bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Objectives

Systemic 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.

Methods

Twenty 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.

Results

Level 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.

Conclusions

DHEAS 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

DNA 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

Limb‐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

Objective

To explore the changes of Sonic Hedgehog (Shh) signaling pathway in the stomach mucosa during the formation of gastric precancerous lesions.

Methods

A 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.

Results

With 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.

Conclusions

Shh 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

Osteosarcoma (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

Long 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

The 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

Investigating 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.
Loss of Lgr4 inhibits differentiation, migration and apoptosis, and promotes proliferation in bone mesenchymal stem cells
Authors: Sun Peng , Jia Kunhang , Zheng Chunbing , Zhu Xinlei , Li Jing , He Liang , Siwko Stefan , Xue Feng , Liu Mingyao , Luo Jian
Published: December 2018

The key signaling networks regulating bone marrow mesenchymal stem cells (BMSCs) are poorly defined. Lgr4, which belongs to the leucine‐rich repeat‐containing G protein‐coupled receptor (LGR) family, is widely expressed in multiple tissues from early embryogenesis to adulthood. We investigated whether Lgr4 functions in BMSCs and in osteogenesis, adipogenesis, and skeletal myoblasts, using mice with a β‐geo gene trap inserted into the Lgr4 gene. Abundant Lgr4 expression was detected in skeletal, adipose and muscular tissue of Lgr4+/– mice at E16.5 by β‐gal staining, and Lgr4‐deficiency promoted BMSC proliferation (16 ± 4 in wild‐type [WT] and 28 ± 2 in Lgr4−/−) using colony forming units‐fibroblast assay, while suppressing BMSC migration (from 103 ± 18 in WT to 57 ± 10 in Lgr4−/−) by transwell migration assay and apoptosis ratio (from 0.0720 ± 0.0123 to 0.0189 ± 0.0051) by annexin V staining assay. Deletion of Lgr4 decreased bone mass (BV/TV from 19.16 ± 2.14 in WT mice to 10.36 ± 1.96 in KO) and fat mass through inhibiting BMSC differentiation to osteoblasts or adipocytes. Furthermore, LGR4‐regulated osteogenic, adipogenic, and myogenic gene expression. Importantly, our data showed that loss of Lgr4‐inhibited fracture healing by suppressing osteoblast differentiation. Moreover, deletion of Lgr4 in BMSCs‐delayed fracture healing following stem cell therapy by BMSC transplantation. Together, our results demonstrated that LGR4 is essential for mesoderm‐derived tissue development and BMSC differentiation, demonstrating that LGR4 could be a promising drug target for related diseases and a critical protein for stem cell therapy.
Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis
Authors: Hosseini Arezoo , Masjedi Ali , Baradaran Behzad , Hojjat‐Farsangi Mohammad , Ghalamfarsa Ghasem , Anvari Enayat , Jadidi‐Niaragh Farhad
Published: December 2018

Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. DMF and its dynamic metabolite, monomethyl fumarate (MMF) are the major compounds that exert therapeutic effects on several pathologic conditions in part, through downregulation of immune responses. The exact mechanism of DMF is yet to be fully understood even though its beneficial effects on the immune system are extensively studied. It has been shown that DMF/MMF can affect various immune cells, which can get involved in both the naive and adaptive immune systems, such as T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells. It is suggested that DMF/MMF may exert their effect on immune cells through inhibition of nuclear factor‐κB translocation, upregulation of nuclear factor erythroid‐derived 2(E2)‐related factor antioxidant pathway, and activation of hydroxyl carboxylic acid receptor 2. In this review, the mechanisms underlying the modulatory functions of DMF or MMF on the main immune cell populations involved in the immunopathogenesis of MS are discussed.
Farnesoid X receptor interacts with cAMP response element binding protein to modulate glucagon‐like peptide‐1 (7–36) amide secretion by intestinal L cell
Authors: Li Pengzhou , Zhu Liyong , Yang Xiangwu , Li Weizheng , Sun Xulong , Yi Bo , Zhu Shaihong
Published: December 2018

