bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propofol partially attenuates complete freund's adjuvant‐induced neuroinflammation through inhibition of the ERK1/2/NF‐κB pathway
Authors: Cheng Lijian , Chen Zhenhong , Wang Lihua , Lan Yunping , Zheng Lihua , Wu Fangpu 
Published: December 2018

AbstractPeripheral inflammation in male C57BL/6 mice was induced by intraplantar injection of 20 μL complete freund's adjuvant (CFA) in the left hind paw. Mice were randomly divided into three groups: Sham, CFA, and propofol+CFA. Mechanical allodynia was assessed by von Frey analysis, and heat hyperalgesia was detected by exposure of the plantar surface to a beam of radiant heat. Propofol significantly attenuated the severity and duration of CFA‐induced pain hypersensitivity, heat hyperalgesia, and paw edema. Propofol inhibited CFA‐induced microglia activation, and markedly decreased CFA‐induced ionized calcium binding adapter molecule 1 (IBA‐1) expression. Propofol inhibited CFA‐induced expression of p‐extracellular signal‐regulated kinase1/2 (p‐ERK1/2) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) p65, as demonstrated by Western blot analysis. In addition, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assays indicated that propofol had no cytotoxic effect on BV2 microglia cells. Reverse transcription‐quantitative‐polymerase chain reaction and enzyme‐linked immunosorbent assay results demonstrated that propofol attenuates CFA‐induced tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, and IL‐1β production in the spinal cord as well as in BV2 cells. Taken together, these results demonstrate that propofol attenuates CFA‐induced neuroinflammation (TNF‐α, IL‐6, and IL‐1β expression) through a mechanism that involves activation of ERK1/2/NF‐κB signaling pathway.
Plumbagin induces autophagy and apoptosis of SMMC‐7721 cells in vitro and in vivo
Authors: Lin Yuning , Chen Yongxin , Wang Shengshan , Ma Jing , Peng Yue , Yuan Xianling , Lv Beibei , Chen Wanjun , Wei Yanfei 
Published: December 2018

AbstractPlumbagin (PL), an active naphthoquinone compound, has been demonstrated to be a potential anticancer agent. However, the underlying anticancer mechanism is not fully understood. In this study, the human hepatocellular carcinoma (HCC) SMMC‐7721 cell line was studied in an in vitro model. The cell proliferation was inhibited by PL in a dose‐ and time‐dependent manner. Electron microscopy, acridine orange staining, and immunofluorescence were used to evaluate autophagosome formation and LC3 protein expression in PL‐treated SMMC‐7721 cells. Real‐time polymerase chain reaction and Western blot showed that PL treatment suppressed the expression of apoptosis and autophagy factors (LC3, Beclin1, Atg7, and Atg5), which are associated with tumor apoptosis and autophagy in SMMC‐7721 cells. In the study of in vitro tumor nude mouse models, PL can inhibit tumor growth. Cell apoptosis and autophagy of the transplanted tumors were evaluated by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling staining, and Western blot. In addition, in the in vivo studies of HCC cells, we found that pretreatment with the autophagy inhibitor 3‐methyladenine blocked the formation of apoptosis induced by PL. In contrast, administration of the apoptosis inhibitor Z‐VAD did not affect PL‐induced autophagy. Taken together, our findings strongly suggest that PL is a promising drug with significant antitumor activity in HCC.
A correlational study between serum asymmetric dimethylarginine level and impaired glucose tolerance patients associated with obesity
Authors: Huang Shan , Xu Yong , Peng Wen‐Fang , Cheng Jie , Li Hui‐Hua , Shen Li‐Sha , Xia Li‐Li 
Published: December 2018

