bluuebunny/crossref_metadata_2025_split huggingface dataset:
One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study
Authors: Lewiecki E Michael , Dinavahi Rajani V , Lazaretti-Castro Marise , Ebeling Peter R , Adachi Jonathan D , Miyauchi Akimitsu , Gielen Evelien , Milmont Cassandra E , Libanati Cesar , Grauer Andreas 
Published: December 2018

ABSTRACT

Romosozumab, a humanized monoclonal antibody that binds and inhibits sclerostin, has the dual effect of increasing bone formation and decreasing bone resorption. As previously reported in the pivotal FRActure study in postmenopausal woMen with ostEoporosis (FRAME), women with a T-score of ≤ –2.5 at the total hip or femoral neck received subcutaneous placebo or romosozumab once monthly for 12 months, followed by open-label subcutaneous denosumab every 6 months for an additional 12 months. Upon completion of the 24-month primary analysis period, eligible women entered the extension phase and received denosumab for an additional 12 months. Here, we report the final analysis results through 36 months, including efficacy assessments of new vertebral, clinical, and nonvertebral fracture; bone mineral density (BMD); and safety assessments. Of 7180 women enrolled, 5743 (80%) completed the 36-month study (2851 romosozumab-to-denosumab; 2892 placebo-to-denosumab). Through 36 months, fracture risk was reduced in subjects receiving romosozumab versus placebo for 12 months followed by 24 months of denosumab for both groups: new vertebral fracture (relative risk reduction [RRR], 66%; incidence, 1.0% versus 2.8%; p &lt; 0.001), clinical fracture (RRR, 27%; incidence, 4.0% versus 5.5%; p = 0.004), and nonvertebral fracture (RRR, 21%; incidence, 3.9% versus 4.9%; p = 0.039). BMD continued to increase for the 2 years with denosumab treatment in both arms. The substantial difference in BMD achieved through 12 months of romosozumab treatment versus placebo was maintained through the follow-up period when both treatment arms received denosumab. Subject incidence of adverse events, including positively adjudicated serious cardiovascular adverse events, were overall balanced between groups. In conclusion, in postmenopausal women with osteoporosis, 12 months of romosozumab led to persistent fracture reduction benefit and ongoing BMD gains when followed by 24 months of denosumab. The sequence of romosozumab followed by denosumab may be a promising regimen for the treatment of osteoporosis. © 2018 American Society for Bone and Mineral Research.
Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis
Authors: Zhu Mo , Yu Binqin , Bai Jiaxiang , Wang Ximing , Guo Xiaobin , Liu Yu , Lin Jiayi , Hu Su , Zhang Wen , Tao Yunxia , Hu Chunhong , Yang Huilin , Xu Yaozeng , Geng Dechun 
Published: December 2018

ABSTRACT

Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the noninflamed synovium and bone tissues. The CB2 selective agonist (JWH133) but not antagonist (SR144528) suppressed CIA in mice without toxic effects, as demonstrated by the decreased synovial hyperplasia, inflammatory responses, cartilage damage, and periarticular and systemic bone destruction. JWH133 treatment decreased the infiltration of pro-inflammatory M1-like macrophages and repolarized macrophages from the M1 to M2 phenotype. Similarly, activation of CB2 increased the expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-1β, and IL-6. In addition, JWH133 treatment attenuated osteoclast formation and osteoclastic bone resorption, and reduced the expression of receptor activators of the nuclear factor-κB (NF-κB) ligand (RANKL), matrix metallopeptidase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and nuclear factor of activated T-cells 1 (NFAT-1) in CIA mice and osteoclast precursors, which were obviously blocked by pretreatment with SR144528. Mechanistically, JWH133 inhibited RANKL-induced NF-κB activation in the osteoclast precursors. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis. © 2018 American Society for Bone and Mineral Research.
Altered levels of focal adhesion and extracellular matrix‐receptor interacting proteins were identified in Hailey‐Hailey disease by quantitative iTRAQ proteome analysis
Authors: Zhang Dingwei , Huo Jia , Li Ruilian , Zhang Yanfei , Wang Zhenghui , Li Xiaoli 
Published: December 2018