Type II diabetes is a complex, chronic, and progressive disease. Glucagon‐like peptide‐1 (7–36) amide (GLP‐1) is a gut hormone released from the L cells which stimulate insulin secretion and promotes insulin gene expression and β‐cell growth and differentiation. Elevated levels of hormones secreted by L cells are an essential reason for diabetes improvement. GLP‐1 secretion has been reported to be regulated by farnesoid X receptor (FXR), a transcriptional sensor for bile acids which also acts on glucose metabolism. Herein, we attempted to evaluate the effect of FXR on GLP‐1 secretion in mouse enteroendocrine L cell line, namely STC‐1, and to investigate the underlying mechanism. FXR inversely regulated GLP‐1 secretion in STC‐1. A total of 24 nonredundant human proteins were shown to be related to FXR by BioGRID; KEGG pathway analysis revealed that FXR was related to glucagon signaling pathway, particularly with the transcriptional activators CREB, PGC1α, Sirt1, and CBP. CREB could positively regulate GLP‐1 secretion in STC‐1 cells. FXR combined with CREB to inhibit its transcriptional activity, thus inhibiting proprotein convertase subtilisin/kexin type 1 protein level and GLP‐1 secretion. In the present study, we demonstrated a negative regulation of GLP‐1 secretion by FXR in L cell line, STC‐1; FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP–CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP‐1 secretion may be a promising strategy for type II diabetes.
The role of microRNAs in prostate cancer migration, invasion, and metastasis
Authors: Aghdam Shirin Golabi , Ebrazeh Mehrdad , Hemmatzadeh Maryam , Seyfizadeh Narges , Shabgah Arezoo Gowhari , Azizi Gholamreza , Ebrahimi Negin , Babaie Farhad , Mohammadi Hamed
Published: December 2018

Prostate cancer (PCa) is considered the most prevalent malignancy and the second major cause of cancer‐related death in males from Western countries. PCa exhibits variable clinical pictures, ranging from dormant to highly metastatic cancer. PCa suffers from poor prognosis and diagnosis markers, and novel biomarkers are required to define disease stages and to design appropriate therapeutic approach by considering the possible genomic and epigenomic differences. MicroRNAs (miRNAs) comprise a class of small noncoding RNAs, which have remarkable functions in cell formation, differentiation, and cancer development and contribute in these processes through controlling the expressions of protein‐coding genes by repressing translation or breaking down the messenger RNA in a sequence‐specific method. miRNAs in cancer are able to reflect informative data about the current status of disease and this might benefit PCa prognosis and diagnosis since that is concerned to PCa patients and we intend to highlight it in this paper.
Protective effects of plant‐derived natural products on renal complications
Authors: Yaribeygi Habib , Simental‐Mendía Luis E. , Butler Alexandra E. , Sahebkar Amirhossein
Published: December 2018

Diabetic nephropathy is the leading cause of renal failure worldwide. This debilitating disorder has several underlying pathophysiologic mechanisms, and therefore a variety of pharmacologic agents have been developed to prevent or treat diabetic nephropathy; however, synthetic drugs may possess unfavorable side effects. In response to this, the global use of herbal‐based pharmacologic agents is increasing among diabetic patients. Numerous studies have reported therapeutic benefits of herbal‐based compounds against diabetes‐induced renal dysfunction. These agents can prevent renal dysfunction and improve renal function by blocking or suppressing deleterious pathways such as oxidative stress, inflammation, apoptosis, necrosis, and nitric oxide deprivation that lead to vascular injuries. In the current study, we have reviewed the beneficial properties of the most common herbal agents used in renal complications and diabetic nephropathy.
Activating Mas receptor protects human pulmonary microvascular endothelial cells against LPS‐induced apoptosis via the NF‐kB p65/P53 feedback pathways
Authors: Huang Weifeng , Cao Yongmei , Liu Yujing , Ping Feng , Shang Jiawei , Zhang Zhongwei , Li Yingchuan
Published: December 2018

