bluuebunny/crossref_metadata_2025 huggingface dataset:
CircABCB10 promotes nonsmall cell lung cancer cell proliferation and migration by regulating the miR‐1252/FOXR2 axis
Authors: Tian Xufeng , Zhang Lin , Jiao Yan , Chen Junsheng , Shan Ying , Yang Wenfeng
Published: November 2018

Circular RNA (circRNA) is a key regulator in the development and progression of human cancers. Previous studies confirmed circRNA‐0008717 (circABCB10) as an oncogene in osteosarcoma, but the regulatory effect of circABCB10 in nonsmall cell lung cancer (NSCLC) is still unclear. In the current study, we examined the expression of circABCB10 in different NSCLC cell lines. Bioinformatics analysis, Cell Counting Kit‐8 assays, Transwell migration, fluorescein reporting experiments, and xenografts in mice were used to detect the effect of circABCB10 on NSCLC cell proliferation and migration in vitro and tumor growth in vivo. The results showed that the expression of circABCB10 in NSCLC cell lines was increased. Downregulation of circABCB10 suppressed NSCLC cell proliferation and migration by promoting microRNA miR‐1252 expression and suppressing Forkhead box 2 (FOXR2). Fluorescein reporting experiments confirmed that circABCB10 expression increased FOXR2 levels by sponging miR‐1252, and in vivo experiments found that knockdown of circABCB10 decreased tumor growth. These data suggested that circABCB10 acted as a tumor promoter through a novel miR‐1252/FOXR2 axis, providing potential biomarkers and therapeutic targets for the management of NSCLC.
The diagnostic accuracy of procalcitonin and C‐reactive protein for sepsis: A systematic review and meta‐analysis
Authors: Tan Meichun , Lu Yunxia , Jiang Hao , Zhang Liandong
Published: November 2018

Background

The objective of this study was to systematically evaluate the clinical value of procalcitonin and C‐reactive protein in the diagnosis of adult patients with sepsis.

Method

PubMed, Cochrane, Embase, Wanfang, China National Knowledge Infrastructure, and VIP database were searched by the index words to identify the qualified prospective studies, and relevant literature sources were also searched. The most recent research was done in the April 2017. The only languages included were English or Chinese. In the experiment group, patients were diagnosed with sepsis, severe sepsis, or septic shock; in the control group, the patients were of noninfectious origin or a systemic inflammatory response syndrome. The diagnostic accuracy was analyzed by heterogeneity, diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and the summary receiver‐operating characteristic curve.

Results

At least nine studies were involved in the meta‐analysis with 495 patients in the sepsis group and 873 patients in the nonsepsis group. In terms of the diagnostic accuracy of C‐reactive protein (CRP) for sepsis, the overall area under the summary receiver operator characteristic (SROC) curve was 0.73 (95% confidence interval [CI], 0.69‐0.77), with a sensitivity and specificity of 0.80 (95% CI, 0.63‐0.90) and 0.61 (95% CI, 0.50‐0.72) respectively, and the DOR was 6.89 (95% CI, 3.86‐12.31). In terms of the diagnostic accuracy of procalcitonin (PCT) for sepsis, the overall area under the SROC curve was 0.85 (95% CI, 0.82‐0.88), with a sensitivity and specificity of 0.80 (95% CI, 0.69‐0.87) and 0.77 (95% CI, 0.60‐0.88) respectively, and the DOR was 12.50 (95% CI, 3.65‐42.80).

Conclusion

In this meta‐analysis, our results together indicate a moderate degree of value of PCT and CRP for the diagnosis of sepsis in adult patients. The diagnosis accuracy and specificity of PCT are higher than those of CRP.
Hypermethylated in cancer 1 (HIC1) suppresses bladder cancer progression by targeting yes‐associated protein (YAP) pathway
Authors: Zhou Xiaoguang , Zhang Peng , Han Hu , Lei Hongen , Zhang Xiaodong
Published: November 2018

Objectives

Bladder cancer (BCa) is the most common malignant tumor in the urinary system. Growing evidence suggests that as a tumor suppressor gene, hypermethylated in cancer 1 (HIC1) is correlated with various malignancies in the modulation of tumor progression. This study aims to investigate the effect of HIC1 on regulating the proliferation, migration, and invasion of BCa.

Methods

Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western blot (WB) were used to evaluate the expression of HIC1 messenger RNA and protein in human BCa tissues and cells. Proliferation, migration and invasion assays, and flow cytometry assay were performed to assess the biological functional role of HIC1 in BCa. Co‐immunoprecipitation (Co‐IP) examined the protein‐protein interaction. The signaling pathways involved in the mode of action of HIC1 in BCa were also investigated.

Results

HIC1 was found downregulated in tested samples. Cloning formation assay and cell‐proliferation activity analysis showed that overexpression of HIC1 significantly inhibited the proliferation of BCa cells, while knockdown led to the opposite, namely the promotion of the proliferation. Flow cytometry assay confirmed the arrest of the cell cycle at the G1 phase with overexpression of HIC1 observed. Moreover, HIC1 inhibited migration and invasion of BCa. Co‐IP showed the binding between YAP (yes‐associated protein) and TEAD (TEA domain/transcription enhancer factor family members) as well as the cancerostatic activity of HIC1, partially manifested via its negative regulation of YAP signaling pathway.