AbstractBenign chronic familial pemphigus or Hailey‐Hailey disease (HHD, OMIM 169600) is a rare, autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. To date, the proteomic changes in skin lesions from HHD patients has not been reported yet. In this study, a sample of skin lesions from HHD patients was collected for isobaric tags for relative and absolute quantitation to analyze proteome changes compared with unaffected individuals. The 134 differentially expressed proteins were assigned to at least one Gene Ontology term, and 123 annotated proteins with significant matches were assigned to 187 known metabolic or signaling pathways listed in the Kyoto Encyclopedia of Genes and Genomes. Most of the altered proteins in skin lesions of HHD patients were enriched in pathways involved in the PI3K‐Akt signaling, focal adhesion, extracellular matrix (ECM)‐receptor interaction, and protein digestion and absorption, such as collagen family members, microfibril‐associated glycoprotein 4 and plakophilin. The changes of proteins related to cell adhesion, ECM‐receptor interaction, and protein folding and glycosylation suggested that strategy targeted to alter cell junction and extracellular microenvironment might provide a potential treatment for HHD.
Geraniol and lupeol inhibit growth and promote apoptosis in human hepatocarcinoma cells through the MAPK signaling pathway
Authors: Shen Xionghu , Cui Xian , Cui Hai , Jin Yongmin , Jin Wenbiao , Sun Honghua 
Published: December 2018

AbstractObjectivesHepatocarcinoma is one of the most lethal cancers, leading to a 5‐year survival rate as low as 30% due to recurrence and metastasis. The treatment of liver cancer includes surgery and medication, of which, the former is more effective. However, surgical resection is applicable in less than 40% of patients. Therefore, it is imperative to find effective medication options for liver cancer therapy.MethodsIn this study, we found that two natural products, geraniol and lupeol, had antiproliferative and proapoptotic effects on the hepatocarcinoma cell lines SMMC7721 and HepG2. We also detected a lower expression level of Bcl‐2 and upregulation of BAX and caspase in the presence of geraniol and lupeol.ResultsFurthermore, geraniol or lupeol also altered the phosphorylation level of extracellular signal‐regulated protein kinase, P38, and c‐Jun NH2‐terminal kinases, suggesting involvement in mitogen‐activated protein kinase signaling.ConclusionsThis study provided direct evidence to support the effect of geraniol and lupeol in hepatocarcinoma cell growth and apoptosis, which indicated the potential application of these two natural products in anti–liver cancer therapy.
Microarray profiling analysis identifies the mechanism of miR‐200b‐3p/mRNA‐CD36 affecting diabetic cardiomyopathy via peroxisome proliferator activated receptor‐γ signaling pathway
Authors: Xu Liqiong , Chen Wei , Ma Min , Chen Anfang , Tang Chengyue , Zhang Chengwei , Cai Lin 
Published: December 2018

AbstractObjectiveCurrent study focused on the influence of miR‐200b‐3p on cardiocyte apoptosis of diabetic cardiomyopathy (DCM) by regulating CD36 and peroxisome proliferator‐activated receptor γ (PPAR‐γ) signaling pathway.MethodsBioinformatic analysis was used to analyze differentially expressed microRNA (miRNAs), messenger RNAs (mRNAs) and activated pathways in DCM. And then quantitative real‐time polymerase chain reaction (qRT‐PCR) was conducted to verify expression of miR‐200b‐3p and CD36 in DCM model rats and glucose treated H9c2 cell line. Luciferase reporter assay was used to verify the transcriptional regulation of agomiR‐200b‐3p and investigate the relationship between miR‐200b‐3p and CD36. Flow cytometry was performed to assess cardiocyte apoptosis in different interference conditions. Echocardiography was used to illustrate the ejection fraction rate and fraction shortening rate of DCM model rats. Next, hematoxylin‐eosin (H&E) staining assay was carried out to reveal structures of cardiocyte tissues with transfection in different conditions. Masson trichrome staining was used to evaluate myocardial fibrosis. Western blot analysis was used to detect the expression levels of PPAR‐γ signaling‐related protein PPAR‐γ and Bcl‐2.ResultsmiR‐200b‐3p was low‐expressed while CD36 was overexpressed in DCM. AgomiR‐200b‐3p could inhibit the expression of CD36 to regulate cardiocyte apoptosis in DCM. CD36 activated PPAR‐γ signaling pathway in DCM. Silencing CD36 or GW9662 treatment protect rat against DCM.ConclusionmiR‐200b‐3p targeted CD36 to regulate cardiocyte apoptosis of DCM by activating PPAR‐γ signaling pathway.
Application of iTRAQ proteomics in identification of the differentially expressed proteins of placenta of pregnancy with preeclampsia
Authors: Feng Yaling , He Yue , Wang Jianxia , Yuan Hua , Zou Jinfang , Yang Lan , Xu Jianjuan 
Published: December 2018