The balance between Ang II/AT1R and Ang‐(1‐7)/Mas plays a pivotal role in the development of lipopolysaccharides (LPS)‐induced acute respiratory distress syndrome. However, the mechanisms underlying the balancing process still remain unclear. Here we investigated the roles of nuclear factor (NF)‐κB and p53 in regulating AT1R and Mas expression. The results demonstrated that Ang II pretreatment resulted in downregulation of Mas and upregulation of AT1R, phosphorylated p65, and apoptosis in LPS‐treated Human pulmonary microvascular endothelial cells (HPMVECs), but had no effect on p53 expression. Lentiviral vector‐mediated P65 knockdown, but not a P53 knockdown, reversed all these effects of Ang II. On the other hand, Ang‐(1‐7) pretreatment lead to an increased in Mas expression and a decrease in AT1R, p53, and phosphorylated p65 expressions with suppressed apoptosis in LPS‐treated cells. P65 knockdown promoted the protein expression of both AT1R and Mas while inhibiting p53 expression. P53 knockdown, but not a p65 knockdown, reversed all these effects of Ang‐(1‐7). Interestingly, p65 overexpression upregulated p53 and AT1R but downregulated Mas. P53 knockdown activated p65. These results suggest that there is a two‐way feedback regulation between AT1R and Mas receptor via the NF‐kB p65/P53 pathway, which may play a key role in LPS‐induced HPMVECs apoptosis.
Long noncoding RNA ATB participates in the development of renal cell carcinoma by downregulating p53 via binding to DNMT1
Authors: Song Chao , Xiong Yunhe , Liao Wenbiao , Meng Lingchao , Yang Sixing
Published: December 2018

Long noncoding RNA (lncRNA) exerts an essential role in the pathological processes of many diseases. Our previous study found that lncRNA ATB was highly expressed in renal cell carcinoma (RCC). Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), and migration‐related assays were conducted to access the regulatory effects of lncRNA ATB on proliferative and migratory capacities of RCC cells. Flow cytometry was carried out to determine cell cycle and apoptosis influenced by lncRNA ATB. The interaction among lncRNA ATB, DNMT1, and p53 was evaluated through RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses. The results showed that lncRNA ATB knockdown in RCC cell line ACHN inhibited proliferative and migratory capacities and promoted apoptosis. Meanwhile, overexpression of lncRNA ATB in RCC cell line A‐498 promoted proliferative and migratory capacities but inhibited apoptosis. RIP and ChIP assays confirmed that lncRNA ATB can bind to DNMT1 and stabilize its expression; meanwhile, it can promote the binding of DNMT1 to p53. Overexpression of p53 partially reversed the proliferative and migratory changes caused by lncRNA ATB. To sum up, our study revealed that high expression of lncRNA ATB could accelerate the proliferative and migratory rates of RCC cells and inhibit cell apoptosis through downregulating p53 via binding to DNMT1.
Effect of experimentally induced hypertension on cerebellum of postmenopausal rat
Authors: El‐Tahawy Nashwa Fathy Gamal , Abdel Hafez Sara Mohamed Naguib , Ramzy Maggie M , Zenhom Nagwa M. , Abdel‐Hamid Heba A.
Published: December 2018

