bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA in leukemia: Tumor suppressors and oncogenes with prognostic potential
Authors: Mardani Rajab , Jafari Najaf Abadi Mohammad Hassan , Motieian Mahsa , Taghizadeh‐Boroujeni Sima , Bayat Amir , Farsinezhad Alireza , Gheibi Hayat Seyed Mohammad , Motieian Mahtab , Pourghadamyari Hossein 
Published: December 2018

AbstractLeukemia is known as a progressive malignant disease, which destroys the blood‐forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR‐15, miR‐16, let‐7, and miR‐127) or oncogene (i.e., miR‐155, miR‐17‐92, miR‐21, miR‐125b, miR‐93, miR‐143‐p3, miR‐196b, and miR‐223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.
Protective effects of either C‐peptide or l‐arginine on pancreatic β‐cell function, proliferation, and oxidative stress in streptozotocin‐induced diabetic rats
Authors: Ragy Merhan Mamdouh , Ahmed Sabreen Mahmoud 
Published: December 2018

AbstractDiabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C‐peptide or l‐arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1—control nondiabetic, 2—diabetic (no treatment), 3—diabetic + C‐peptide, and 4—diabetic +
l‐arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B‐cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C‐peptide or
l‐arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C‐peptide treatment of the diabetic rats completely corrected these errors, while
l‐arginine partially antagonized the above diabetic complications. So the administration of C‐peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.
Intracellular delivery of nucleic acid by cell‐permeable hPP10 peptide
Authors: Ding Yi , Zhao Xueli , Geng Jingping , Guo Xiangli , Ma Jielan , Wang Hu , Liu Changbai 
Published: December 2018

AbstractAlthough gene therapy offers hope against incurable diseases, nonreplicating transduction vectors remain lacking. We have previously characterized a cell‐penetrating peptide hPP10 for the delivery of various cargoes; however, whether hPP10 can mediate nucleic acid delivery is still unknown. Here, examining via different ways, we demonstrate that hPP10 stably complexes with plasmid DNA (pDNA) and safely mediates nucleic acid transfection. hPP10 can mediate GFP‐, dsRed‐, and luciferase‐expressing plasmids into cells with nearly the same efficiency as commercial transfection reagents Turbofectin or Lipofect. Furthermore, hPP10 can mediate Cre fusion protein delivery and pDNA transfection simultaneously in the Cre/loxp system in vitro. In addition, hPP10 fused with an RNA‐binding domain can mediate delivery of small interfering RNA into cells to silence the reporter gene expression. Collectively, our results suggest that hPP10 is an option for nucleic acid delivery with efficiencies similar to that of commercial reagents.
Inhibition of microRNA‐129‐5p expression ameliorates ultraviolet ray‐induced corneal epithelial cell injury via upregulation of EGFR
Authors: Yang Ying , Gong Bo , Wu Zheng‐Zheng , Shuai Ping , Li Dong‐Feng , Liu Ling‐Lin , Yu Man 
Published: December 2018

AbstractExisting evidence has highlighted the effect of ultraviolet light radiation leading to corneal epithelium impairment. During this study, we aim to investigate the effect of microRNA‐129‐5p (miR‐129‐5p) on the wound healing process of corneal epithelial cells (CECs) induced by ultraviolet rays in mice by targeting epidermal growth factor receptor (EGFR). First, mouse models of ultraviolet ray‐induced CEC injury were established and intrastromally injected with different mimic, inhibitor, and short interfering RNA (siRNA) to detect the effect of miR‐129‐5p on CEC injury. Subsequently, the corneal tissues were obtained to detect the antioxidant ability and EGFR‐positive expression rate. The dual‐luciferase reporter gene assay was used to test whether EGFR could directly target miR‐129‐5p. To further investigate the specific mechanism of miR‐129‐5p and EGFR in CEC injury, CECs were cultured and transfected with miR‐129‐5p mimic, miR‐129‐5p inhibitor, siRNA‐EGFR, and miR‐129‐5p inhibitor + siRNA‐EGFR. miR‐129‐5p has been proven to directly target EGFR. Inhibition of miR‐129‐5p is able to increase the antioxidant capacity, EGFR‐positive rate and the expressions of EGFR, B‐cell lymphoma‐2, zonula occluden‐1, occludin, and keratinocyte growth factor‐2, but decrease the expression of vascular endothelial growth factor, BCL2‐associated X protein, interleukin (IL)‐1β, and IL‐4. Inhibition of miR‐129‐5p arrests cells at the S and G2 phases and decreases apoptosis. Our study provides evidence stating that inhibiting miR‐129‐5p and upregulating EGFR could aid in the repair of mice CEC injury induced by ultraviolet radiation. Therefore, inhibition of miR‐129‐5p might provide a basic theory in the repair of CEC injury caused by ultraviolet rays.
RUNX1‐dependent mechanisms in biological control and dysregulation in cancer
Authors: Hong Deli , Fritz Andrew J. , Gordon Jonathan A. , Tye Coralee E. , Boyd Joseph R. , Tracy Kirsten M. , Frietze Seth E. , Carr Frances E. , Nickerson Jeffrey A. , Van Wijnen Andre J. , Imbalzano Anthony N. , Zaidi Sayyed K. , Lian Jane B. , Stein Janet L. , Stein Gary S. 
Published: December 2018