Conclusions

Our data unprecedently showed that HIC1 was responsible for the inhibition of proliferation, migration, and invasion of BCa via the YAP signaling pathway. These findings suggested that therapeutic strategies regulating HIC1 expression might provide effective treatments for BCa.
Wnt/β‐catenin signaling enhances transcription of the CX43 gene in murine Sertoli cells
Authors: López Camila , Aguilar Rodrigo , Nardocci Gino , Cereceda Karina , Vander Stelt Karen , Slebe Juan Carlos , Montecino Martin , Concha Ilona I.
Published: November 2018

Sertoli cells provide the nutritional and metabolic support for germ cells. Wnt/β‐catenin signaling is important for the development of the seminiferous epithelium during embryonic age, although after birth this pathway is downregulated. Cx43 gene codes for a protein that is critical during testicular development. The Cx43 promoter contains TCF/β‐catenin binding elements (TBEs) that contribute CX43 expression in different cell types and which may also be regulating the expression of this gene in Sertoli cells. In this study, we demonstrate that 42GPA9 Sertoli cells respond to treatments that result in accumulation of β‐catenin within the nucleus and in upregulation of CX43 gene transcription. β‐Catenin binds to TBEs located both upstream and downstream of the transcriptional start site (TSS). Luciferase reporter experiments revealed that TBEs located upstream of the TSS are necessary for β‐catenin‐mediated upregulation. Our results also indicate that the Wnt/β‐catenin‐dependent upregulation of the Cx43 gene in Sertoli cells is accompanied by changes in epigenetic parameters that may be directly contributing to generating a chromatin environment that facilitates the establishment of the transcriptional machinery at this promoter.
Epitope‐based immunoinformatics approach on RNA‐dependent RNA polymerase (RdRp) protein complex of Nipah virus (NiV)
Authors: Ravichandran Lavanya , Venkatesan Arthi , Febin Prabhu Dass J.
Published: November 2018

Persistent outbreaks of Nipah virus (NiV) with severe case fatality throw a major challenge on researchers to develop a drug or vaccine to combat the disease. With little knowledge of its molecular mechanisms, we utilized the proteome data of NiV to evaluate the potency of three major proteins (phosphoprotein, polymerase, and nucleocapsid protein) in the RNA‐dependent RNA polymerase complex to count as a possible candidate for epitope‐based vaccine design. Profound computational analysis was used on the above proteins individually to explore the T‐cell immune properties like antigenicity, immunogenicity, binding to major histocompatibility complex class I and class II alleles, conservancy, toxicity, and population coverage. Based on these predictions the peptide ‘ELRSELIGY’ of phosphoprotein and ‘YPLLWSFAM’ of nulceocapsid protein were identified as the best‐predicted T‐cell epitopes and molecular docking with human leukocyte antigen‐C (HLA‐C*12:03) molecule was effectuated followed by validation with molecular dynamics simulation. The B‐cell epitope predictions suggest that the sequence positions 421 to 471 in phosphoprotein, 606 to 640 in polymerase and 496 to 517 in nucleocapsid protein are the best‐predicted regions for B‐cell immune response. However, the further experimental circumstance is required to test and validate the efficacy of the subunit peptide for potential candidacy against NiV.
Evaluation of Osteopontin and Pokémon genes expression in hepatitis C virus–associated hepatocellular carcinoma
Authors: El‐Khazragy Nashwa , Khalifa Mona M. , Salem Ahmed M. , Swellam Menha , Hegazy Marwa
Published: November 2018

Osteopontin and Pokémon genes may have an important role in the pathogenesis of different malignancies. Osteopontin is a glycoprotein of the extracellular matrix, and Pokémon is a regulator of transcription. Both have been hypothesized to be useful as therapeutic targets or diagnostic markers. We aim to assess the role of both in hepatocellular carcinoma and liver fibrosis due to hepatitis C virus (HCV) infection. We conducted our study on 50 patients and classified them into three groups—Group I: Patients with HCV‐related hepatocellular carcinoma (HCC) (n = 30); Group II: Patients with hepatitis C cirrhosis (n = 10); and Group III: Patients with hepatitis C fibrosis (n = 10). We found high levels of Osteopontin and Pokémon gene expression in group I. Osteopontin levels were higher also in patients with liver fibrosis was correlated to high levels of parameters such as alpha fetoprotein and caspase. We conclude that HCC is associated with overexpression of both Osteopontin and Pokémon and that Osteopontin plays a significant role in liver fibrosis due to hepatitis C infection.
Retracted: Long noncoding RNA MEG3 inhibits proliferation and migration but induces autophagy by regulation of Sirt7 and PI3K/AKT/mTOR pathway in glioma cells
Authors: Xu Dong‐Hui , Chi Guo‐Nan , Zhao Cong‐Hai , Li Dong‐Yuan
Published: November 2018

