARP‐1) during
D. discoideum growth by its constitutive downregulation as well as by its ortholog overexpression. The current study now analyzes and strengthens the role of the PARP‐1 ortholog in cellular proliferation of
D. discoideum.
ADPRT1A was knocked out (KO) from
D. discoideum and studied for its effect on cell growth, cell cycle, morphology, and oxidative stress. The present findings show that
ADPRT1A KO (
A KO) cells exhibited reduced cellular proliferation, stressed phenotype, and cell cycle arrest in G2‐M phase. Under oxidative stress,
A KO cells exhibited slower growth and DNA damage. This is the first report where the involvement of ADPRT1A in growth in
D. discoideum is established.
Predictive and therapeutic biomarkers in chimeric antigen receptor T‐cell therapy: A clinical perspective
Authors: Mirzaei Hamid Reza , Mirzaei Hamed , Namdar Afshin , Rahmati Majid , Till Brian G. , Hadjati Jamshid 
Published: October 2018

AbstractThe adoptive transfer of genetically engineered T cells modified to express a chimeric antigen receptor (CAR) has shown remarkable activity and induces long‐term remissions in patients with advanced hematologic malignancies. To date, little is known about predictive indicators of therapeutic efficacy or serious toxicity after CAR T‐cell therapy in clinical practice. Biomarkers are not only potentially able to inform physicians and researchers of immunotherapy targets in particular but could also be used to monitor the effectiveness of treatments and to predict incidence of side effects in some circumstances. Identification of new biomarkers can therefore not only contribute to the development of new therapeutic and prognostic strategies for CAR T‐cell therapy for cancer but also help to generate improved clinical practices for early recognition and minimization of adverse effects while preserving the antitumor activity of the CAR T cells. Herein, we will consider a variety of predictive and therapeutic biomarkers in CAR T‐cell therapy and the state of current understanding of their clinical utility. The incorporation of biomarker studies in CAR T‐cell clinical trials and practice will help to realize the potential clinical benefit of biomarker‐guided therapy.
Physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway
Authors: Ding Ning , Wang Yuxing , Dou Ce , Liu Feila , Guan Ge , Wei Keyu , Yang Jingyuan , Yang Mingcan , Tan Ju , Zeng Wen , Zhu Chuhong 
Published: October 2018

AbstractThe in vitro and in vivo effects of physalin D on macrophage M1/M2 polarization were investigated. In silico analysis was first performed for biological function prediction of different physalins. The results suggest physalins have similar predicted biological functions due to their similarities in chemical structures. The cytotoxicity of physalins was then analyzed based on cell apoptosis rate and cell viability evaluation. Physalin D was chosen for further study due to its minimal cytotoxicity. Bone marrow macrophages were isolated and induced with lipopolysaccharide/interferon (IFN)‐γ for M1 polarization and interleukin (IL)‐4/IL‐13 for M2 polarization. The results showed that physalin D can repolarize M1 phenotype cells toward M2 phenotype. In addition, physalin D is protective in M2 macrophages to maintain the M2 phenotype in the presence of IFN‐γ. On the molecular level, we found that physalin D suppressed the signal transducers and activators of transcription (STAT)1 activation and blocked STAT1 nuclear translocation. Conversely, physalin D can also activate STAT6 and enhance STAT6 nuclear translocation for M2 polarization. Taken together, these results suggested that physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway.
Notch signaling inhibits cardiac fibroblast to myofibroblast transformation by antagonizing TGF‐β1/Smad3 signaling
Authors: Zhou Xue‐liang , Fang Yi‐hu , Wan Li , Xu Qi‐rong , Huang Huang , Zhu Rong‐rong , Wu Qi‐cai , Liu Ji‐chun 
Published: October 2018