AbstractThe RUNX1 transcription factor has recently been shown to be obligatory for normal development. RUNX1 controls the expression of genes essential for proper development in many cell lineages and tissues including blood, bone, cartilage, hair follicles, and mammary glands. Compromised RUNX1 regulation is associated with many cancers. In this review, we highlight evidence for RUNX1 control in both invertebrate and mammalian development and recent novel findings of perturbed RUNX1 control in breast cancer that has implications for other solid tumors. As RUNX1 is essential for definitive hematopoiesis, RUNX1 mutations in hematopoietic lineage cells have been implicated in the etiology of several leukemias. Studies of solid tumors have revealed a context‐dependent function for RUNX1 either as an oncogene or a tumor suppressor. These RUNX1 functions have been reported for breast, prostate, lung, and skin cancers that are related to cancer subtypes and different stages of tumor development. Growing evidence suggests that RUNX1 suppresses aggressiveness in most breast cancer subtypes particularly in the early stage of tumorigenesis. Several studies have identified RUNX1 suppression of the breast cancer epithelial‐to‐mesenchymal transition. Most recently, RUNX1 repression of cancer stem cells and tumorsphere formation was reported for breast cancer. It is anticipated that these new discoveries of the context‐dependent diversity of RUNX1 functions will lead to innovative therapeutic strategies for the intervention of cancer and other abnormalities of normal tissues.
Effect of Gpx3 gene silencing by siRNA on apoptosis and autophagy in chicken cardiomyocytes
Authors: Gong Yafan , Yang Jie , Cai Jingzeng , Liu Qi , Zhang Jun min , Zhang Ziwei 
Published: December 2018

AbstractGlutathione peroxidase 3 (Gpx3), as an important selenoprotein, is the most crucial antioxidant defense in cardiomyocytes. However, the role of Gpx3 in Se‐deficient cardiomyocyte damage still less reported. Here, we developed Gpx3 silence cardiomyocytes culture model (small interfering RNA; siRNA) for research the crosstalk between autophagy and apoptosis. Quantitative real‐time PCR and western blot analysis are performed to detect the expression of apoptosis and autophagy‐related genes. MDC stain, flow cytometry, AO/EB stain, and electron microscope were performed to observe the changes of cell morphology. Our results reveal that Gpx3 suppression can significant increases in ROS (p < 0.05) levels, which further induced apoptosis through upregulated the expression of Caspase‐3 in cardiomyocytes. Meanwhile, we also found that the whole process is accompanied by the occurrence of autophagy, which are promoted by inhibiting the mTOR, and increasing the expression of ATG‐7, ATG‐10, and ATG‐12. Altogether, we conclude that the apoptotic and autophagic response machineries share antagonistic function in Gpx3 knockdown cardiomyocytes.
Antidiabetic potential of saffron and its active constituents
Authors: Yaribeygi Habib , Zare Vahid , Butler Alexandra E. , Barreto George E. , Sahebkar Amirhossein 
Published: December 2018