Glioma is a common primary brain tumor with high mortality rate and poor prognosis. Long noncoding RNA maternally expressed gene 3 (MEG3) is a tumor suppressor in diverse cancer types. However, the role of MEG3 in glioma remains unclear. We aimed to explore the effects of MEG3 on U251 cells as well as the underlying mechanisms. U251 cells were stably transfected with different recombined plasmids to overexpress or silence MEG3. Effects of aberrantly expressed MEG3 on cell viability, migration, apoptosis, expressions of apoptosis‐associated and autophagy‐associated proteins, and phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathway were all evaluated. Then, messenger RNA (mRNA) and protein expression of Sirt7 in cells abnormally expressing MEG3 were estimated. In addition, effects of abnormally expressed MEG3 and Sirt7 on U251 cells were determined to reveal the underlying mechanism of MEG3‐associated modulation. Cell viability and migration were significantly reduced by MEG3 overexpression whereas cell apoptosis as well as Bax and cleaved caspase‐3/‐9 proteins were obviously induced. Beclin‐1 and LC3‐II/LC3‐I were upregulated and p62 was downregulated in MEG3 overexpressed cells. In addition, the autophagy pharmacological inhibitor (3‐methyladenine, 3‐MA) affected the effect of MEG3 overexpression on cell proliferation. Furthermore, the phosphorylated levels of key kinases in the PI3K/AKT/mTOR pathway were all reduced by MEG3 overexpression. Sirt7 was positively regulated by MEG3 expression, and effects of MEG3 overexpression on U251 cells were ameliorated by Sirt7 silence. MEG3 suppressed cell proliferation and migration but promoted autophagy in U251 cells through positively regulating Sirt7, involving in the inhibition of the PI3K/AKT/mTOR pathway.
miR‐129‐5p and ‐3p co‐target WWP1 to suppress gastric cancer proliferation and migration
Authors: Ma Lianjun , Chen Xiaorui , Li Chang , Cheng Rongjie , Gao Zhuo , Meng Xiangbo , Sun Chen , Liang Chenxi , Liu Yanqing
Published: November 2018

Gastric cancer (GC) is a worldwide health problem. Uncovering the underlining molecular mechanisms of GC is of vital significance. Here, we identified a novel oncogene WW domain‐containing E3 ubiquitin protein ligase 1 (WWP1) in GC. WWP1 could promote GC cell proliferation and migration in vitro and expedite GC growth in vivo. We also found out two microRNAs (miRNAs): miR‐129‐5p and ‐3p could both target WWP1. Interestingly, miR‐129‐5p bound to the CDS region of WWP1 mRNA. The miR‐129 pairs (miR‐129‐5p and ‐3p) play pivotal roles in GC to suppress its proliferation and migration in vitro and slow down GC growth in vivo by repressing WWP1. In summary, we identified two tumor suppressive miRNAs which share the same precursor that could regulate the same oncogene WWP1 in GC. Our finding would add new route for GC research and treatment.
Mechanically stimulated osteocytes reduce the bone‐metastatic potential of breast cancer cells in vitro by signaling through endothelial cells
Authors: Ma Yu‐Heng Vivian , Xu Liangcheng , Mei Xueting , Middleton Kevin , You Lidan
Published: November 2018

Bone metastases occur in 65% to 75% of patients with advanced breast cancer and significantly worsen their survival and quality of life. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced the transendothelial migration of breast cancer cells. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. In this study, we investigated the specific effects of flow‐stimulated osteocytes on the interaction between endothelial cells and breast cancer cells in vitro. We observed that CM from flow‐stimulated osteocytes reduced endothelial permeability by 15% and breast cancer cell adhesion onto endothelial monolayers by 18%. The difference in adhesion was abolished with anti‐intercellular adhesion molecule 1 (ICAM‐1) neutralizing antibodies. Furthermore, CM from endothelial cells conditioned in CM from flow‐stimulated osteocytes significantly altered the gene expression in bone‐metastatic breast cancer cells, as shown by RNA sequencing. Specifically, breast cancer cell expression of matrix metallopeptidase 9 (MMP‐9) was downregulated by 62%, and frizzled‐4 (FZD4) by 61%, when the osteocytes were stimulated with flow. The invasion of these breast cancer cells across Matrigel was also reduced by 47%, and this difference was abolished by MMP‐9 inhibitors. In conclusion, we demonstrated that flow‐stimulated osteocytes downregulate the bone‐metastatic potential of breast cancer cells by signaling through endothelial cells. This provides insights into the capability of bone mechanical regulation in preventing bone metastases; and may assist in prescribing exercise or bone‐loading regimens to patients with breast cancers.
Semiconducting polymer dots as near‐infrared fluorescent probes for bioimaging and sensing
Authors: Tsai Wei‐Kai , Chan Yang‐Hsiang
Published: November 2018

In recent years, semiconducting polymer dots (Pdots) have emerged as a new type of ultrabright fluorescent probes, which have been proved to be very useful for biomedical imaging. Pdots possess several exceptional advantages including high fluorescence brightness, fast radiative rate, excellent photostability, and negligible cytotoxicity. Among these new types of Pdots, the near‐infrared (NIR) fluorescent Pdots appear to be the most urgent and important owing to their promising deep‐tissue imaging in the clinic. This mini‐review highlights the recent progress in the design of NIR‐emitting Pdots and their biomedical applications both in vitro and in vivo.
The role of DEAD‐box RNA helicase p68 (DDX5) in the development and treatment of breast cancer
Authors: Hashemi Vida , Masjedi Ali , Hazhir‐karzar Bita , Tanomand Asghar , Shotorbani Siamak Sandoghchian , Hojjat‐Farsangi Mohammad , Ghalamfarsa Ghasem , Azizi Gholamreza , Anvari Enayat , Baradaran Behzad , Jadidi‐Niaragh Farhad
Published: November 2018

