bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of osseodensification drilling for endosteal implants with different surface treatments: A study in sheep
Authors: Lahens Bradley , Lopez Christopher D. , Neiva Rodrigo F. , Bowers Michelle M. , Jimbo Ryo , Bonfante Estevam A. , Morcos Jonathan , Witek Lukasz , Tovar Nick , Coelho Paulo G. 
Published: August 2018

AbstractThis study investigated the effects of osseodensification drilling on the stability and osseointegration of machine‐cut and acid‐etched endosteal implants in low‐density bone. Twelve sheep received six implants inserted into the ilium, bilaterally (n = 36 acid‐etched, and n = 36 as‐machined). Individual animals received three implants of each surface, placed via different surgical techniques: (1) subtractive regular‐drilling (R): 2.0 mm pilot, 3.2 and 3.8 mm twist drills); (2) osseodensification clockwise‐drilling (CW): Densah Bur (Versah, Jackson, MI) 2.0 mm pilot, 2.8, and 3.8 mm multifluted tapered burs; and (3) osseodensification counterclockwise‐drilling (CCW) Densah Bur 2.0 mm pilot, 2.8 mm, and 3.8 mm multifluted tapered burs. Insertion torque was higher in the CCW and CW‐drilling compared to the R‐drilling (p < 0.001). Bone‐to‐implant contact (BIC) was significantly higher for CW (p = 0.024) and CCW‐drilling (p = 0.006) compared to the R‐drilling technique. For CCW‐osseodensification‐drilling, no statistical difference between the acid‐etched and machine‐cut implants at both time points was observed for BIC and BAFO (bone‐area‐fraction‐occupancy). Resorbed bone and bone forming precursors, preosteoblasts, were observed at 3‐weeks. At 12‐weeks, new bone formation was observed in all groups extending to the trabecular region. In low‐density bone, endosteal implants inserted via osseodensification‐drilling presented higher stability and no osseointegration impairments compared to subtractive regular‐drilling technique, regardless of evaluation time or implant surface. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 615–623, 2019.
Roles of TREM2 in degeneration of human nucleus pulposus cells via NF‐κB p65
Authors: Bai Ming , Yin He‐Ping , Zhao Jian , Li Yang , Wu Yi‐Min 
Published: August 2018

AbstractNuclear factor (NF)‐κB p65 plays a key role in the development of intervertebral disc degeneration (IDD). Herein, we found that messenger RNA levels of human triggering receptor expressed on myeloid cells‐2 (TREM2) and NF‐κB p65 were upregulated and strongly positive correlated (r2 = 0.299, P = 0.0126) in nucleus pulposus (NP) tissues of patients with IDD. To investigate the role of TREM2 in the development of IDD and whether NF‐κB p65 was the underlying mechanism, whereby TREM2 played its role, we established TREM2‐siRNA–transfected human degenerative NP cells and TREM2‐overexpression vector–transfected human normal NP cells. Degeneration of human NP cells was assessed by measuring cell apoptosis, cell proliferation, and the secretion of tumor necrosis factor‐α, interleukin (IL)‐1β, and IL‐6. Protein levels of Bcl2, Bax, total NF‐κB p65 in whole cell lysates, cytoplasm NF‐κB p65, and nuclear NF‐κB p65 were determined to evaluate underlying mechanisms. Our data elucidated that TREM2 silencing was a therapy for human degenerative NP cells through inhibiting cell apoptosis, promoting cell proliferation, suppressing production of tumor necrosis factor‐α, IL 1β, and IL‐6, and the mechanisms included decreasing Bax while enhancing Bcl2, downregulating total NF‐κB p65, and retarding NF‐κB p65 nuclear translocation. On the contrary, upregulated TREM2 showed the opposite effects, accelerating the degeneration of human normal NP cells. Downregulating TREM2 and total NF‐κB p65 and inhibiting NF‐κB p65 nucleus translocation were also confirmed in NP tissue samples of four IDD rats. We concluded that TREM2 functioned as a promoter in the degeneration of human NP cells. Downregulating TREM2 may be a novel therapeutic strategy for human IDD.
Molecular insights into the effect L17A/F19A double mutation on the structure and dynamics of Aβ40: A molecular dynamics simulation study
Authors: Saini Rajneet Kaur , Shuaib Suniba , Goyal Deepti , Goyal Bhupesh 
Published: August 2018

