bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of m6A on FAM134B promotes adipogenesis in porcine adipocytes through m6A‐YTHDF2‐dependent way
Authors: Cai Min , Liu Qing , Jiang Qin , Wu Ruifan , Wang Xinxia , Wang Yizhen
Published: December 2018

N6‐methyladenosine (m6A) mRNA modification plays an important role in adipogenesis, but its role on single gene remains unexplored. Family with Sequence Similarity 134, Member B (FAM134B) is a cis‐Golgi transmembrane protein that known to be necessary for the long‐term survival of nociceptive and autonomic ganglion neurons. Recent work has shown that FAM134B plays a pivotal role in lipid homeostasis and was identified as its significant m6A level difference between Chinese local Jinhua pigs and Landrace through RNA‐sequence. Here, we construct the non‐m6A FAM134B coding sequence (CDS) plasmid (FAM134B‐MUT) and found one important m6A site on its CDS. Expression of FAM134B‐MUT was more effective in promoting porcine preadipocytes adipogenic differentiation and lipid deposition than wild‐type FAM134B (FAM134B‐WT) both in early and ultimate differentiation stage. FAM134B‐MUT functions better in promoting fat deposition by upregulating peroxisome proliferator‐activated receptor γ (PPARγ) and CCAAT/enhancer‐binding protein (C/EBPα) level. The m6A reader protein YTH m6A RNA binding protein 2 (YTHDF2) interacts with FAM134B mRNA and down regulated its protein level. These results demonstrate that FAM134B was the target of YTHDF2, which may recognize and binds the m6A site of FAM134B to reduce its mRNA lifetime and reduce its protein abundance. © 2018 IUBMB Life, 71(5):580–586, 2019
Vasculature reconstruction of decellularized liver scaffolds via gelatin‐based re‐endothelialization
Authors: Meng Fanwei , Almohanna Falah , Altuhami Abdullah , Assiri Abdallah M. , Broering Dieter
Published: December 2018

Decellularized liver scaffolds based liver engineering is a promising approach toward developing functional liver surrogates. However, a major obstacle to long‐term transplantation is the hemocompatibility of the bioengineered liver surrogates. One approach to improve the hemocompatibility of engineered liver surrogates is re‐endothelialization. In the current study, immortalized endothelial cells were perfused for re‐endothelialization of decellularized rat liver scaffolds. When compared to the media‐based perfusion approach, gelatin hydrogels‐based perfusion significantly increased the number of cells that were retained in the decellularized liver scaffolds and the vascular lumen coverage ratio. Endothelial cells were lining along the vasculatures of the decellularized liver scaffolds and actively proliferating. Re‐endothelialization improved the blood retention ability of the liver scaffold vasculatures. Doppler ultrasound detected active blood flows within the re‐endothelialized liver scaffold transplants 8 days post‐transplantation. Our results strengthened the feasibility of developing bioengineered liver surrogates utilizing decellularized liver scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 392–402, 2019.
Fabrication and characterization of the 3D‐printed polycaprolactone/fish bone extract scaffolds for bone tissue regeneration
Authors: Heo Seong‐Yeong , Ko Seok‐Chun , Oh Gun‐Woo , Kim Namwon , Choi Il‐Whan , Park Won Sun , Jung Won‐Kyo
Published: December 2018

Fish bone extract (FBE) containing a trioligopeptide (FBP‐KSA, Lys‐Ser‐Ala) isolated fromJohnius belengeriicould induce osteogenic activities on MC3T3‐E1 pre‐osteoblasts in our previous study. Regarding the osteogenic effect of FBE, in the present study, we fabricated the three‐dimensional (3D) interconnected polycaprolactone (PCL)/FBE scaffolds for bone tissue regeneration. After fabrication of PCL scaffolds using 3D printing, FBE was coated on the surface of PCL scaffolds by self‐assembly process. In the physical characteristic and mechanical property tests, the results demonstrated that the fabricated scaffolds have the strut diameter (between 340 and 345 μm), pore size (between 470 and 480 μm), porosity (between 50% and 55%), and tensile properties (Young's modulus: 9.18–9.42 MPa; max tensile strengths 82.3–87.4 MPa) were similar to those of PCL scaffold. In the cell proliferation and osteogenic assay, the results showed that PCL/FBE scaffolds could significantly induce cell proliferation, calcium deposition, and the expression of osteogenic phenotype markers such as alkaline phosphatase, osteopontin, osteocalcin, and bone morphogenetic protein‐2 in the osteoblasts. These results suggest that FBE‐coated PCL scaffolds are promising materials for use in biomedical application to promote bone tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1937–1944, 2019.
Bone as a Preferential Site for Metastasis
Authors: Sowder Miranda E , Johnson Rachelle W
Published: December 2018