RNA helicase p68 or DEAD (Asp‐Glu‐Ala‐Asp) box polypeptide 5 (DDX5) is a unique member of the highly conserved protein family, which is involved in a broad spectrum of biological processes, including transcription, translation, precursor messenger RNA processing or alternative splicing, and microRNA (miRNA) processing. It has been shown that p68 is necessary for cell growth and participates in the early development and maturation of some organs. Interestingly, p68 is a transcriptional coactivator of numerous oncogenic transcription factors, including nuclear factor‐κβ (NF‐κβ), estrogen receptor α (ERα), β‐catenin, androgen receptor, Notch transcriptional activation complex, p53 and signal transducer, and activator of transcription 3 (STAT3). Recent studies on the role of p68 (DDX5) in multiple dysregulated cellular processes in various cancers and its abnormal expression indicate the importance of this factor in tumor development. Discussion of the precise role of p68 in cancer is complex and depends on the cellular microenvironment and interacting factors. In terms of the deregulated expression of p68 in breast cancer and the high prevalence of this cancer among women, it can be informative to review the precise function of this factor in the breast cancer. Therefore, an attempt will be made in this review to clarify the tumorigenic function of p68 in association with its targeting potential for the treatment of breast cancer.
Fusion with mesenchymal stem cells differentially affects tumorigenic and metastatic abilities of lung cancer cells
Authors: Zhang Li‐Na , Kong Chen‐Fei , Zhao Dan , Cong Xian‐Ling , Wang Shen‐Sen , Ma Ling , Huang Ying‐Hui
Published: November 2018

Cell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP‐2 and MMP‐9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G0/G1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial‐mesenchymal transition (EMT) change with downregulation of E‐cadherin and upregulation of N‐cadherin, Vimentin, α‐SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell‐like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.
MiRNAs and inflammatory bowel disease: An interesting new story
Authors: Moein Soheila , Vaghari‐Tabari Mostafa , Qujeq Durdi , Majidinia Maryam , Nabavi Seyed Mohammad , Yousefi Bahman
Published: November 2018

Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD; numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.
Osteoblast autophagy in glucocorticoid‐induced osteoporosis
Authors: Wang Lufei , Heckmann Bradlee L. , Yang Xianrui , Long Hu
Published: November 2018

Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid‐induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.
Understanding molecular biology of codon usage in mitochondrial complex IV genes of electron transport system: Relevance to mitochondrial diseases
Authors: Uddin Arif , Mazumder Tarikul Huda , Chakraborty Supriyo
Published: November 2018

The mitochondrial cytochrome oxidase (CO) genes are involved in complex IV of the electron transport system, and dysfunction of CO genes leads to several diseases. However, no work has been reported on the codon usage pattern of these genes. We used bioinformatic methods to analyze the compositional properties and the codon usage pattern of the COI, COII, and COIII genes in fishes, birds, and mammals to understand the similarities and dissimilarities of codon usage in these genes, which gave an insight into the molecular biology of these genes. The effective number of codons (ENC) value of genes was high in different species of fishes, birds and mammals, which indicates that the codon bias of CO genes was low and the ENC values were significantly different among fishes, birds, and mammals, as revealed from the t test. The overall guanine and cytosine (GC) content in fishes, birds, and mammals was lower than 50% in all genes, indicating that the genes were AT‐rich and significantly different among fishes, birds, and mammals. The TCA codon was overrepresented in fishes, birds, and mammals for the COI gene, in birds and mammals for the COII gene, but it was not overrepresented in others. Only three codons, namely CTA, CGA, and AAA, were overrepresented in all three groups for the COI, COII, and COIII genes, repectively. From the neutrality plot in fishes, birds, and mammals, it was observed that the slopes of the regression lines (regression coefficients) in the COI, COII, and COIII genes were <0.5, suggesting that natural selection played a major role, whereas mutation pressure played a minor role.
Extended proliferation of chicken‐ and Okinawa rail‐derived fibroblasts by expression of cell cycle regulators
Authors: Katayama Masafumi , Kiyono Tohru , Ohmaki Hitomi , Eitsuka Takahiro , Endoh Daiji , Inoue‐Murayama Miho , Nakajima Nobuyoshi , Onuma Manabu , Fukuda Tomokazu
Published: November 2018

Although immortalized cultured cells are useful for various functional assays or transcriptome analysis, highly efficient and reproducible immortalization methods have not been developed in avian‐derived cells. We introduced the simian virus 40 T antigen (SV40T) and human papillomavirus
(HPV)‐E6E7 to chick and Okinawa rail (endangered species)derived fibroblast. As a result, neither the
SV40T nor
E6E7 genes could induce avian cell immortality. Accordingly, we attempted to use a recently developed immortalization method, which involved the coexpression of mutant cyclin‐dependent kinase 4 (CDK4), Cyclin D, and TERT (K4DT method) in these avian cells. Although the K4DT method could not efficiently induce the efficient immortalization in mass cell population, cellular division until the senescence was significantly extended by K4DT, we succeeded to obtain the immortalized avian cells (chick K4DT: one clone, Okinawa rail K4DT: three clones, Okinawa rail K4DT + telomerase RNA component: one clone) with K4DT expression. We conclude that K4DT expression is used to extend the cell division and immortalization of avian‐derived cells.
Interleukin‐18 and diabetic nephropathy: A review
Authors: Yaribeygi Habib , Atkin Stephen L. , Sahebkar Amirhossein
Published: November 2018