AbstractPurposeDuring myocardial infarction (MI), cardiac fibroblasts (CFs) transform into myofibroblast (CMT). This study aimed to investigate the crosstalk of Notch1 and transforming growth factor‐β1 (TGF‐β1)/Smad3 signaling in the regulation of CMT and myocardial fibrosis.MethodsPrimary CFs were isolated from young rats and treated with TGF‐β1 or adenovirus to overexpress or knockdown Notch1 intracellular domain (N1ICD) or Smad3.ResultsTGF‐β1 decreased the expression of fibroblast markers but increased the expression of myofibroblast markers in rat CFs. TGF‐β1 increased the proliferation, invasion, and adhesion, and the secretion of collagen I of CFs, and these effects were inhibited by N1ICD overexpression. Moreover, endogenous Smad3 phosphorylation in CFs was enhanced by N1ICD knockdown, whereas TGF‐β1 induced Smad3 phosphorylation was antagonized by the N1ICD overexpression. Conversely, endogenous N1ICD activation in CFs was antagonized by Smad3, whereas TGF‐β1 induced N1ICD inactivation was antagonized by Smad3 knockdown. Coimmunoprecipitation showed that N1ICD interacted with Smad3 and immunostaining revealed the colocalization of N1ICD and Smad3 in the nuclei of CFs. Moreover, we demonstrated the functional antagonism of N1ICD and Smad3 on the phenotypes of CFs. Finally, TGF‐β1/Smad3 signaling promoted whereas Notch signaling inhibited myocardial fibrosis in rat MI model.ConclusionNotch signaling inhibits CMT by antagonizing TGF‐β1/Smad3 signaling. Notch signaling activators and TGF‐β1/Smad3 signaling inhibitors could be exploited for therapeutic intervention to inhibit myocardial fibrosis after MI.
P2X7, a critical regulator and potential target for bone and joint diseases
Authors: Zeng Dehui , Yao Pingbo , Zhao Hong 
Published: October 2018

AbstractAbundant evidence indicted that P2X7 receptor show a essential role in human health and some human diseases including hypertension, atherosclerosis, pulmonary inflammation, tuberculosis infection, psychiatric disorders, and cancer. P2X7 receptor also has an important role in some central nervous system diseases such as neurodegenerative disorders. Recently, more research suggested that P2X7 receptor also plays a crucial role in bone and joint diseases. But the effect of P2X7 receptor on skeletal and joint diseases has not been systematically reviewed. In this article, the role of P2X7 receptor in skeletal and joint diseases is elaborated. The activation of P2X7 receptor can ameliorate osteoporosis by inducing a fine balance between osteoclastic resorption and osteoblastic bone formation. The activation of P2X7 receptor can relieve the stress fracture injury by increasing the response to mechanical loading and inducing osteogenesis. But the activation of P2X7 receptor mediates the cell growth and cell proliferation in bone cancer. In addition, the activation of P2X7 receptor can aggravate the process of some joint diseases such as osteoarthritis, rheumatoid arthritis, and acute gouty arthritis. The inhibition of P2X7 receptor can alleviate the pathological process of joint disease to some extent. In conclusion, P2X7 receptor may be a critical regulator and therapeutic target for bone and joint diseases.
Analysis of gene expression and methylation datasets identified ADAMTS9, FKBP5, and PFKBF3 as biomarkers for osteoarthritis
Authors: Li ZhaoFang , Zhang RongQiang , Yang XiaoLi , Zhang DanDan , Li BaoRong , Zhang Di , Li Qiang , Xiong YongMin 
Published: October 2018