Bone marrow provides a unique microenvironment favoring the colonization and outgrowth of metastatic tumor cells. Despite the high incidence of bone metastasis in breast and prostate cancer patients, many of the molecular mechanisms controlling metastatic progression remain unclear. Several gene signatures associated with bone metastasis have been reported, but no metastasis‐specific gene alterations have been identified. Therefore, there has been considerable interest in understanding how the bone microenvironment impacts the behavior of disseminated tumor cells (DTCs) prior to and following colonization of the bone. Substantial evidence indicates that disruption of normal bone homeostasis by tumor‐derived factors establishes a premetastatic niche within the bone that favors DTC colonization. Following dissemination, bone resident cells and the surrounding stroma provide critical signals that support tumor cell colonization, survival, and eventual outgrowth. Clinical data suggest that patients can harbor DTCs for years to decades prior to developing overt bone metastases, suggesting a period of tumor dormancy occurs in the bone marrow. Several dormancy‐promoting factors have been recently identified; however, critical questions surrounding the molecular triggers and timing of tumor cell emergence from dormancy remain. Here, we review how metastatic tumor cells co‐opt the bone marrow microenvironment for metastatic progression and discuss emerging insights into how to more effectively target DTCs and prevent metastasis. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research
Predictors of Imminent Risk of Nonvertebral Fracture in Older, High‐Risk Women: The Framingham Osteoporosis Study
Authors: Hannan Marian T , Weycker Derek , McLean Robert R , Sahni Shivani , Bornheimer Rebecca , Barron Richard , Travison Thomas G , Kiel Douglas P
Published: December 2018

Osteoporosis treatment decisions are often based solely on BMD or on 10‐year fracture risk; little is known about factors increasing imminent fracture risk. Understanding factors contributing to imminent risk of fracture is potentially useful for personalizing therapy, especially among those at high risk. Our aim was to identify predictors of nonvertebral fracture for 1‐ and 2‐year periods in women at high risk for fracture. The Framingham Osteoporosis Study cohort included 1470 women (contributing 2778 observations), aged ≥65 years with BMD hip T‐score ≤ −1.0, or history of fragility fracture (irrespective of T‐score). Nonvertebral fractures were ascertained prospectively over 1 year and 2 years following a baseline BMD scan. Potential risk factors included age, anthropometric variables, comorbidities/medical history, cognitive function, medications, history of fracture, self‐rated health, falls in the past year, smoking, physical performance, hip BMD T‐score, Activities of Daily Living (ADL) score, and caffeine and alcohol intakes. Predictive factors with p value ≤ 0.10 in bivariate Cox proportional hazards regression models were subsequently considered in multivariable models. Mean baseline age was 75 years (SD 6.0). During 1‐year follow‐up, 89 nonvertebral fractures occurred; during 2‐year follow‐up, 176 fractures occurred. Of the variables considered in the bivariate models, significant predictors of nonvertebral fractures included age, history of fracture, self‐rated health, falls in the prior year, BMD T‐score, ADL, renal disease, dementia, and current use of nitrates, beta‐blockers, calcium channel blockers, or antidepressants. In multivariable models, significant independent risk factors were history of fracture, self‐rated health, hip BMD T‐score, and use of nitrates. Significant 1‐year results were attenuated at the 2‐year follow‐up. In addition to the traditional factors of BMD and fracture history, self‐rated health and use of nitrates were independently associated with imminent risk of fracture in older, high‐risk women. These specific risk factors thus may be useful in identifying which women to target for therapy. ©2018 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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

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 < 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

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

Benign 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

Objectives

Hepatocarcinoma 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.

Methods

In 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.

Results

Furthermore, 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.

Conclusions

This 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

Objective

Current 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.

Methods

Bioinformatic 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.

Results

miR‐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.

Conclusion

miR‐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

Objective

To explore the differential protein profile of preeclampsia and identify its potential biomarker.

Methods

Around 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.

Results

There 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.

Conclusion

iTRAQ 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

Colorectal 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

Glioma 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

Introduction

Lecithin 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 Methods

Eight patients with corneal opacification and renal defect were analyzed for mutations in the LCAT gene by PCR sequencing.