The inflammatory response has an important role in the pathophysiology of diabetic nephropathy that is contributed to by inflammatory mediators such as interleukin‐1 (IL‐1), IL‐6, IL‐18, tumor necrosis factor‐α, and macrophage chemotactic protein‐1; however, the role of IL‐18 seems to be more specific than other cytokines in the inflammatory process. IL‐18 is expressed in renal tissue and is upregulated by several stimuli including hyperglycemia. The expression/urinary level of IL‐18 is positively correlated with the progression of diabetic nephropathy and the urinary albumin excretion rate. In this review, we have focused on the molecular pathways modulating the relationship between IL‐18 and diabetic nephropathy.
MicroRNAs and signaling networks involved in epithelial–mesenchymal transition
Authors: Musavi Shenas Mohammad Hossein , Eghbal‐Fard Shadi , Mehrisofiani Vahid , Abd Yazdani Nima , Rahbar Farzam Omid , Marofi Faroogh , Yousefi Mehdi
Published: November 2018

Epithelial–mesenchymal transition (EMT) is a phenomenon in which epithelial cells lose their cell‐to‐cell connection and are detached from the base membrane. EMT is fundamental for many biological processes such as embryonic development and neurogenesis. It also plays a significant role in cancer progression and metastasis. EMT regulation occurs through a sophisticated network of transcription regulations that include many signaling pathways. The exact mechanism of cancer gene regulation has not been understood yet. However, it is interesting to study the role of microRNAs and epigenetics mechanism in the cancer development. In this review, the transcription regulation of EMT and the analysis of possible overlap between microRNAs and their targets which are involved in the cancer development are scrutinized.
Serenoa repens and N‐acetyl glucosamine/milk proteins complex differentially affect the paracrine communication between endothelial and follicle dermal papilla cells
Authors: Bassino Eleonora , Gasparri Franco , Munaron Luca
Published: November 2018

Current treatments for hair follicle (HF) disruption are based on 5‐α reductase inhibitors and prostaglandin modulators. Botanicals and nutraceutical compounds interfere with hair loss or stimulate its partial regrowth. Here, we used in vitro cocultures to investigate the activity of Serenoa repens (
SR) and
N‐acetyl glucosamine + milk proteins (NAG/Lac) on the paracrine interactions between human microvascular endothelial cells (HMVEC) and HF dermal papilla cells (FDPC). Both
SR and NAG/Lac‐induced endothelial tubulogenesis were enhanced by FDPC.
SR promoted proliferation of both the cell types, while NAG/Lac was effective on endothelium. Vascular endothelial growth factor production, enhanced by
SR, was further augmented by FDPC. In FDPC 5‐α reductase‐II and β‐catenin expressions were modified by
SR and less by NAG/Lac, with no additional effect by HMVEC.
SR and NAG/Lac prevented lipid peroxidation, whereas NAG/Lac was effective on interleukin 1β production. Finally,
SR and NAG/Lac differentially affected HMVEC permeability and tight junction proteins content. These data provide a mechanistic background for the potential use of these compounds as promoters of HF vascularization.
miR‐124 promotes neural differentiation in mouse bulge stem cells by repressing Ptbp1 and Sox9
Authors: Mokabber Haleh , Najafzadeh Nowruz , Mohammadzadeh Vardin Mohammad
Published: November 2018

Hair follicle stem cells (HFSCs) are able to differentiate into neurons and glial cells. Distinct microRNAs (miRNAs) regulate the proliferation and differentiation of HFSCs. However, the exact role of miR‐124 in the neural differentiation of HFSCs has not been elucidated. HFSCs were isolated from mouse whisker follicles. miR‐9, let‐7b, and miR‐124, Ptbp1 , and Sox9 expression levels were detected by real‐time polymerase chain reaction (RT‐PCR). The influence of miR‐124 transfection was evaluated using immunostaining. We demonstrated that miR‐124 and let‐7b expression levels were significantly increased after the neural differentiation. Sox9 and Ptbp1 were identified as the target of miR‐124 in the HFSCs. During neural differentiation and miR‐124 mimicking, Ptbp1 and Sox9 levels were decreased. Moreover, the miR‐124 overexpression increased MAP2 (58.43 ± 11.26) and NeuN (48.34 ± 11.15) proteins expression. The results demonstrated that miR‐124 may promote the differentiation of HFSCs into neuronal cells by targeting Sox9 and Ptbp1.
Noncoding transcribed ultraconserved region (T‐UCR) UC.48+ is a novel regulator of high‐fat diet induced myocardial ischemia/reperfusion injury
Authors: Ding Lu , Gong Chengxin , Zhao Jiani , Liu Xingzi , Li Tao , Rao Shenqiang , Wang Shuo , Liu Yuanyuan , Peng Shanping , Xiao Wen , Xiong Chaopeng , Wang Rumeng , Liang Shangdong , Xu Hong
Published: November 2018