AbstractBackground: Osteoarthritis (OA) is a kind of chronic osteoarthropathy and degenerative joint disease. Epigenetic regulation in the gene expression dynamics has become increasingly important in OA. We performed a combined analysis of two types of microarray datasets (gene expression and DNA methylation) to identify methylation‐based key biomarkers to provide a better understanding of molecular biological mechanisms of OA.Methods: We obtained two expression profiling datasets (GSE55235, GSE55457) and one DNA methylation profiling data set (GSE63695) from the Gene Expression Omnibus. First, differentially expressed genes (DEGs) between patients with OA and controls were identified using the Limma package in R(v3.4.4). Then, function enrichment analysis of DEGs was performed using a DAVID database. For DNA methylation datasets, ChAMP methylation analysis package was used to identify differential methylation genes (DMGs). Finally, a comprehensive analysis of DEGs and DMGs was conducted to identify genes that exhibited differential expression and methylation simultaneously.Results: We identified 112 DEGs and 2,896 DMGs in patients with OA compared with controls. Functional analysis of DEGs obtained that inflammatory responses, immune responses, and positive regulation of apoptosis, tumor necrosis factor (TNF) signaling pathway, and osteoclast differentiation may be involved in the pathogenesis of OA. Cross‐analysis revealed 26 genes that exhibited differential expression and methylation in OA. Among them, ADAMTS9, FKBP5, and PFKBF3 were identified as valuable methylation‐based biomarkers for OA.Conclusion: In summary, our study identified different molecular features between patients with OA and controls. This may provide new clues for clarifying the pathogenetic mechanisms of OA.
Mutations in GAS5 affect the transformation from benign prostate proliferation to aggressive prostate cancer by affecting the transcription efficiency of GAS5
Authors: Zhu Lizhen , Zhu Qi , Wen Huihuang , Huang Xiang , Zheng Ge 
Published: October 2018

AbstractBackgroundIn this study, we aimed to explore the effects of GAS5 single‐nucleotide polymorphisms (SNPs) on GAS5 expression. And the signaling pathways underlying the function of GAS5 during the pathogenesis of prostate cancer (PC) were clarified.Materials and methodsPatients with PC were recruited and grouped according to their specific genotypes of rs55829688 and rs145204276. Kaplan–Meier overall survival curves were calculated and compared among different groups. Real‐time polymerase chain reaction (RT‐PCR), western blot, and immunohistochemistry (IHC) assays were conducted to examine the expression of different factors involved in PC. And computational analyses and luciferase assays were conducted to clarify the regulatory relationships among the above factors. MTT (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide), flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to evaluate cell viability and apoptosis.ResultsThe expression of GAS5, PDCD4, PTEN, and AKT was decreased gradually in the order of patient Group 1–4, whereas the expression of microRNA‐21 (miR‐21) and miR‐1284 showed an opposite trend. GAS5 was identified to target miR‐21 and miR‐1284, whereas miR‐21 and miR‐1284 regulated the expression of PDCD4/PTEN and AKT, respectively. Moreover, the GAS5/miR‐21/PDCD4/PTEN and GAS5/miR‐1284/AKT signaling pathway was found to be closely related to the tumorigenesis of PC.ConclusionsGAS5 SNPs affected the survival rate and prognosis in patients with PC via regulating the expression of miR‐21/miR‐1284, which in turn affected the expression of PDCD4, PTEN, and AKT. GAS5 downregulated the expression of miR‐21/miR‐1284, thus leading to the elevated expression of key regulators of apoptosis. Therefore, the GAS5 SNPs may be used as key indicators for the diagnosis and prognosis prediction of PC.
Zebrafish znfl1s regulate left‐right asymmetry patterning through controlling the expression of fgfr1a
Authors: Li Jingyun , Gao Feng , Zhao Yingmin , He Luqingqing , Huang Yun , Yang Xiaojing , Zhou Yahui , Yu Lingling , Zhao Qingshun , Dong Xiaohua 
Published: October 2018