Results

Sequencing 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.

Conclusion

In 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

Motor 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

Osteoporosis (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

Hepatocellular 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

Postoperative 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.
Overexpression of lncRNA snaR is correlated with progression and predicts poor survival of laryngeal squamous cell carcinoma
Authors: Liang Kun , Yang Ying , Zha Dingjun , Yue Bo , Qiu Jianhua , Zhang Changming
Published: December 2018

Long noncoding RNAs (lncRNA) snaR is a characterized oncogenic lncRNA in triple negative breast cancer and ovarian cancer, while its role in other human diseases is unknown. In the present study, we found that plasma levels of snaR were upregulated in patients with laryngeal squamous cell carcinoma (LSCC) than in healthy controls. Plasma levels of snaR increased with increase in AJCC stages. Follow‐up study showed that high plasma levels of snaR were correlated with poor overall survival. Plasma levels of snaR were positively correlated with transforming growth factor beta (TGF‐β1) in patients with LSCC but not in healthy controls. Overexpression of snaR resulted in upregulation of TGF‐β1 in cells of human LSCC cell lines, while exogenous TGF‐β1 treatment showed no significant effect on snaR expression. snaR overexpression and exogenous TGF‐β1 treatment promoted LSCC cell proliferation, migration, and invasion. In addition, TGF‐β inhibitor partially reduced the enhancing effects of snaR overexpression on LSCC cell proliferation, migration, and invasion. Therefore, overexpression of lncRNA snaR is correlated with progression and predicts poor survival of LSCC and the mechanism of its actions is likely related to TGF‐β1.
MicroRNA‐543 promotes ovariectomy‐induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2
Authors: Li Xiang , Ning Lei , Zhao Xiangde , Wan Shuanglin
Published: December 2018

The present study aimed to determine the roles of miRNA‐543 in osteoporosis in rats induced by ovariectomy. The osteoporosis rat model was established by ovariectomy induction. MiRNA‐543 expression in osteoblasts was measured by quantitative real‐time polymerase chain reaction. The cell proliferation and apoptosis were measured by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and flow cytometry assays, respectively. Western blot analysis was conducted to examine the expression of YAF‐2 and AKT signaling. TargetScan analysis and dual‐luciferase reporter assay were performed to determine the target gene of miRNA‐543. MiRNA‐543 was significantly upregulated in osteoporosis rat model. Overexpression of miRNA‐543 significantly suppressed cell growth and promoted apoptosis in osteoblasts, whereas downregulation of miRNA‐543 significantly enhanced cell growth and inhibited apoptosis. MiRNA‐543 upregulation significantly inhibited YAF‐2 expression and suppressed the phosphorylation and expression of AKT and p38 mitogen‐activated protein kinases (MAPK) in osteoblasts. Furthermore, YAF‐2 knockdown enhanced the effects of miRNA‐543 on apoptosis in osteoblasts. AKT inhibitor MK2206 and p38 MAPK inhibitor SB203580 also enhanced the effects of miRNA‐543 on apoptosis in osteoblasts. Our findings revealed that inhibition of miRNA‐543 could protect osteoblasts against ovariectomy‐induced osteoporosis through AKT/p38 MAPK signaling pathway by targeting YAF2.
Integrative analyses of genes associated with idiopathic pulmonary fibrosis
Authors: Wang Huimei , Xie Qiqi , Ou‐Yang Wen , Zhang Mingwei
Published: December 2018

Idiopathic pulmonary fibrosis (IPF), characterized by irreversible scarring and progressive destruction of the lung tissue, is one of the most common types of idiopathic interstitial pneumonia worldwide. However, there are no reliable candidates for curative therapies. Hence, elucidation of the mechanisms of IPF genesis and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis and treatment of IPF. Recently, efficient microarray and bioinformatics analyses have promoted an understanding of the molecular mechanisms of disease occurrence and development, which is necessary to explore genetic alternations and identify potential diagnostic biomarkers. However, high false‐positive rates results have been observed based on single microarray datasets. In the current study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of IPF‐related genes. Three publicly available microarray datasets including 54 IPF samples and 34 normal samples were integrated by performing gene set enrichment analysis and analyzing differentially expressed genes (DEGs). Our results identified 350 DEGs genetically associated with IPF. Gene ontology analyses revealed that the changes in the modules were mostly enriched in the positive regulation of smooth muscle cell proliferation, positive regulation of inflammatory responses, and the extracellular space. Kyoto encyclopedia of genes and genomes enrichment analysis of DEGs revealed that IPF involves the TNF signaling pathway, NOD‐like receptor signaling pathway, and PPAR signaling pathway. To identify key genes related to IPF in the protein‐protein interaction network, 20 hub genes were screened out with highest scores. Our results provided a framework for developing new pathological molecular networks related to specific diseases in silico.
Clinical aspects of circulating miRNA‐335 in breast cancer patients: A prospective study
Authors: Swellam Menha , Mahmoud Magda Sayed , Hashim Maha , Hassan Naglaa M , Sobeih Mohamed Emam , Nageeb Amira M
Published: December 2018