Cerebellum seems to be a specific target for both the decrease of estrogen and hypertension in menopause. The aim of this study was to investigate the hypertension and menopause‐induced changes in rat’s cerebellar cortex and the possible mechanisms of these changes. Rats were divided into four groups: the sham‐operated control (SC‐group), the ovariectomized (OVX‐group), the hypertensive (H‐group), and the ovariectomized‐hypertensive (OVX‐H‐group) group. The mean arterial pressure (MAP), serum nitric oxide (NO), lipid peroxides and antioxidant catalase enzyme levels were assayed. Cerebellar tissue homogenization for analysis of lipid peroxides, antioxidant catalase enzyme, tumor necrosis factor‐α (TNF‐α), and estradiol was done. Quantification of adrenomedullin (AM) and interleukin‐10 (IL‐10) mRNA was also done. Cerebella were processed for histological, immunohistochemical and transmission electron microscopic examination. In the OVX‐group, insignificant structural and biochemical changes were observed compared with the SC‐group apart from the significantly increased lipid peroxides and decreased NO and catalase levels in serum. The H‐group showed an elevated lipid peroxides and TNF‐α levels, reduced catalase level, numerous degenerated Purkinje cells, vacuolations of the neuropil, some axonal degeneration, and few ghosts in the granular cell layer (GL). However, in OVX‐H‐group, oxidative stress, inflammation, and cerebellar damage were exacerbated and cerebellar estrogen was reduced associated with reduction in GL thickness and decreased Purkinje cells number. Most axoplasms had degenerated neurofilaments with abnormal myelination. The immunoexpression of glial fibrillary acidic protein were significantly increased in both OVX‐group and H‐group and significantly decreased in OVX‐H group. Gene expression of AM and IL‐10 were increased in cerebellar tissues of H‐group compared with the SC‐group but it was significantly decreased in OVX‐H‐group compared with H‐group. Taken together, postmenopausal rats with hypertension suffered from structural cerebellar changes than rats with only hypertension or estrogen deficiency separately due to augmentation of the increased oxidative stress markers and the proinflammatory cytokines (TNF‐α) with down regulation of the anti‐inflammatory cytokine (IL‐10) and the blood pressure regulator, AM. These suggested that high blood pressure is a critical factor for postmenopausal cerebellum.
Long noncoding RNA Breast cancer antiestrogen resistance 4 is associated with cancer progression and its significant prognostic value
Authors: Zhao Wenqiu , Wang Zhenlin , Fang Xiao , Li Na , Fang Jian
Published: December 2018

Breast cancer antiestrogen resistance 4 (BCAR4) is a novel long noncoding RNA. It was originally identified in a screen for genes responsible for the development of resistance to antiestrogens in breast cancer cells and plays a major role in various tumors. However, the clinical diagnostic role of BCAR4 in tumors is not completely understood. This current meta‐analysis aimed to comprehensively explore the potential role of BCAR4 as a prognostic biomarker in a number of cancers. Five public databases PubMed, EMBASE, Web of Science, Wiley Online Library, and Medline were used to search for articles. Nine studies comprising 1,293 patients were included in this meta‐analysis. The results of analysis showed that BCAR4 expression in human cancer was significantly associated with poor overall survival (hazard ratio [HR] = 1.98, confidence interval [CI]: [1.71–2.29]), p < 0.00001, and high BCAR4 expression was associated with clinical stage (OR and its 95% CI was 3.30 [1.99–5.46], p < 0.00001), distant metastasis (OR = 3.83, 95% CI: 2.15–6.82, p < 0.00001), and lymph node metastasis (OR and its 95% CI was 2.91 [1.62–5.25], p = 0.0004) in patients with cancer. Furthermore, the results revealed the prognostic significance of BCAR4 in gastrointestinal malignancy, breast cancer, and osteosarcoma (HR and its 95% CI were 2.05 [1.56–2.68], p < 0.00001; 1.78 [1.46–2.16], p < 0.00001; and 2.47 [1.41–4.34], p < 0.00001, respectively). This meta‐analysis indicated the potential value of BCAR4 as a biomarker for predicting a poor prognosis in patients with cancer.
Calcitonin administration improves endometrial receptivity via regulation of LIF, Muc‐1 and microRNA Let‐7a in mice
Authors: Shokrzadeh Naser , Alivand Mohammad Reza , Abedelahi Ali , Hessam Shariati Mohammad B. , Niknafs Behrooz
Published: December 2018