AbstractAsymmetric dimethylarginine (ADMA) plays a vital role in the regulation of insulin sensitivity and has been shown as a potential marker for various disease, including type 2 diabetes mellitus (DM2). However, the correlation between ADMA and impaired glucose tolerance (IGT) and obesity has not been studied. A total of 195 subjects were involved in our study. The characteristics of the subjects in the study cohort were measured and analyzed. We found that the serum ADMA and C‐reactive protein levels were significantly increased in IGT and diabetic patients, whereas the levels of lipoprotein A and adiponectin were decreased, especially in diabetic patients with obesity. The serum ADMA level was positively correlated to a homeostatic model assessment for insulin resistance, and multivariate regression analysis further indicated that ADMA was an independent factor for DM patients with obesity. Our study expands the understanding of the complicated relationship between obesity, insulin resistance, IGT, and ADMA. In addition, we demonstrated that the serum ADMA level could serve as a diagnositic biomarker of the early signs for IGT patients with obesity.
Preventive effect of omega‐3 fatty acids in a rat model of stress‐induced liver injury
Authors: Ali Fatma Farrag , Rifaai Rehab Ahmed 
Published: December 2018

AbstractOmega‐3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega‐3 fatty acids related to acute cold‐restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega‐3 group, each rat was pretreated with omega‐3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega‐3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor‐α (TNF‐α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase‐3. Results showed that pretreatment of stressed rats with omega‐3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF‐α. Also, they improved liver damage and suppressed hepatic caspase‐3 expression. In conclusion, pretreatment of stressed rats with omega‐3 fatty acids has ameliorated stress‐induced liver damage due to their antioxidant, anti‐inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver.
Activation of TGF‐β1/Smad3 signaling pathway inhibits the development of ovarian follicle in polycystic ovary syndrome by promoting apoptosis of granulosa cells
Authors: Shen Haoran , Wang Yao 
Published: December 2018

AbstractObjective: To investigate the role of the transforming growth factor‐β1 (TGF‐β1)/Smad3 signaling pathway in development of ovarian follicle by promoting apoptosis of granulosa cells in polycystic ovary syndrome (PCOS).MethodsA total of 54 female rats were obtained and randomly assigned into the PCOS (n = 27) and control groups (
n = 27). PCOS rat models were constructed using the dehydroepi‐androsterone method to observe ovarian morphology and ultrastructure. Chemiluminescence immunoassay was performed to detect the levels of luteinizing hormone, follicle stimulating hormone, estradiol, progesterone, and testosterone. The release of TGF‐β1 in follicular fluid and serum was tested by the enzyme‐linked immunosorbent assay.ResultsExpression of p‐Smad3 significantly increased in granulosa cells of PCOS group. In terms of the Smad2 protein, there was no significant difference between the PCOS and control group. In comparison to the control group, the number of normal secondary follicles and normal antral follicles were significantly decreased, whereas the number of hypogenetic secondary follicles undergoing atresia and antral follicles were significantly elevated in the PCOS group. Furthermore, the thickness of granulosa cells decreased and the apoptosis of granulosa cells increased in the PCOS group compared with the control one.ConclusionThese results indicate that p‐Smad3 may have a close relationship with apoptosis of granulosa cells, the mechanism is that the TGF‐β1/Smad3 signaling pathway may inhibit development of ovarian follicle of PCOS by regulating the apoptosis of granulosa cells.
Strategies toward rheumatoid arthritis therapy; the old and the new
Authors: Abbasi Mojtaba , Mousavi Mohammad Javad , Jamalzehi Sirous , Alimohammadi Reza , Bezvan Maryam Hasanzadeh , Mohammadi Hamed , Aslani Saeed 
Published: December 2018

AbstractCurrently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti‐inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease‐modifying antirheumatic drugs (DMARDs), administered as first‐line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti‐CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor‐α (TNF‐α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin‐1 (IL‐1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF‐α inhibitors, JAK inhibitors, anti‐interleukin‐6‐receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat‐to‐target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation.
In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis‐related genes in patients with systemic lupus erythematosus
Authors: Yousefi Bahman , Rastin Maryam , Hatef Mohammad Reza , Shariati Jaleh , Alimohammadi Reza , Mahmoudi Mahmoud 
Published: December 2018

AbstractObjectivesSystemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients.MethodsTwenty SLE patients and 20 age‐ and sex‐matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme‐linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5‐µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante‐conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis‐related genes (Fas, Fas‐L, Bcl‐2, and Bax) in PBLs was measured using real‐time PCR before and after treating with DHEAS.ResultsLevel of DHEAS was low in SLE patients compared with healthy controls (p < 0.05). After treating with DHEAS, the percentage of apoptotic cells in SLE patients was decreased in comparison with healthy controls. DHEAS treatment increased the mRNA expression level of Bcl‐2 in PBLs from SLE patients.ConclusionsDHEAS reduced the apoptosis rate in PBLs from SLE patients and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients.
Integrative analysis of DNA methylation and gene expression identify a six epigenetic driver signature for predicting prognosis in hepatocellular carcinoma
Authors: Li Gan‐xun , Ding Ze‐yang , Wang Yu‐wei , Liu Tong‐tong , Chen Wei‐xun , Wu Jing‐jing , Xu Wei‐qi , Zhu Peng , Zhang Bi‐xiang 
Published: December 2018

AbstractDNA methylation is a crucial regulator of gene transcription in the etiology and pathogenesis of hepatocellular carcinoma (HCC). Thus, it is reasonable to identify DNA methylation‐related prognostic markers. Currently, we aimed to make an integrative epigenetic analysis of HCC to identify the effectiveness of epigenetic drivers in predicting prognosis for HCC patients. By the software pipeline TCGA‐Assembler 2, RNA‐seq, and methylation data were downloaded and processed from The Cancer Genome Atlas. A bioconductor package MethylMix was utilized to incorporate gene expression and methylation data on all 363 samples and identify 589 epigenetic drivers with transcriptionally predictive. By univariate survival analysis, 72 epigenetic drivers correlated with overall survival (OS) were selected for further analysis in our training cohort. By the robust likelihood‐based survival model, six epi‐drivers (doublecortin domain containing 2, flavin containing monooxygenase 3, G protein‐coupled receptor 171, Lck interacting transmembrane adaptor 1, S100 calcium binding protein P, small nucleolar RNA host gene 6) serving as prognostic markers was identified and then a DNA methylation signature for HCC (MSH) predicting OS was identified to stratify patients into low‐risk and high‐risk groups in the training cohort (p < 0.001). The capability of MSH was also assessed in the validation cohort (p = 0.002). Furthermore, a receiver operating characteristic curve confirmed MSH as an effective prognostic model for predicting OS in HCC patients in training area under curve (AUC = 0.802) and validation (AUC = 0.691) cohorts. Finally, a nomogram comprising MSH and pathologic stage was generated to predict OS in the training cohort, and it also operated effectively in the validation cohort (concordance index: 0.674). In conclusion, MSH, a six epi‐drivers based signature, is a potential model to predict prognosis for HCC patients.
Prevalence, pathological mechanisms, and genetic basis of limb‐girdle muscular dystrophies: A review
Authors: Taghizadeh Eskandar , Rezaee Mehdi , Barreto George E. , Sahebkar Amirhossein 
Published: December 2018

AbstractLimb‐girdle muscular dystrophies (LGMDs) are a highly heterogeneous group of neuromuscular disorders that are associated with weakness and wasting of muscles in legs and arms. Signs and symptoms may begin at any age and usually worsen by time. LGMDs are autosomal disorders with different types and their prevalence is not the same in different areas. New technologies such as next‐generation sequencing can accelerate their diagnosis. Several important pathological mechanisms that are involved in the pathology of the LGMD include abnormalities in dystrophin–glycoprotein complex, the sarcomere, glycosylation of dystroglycan, vesicle and molecular trafficking, signal transduction pathways, and nuclear functions. Here, we provide a comprehensive review that integrates LGMD clinical manifestations, prevalence, and some pathological mechanisms involved in LGMDs.
Dynamic changes of Sonic Hedgehog signaling pathway in gastric mucosa of rats with MNNG‐induced gastric precancerous lesions
Authors: Cai Danli , Yu Jianshun , Qiu Jing , He Beihui , Chen Zhiyun , Yan Maoxiang , Liu Qingsheng 
Published: December 2018