AbstractThe prevalence of diabetes mellitus is growing rapidly worldwide. This metabolic disorder affects many physiological pathways and is a key underlying cause of a multitude of debilitating complications. There is, therefore, a critical need for effective diabetes management. Although many synthetic therapeutic glucose‐lowering agents have been developed to control glucose homeostasis, they may have unfavorable side effects or limited efficacy. Herbal‐based hypoglycemic agents present an adjunct treatment option to mitigate insulin resistance, improve glycemic control and reduce the required dose of standard antidiabetic medications. Saffron (Crocus sativus L.), whilst widely used as a food additive, is a natural product with insulin‐sensitizing and hypoglycemic effects. Saffron contains several bioactive β carotenes, which exert their pharmacological effects in various tissues without any obvious side effects. In this study, we discuss how saffron and its major components exert their hypoglycemic effects by induction of insulin sensitivity, improving insulin signaling and preventing β‐cell failure, all mechanisms combining to achieve better glycemic control.
Oncolytic adenovirus: A tool for cancer therapy in combination with other therapeutic approaches
Authors: Goradel Nasser Hashemi , Mohajel Nasir , Malekshahi Ziba Veisi , Jahangiri Samira , Najafi Masoud , Farhood Bagher , Mortezaee Keywan , Negahdari Babak , Arashkia Arash 
Published: December 2018

AbstractCancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue‐ or tumor‐specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach.
Upregulated microRNAs in membranous glomerulonephropathy are associated with significant downregulation of IL6 and MYC mRNAs
Authors: Barbagallo Cristina , Passanisi Roberta , Mirabella Federica , Cirnigliaro Matilde , Costanzo Arianna , Lauretta Giovanni , Barbagallo Davide , Bianchi Cristina , Pagni Fabio , Castorina Sergio , Granata Antonio , Di Pietro Cinzia , Ragusa Marco , Malatino Lorenzo S. , Purrello Michele 
Published: December 2018

AbstractMembranous glomerulonephropathy (MGN) is a glomerulopathy characterized by subepithelial deposits of immune complexes on the extracapillary side of the glomerular basement membrane. Insertion of C5b‐9 (complement membrane‐attack complex) into the membrane leads to functional impairment of the glomerular capillary wall. Knowledge of the molecular pathogenesis of MGN is actually scanty. MicroRNA (miRNA) profiling in MGN and unaffected tissues was performed by TaqMan Low‐Density Arrays. Expression of miRNAs and miRNA targets was evaluated in Real‐Time polymerase chain reaction (PCR). In vitro transient silencing of miRNAs was achieved through transfection with miRNA inhibitors. Ten miRNAs (let‐7a‐5p, let‐7b‐5p, let‐7c‐5p, let‐7d‐5p, miR‐107, miR‐129‐3p, miR‐423‐5p, miR‐516‐3p, miR‐532‐3p, and miR‐1275) were differentially expressed (DE) in MGN biopsies compared to unaffected controls. Interleukin 6 (IL6) and MYC messenger RNAs (mRNAs; targets of DE miRNAs) were significantly downregulated in biopsies from MGN patients, and upregulated in A498 cells following let‐7a‐5p or let‐7c‐5p transient silencing. Gene ontology analysis showed that DE miRNAs regulate pathways associated with MGN pathogenesis, including cell cycle, proliferation, and apoptosis. A significant correlation between DE miRNAs and mRNAs and clinical parameters (i.e., antiphospholipid antibodies, serum creatinine, estimated glomerular filtration, proteinuria, and serum cholesterol) has been detected. Based on our data, we propose that DE miRNAs and their downstream network may be involved in MGN pathogenesis and could be considered as potential diagnostic biomarkers of MGN.
Evaluation of efficacy on RANKL induced osteoclast from RAW264.7 cells
Authors: Song Chengchao , Yang Xiaobin , Lei Yongsheng , Zhang Zhen , Smith Wanli , Yan Jinglong , Kong Lingbo 
Published: December 2018