AbstractObjectiveTo explore the differential protein profile of preeclampsia and identify its potential biomarker.MethodsAround 20 pregnant women with preeclampsia (preeclampsia group) and 20 normal‐term pregnancy (normal group) were collected from 2017 to 2018 in the study. Total protein of placenta tissues was extracted, denaturized, deoxidized, and enzymolyzed. The sample was labeled with isobaric tags for relative and absolute quantitation (iTRAQ) and analyzed with mass spectrum to identify differentially expressed proteins.ResultsThere were 37 proteins, which were differentially expressed with significance (P < 0.05). Among them, 17 proteins were upregulated and 20 proteins were downregulated with significance in the placenta of preeclampsia group compared with control group, those proteins may have an induction or protection function during the development of preeclampsia.ConclusioniTRAQ technology can effectively screen the differentially expressed proteins in the placenta, which can effectively diagnose the preeclampsia during pregnancy.
Overexpression of microRNA‐98 inhibits cell proliferation and promotes cell apoptosis via claudin‐1 in human colorectal carcinoma
Authors: Zheng Yi‐Feng , Luo Jie , Gan Guo‐Lian , Li Wei 
Published: December 2018

AbstractColorectal carcinoma (CRC) is a major cause of cancer‐related deaths worldwide, and investigations on novel targets are imperative. MiR‐98 has been reported to act as a tumor suppressor in several cancers. To evaluate miR‐98 as a novel anticancer molecule for CRC, examinations to validate whether miR‐98 conferred an inhibiting effect on proliferation, migration, and invasion were performed. The microarray‐based gene expression profiling involving CRC was used to identify the differentially expressed genes. The potential relationship between miR‐98 and CLDN1 was analyzed by cell experimentation. Then, the CRC cells were transfected with miR‐98 mimic or miR‐98 inhibitor to investigate the potential effect of miR‐98 overexpression and depletion on CRC cell proliferation, migration, invasion, and apoptosis. The expressions of CLDN1, Bcl‐2 associated protein x (Bax), runt‐related transcription factor 3 (RUNX3), B‐cell lymphoma 2 (Bcl‐2), C‐myc, and proliferating cell nuclear antigen (PCNA) were determined. The downregulated miR‐98 along with an upregulated CLDN1 was observed in CRC, in which miR‐98 could target to regulate CLDN1. The overexpression of miR‐98 or silencing of CLDN1 was shown to increase the expression of Bax and RUNX3 along with promoted cell apoptosis and arrested cells in G1 phase, while decreasing the expression of CLDN1, Bcl‐2, C‐myc, and PCNA with suppressed proliferation, migration, and invasion. Collectively, the current study supports the notion that miR‐98 plays an inhibitory role in human CRC cell proliferation, migration, and invasion and act as a contributor for cell apoptosis by downregulating CLDN1. The current study highlights a potential future strategy to help prevent the development of CRC.
Circular RNA hsa_circ_0076248 promotes oncogenesis of glioma by sponging miR‐181a to modulate SIRT1 expression
Authors: Lei Bingxi , Huang Yutao , Zhou Zhiwei , Zhao Yiying , Thapa Ashish Jung , Li Wenpeng , Cai Wangqing , Deng Yuefei 
Published: December 2018

AbstractGlioma is one of the most common primary malignancies of the central nervous system, which has aggressive clinical behavior and a poorer prognosis. MicroRNAs (miRs) are a class of small noncoding RNAs that function as mediators of gene expression, which can be sponged by circRNA provided with a closed circular structure. Dysregulations of circular RNAs (circRNAs) and miRs have been implicated in the development and progression of glioma. In the current study, we investigated the role of circular RNA hsa_circ_0076248 in mediating the oncogenesis of glioma by sponging miR‐181a to modulate silent information regulator 1 (SIRT1) expression in vitro and in vivo. The quantitative real‐time polymerase chain reaction results showed that the expression of miR‐181a was significantly decreased in glioma tissues and cell lines compared with normal brain tissues and normal gliocyte, respectively, and the expression of hsa_circ_0076248 and SIRT1 demonstrated the opposite. Bioinformatics analysis identified hsa_circ_0076248 could sponge miR‐181a, and miR‐181a could target the mRNA of SIRT1. Our results verified that downregulating hsa_circ_0076248 or upregulating miR‐181a could depress the proliferation and invasion of glioma in vitro and in vivo. The experiment also showed that downregulating hsa_circ_0076248 or upregulating miR‐181a could remarkably promote the temozolomide chemotherapy sensitivity. Furthermore, Western blot analysis testified that downregulating hsa_circ_0076248 or upregulating miR‐181a could promote the expression of p53 and SIRT1. In summary, our study sheds light on the regulatory mechanism of hsa_circ_0076248 in glioma growth and invasion via sponging miR‐181a, which downregulates the SIRT1 expression and also suggests that hsa_circ_0076248, miR‐181a, and SIRT1 may serve as potential therapeutic targets for glioma.
Finding a very rare mutation in non‐Caucasian LCAT patients from Southwest Asia for the first time
Authors: Oliaei Farshid , Batebi Behdokht , Tabaripour Reza , Akhavan Niaki Haleh 
Published: December 2018