Calcitonin (CT) is one of the factors affecting the embryo implantation, but its effects on the implantation window have not been fully investigated. The current study investigated the effects of CT on the endometrium receptivity by morphological study and evaluation of leukemia inhibitory factor (LIF), mucin 1 (Muc‐1), and microRNA (miRNA) Let‐7a in the ovarian stimulation and the normal ovarian cycle. Then the mechanism of the CT effects through the mammalian target of rapamycin (mTOR) signaling pathway was studied by using PP242. A total of 64 BALB/c mice were divided into the normal ovarian cycle and ovarian stimulation groups. Each group consisted of four subgroups: control, calcitonin, PP242, and calcitonin+PP242. CT and PP242 were injected on the fourth of pregnancy into the mice and 24 hr later all the mice were killed. The uterine tissue samples were used for morphological analysis, and endometrial cells were mechanically isolated for evaluation of gene and protein expression. The results showed that ovarian stimulation induced mTOR phosphorylation as well as increased expression of the Let‐7a miRNA. In addition, CT injection increased the expression of LIF and miRNA Let‐7a in ovarian stimulation similar to that in normal ovarian cycles. However, injection of PP242 reduced expression of miRNA Let‐7a and increased Muc‐1 expression in ovarian stimulation group. In conclusion, the administration of CT improved endometrial receptivity in mice. This phenomenon occurred by upregulation of LIF, miRNA Let‐7a and downregulation of Muc‐1 via mTOR signaling pathway.
High expression of LASS2 is associated with unfavorable prognosis in patients with ovarian cancer
Authors: Sheng Ning , Wang Yanyan , Xie Ying , Chen Sihan , Lu Jun , Zhang Zifeng , Li Mengqiu , Shan Qun , Wu Dongmei , Zheng Guihong , Zheng Yuanlin , Fan Shaohua
Published: December 2018

Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), is a gene isolated from a human liver complementary DNA library. In this study, we found that LASS2 protein level was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage and LASS2‐negative tumors showed significant association with longer disease‐free survival (DFS) and overall survival (OS) in ovarian cancer patients. The heterogeneous expression of LASS2 had been exhibited in diverse ovarian cancer cells. A significantly lower messenger RNA (mRNA) and protein level of LASS2 was seen in 3AO cell compared with those in other types of ovarian cancer cells. Meanwhile, the mRNA and protein levels of LASS2 in ES‐2 and NIH:OVCAR‐3 cells were obviously higher. LASS2 overexpression in 3AO cell could promote migration, invasion, and metastasis abilities in vitro and in vivo, while LASS2 knockdown in ES‐2 and NIH:OVCAR‐3 cells had the opposite effects. The oncogenic capacity of LASS2 in ovarian cancer may be mediated by increased expression of YAP/TAZ. It is indicated that lowering the expression of LASS2 is likely to serve as an unprecedented approach for the treatment of ovarian cancer.
Transvaginal ultrasound training for the obstetrics and gynecology resident: A multisite randomized controlled trial of educational DVD
Authors: McCurdy Rebekah J. , High Brooke , Schnatz Peter F. , Baxter Jason , Jiang Xuezhi
Published: December 2018

Purpose

Residents in obstetrics and gynecology are deemed to be proficient in transvaginal ultrasound (TVUS) upon graduation, although TVUS education in residency is not standardized. The objective of this study is to assess for improvement in TVUS knowledge among residents after viewing an educational DVD.

Methods

This is a multisite prospective randomized controlled trial using an educational DVD (“Gynecology: Beginners Only”), compared to routine education. All participants completed a pretest on TVUS images and principles. The intervention group repeated the test after DVD viewing. During the trial, performing and logging TVUS examinations were encouraged. All enrolled residents repeated the test 6–10 months later.

Results

Fifty‐seven residents completed the study with a mean pretest score of 9.7 (1st year resident 9.8, 2nd year resident 9.6, 3rd year resident 10.1, 4th year resident 9.4, P = .763), with a mean of 31.5 TVUS examinations logged prior to intervention. The mean score in the intervention group (n = 34) improved significantly after viewing (11.2, P < 0.003). This improvement did not persist 6‐10 months later on a follow‐up quiz (mean 10.7, P = .894). At completion of the study, participants logged an average of 56.7 TVUS examinations.