AbstractEstablished RAW264.7 cell lines for osteoclastic differentiation has been widely engaged in bone homeostasis research, however, the efficacy of RANKL independently stimulating has rarely been defined, because protocols were usually developed and modified by various laboratories. Otherwise, problematic issues are also lie in the cell's seeding density, RANKL stimulating time point, and distinguishing osteoclastogenesis ability of RANKL‐treated RAW264.7 cells. Therefore, in the current study, we examined the efficacy of various concentrations of RANKL‐treated RAW264.7 for its osteoclastic differentiation with or without pretreated other costimulators such as: LPS and/or M‐CSF. The oteoclastogenesis ability of RANKL‐treated RAW264.7 cells was demonstrated by bone resorption pit, F‐actin, and osteoclastogenesis specific marker studies. Besides that, through tartrate‐resistant acid phosphatase (TRAP) staining, we clarified to start the treatment with 30 ng/ml RANKL at 12 hr after seeded RAW264.7 with the density of 6.25 × 10
3 cells/cm
2 manifested an significantly increased number of multinucleated osteoclastic cells. Overall, our results establishing an optimal method for RANKL independently inducing RAW 264.7 cell osteoclastic differentiation, which could efficiently generate osteoclasts in vitro for significant advances in our understanding of bone biology.
Evaluation of ovarian cancer risk in granulosa cells treated with steroid‐depleted endometriosis serum: Role of NF‐κB/RelA and AKT
Authors: Asghari Samira , Valizadeh Dizajeykan Amir , Ahmadi Majid , Barzegari Abolfazl , Rikhtegar Reza , Dolati Sanam , Danaii Shahla , Abdollahi‐Fard Sedigheh , Nouri Mohammad , Mahdipour Mahdi , Yousefi Mehdi 
Published: December 2018

AbstractBackgroundDespite at the beginning known as a benign disease, endometriosis is defined as a risk factor for developing ovarian carcinoma. The effect of endometriosis on ovarian malignancy is known but its role in granulosa cell tumor is still unclear.Methods and MaterialsIn this study, serum samples were collected from patients with endometriosis and divided into whole and steroid‐depleted groups. Desertification was performed according to the charcoal–dextran protocol and sera were added to the culture media of granulosa cells retrieved from tubal or male factor infertile women. Quantitative real‐time polymerase chain reaction and flow cytometry were performed to determine the expression level of inflammatory and apoptotic genes and apoptosis level of granulosa cells. The total concentration of lipid was measured using gas chromatography method in the granulosa cells.ResultsResults revealed that the expression of AKT and NF‐κB/RelA gene was significantly higher in the granulosa cells treated with steroid‐depleted serum obtained from patients with distrificated endometriosis (DE) compared with the control group (9.39‐ and 7.9‐folds, respectively; p < 0.0001). In the DE group, the declined pattern of expression was observed for the genes related to apoptosis. The synthesis of saturated fatty acids was significantly decreased; however, unsaturated fatty acids showed increased levels in the DE group.ConclusionThe effect of steroids on endometriosis is contradictory. The level of cortisol and sex hormones could be affected by endometriosis, causing alterations of the disease progression. Reduced level of steroid hormones in patients with endometriosis may be considered as a critical risk factor for granulosa cell tumor.
Recent advances in TMEM16A: Structure, function, and disease
Authors: Ji Qiushuang , Guo Shuai , Wang Xuzhao , Pang Chunli , Zhan Yong , Chen Yafei , An Hailong 
Published: December 2018