Increasing evidence has suggested high‐fat diet (HFD) is an independent risk factor for myocardial ischemia/reperfusion (MI/R) injury. Long noncoding RNAs (lncRNAs) recently attracted much attraction in the study of MI/R injury. However, the functional questions of specific lncRNAs in HFD‐induced MI/R injury have not been well elucidated. Uc.48+ is a lncRNA from a transcribed ultraconserved region (T‐UCR) of human, mouse, and rat genomes. Here, we explored the aggravating role of uc.48+and identified purinergic P2X7 receptor (P2X7R) as a downstream regulator of uc.48+ in HFD‐induced MI/R vulnerability. We demonstrated uc.48+ expression was upregulated, accompanied by the corresponding upregulation of P2X7R in HFD I/R myocardium and HFD‐induced MI/R vulnerability. Overexpression of uc.48+enhanced, whereas silencing of uc.48 + decreased the expression of P2X7R, cardiomyocyte apoptosis, and MI/R injury. The functional relevance of uc.48+ regulated P2X7R expression and the subsequent NF‐κB signaling to promote cardiomyocyte apoptosis was supported by inhibition of P2X7R with its specific antagonist (A438079) as well as the inhibitor of NF‐κB signaling (pyrrolidine dithiocarbamate, PDTC) in H9c2 hypoxia/reoxygenation (H/R) cells transfected with pcDNA3.0‐uc.48 + plasmid, and RNA immunoprecipitation (RIP) suggested uc.48+ could interact with transcription factor Sp1. Importantly, Sp1 inhibitor (mithramycin, MIT) was found to suppress uc.48+ ‐induced P2X7R expression and the NF‐κB signaling and cardiomyocyte apoptosis. Our findings provide a potential novel mechanism through which uc.48+ boosts cardiomyocyte apoptosis and MI/R vulnerability to HFD. Thus, uc.48+ is a novel regulator of HFD‐induced MI/R injury; targeting uc.48+ may be a novel therapeutic approach of MI/R vulnerability to HFD.
Sulfonyl(thio)urea derivative induction of insulin secretion is mediated by potassium, calcium, and sodium channel signal transduction
Authors: Sulis Paola Miranda , Dambrós Betina Fernanda , Mascarello Alessandra , dos Santos Adair Roberto Soares , Yunes Rosendo Augusto , Nunes Ricardo José , Frederico Marisa Jádna Silva , Barreto Silva Fátima Regina Mena
Published: November 2018

Aim

To investigate the mechanism of action of sulfonyl(thio)urea derivative (SD) on glycemia and on insulin secretion in pancreatic islets.

Methods

Wistar rats were divided into hyperglycemic control group, rats received 4 g/kg body weight glucose plus sitagliptin 10 mg/kg (p.o.); hyperglycemic plus SD 10 mg/kg (p.o.); hyperglycemic plus SD plus sitagliptin. Blood was collected before glucose overloading (zero time), and at 15, 30, 60, and 180 min after glucose, from the afore mentioned groups for glycemia and glucagon‐like peptide 1 (GLP‐1) measurements and intestinal disaccharidases activity. Pancreatic islets were isolated for the calcium influx and insulin secretion in in vitro studies.

Results

SD reduced glycemia and increased GLP‐1 secretion, while inhibited sucrase and lactase activity. This SD (1.0 and 10.0 µM) stimulated calcium influx in a similar percentile to that of glibenclamide, and in a nonsynergic manner. In addition, the trigger effect of SD on calcium influx was through the K+‐ATP‐dependent channels, and partially by activating voltage‐dependent K
+ channels and voltage‐dependent calcium channels. Furthermore, SD‐stimulated Na
+ and Ca
2+ entry, induced by the transient receptor potential ankyrin 1 and by modulation of Na
+/Ca
2+ exchange. The activation of these pathways by SD culminated in in vitro insulin secretion, reinforcing the critical role of K
+‐ATP channels in the secretagogue effect of SD.

Conclusions

SD diminish glycemia by inducing GLP‐1 secretion and inhibiting disaccharidases. To our knowledge, this is the first report of an insulin secretagogue effect of SD that is mediated by potassium and calcium, as well as sodium, signal transduction.
Formation and activation induction of primordial follicles using granulosa and cumulus cells conditioned media
Authors: Atrabi Mohammad Jafari , Akbarinejad Vahid , Khanbabaee Ramazan , Dalman Azam , Amorim Christiani Andrade , Najar‐Asl Mustafa , Valojerdi Mojtaba Rezazadeh , Fathi Rouhollah
Published: November 2018

Fertility preservation of prepubertal girls subjected to invasive cancer therapy necessitates defining protocols for activation of isolated primordial follicles. Granulosa (GCs) and cumulus cells (CCs) play pivotal role in oocyte development. Although GCs and CCs share some similarities, they differ in growth factors production. The current study was conducted to evaluate the effects of GCs, CCs and their conditioned media on mice primordial follicles activation. One‐day‐old mice ovaries were subjected to 6‐day culture with base medium (BM), GC conditioned medium (GCCM), GC coculture (GCCC), CC conditioned medium (CCCM) or CC coculture (CCCC). Follicular growth and primordial to primary follicle transition was observed during 6‐day culture, and follicular activation rate tended to be greater in GCCM than other groups (0.05 <P < 0.10). On Day 6, the expression of phosphatase and tensin homolog (PTEN) in GCCM group was lower than that in BM group (P = 0.020), the expression of phosphoinositide‐3‐kinase was higher in CCCC group than BM, GCCM and CCCM groups (P < 0.05), and the expression of connexin 37 was greater in the CCCM group as compared with BM, GCCC, and CCCC groups (P < 0.01). In conclusion, the current study showed that condition medium of GCs could enhance in vitro activation of primordial follicles, probably through downregulation of PTEN.
Fifteen hub genes associated with progression and prognosis of clear cell renal cell carcinoma identified by coexpression analysis
Authors: Wang Yejinpeng , Chen Liang , Wang Gang , Cheng Songtao , Qian Kaiyu , Liu Xuefeng , Wu Chin‐Lee , Xiao Yu , Wang Xinghuan
Published: November 2018