AbstractIntroductionLecithin cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder occurred by different mutations in the LCAT gene that cause two extremely rare syndromes including familial LCAT deficiency (FLD) and fish‐eye disease (FED). Unlike FED in FLD renal failure is the most important defect due to deposition of abnormal lipoproteins in the renal stroma. In this study, FLD patients from the North of Iran were investigated for mutations in the LCAT gene.Materials and MethodsEight patients with corneal opacification and renal defect were analyzed for mutations in the LCAT gene by PCR sequencing.ResultsSequencing analysis revealed a missense pathogenic variation c.301 G>A in exon 2 of LCAT gene in all patients changing the amino acid aspartate to asparagine at the conserved position of amino acid 101 of LCAT protein.ConclusionIn this study, a very rare variation was reported for the first time in this part of the world. Investigation of a larger number of LCAT patients in different parts of Iran can provide availability of mutations panel that is useful for phenotype prediction and also prenatal diagnosis programming in families with a previous history of the disease.
MNX1‐AS1 is a novel biomarker for predicting clinical progression and poor prognosis in lung adenocarcinoma
Authors: Yang Ronghua , Wang Lei , Han Minghui 
Published: December 2018

AbstractMotor neuron and pancreas homeobox 1‐antisense RNA1 (MNX1‐AS1) is a novel long noncoding RNA and has been suggested to be overexpressed in human ovarian cancer and glioma. The role of MNX1‐AS1 in lung cancer was still unknown. In our study, we observed levels of MNX1‐AS1 expression through analyzing The Cancer Genome Atlas and found MNX1‐AS1 expression was highly expressed in lung adenocarcinoma tissues compared with normal lung tissues, but there was no statistical difference between lung squamous cell carcinoma tissues and normal lung tissues. Furthermore, we conducted quantitative real‐time polymerase chain reaction, and confirmed that the expression of MNX1‐AS1 was definitely higher in lung adenocarcinoma tissue samples, but not in lung squamous cell carcinoma tissue samples. In addition, high MNX1‐AS1 expression was found to be associated with the low differentiated degree, advanced clinical stage, big tumor size, lymph node metastasis, and distant metastasis in lung adenocarcinoma patients. High expression of MNX1‐AS1 was negatively correlated with overall survival time and served as an independent unfavorable prognostic factor in patients with lung adenocarcinoma. The in vitro functional studies suggested that suppression of MNX1‐AS1 inhibited lung adenocarcinoma cell proliferation and migration, and promoted apoptosis. In conclusion, MNX1‐AS1 is overexpressed in lung adenocarcinoma, and associated with clinical progression and poor prognosis.
RETRACTED: Cryptotanshinone inhibits RANKL‐induced osteoclastogenesis by regulating ERK and NF‐κB signaling pathways
Authors: Wang Weizhuo , Huang Mengdi , Hui Yigeng , Yuan Puwei , Guo Xiong , Wang Kunzheng 
Published: December 2018