Conclusion

An educational DVD is easily implemented and demonstrates short‐term benefit. Exploration of different teaching modalities in development of a comprehensive training program may improve long‐term retention.
Cross‐infection control in clinical training: Development of a device for storing a composite resin in restorative dentistry
Authors: de Oliveira Ana Luísa Botta Martins , Wajngarten Danielle , Presoto Cristina Dupim , de Oliveira Barud Hélida Gomes , Domeneguetti Rafael Romano , Botta Ana Carolina , Garcia Patricia Petromilli Nordi Sasso
Published: December 2018

This study presented a biosafety device for the hygienic storage of composite resin during restorative procedures in teaching clinics, RESTAURASAFE, and to compare the color stability, surface hardness, and degree of conversion of the composite resin made with the proposed device to those of conventionally made resins. Esthet‐X HD composite was manipulated directly from the syringe, fractionated doses, dappen dish or RESTAURASAFE. Disc‐shaped specimens were immersed in artificial saliva and coffee for 60 days and the color stability and the Vickers surface hardness were evaluated during 60 days. Degree of conversion was assessed after immersing specimens in saliva (baseline). The surface morphology analysis of composite resin has taken by scanning electron microscopy (SEM). The data were evaluated statistically by repeated measures ANOVA (α=.05). No difference of color stability was observed for saliva and coffee regardless of storing devices. The resin manipulated directly from the syringe presented lower hardness, and fractionated doses presented lower degree of conversion than the RESTAURASAFE. SEM analysis showed that after artificial aging in coffee for 60 days, the specimens prepared with fractionated doses of resin displayed the fewest changes in surface morphology, followed by those prepared with the RESTAURASAFE. We conclude that RESTAURASAFE allows to obtain similar color stability, higher hardness, and degree of conversion of the composite in comparison to the other storing devices.
A case of ultrashort‐acting beta‐blocker landiolol hydrochloride for takotsubo syndrome with left ventricular outflow tract obstruction
Authors: Takama Takuro , Fukue Mitsunori , Sato Hiroyuki , Taniuchi Masato
Published: December 2018

Takotsubo syndrome (TTS) has been known to have a favorable prognosis. Beta‐blockers are reported to be effective for TTS patients with cardiogenic heart failure due to left ventricular outflow tract (LVOT) obstruction. However, there is no report on ultrashort‐acting beta‐blockers being used for treating TTS, and there are no clear guidelines for their dosages or applications. Herein, we describe a 72‐year‐old woman in whom landiolol hydrochloride was used in the acute phase of TTS with LVOT obstruction. In this case, the dose of landiolol hydrochloride was increased to 10 μg/kg/min, resulting in improvement of LVOT obstruction, which led to hemodynamic stabilization.
Compositional elucidation of heavy petroleum base oil by GC × GC‐EI/PI/CI/FI‐TOFMS
Authors: Giri Anupam , Coutriade Marion , Racaud Amandine , Stefanuto Pierre‐Hugues , Okuda Koji , Dane John , Cody Robert B. , Focant Jean‐François
Published: December 2018

Comprehensive two‐dimensional gas chromatography (GC × GC) coupled to time‐of‐flight mass spectrometry is a powerful separation tool for complex petroleum product analysis. However, the most commonly used electron ionization (EI) technique often makes the identification of the majority of hydrocarbons impossible due to the exhaustive fragmentation and lack of molecular ion preservation, prompting the need of soft‐ionization energies. In this study, three different soft‐ionization techniques including photo ionization (PI), chemical ionization (CI), and field ionization (FI) were compared against EI to elucidate their relative capabilities to reveal different base oil hydrocarbon classes. Compared with EI (70 eV), PI (10.8 eV) retained significant molecular ion (M+·) information for a large number of isomeric species including branched‐alkanes and saturated monocyclic hydrocarbons along with unique fragmentation patterns. However, for bicyclic/polycyclic naphthenic and aromatic compounds, EI played upper hand by retaining molecular as well as fragment ions to identify the species, whereas PI exhibited mainly molecular ion signals. On the other hand, CI revealed selectivity towards different base oil groups, particularly for steranes, sulfur‐containing thiophenes, and esters, yielding protonated molecular ions (M + H)+ for unsaturated and hydride abstracted ions (M‐H+) for saturated hydrocarbons. FI, as expected, generated intact molecular ions (M+·) irrespective to the base oil chemical classes. It allowed elemental composition by TOFMS with a mass resolving power up to 8000 (FWHM) and a mass accuracy of 1 mDa, leading to the calculation of heteroatomic content, double bond equivalency, and carbon number of the compounds. The qualitative and quantitative results presented herein offer a unique perspective into the detailed comparison of different ionization techniques corresponding to several hydrocarbon classes.
Study of dry‐ and wet‐process amorphous arsenic sulfides: Synthesis, Raman reference spectra, and identification in historical art materials
Authors: Vermeulen Marc , Palka Karel , Vlček Miroslav , Sanyova Jana
Published: December 2018