AbstractProper left‐right (LR) axis establishment is critical for organogenesis in vertebrates. Previously, we reported that zinc finger transcription factors zinc finger transcription factor 1 (znfl1s) are expressed in the tailbud and axial mesoderm in zebrafish. However, a role of
znfl1s in LR axis development has not been demonstrated. Here, we discovered that the knockdown of
znfl1s using morpholino (MO) in whole embryos or dorsal forerunner cells (DFCs) interrupted LR asymmetry and normal development of the heart, liver, and pancreas. Whole‐embryo knockdown of
znfl1s by MO or clustered regularly interspaced short palindromic repeat (CRISPR) interference (CRISPRi) resulted in the absent expression of nodal gene
spaw and Nodal signaling‐related genes
lft1,
lft2, and
pitx2c in the left lateral plate mesoderm (LPM), and Spaw, Lft1, Lft2, and Pitx2c play important roles in LR axis development in zebrafish. However, specific knockdown of
znfl1s in DFCs resulted in random expression of
spaw,
lft1,
lft2, and
pitx2c. Knockdown of
znfl1s led to abnormal cilia formation by the downregulation of
fgfr1a and
foxj1a expression. The expression of
spaw,
lft1,
lft2, and
pitx2c was partially rescued by the overexpression of
fgfr1a mRNA in
znfl1s morphants. Taken together, our results suggest that
znfl1s regulate laterality development in zebrafish embryos through controlling the expression of
fgfr1a.
Spindlin1 alters the metaphase to anaphase transition in meiosis I through regulation of BUB3 expression in porcine oocytes
Authors: Choi Jeong‐Woo , Zhou Wenjun , Nie Zheng‐Wen , Niu Ying‐Jie , Shin Kyung‐Tae , Cui Xiang‐Shun 
Published: October 2018

AbstractSpindlin 1 (SPIN1), which contains Tudor‐like domains, regulates maternal transcripts via interaction with a messenger RNA (mRNA)‐binding protein. SPIN1 is involved in tumorigenesis in somatic cells and is highly expressed in cancer cells. Nevertheless, the role of SPIN1 in porcine oocyte maturation remains totally unknown. To explore the function of SPIN1 in porcine oocyte maturation, knockdown, and overexpression techniques were used. SPIN1 mRNA was identified in maternal stages ranging from GV to MII. SPIN1 was localized in the cytoplasm and to chromosomes during meiosis. SPIN1 knockdown accelerated first polar body extrusion. Oocytes with overexpressed SPIN1 were arrested at the MI stage. SPIN1 depletion caused meiotic spindle defects and chromosome instability. The BUB3 signal was investigated, confirming that SPIN1 affects the stability of Bub3 mRNA as well as BUB3 expression. Further, overexpression of SPIN1 inhibited the degradation and regulation of G2/mitotic‐specific cyclin‐B1. In summation, SPIN1 regulates the meiotic cell cycle by modulating the activation of the spindle assembly checkpoint.
Long noncoding RNA APTR contributes to osteosarcoma progression through repression of miR‐132‐3p and upregulation of yes‐associated protein 1
Authors: Guan Hongya , Shang Guowei , Cui Yuanbo , Liu Jiu , Sun Xiaoya , Cao Wei , Wang Yisheng , Li Yuebai 
Published: October 2018

AbstractA growing amount of evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in osteosarcoma (OS). However, little knowledge is available about the functional roles and molecular mechanisms of lncRNA Alu‐mediated p21 transcriptional regulator (APTR) in OS. Herein, APTR expression was demonstrated to be significantly upregulated in OS tumor tissues and four OS cell lines (including MG63, 143B, Saos‐2, and HOS) compared with the adjacent tissues and human osteoblast cell line hFOB1.19, respectively. We confirmed miR‐132‐3p to be a target for APTR, and its expression was demonstrated to be inhibited by APTR. In functional terms, knockdown of APTR and overexpression of miR‐132‐3p both, remarkably repressed human OS cell proliferation, invasion and migration, and induced apoptosis. Also, Yes‐associated protein 1 (YAP1) was determined as an inhibitory target of miR‐132‐3p. Moreover, our findings demonstrated that the repression of YAP1 protein expression and the suppression of Ki‐67, MMP9, and Bcl2 expression induced by APTR knockdown required increased miR‐132‐3p. Thus, APTR contributed to OS progression through repression of miR‐132‐3p and upregulation of YAP1 expression. Therefore, we have uncovered a novel regulatory mechanism by which the APTR/miR‐132‐3p/YAP1 axis can regulate OS progression.
Identification of TAF1, HNF4A, and CALM2 as potential therapeutic target genes for liver fibrosis
Authors: Ji Dong , Chen Guo‐Feng , Wang Jin‐Cheng , Cao Li‐Hua , Lu Fengmin , Mu Xiao‐Xin , Zhang Xiao‐Yu , Lu Xiao‐Jie 
Published: October 2018