AbstractOsteoporosis (OS) is one of the most common healthy problems characterized by low bone mass. Osteoclast, the primary bone‐resorbing cell, is responsible for destructive bone diseases including osteoporosis (OS). Cryptotanshinone (CTS), an active component extracted from the root of Salvia miltiorrhiza bunge, has been shown to prevent the destruction of cartilage and the thickening of subchondral bone in mice osteoarthritis models. However, its molecular mechanism in osteoclastogenesis needs to be determined. The aim of the current study was to explore the effect of CTS on osteoclastogenesis and further evaluate the underlying mechanism. Our results showed that CTS inhibited receptor activator of NF‐κB ligand (RANKL)‐induced the increase in tartrate‐resistant acid phosphatase (TRAP) activity in bone marrow–derived macrophages (BMMs). In addition, the expressions of osteoclastogenesis‐related marker proteins and nuclear factor of activated T‐cells (NFAT) activation were suppressed by CTS treatment in BMMs. Furthermore, CTS attenuated RANKL‐induced ERK phosphorylation and NF‐κB activation in BMMs. These findings indicated that CTS inhibited RANKL‐induced osteoclastogenesis by inhibiting ERK phosphorylation and NF‐κB activation in BMMs. Thus, CTS may function as an inhibitor of osteoclastogenesis and may be considered as an alternative medicine for the prevention and treatment of OS.
LINC00857 contributes to hepatocellular carcinoma malignancy via enhancing epithelial‐mesenchymal transition
Authors: Xia Chaofeng , Zhang Xiao‐Yu , Liu Wenhui , Ju Man , Ju Yingdong , Bu Yan‐Zhi , Wang Weixing , Shao Hongjin 
Published: December 2018

AbstractHepatocellular carcinoma (HCC) remains the fifth most frequent cancer with high mortality rate worldwide. However, the underlying molecular mechanisms of HCC progression are still barely known. Long noncoding RNAs (lncRNAs) have been recognized as significant therapeutic targets for HCC. Recently, the biological role of LINC00857 in several cancer types has been reported. Our present study was aimed to investigate the role of LINC00857 in HCC progression. We observed that LINC00857 was overexpressed in HCC cell lines (Huh7, Hep3B, HepG2, MHCC‐97H, and SNU449). Knockdown of LINC00857 significantly repressed Hep‐3B and SNU449 cell proliferation and inhibited the HCC cell colony formation. In addition, cell apoptosis was induced by the silence of LINC00857 and cell cycle progression was blocked in G1 phase. Besides these, downregulation of LINC00857 was able to restrain HCC cell migration and invasion capacity via enhancing epithelial‐mesenchymal transition (EMT) process. As displayed, E‐cadherin protein expression was increased by LINC00857 silence, while N‐cadherin protein level was repressed by LV‐shLINC00857 in HCC cells. Finally, the in vivo assays were used and the data indicated that LINC00857 could also obviously suppress the HCC tumor growth in vivo. In conclusion, our study revealed that LINC00857 might provide a novel perspective for the HCC treatment.
Prognostic evaluation of NANOG and OCT4 expression for posttransplantation hepatocellular carcinoma recurrence
Authors: Cai Wenjuan , Wang Zhenglu , Wei Chunfang , Wu Meng , Zheng Weiping , Zhang Haiming , Liu Chenghu , Liu Lei 
Published: December 2018

AbstractPostoperative hepatocellular carcinoma (HCC) recurrence and metastasis throw great threaten to its overall survival (OS). This paper focus on exploring the prognostic significance of NANOG and OCT4 expression in HCC recurrence and OS after liver transplantation. Eighty‐six patients who meet University of California San Francisco (UCSF) criteria and underwent liver transplantation in Tianjin First Central Hospital between August 2010 and August 2013 were included. Expression of NANOG and OCT4 was determined by immunohistochemistry. The relationships between NANOG and OCT4 expression with tumor recurrence, tumor count, histology stage, lymph node metastasis (LNM) and microvascular invasion (MVI) were explored through the χ2 test and Cox regression analysis. We found that 19/26 and 20/24 patients with positive expression of NANOG and OCT4 relapsed. Combination of NANOG and OCT4 expression was indicated as valuable prognostic signature for HCC recurrence prediction (P < 0.0011). Besides, we identified other key factors with significant correlations with recurrence, such as LNM (P = 0.011) and MVI (P = 0.024). Strikingly, recurrence sites could significantly affect recurrence time (P = 0.0062) and patients with recurrence in transplanted liver have longer recurrence time. In conclusions, we analyzed the relationships between NANOG/OCT4 expression, clinicopathology features, HCC recurrence, and OS after liver transplantation for the first time. Combination of NANOG, OCT4, LNM, histopathological stage, and MVI may be predictor for HCC recurrence posttransplantation. Comprehensive of histopathological stage grade and LNM were considered as prognosis factor for OS after liver transplantation. This should be helpful for treatment method selection for HCC patients after liver transplantation.