Renal cell carcinoma (RCC) is the most common type of renal tumor, and the clear cell renal cell carcinoma (ccRCC) is the most frequent subtype. In this study, our aim is to identify potential biomarkers that could effectively predict the prognosis and progression of ccRCC. First, we used The Cancer Genome Atlas (TCGA) RNA‐sequencing (RNA‐seq) data of ccRCC to identify 2370 differentially expressed genes (DEGs). Second, the DEGs were used to construct a coexpression network by weighted gene coexpression network analysis (WGCNA). Moreover, we identified the yellow module, which was strongly related to the histologic grade and pathological stage of ccRCC. Then, the functional annotation of the yellow module and single‐samples gene‐set enrichment analysis of DEGs were performed and mainly enriched in cell cycle. Subsequently, 18 candidate hub genes were screened through WGCNA and protein–protein interaction (PPI) network analysis. After verification of TCGA’s ccRCC data set, Gene Expression Omnibus (GEO) data set (GSE73731) and tissue validation, we finally identified 15 hub genes that can actually predict the progression of ccRCC. In addition, by using survival analysis, we found that patients of ccRCC with high expression of each hub gene were more likely to have poor prognosis than those with low expression. The receiver operating characteristic curve showed that each hub gene could effectively distinguish between localized and advanced ccRCC. In summary, our study indicates that 15 hub genes have great predictive value for the prognosis and progression of ccRCC, and may contribute to the exploration of the pathogenesis of ccRCC.
Ecto‐5′‐nucleotidase (CD73) is a potential target of hepatocellular carcinoma
Authors: Shali Shalaimaiti , Yu Jiangang , Zhang Xin , Wang Xue , Jin Youping , Su Minsheng , Liao Xiaohong , Yu Jerry , Zhi Xiuling , Zhou Ping
Published: November 2018

High expression of ecto‐5′‐nucleotidase (CD73) has been reported in a number of epithelium origin malignancies. Here, we hypothesize that CD73 promotes hepatocellular carcinoma (HCC) growth and metastasis and that the effect is mediated by epithelial growth factor receptor (EGFR). HCC cells with different malignancies and Tissue microarrays of the tumor and peritumoral liver tissues from 30 independent patients were used to examine CD73 and EGFR expression. Then, MTT and Ki67 detection, together with cell adhesion, invasion, and migration assays were used to evaluate the effects of CD73 on cell growth and metastasis. The expression of EGFR in HCC cells was also tested after suppressing or overexpressing CD73. Lastly, tumor tissues from nude mice, which had been injected subcutaneously with HCC cells, were transplanted subcutaneously into CD73−/− and wild‐type (WT) C57 mice. CD73 expression was higher in HCC cells with greater metastatic potentials and tumor tissues compared with low metastatic cells and peritumor tissues. CD73 and EGFR were coexpressed and positively correlated in tumor and peritumor liver tissues in HCC tissue microarrays. Up‐regulationof CD73 by plasmid transfection or by pharmacological agents promoted EGFR expression in HCC cells, whereas suppression of CD73 inhibited these effects. The growth of transplanted tumor tissues was dramatically slower in CD73−/− mice than in WT type mice in the in vivo experiments. CD73 promotes HCC growth and metastasis and upregulated the expression of EGFR in HCC. Thus, CD73 and EGFR are potential targets in the treatment of HCC.
Impaired DNA double‐strand breaks repair by kinesin family member 4A inhibition renders human H1299 non‐small‐cell lung cancer cells sensitive to cisplatin
Authors: Wan Qing , Shen Yong , Zhao Huzi , Wang Bei , Zhao Lei , Zhang Yongchen , Bu Xiaodong , Wan Meiling , Shen Chuanlu
Published: November 2018

Patients with non‐small‐cell lung cancer (NSCLC) are routinely treated with the platinum‐based chemotherapeutics such as cisplatin. The drug exerts anticancer effects via multiple mechanisms, including DNA double‐strand breaks (DSBs). Enhanced DNA DSB repair capacity would be associated with innate or acquired drug resistance. However, despite strong evidence for the role of the chromokinesin kinesin family member 4A (KIF4A) in DSB repair, the relationship between the chromokinesin and cisplatin sensitivity of human NSCLC cells remains unknown. Furthermore, little is known regarding the effect of targeting KIF4A on the function of DSB repair‐related proteins in these cells. In the current study, we demonstrated that cisplatin treatment stimulated the expression of KIF4A protein in human NSCLC cells. Depletion of KIF4A by small interfering RNA significantly enhanced cisplatin‐induced cell cycle arrest in S and G2/M phases and cytotoxicity in human NSCLC cells. Furthermore, we found that KIF4A inhibition suppressed the ability of cisplatin to induce BRCA2 and Rad51 focus formation and limits the further increase in poly(ADP‐ribose) polymerase 1 activity induced by cisplatin treatment in human NSCLC cells. These studies thus identify the chromokinesin KIF4A as a novel modulator of cisplatin sensitivity that is significantly enhanced by the chromokinesin in human NSCLC cells via multiple mechanisms.
A2a adenosine receptor agonist improves endoplasmic reticulum stress in MIN6 cell line through protein kinase A/ protein kinase B/ Cyclic adenosine monophosphate response element‐binding protein/ and Growth Arrest And DNA‐Damage‐Inducible 34/ eukaryotic Initiation Factor 2α pathways
Authors: Arasi Fatemeh P. , Shahrestanaki Mohammad K. , Aghaei Mahmoud
Published: November 2018