AbstractThe molecular mechanism of liver fibrosis caused by hepatitis C virus (HCV) is not clear. The aim of this study is to understand the molecular mechanism of liver fibrosis induced by HCV and to identify potential therapeutic targets for hepatic fibrosis. We analyzed gene expression patterns between high liver fibrosis and low liver fibrosis samples, and identified genes related to liver fibrosis. We identified TAF1, HNF4A, and CALM2 were related to the development of liver fibrosis. HNF4A is important for hepatic fibrogenesis, and upregulation of HNF4A is an ideal choice for treating liver fibrosis. The gene expression of CALM2 is significantly lower in liver fibrosis samples than nonfibrotic samples. TAF1 may serve as a biomarker for liver fibrosis. The results were further validated by an independent data set GSE84044. In summary, our study described changes in the gene expression during the occurrence and development of liver fibrosis. The TAF1, HNF4A, and CALM2 may serve as novel targets for the treatment of liver fibrosis.
Overview of CD24 as a new molecular marker in ovarian cancer
Authors: Tarhriz Vahideh , Bandehpour Mojgan , Dastmalchi Siavoush , Ouladsahebmadarek Elaheh , Zarredar Habib , Eyvazi Shirin 
Published: October 2018

AbstractOvarian cancer (OC) is the fifth leading cause of cancer‐related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor‐targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor. It has been reported that CD24 is overexpressed in many cancers including OC. Also, CD24 is identified as a cancer stem cell marker in OC. The CD24 expression is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in cancer cells is not clearly understood. Recently, CD24 has been identified as an independent prognostic marker of survival in patients with OC. In this study, we reviewed the molecular targets in OC immune‐targeted therapy and also presented an overview of the new molecular marker CD24 and its association with the OC by reviewing the recent literature.
Oleuropein inhibits migration ability through suppression of epithelial‐mesenchymal transition and synergistically enhances doxorubicin‐mediated apoptosis in MCF‐7 cells
Authors: Choupani Jalal , Alivand Mohammad R. , M. Derakhshan Sima , Zaeifizadeh Mohammad , S. Khaniani Mahmoud 
Published: October 2018

AbstractDistinct metastasis is one of the main causes of breast cancer (BC)‐related mortality and epithelial‐mesenchymal transition (EMT) is a primary step in metastasis dissemination. On the other hand, doxorubicin (DOX) is an effective chemotherapeutic agent against BC; unfortunately, its clinical use is limited by dose‐dependent side effects. Therefore, extensive efforts have been dedicated to suppressing metastasis of BC and also to overcome DOX side effects together with keeping its antitumor efficacy. Studies supported the role of oleuropein (OLEU) in reducing DOX‐induced side effects besides its antitumor actions. In this study, the antimigratory effect of OLEU was assessed and real‐time PCR (RT‐PCR) was used to detect OLEU effect on the expression level of EMT markers, in MCF‐7 cells. The cytotoxic effect of OLEU and DOX was assessed by MTT assay, whereas the ratio of apoptosis was investigated by flow cytometry. The results showed that migration ability of MCF‐7 cells remarkably decreased in OLEU treated group and RT‐PCR results showed that OLEU may exert its antimigratory action by suppressing EMT through downregulation of sirtuin1 (SIRT1). Also, the results indicated that both OLEU and DOX were cytotoxic to MCF‐7 cells, whereas DOX‐OLEU cotreatment led to additive cytotoxicity and apoptosis rate. This study provides evidence regarding the suppressive role of OLEU on MCF‐7 cells migration ability through suppression of EMT, and for the first time, it was proposed that SIRT1 downregulation can be involved in the OLEU antimigratory effect. Also, the findings demonstrated that OLEU can reduce DOX‐induced side effects by reducing its effective dose.