Background

The impact of aberrant expression of miRNAs, small noncoding RNAs of 19 to 23 nucleotide, has been reported in different types of cancer, such as breast cancer. Authors aim to investigate the role of circulating miRNA‐335 as a diagnostic and prognostic marker for breast cancer.

Materials and Methods

miRNA‐335 expression was measured in primary breast cancer patients (n = 106), patients with benign breast lesion (n = 49) and healthy individuals as control (n = 40) using quantitative real‐time polymerase chain reaction and its diagnostic efficacy, relation with clinicopathological factors, and disease‐free survival (DFS) and overall survival (OS) were assessed.

Results

A significant decrease in miRNA‐335 expression was reported in patients with breast cancer as compared to the other two investigated groups. The positivity rate for miRNA were related to adverse clinical features of primary breast cancer as high histological grading (X2 = 7.72, P = 0.016), presence of metastasis to lymph node (X2 = 21.8, P < 0.001), large tumor size (X2 = 6.41, P = 0.041), and hormonal status (P < 0.001). miRNA‐335 mean rank level was significantly different among breast cancer subtypes and its level was inferior in triple negative breast cancer. Worse DFS (X2 = 7.76, P = 0.005) and OS (X2 = 9.3, P = 0.002) were reported with decreased miRNA‐335 level.

Conclusion

Assessment of circulating miRNA expression level is a promising minimal invasive marker for diagnosis and prediction of breast cancer prognosis with significant discrepancies among molecular breast cancer subtypes.
Association of the human aryl hydrocarbon receptor repressor (AhRR)‐c.565C>G transversion with male infertility: A case‐control study from Iran
Authors: Mohammad‐Hasani Azadeh , Hosseinzadeh Colagar Abasalt , Fallah Ali
Published: December 2018

Dioxins (eg, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin/TCDD), as environmental endocrine disruptors and toxic carcinogens, can affect male reproductive health. The influence of dioxins is mediated via the aryl hydrocarbon receptor (AhR) pathway and its repressor (AhRR). In this study, we investigated the association of AhRR‐c.565C>G transversion polymorphism with male infertility. In a hospital‐based case‐control study, 221 semen samples (111 infertile and 110 healthy controls) based on World Health Organization guidelines were collected from in vitro fertilization centers of Babol, Iran. The AhRR‐c.565C>G (rs2292596) polymorphism was genotyped using a polymerase chain reaction‐restriction fragment length polymorphism analysis. The difference in the allele frequency of AhRR‐c.565C>G transversion polymorphism did not reach a significant level. The genotype frequency was statistically significantly different between fertile and infertile men. We found that polymorphism rs2292596 (Pro185Ala) was statistically significantly associated with the risk of male infertility. In addition, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. The 185 Pro wild‐type alleles of AhRR may be associated with the risk of male infertility. The proallele also may diminish inhibition of AhR‐mediated signaling of exposure to environmental pollutants.
Total circulating cell‐free miRNA in plasma as a predictive biomarker of the thyroid diseases
Authors: Caglar Ozge , Cayir Akin
Published: December 2018

Background

Thyroid cancer is a common endocrine cancer. Great progress has been made in resolving its molecular mechanisms in recent years. The molecular changes observed in thyroid cancer can be used as biomarkers for diagnostic, prognostic and therapeutic purposes. MicroRNAs (miRNAs) are important components in biological and metabolic pathways, such as developmental stages, signal transduction, cell maintenance, and differentiation. Hence, their malfunctioning can expose humans to malignancies. miRNA expressions have been shown to be dysregulated in different tumor types, like thyroid cancer, and may cause tumor initiation and progression.

In previous studies, only cancer has been studied, and miRNA has been detected from the tissues in all the studies performed. In this study, we have focused on thyroid diseases such as bening nodules and Hashimoto's disease, which might be the cause of thyroid cancer, and have carried out miRNA tests in the blood samples taken from the arms thyroid patients.