Endoplasmic reticulum (ER) stress is one of the main molecular events underlying pancreatic beta cell (PBC) failure, apoptosis, and a decrease in insulin secretion. Recent studies have highlighted the fundamental role of A2a adenosine receptor (A2aR) in potentiation of insulin secretion and proliferation of PBCs. However, possible protective effects of A2aR signaling against ER stress have not been elucidated yet. Thus, in the present study, we aimed to investigate the effects of A2aR activation in MIN6 beta cells undergoing tunicamycin (TM)‐mediated ER stress. A2aR expression and activity were evaluated using real‐time polymerase chain reaction and measurement of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), phospho‐protein kinase B or Akt (p‐Akt)/Akt, and phospho‐Cyclic adenosine monophosphate response element‐binding protein/CREB levels in response to a specific agonist (CGS 21680). Survival and proliferation in TM and CGS 21680 cotreated cells were evaluated using 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), annexin V–fluorescein isothiocyanate (FITC)/propidium iodide staining, colony formation, and 5‐bromo‐2′‐deoxyuridine (Brdu) assays. In addition, the effects of A2aR stimulation on insulin secretion were evaluated using the enzyme‐linked immunosorbent assay. B‐cell lymphoma 2 (Bcl‐2), phospho‐eukaryotic Initiation Factor 2α (p‐eIF2α)/eIF2α, growth arrest and DNA‐damage‐inducible 34 (GADD34), X‐box binding protein 1 (XBP‐1), spliced X‐box binding protein 1 (XBP‐1s), immunoglobulin heavy‐chain‐binding protein (BIP), and CCAAT‐enhancer‐binding protein homologous protein (CHOP) levels were evaluated using western blotting. Our results showed a decrease in A2aR expression and p‐Akt/Akt and p‐CREB/CREB levels in TM‐pretreated cells. We also mentioned that CGS 21680 effectively increased cell survival, proliferation, and insulin secretion in TM‐treated cells. The antiapoptotic effects were possibly mediated through Bcl‐2 upregulation. Our western blotting results indicated that A2aR effectively downregulated p‐eIF2α/eIF2α, XBP‐1, XBP‐1s, BIP, and CHOP levels, whereas GADD34 was upregulated. Altogether, the present study revealed that A2aR signaling through PKA/Akt/CREB mediators alleviated TM cytotoxicity effects in MIN6 beta cells. Thus, the stimulation of this receptor was seen as a new approach to control ER stress in the PBC cells.
Medical Cannabis: A plurimillennial history of an evergreen
Authors: Pisanti S. , Bifulco M.
Published: November 2018

The history of Cannabis goes along that of humankind, as speculated based on geographical and evolutionary models together with historic data collected to date. Its medical use is several thousand years old, as attested both by archeobotanical evidence of Cannabis remains and written records found in ancient texts from the sacred Vedic foundational texts of Ayurvedic medicine (about 800 before current era [BCE]) to the first known Pharmacopoea, the Chinese “Shen Nung Pen Ts'ao Ching” (1 century BCE). In this paper, we retrace the history of Cannabis traveling through the key stages of its diffusion among the most important ancient cultures up to our days, when we are facing a renaissance of its medical employment. We report through the centuries evidence of its use in numerous pathologic conditions especially for its anti‐inflammatory, antiseptic, and anticonvulsing properties that support the requirement to direct our present research efforts into the definitive understanding of its efficacy.
Periodontitis is associated with systemic inflammation and vascular endothelial dysfunction in patients with lacunar infarct
Authors: Leira Yago , Rodríguez‐Yáñez Manuel , Arias Susana , López‐Dequidt Iria , Campos Francisco , Sobrino Tomás , D'Aiuto Francesco , Castillo José , Blanco Juan
Published: November 2018

Background

Periodontitis has been associated with lacunar infarct (LI), a type of cerebral small vessel disease. The objective of this study was to ascertain whether periodontitis is associated with increased circulating levels of systemic inflammation and endothelial dysfunction biomarkers in patients with LI.

Methods

One hundred twenty patients with LI and 120 healthy controls underwent a full‐mouth periodontal examination. The periodontal inflamed surface area (PISA) was calculated for each participant. Demographic, medical, and neurological information were recorded from all of them. In addition, blood samples were collected in order to investigate differences in terms of interleukin (IL)‐6, IL‐10, pentraxin (PTX) 3, soluble fragment of tumor necrosis factor‐like weak inducer of apoptosis (sTWEAK) and amyloid‐beta (Aβ) peptides (i.e., Aβ1‐40, and Aβ1‐42) measured in serum.

Results

Periodontitis was independently associated with increased levels of IL‐6 (R2 = 0.656, P < 0.001), PTX3 (R2 = 0.115, P < 0.001), sTWEAK (R2 = 0.527, P < 0.001), and Aβ1‐40 (R2 = 0.467, P < 0.001) in patients with LI. Within patients with poor outcome, PISA positively correlated with IL‐6 (r = 0.738, P < 0.001), PTX3 (r = 0.468, P = 0.008), sTWEAK (r = 0.771, P < 0.001), and Aβ1‐40 (r = 0.745, P < 0.001).

Conclusions

Our data suggest a link between periodontitis, systemic inflammatory response, and disruption of the vascular endothelial function in patients with LI. Experimental studies are needed to elucidate possible pathways through which periodontitis could lead to this systemic inflammatory state with impairment of the endothelial function in LI. Further longitudinal studies with large samples are warranted to confirm our findings.