This paper reports the dry and wet synthetic procedures and characterization by Raman spectroscopy of amorphous arsenic sulfide reference pigments. Reference spectra of two amorphous materials obtained by wet process methods and four dry process references of amorphous arsenic sulfide pigments of known composition are presented and discussed.

While all materials present a main band characteristic for the amorphous pigment centered on 341 cm−1, additional small contributions indicate the presence of sulfur, arsenic oxide, and crystalline nano phases embedded in the amorphous matrix. Although only the broad 341‐cm−1 peak is necessary to identify the arsenic sulfide as an amorphous material, the smaller additional features allow for the characterization of the various manufacturing processes and initial materials used. In ideal conditions, these small features also enable to assess the As/S ratio of the studied amorphous arsenic sulfide pigments based on their relative intensity. In this context, the latter reference spectra were used to characterize the amorphous arsenic sulfide pigments and their arsenic to sulfur elemental composition in four 18th‐ to 20th‐century historical samples and compared with scanning electron microscopy with energy dispersive X‐ray semiquantitative analyses. The identification of the amorphous arsenic sulfide used in these historical samples was compared with the description of the manufacturing processes reported in historical sources of the time, allowing for a better understanding of the evolution of the amorphous arsenic sulfide pigments manufacturing methods.
Arachnoid cysts of the internal auditory canal: An underappreciated entity?
Authors: Ungar Omer J. , Franck Madeline , Nadol Joseph B. , Santos Felipe
Published: December 2018

Objectives/Hypothesis

To describe the histopathologic findings and clinical presentation of arachnoid cysts (ACs) within the human temporal bone.

Study Design

Retrospective cohort analysis.

Methods

An analysis of all medical records of patients diagnosed with an AC was performed. Temporal bones underwent standard processing for histologic examination. The slides were examined by light microscopy. The histologic findings were compared to premortem clinical data.

Results

Twenty‐seven ACs were identified in 22 patients. Twenty ears (74%) had no identified risk factor for AC development. The median volume was 12.8 mm3. The most prevalent location of the ACs was at the fundus (16 ACs) followed by the middle portion of the internal auditory canal (IAC) (six ACs). Nine ACs were asymptomatic. Among the 18 symptomatic ACs, the most common presentation was sensorineural hearing loss (SNHL) (94%), followed by tinnitus (22%). The most affected structure was the cochlear nerve (59%), followed by the vestibular nerve (41%). The average hearing threshold was of moderately severe SNHL and speech discrimination was in the range of 50% on monosyllabic word tests. The median time interval from initial presentation to death was 12 years. No correlation was found between duration of symptoms and AC volume.

Conclusions

AC of the IAC is not uncommon. Its presentation is variable, ranging from asymptomatic to SNHL, with poor speech discrimination, tinnitus, and vertigo. This diagnosis should be kept in the differential diagnosis of retrocochlear pathologies.

Level of Evidence

4

Laryngoscope, 129:1667–1674, 2019
Risk Factors for Multiple Hemorrhages Following Tonsil Surgery in Children
Authors: McKeon Mallory , Kirsh Elliana , Kawai Kosuke , Roberson David , Watters Karen
Published: December 2018

Objectives/Hypothesis

Although much is known about the incidence and risk factors for hemorrhage after tonsil surgery, the incidence and factors related to multiple episodes of hemorrhage are not well examined. Our objective was to identify risk factors that may contribute to multiple hemorrhages following tonsil surgery in children.

Study Design

Retrospective chart review.