AbstractTMEM16A (also known as anoctamin 1, ANO1) is the molecular basis of the calcium‐activated chloride channels, with ten transmembrane segments. Recently, atomic structures of the transmembrane domains of mouse TMEM16A (mTMEM16A) were determined by single‐particle electron cryomicroscopy. This gives us a solid ground to discuss the electrophysiological properties and functions of TMEM16A. TMEM16A is reported to be dually regulated by Ca2+ and voltage. In addition, the dysfunction of TMEM16A has been found to be involved in many diseases including cystic fibrosis, various cancers, hypertension, and gastrointestinal motility disorders. TMEM16A is overexpressed in many cancers, including gastrointestinal stromal tumors, gastric cancer, head and neck squamous cell carcinoma (HNSCC), colon cancer, pancreatic ductal adenocarcinoma, and esophageal cancer. Furthermore, overexpression of TMEM16A is related to the occurrence, proliferation, and migration of tumor cells. To date, several studies have shown that many natural compounds and synthetic compounds have regulatory effects on TMEM16A. These small molecule compounds might be novel drugs for the treatment of diseases caused by TMEM16A dysfunction in the future. In addition, recent studies have shown that TMEM16A plays different roles in different diseases through different signal transduction pathways. This review discusses the topology, electrophysiological properties, modulators and functions of TMEM16A in mediates nociception, gastrointestinal dysfunction, hypertension, and cancer and focuses on multiple regulatory mechanisms regarding TMEM16A.
Alpinate Oxyphyllae extracts enhance the longevity and homing of mesenchymal stem cells and augment their protection against senescence in H9c2 cells
Authors: Chang Yung‐Ming , Asokan Shibu Marthandam , Tsai Chuan‐Te , Tsai Chin‐Chuan , Lin Shu‐Luan , Chang Chia‐Cheng , Viswanadha Vijaya Padma , Chen Ray‐Jade , Chang Julia Huei‐Mei , Huang Chih‐Yang 
Published: December 2018

AbstractAdipose‐derived mesenchymal stem cells (ADMSCs) are easily accessible and are attractive mesenchymal stem cells for use in regenerative medicine; however their application is frequently restricted due to various challenges present in the environment they are administered. Therefore ADMSCs are preferably preconditioned with various stimulating factors to overcome the barriers developed in any pathological conditions. Here we used ADMSCs from rat adipose based on the abundance of positive markers and preconditioned the cells with extracts from Alpinate Oxyphyllae Fructus (AOF), a traditional Chinese herb used for antiaging, associated various health benefits. The preconditioned stem cells were tested for their potential to drive H9c2 from doxorubicin (Dox)‐induced aging. The AOF‐treated stem cells enriched stemness in ADMSCs with respect to their stem cells' positive marker, and enhanced their longevity mechanism and elevated the stem cell homing‐associated C‐X‐C chemokine receptor type 7 (CXCR7). The AOF preconditioned stem cells, when cocultured with H9c2 cells, showed effective protection to Dox‐induced senescence and stem cell homing to damaged H9c2 cells. The presence of AOF provided greater protective effects in the Dox environment. In addition, AOF‐pretreated ADMSCs showed enhanced migration than those treated with AOF in Dox environment. Therefore, our results show that administration of AOF preconditioned stem cells is potentially an effective strategy in the management of aging‐associated cardiac disorders.
Cajaninstilbene acid inhibits osteoporosis through suppressing osteoclast formation and RANKL‐induced signaling pathways
Authors: Sun Youqiang , Liu Yuhao , He Wei , Wang Chao , Tickner Jennifer , Kuek Vincent , Zhou Chi , Wang Haibin , Zou Xuting , Hong Zhinan , Yang Fan , Shao Min , Chen Leilei , Xu Jiake 
Published: December 2018

AbstractOsteoporosis is a form of osteolytic disease caused by an imbalance in bone homeostasis, with reductions in osteoblast bone formation, and augmented osteoclast formation and resorption resulting in reduced bone mass. Cajaninstilbene acid (CSA) is a natural compound derived from pigeon pea leaves. CSA possesses beneficial properties as an anti‐inflammatory, antibacterial, antihepatitis, and anticancer agent; however, its potential to modulate bone homeostasis and osteoporosis has not been studied. We observed that CSA has the ability to suppress RANKL‐mediated osteoclastogenesis, osteoclast marker gene expression, and bone resorption in a dose‐dependent manner. Mechanistically, it was revealed that CSA attenuates RANKL‐activated NF‐κB and nuclear factor of activated T‐cell pathways and inhibited phosphorylation of key signaling mediators c‐Fos, V‐ATPase‐d2, and ERK. Moreover, in osteoclasts, CSA blocked RANKL‐induced ROS activity as well as calcium oscillations. We further evaluated the therapeutic effect of CSA in a preclinical mouse model and showed that in vivo treatment of ovariectomized C57BL/6 mice with CSA protects the mice from osteoporotic bone loss. Thus, this study demonstrates that osteolytic bone diseases can potentially be treated by CSA.