AbstractObjectiveTo explore the changes of Sonic Hedgehog (Shh) signaling pathway in the stomach mucosa during the formation of gastric precancerous lesions.MethodsA total of 72 suckling rats in half genders were randomly and equally divided into the normal group and model group. The rats in the model group were administered with 0.1 ml 1‐methyl‐3‐nitro‐1‐nitrosoguanidine (MNNG) at the dosage of 800 mg/L for 10 days, whereas the rats in the normal group were similarly administered with normal saline. A total of 12 rats in each group were killed at the end of 10th, 22nd, and 34th weeks in half gender, respectively. Histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (HE) staining; the levels of Shh, Ptch1, Smo, Gli1, Gli2, Gli3, SuFu, Cyclin D1, Cyclin E1, c‐Myc, and β‐actin mRNAs in the gastric mucosa were determined by real‐time polymerase chain reaction; while the protein expression of Shh, Ptch1, Smo, Gli1, SuFu, Cyclin D1, Cyclin E1, c‐Myc, and p‐c‐Myc was detected by western blot analysis.ResultsWith the development of atrophy and dysplasia of gastric mucosa, the levels of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and c‐Myc mRNAs increased, while those of Ptch1 and SuFu decreased. The expression of Shh, Smo, Gli1, Cyclin D1, Cyclin E1, and p‐c‐Myc proteins were elevated, while the expression of Ptch1 and SuFu proteins were decreased, however, without statistical difference.ConclusionsShh signaling is activated during the formation of gastric precancerous lesions, which indicates that the Shh signaling pathway participates in the development and progression of gastric precancerous lesions.
Therapeutic potential of nvp‐bkm120 in human osteosarcomas cells
Authors: Bavelloni Alberto , Focaccia Enrico , Piazzi Manuela , Orsini Arianna , Ramazzotti Giulia , Cocco Lucio , Blalock William , Faenza Irene 
Published: December 2018

AbstractOsteosarcoma (OS) is the most common pediatric malignant neoplasia of the skeletal system. It is characterized by a high degree of malignancy and a severe tendency to metastasize. In the past decade, many studies have provided evidence that the phosphoinositide 3‐kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancer, and has a critical role in driving tumor initiation and progression. Here, we have analyzed the therapeutic potential of the pan‐PI3K inhibitor NVP‐BKM120, which has recently entered clinical Phase II for treatment of PI3K‐dependent cancers on three OS cell lines. We observed a concentration‐ and time‐dependent decrease of Ser473 p‐Akt as well as reduced levels of Thr37/46 p‐4E‐BP1, an indicator of the mammalian target of rapamycin complex 1 activity. All OS cell lines used in this study responded to BKM120 treatment with an arrest of cell proliferation, an increase in cell mortality, and an increase in caspase‐3 activity. MG‐63 cells were the most responsive cell line, demonstrating a significant increase in sub‐G1 cells, and a rapid induction of cell death. Furthermore, we demonstrate that BKM120 is more effective when used in combination with other standard chemotherapeutic drugs. Combining BKM120 with vincristine demonstrated a more synergistic effect than BKM120 with doxorubicin in all the lines. Hence, we suggest that BKM120 may be a novel therapy for the treatment of OS presenting with anomalous upregulation of the PI3K signaling pathway.
Long noncoding RNA HOXC13‐AS positively affects cell proliferation and invasion in nasopharyngeal carcinoma via modulating miR‐383‐3p/HMGA2 axis
Authors: Gao Changhui , Lu Wuhao , Lou Weihua , Wang Liang , Xu Qiang 
Published: December 2018