Material and method

The present study was conducted on the blood samples of 100 thyroid patients. Of the 100 patients in our study, 33 consisted of patients with thyroiditis, while 37 patients were diagnosed with benign thyroid nodules and 30 patients had thyroid cancer. For the control group, 18 patients were included. The plasma samples were analyzed, and the total miRNA levels were determined.

Results

We found that the ccf‐miRNA amount of benign patients is significantly lower than that of the controls. Similarly, the miRNA amount in the controls is significantly higher than that of the thyroiditis (P = 0.06) and the malign groups miRNA (P = 0.084). Although the present study has a low number of patients, the plasma samples could be used as a source of circulating miRNAs. In addition, the total miRNA of thyroid diseases could be used as a biomarker for different types of thyroid diseases. We could suggest, for future study, that specific miRNAs in bodily fluid might show specific properties to be used as biomarkers of thyroid diseases.
An in silico pharmacological approach toward the discovery of potent inhibitors to combat drug resistance HIV‐1 protease variants
Authors: Nayak Chirasmita , Chandra Ishwar , Singh Sanjeev Kumar
Published: December 2018

Protease inhibitors (PIs) are crucial drugs in highly active antiretroviral therapy for human immunodeficiency virus‐1 (HIV‐1) infections. However, resistance owing to mutations challenge the long‐term efficacy in the medication of HIV‐1‐infected individuals. Lopinavir (LPV) and darunavir (DRV), two second‐generation drugs are the most potent among PIs, hustling the drug resistance when mutations occur in the active and nonactive site of the protease (PR). Herein, we strive for compounds that can stifle the function of wild‐type (WT) HIV‐1 PR along with four major single mutants (I54M, V82T, I84V, and L90M) instigating resistance to the PIs using in silico approach. Six common compounds are retrieved from six databases using combined pharmacophore‐based and structure‐based virtual screening methodology. LPV and DRV are docked and the binding free energy is calculated to set the cut‐off value for selecting compounds. Further, to gain insight into the stability of the complexes the molecular dynamics simulation (MDS) is carried out, which uncovers two lead molecules namely NCI‐524545 and ZINC12866729. Both the lead molecules connect with WT and mutant HIV‐1 PRs through strong and stable hydrogen bond interactions when compared with LPV and DRV throughout the trajectory analysis. Interestingly, NCI‐524545 and ZINC12866729 exhibit direct interactions with I50/50′ by replacing the conserved water molecule as evidenced by MDS, which indicates the credible potency of these compounds. Hence, we concluded that NCI‐524545 and ZINC12866729 have great puissant to restrain the role of drug resistance HIV‐1 PR variants, which can also show better activity through in vivo and in vitro conditions.
A benzoxazole derivative PO‐296 inhibits T lymphocyte proliferation by the JAK3/STAT5 signal pathway
Authors: Luo Xing‐yan , Zhou Hong , Wang Si‐yu , Xiong Jing , Mo Chun‐fen , Guo Hui‐jie , Wang Yan‐tang , Yang Shu‐xia , Li Li‐mei , Zou Qiang , Liu Yang
Published: December 2018

Immunosuppressants have shown striking achievements in treating autoimmune diseases in recent years. It is urgent to develop more immunosuppressants to provide more options for patients. PO‐296 [2‐(6‐chlorobenzo[d]oxazol‐2‐yl)‐4,5,6,7‐tetrahydro‐2H‐indazol‐3‐ol] was identified as a novel benzoxazole derivative. We observed that it exhibits an obvious immunosuppressive activity to T lymphocytes. PO‐296 significantly inhibited the proliferation of activated human T lymphocyte without cytotoxicity. Moreover, PO‐296 did not affect the expression of cluster of differentiation (CD)‐25 or CD69 but induced T lymphocyte cycle arrest in the G0/G1 phase. Furthermore, PO‐296 inhibited interleukin (IL)‐6, IL‐17, and interferon gamma expression but had no effect on IL‐2, IL‐4, or IL‐10. Yet, importantly, PO‐296 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5), increased the phosphorylation of p70S6K, but did not affect the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/mitogen‐activated protein kinase pathway. In conclusion, these findings indicate that PO‐296 inhibits human activated T‐lymphocyte proliferation by affecting the janus kinase 3 (JAK3)/STAT5 pathway. PO‐296 possesses a potential lead compound for the design and development of new immunosuppressants for the treatment of autoimmune diseases.