bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractDimethyl 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

AbstractType 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

AbstractProstate 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

AbstractDiabetic 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

AbstractThe 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

AbstractLong 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

AbstractCerebellum 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

AbstractBreast 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

AbstractCalcitonin (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

AbstractHomo 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

AbstractPurposeResidents 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.MethodsThis 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.ResultsFifty‐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.ConclusionAn 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

AbstractThis 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

AbstractTakotsubo 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.