AbstractLong noncoding RNAs have been reported to be important regulators in numerous cancers. In this study, we found that HOXC13 antisense RNA (HOXC13‐AS) was highly expressed in head and neck squamous carcinoma (HNSC) tissues in The Cancer Genome Atlas database. Nasopharyngeal carcinoma (NPC) belongs to HNSC. Therefore, we further investigated the potential role of HOXC13‐AS in NPC. Quantitative reverse transcription polymerase chain reaction examination revealed that HOXC13‐AS was markedly upregulated in NPC tissues and cell lines. Furthermore, HOXC13‐AS was identified as an independent prognosis factor by Cox regression analyses. Subsequently, functional assay revealed that knockdown of HOXC13‐AS impaired cell proliferation, migration, and invasion. Mechanistically, RIP and luciferase reporter analysis confirmed that miR‐383‐3p was a target of HOXC13‐AS. Besides, high mobility group AT‐hook 2 (HMGA2) was proved to be a target of miR‐383‐3p in NPC. Finally, rescue assays demonstrated that HOXC13‐AS functioned as a competing endogenous RNAs to enhance the expression of HMGA2 via sponging miR‐383‐3p. This study suggested that HOXC13‐AS exerted oncogenic function in NPC via regulating miR‐383‐3p/HMGA2 axis, indicating HOXC13‐AS may be a potential therapeutic target for patients with NPC.
Myeloid‐derived suppressor cells and tumor: Current knowledge and future perspectives
Authors: Safari Elahe , Ghorghanlu Sajjad , Ahmadi‐khiavi Homayoun , Mehranfar Sahar , Rezaei Ramazan , Motallebnezhad Morteza 
Published: December 2018

AbstractThe immunosuppressive features of tumor lesions participate not only as one of the major players inducing cancer progression but also a big challenge for effective immunotherapy. It has been found that immunosuppression associated with chronic inflammatory factors, such as growth factors, cytokines, and chemokines is generated by stroma and tumor cells. Chronic and exhaustive secretion of these mediators triggers the generation of myeloid‐derived suppressor cells (MDSCs) demonstrating one of the key players engaged in tumor immunosuppression. In point of fact, direct cell‐to‐cell contact is a prerequisite for immunosuppressive functions of MDSCs. From the clinical perspective, the frequency of peripheral blood MDSCs is correlated with clinical stage and therapeutic response in various cancers. Furthermore, MDSCs are involved in chemoresistant settings. Altogether, it is a rational therapeutic approach to block the fierce cycle in which MDSCs are developed and infiltrated to favor cancer progression. In this review, we will summarize recent findings of MDSCs in tumor progression and discuss potential therapeutic strategies that could be evaluated in future clinical trials.
LncRNA MALAT1 protects cardiomyocytes from isoproterenol‐induced apoptosis through sponging miR‐558 to enhance ULK1‐mediated protective autophagy
Authors: Guo Xiaoyan , Wu Xiaoguang , Han Yan , Tian Erhu , Cheng Jiangtao 
Published: December 2018

AbstractInvestigating the molecular mechanisms of myocardial infarction (MI) and subsequent heart failure have gained considerable attention worldwide. Long noncoding RNA (lncRNA) metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been previously demonstrated to regulate the proliferation and metastasis of several tumors. However, little is known about the effects of MALAT1 in MI and in regulating the cell date after MI. In our study, first, it was shown that the expression levels of MALAT1 were increased in the MI samples compared with normal tissues using quantitative reverse‐transcription polymerase chain reaction. Then, MALAT1 knockdown could significantly decrease the cell viability and increase the apoptotic rates in isoproterenol (ISO)‐treated H9C2 cells. In addition, we screened the possible target and found that miR‐558 is its direct target using dual luciferase reporter assay, indicating that MALAT1 functioned as decoys sponging miR‐558. Transfection of miR‐558 mimic decreased the cell viability and enhanced the apoptosis. Furthermore, we revealed that miR‐558 could downregulate ULK1 expression and suppressed ISO‐induced protective autophagy. Activation of MALAT1/miR‐558/ULK1 pathway protected H9C2 cells from ISO‐induced mitochondria‐dependent apoptosis. Finally, we used MALAT1‐knockout mice to further demonstrated that MALAT1 protected cardiomyocytes from apoptosis and partially improved the cardiac functions upon ISO treatment. In conclusion, we elucidated that lncRNA MALAT1 protected cardiomyocytes from ISO‐induced apoptosis by sponging miR‐558 thus promoting ULK1‐dependent autophagy. Targeting lncRNA MALAT1 might become a potential strategy in protecting cardiomyocytes during MI.