Methods

A retrospective review was conducted of pediatric patients who experienced one or more hemorrhages following tonsillectomy/tonsillotomy, with or without adenoidectomy, between 2010 and 2016 at a single, tertiary‐care hospital. Risk factors for multiple hemorrhages were examined using a multivariable logistic regression model.

Results

Among the 11,140 patients who underwent tonsil surgery, 452 patients experienced one or more hemorrhages; 32 of these had multiple episodes of hemorrhage (7.1% of all patients with bleeds/0.3% of all patients). Older age (≥12 years: adjusted odds ratio [OR]: 3.13; 95% confidence interval [CI]: 1.47‐6.68) and high body mass index for age (≥85th percentile: adjusted OR: 2.26; 95% CI: 1.06‐4.85) were significantly associated with an increased risk of multiple hemorrhages in the multivariable model. Medical comorbidities, indications for surgery, surgical technique, intraoperative blood loss, and perioperative medications were not associated with multiple episodes of bleeding.

Conclusions

Multiple hemorrhages after tonsillectomy/tonsillotomy are uncommon. The risk of a second PTH after an initial episode is 7.1%, almost double the risk of a bleed after the initial tonsil surgery. Age > 12 years and high BMI for age may be associated with increased risk of rebleeding. After an initial bleed, increased surveillance may be warranted, particularly for patients with risk factors.

Level of Evidence

4 Laryngoscope, 129:2765–2770, 2019
Living Donor Liver Transplantation for Acute‐on‐Chronic Liver Failure
Authors: Yadav Sanjay Kumar , Saraf Neeraj , Choudhary Narendra S. , Sah Jayant Kumar , Sah Sujeet Kumar , Rastogi Amit , Bhangui Prashant , Saigal Sanjiv , Soin Arvinder Singh
Published: December 2018

Acute‐on‐chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of previously diagnosed or undiagnosed liver disease with organ failure(s) with high short‐term mortality. This study was conducted to report the outcomes of living donor liver transplantation (LDLT) in ACLF and assess the survival benefit of liver transplantation (LT) in these patients. It was a retrospective study of 218 ACLF patients on the basis of European Association for the Study of the Liver (EASL)–chronic liver failure criteria from January 2014 through November 2017. Patients were considered for LDLT if there was no improvement on standard medical therapy for 5‐10 days. Prior to LDLT, active sepsis was excluded/treated, and renal, circulatory, and respiratory failures were improved to the greatest extent possible. The mean age was 42.9 years, and 181 patients were male. Sepsis was the most common acute precipitating event followed by alcohol. Of the patients, 35 (16.1%), 66 (30.3%), and 117 (53.7%) were classified into ACLF grades 1, 2, and 3, respectively. Although 80% of the ACLF 1 group and 72.7% of the ACLF 2 group underwent LDLT, only 35% of the ACLF 3 group could undergo LDLT. The circulatory and respiratory failures at admission were significantly higher in the nontransplant group with poor subsequent response to standard medical therapy, exclusion from LDLT, and poor outcomes. None of the patients on high support for circulatory and respiratory failure underwent LDLT. Posttransplant survival at 1 year was comparable among different grades of ACLF (92.9%, 85.4%, and 75.6%; P = 0.15). Among patients in the ACLF 3 group, survival at 90 days was extremely poor in those who could not undergo LDLT (5.9% versus 78%; P < 0.001). In conclusion, LDLT results in good survival with acceptable post‐LT morbidity in patients with ACLF.
Isomorphisms of spaces with large distortion
Authors: Medina Galego Elói , Porto da Silva André Luis
Published: December 2018

Let K and S be locally compact Hausdorff spaces and let X be a strictly convex Banach space of finite dimension at least 2. In this paper, we prove that if there exists an isomorphism T from onto satisfying
urn:x-wiley:0025584X:media:mana201800038:mana201800038-math-0007then K and S are homeomorphic. Here denotes the Schäffer constant of X. Even for the classical cases , and , this result is the X‐valued Banach–Stone theorem via isomorphism with the largest distortion that is known so far, namely . On the other hand, it is well known that this result is not true for , even though K and S are compact Hausdorff spaces.