AbstractThe aggregation of amyloid‐β (Aβ) peptide has been associated with the pathogenesis of Alzheimer disease. The recent studies highlighted that L17A/F19A double mutation increases the structural stability of Aβ40 and diminish Aβ40 aggregation. However, the underlying effect of L17A/F19A double mutation on the Aβ40 structure and dynamics remain elusive. In this regard, the influence of L17A/F19A double mutation on the structure and dynamics of Aβ40 was investigated using all‐atom molecular dynamics (MD) simulation. MD simulation reveals that mechanism behind modulation of Aβ40 aggregation is associated with a decrease in the β‐sheet content and dynamics of the salt bridge D23‐K28. The secondary structure analysis highlight more abundant α‐helix content in the central hydrophobic core and C‐terminal region of Aβ40 upon L17A/F19A double mutation that is consistent with circular dichroism (CD) results. The free‐energy landscape reveal that coil conformation is the most dominant conformation in Aβ40 whereas the helical conformation is the most‐populated and energetically favorable conformation in Aβ40(L17A/F19A). MD simulation, in accord with the experiment, highlight that L17A/F19A double mutation diminish Aβ40 aggregation as the population of the fibril‐prone state substantially decreased. The present study, in conjunction with experiment, highlight that L17 and F19 are the critical residues involved in the conformational change that triggers a neurotoxic cascade of Aβ40. Overall, MD simulation provides key structural and physical insights into the reduced Aβ40 aggregation upon L17A/F19A double mutation and an atomic picture of the L17A/F19A‐mediated conformational changes in Aβ40.
Retracted: MicroRNA‐136 promotes lipopolysaccharide‐induced ATDC5 cell injury and inflammatory cytokine expression by targeting myeloid cell leukemia 1
Authors: Wang Yang , Kong Daliang 
Published: August 2018

AbstractOsteoarthritis is the most frequent chronic bone and joint diseases in older populations all over the world. Lipopolysaccharide (LPS)‐induced murine chondrogenic ATDC5 cell model has been widely used for testing new osteoarthritis therapeutic targets. This study aimed to explore the effects of microRNA‐136 (miR‐136) on LPS‐induced ATDC5 cell injury and inflammatory cytokine expression, as well as underlying potential mechanism. We found that LPS remarkably inhibited ATDC5 cell viability, induced ATDC5 cell apoptosis, and upregulated the expression of inflammatory cytokines, including interleukin 1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor α (TNF‐α; P < .01 or  < .001). Moreover, LPS obviously upregulated the expression of miR‐136 in ATDC5 cells (P < .05). Overexpression of miR‐136 markedly exacerbated the LPS‐induced ATDC5 cell viability inhibition, cell apoptosis enhancement, and inflammatory cytokine expression (P < .05), and suppression of miR‐136 had opposite effects (P < .05). Myeloid cell leukemia 1 (Mcl‐1) was a direct target gene of miR‐136, which participated in the effect of miR‐136 on LPS‐induced ATDC5 cell inflammatory injury. Overexpression of Mcl‐1 alleviated the LPS‐induced inactivation of Wnt/β‐catenin and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways, while suppression of Mcl‐1 had opposite effects. To conclude, this study verified that miR‐136 promoted LPS‐induced ATDC5 cell injury and inflammatory cytokine expression by targeting Mcl‐1, and Mcl‐1 was involved in the regulatory effects of LPS on Wnt/β‐catenin and JAK/STAT signaling pathways in ATDC5 cells.
Role of microRNA‐410 in molecular oncology: A double edged sword
Authors: Wen Ru , Umeano Afoma C. , Essegian Derek J. , Sabitaliyevich Uteuliyev Yerzhan , Wang Kai , Farooqi Ammad Ahmad 
Published: August 2018

AbstractMicroRNAs (miRNAs) are short non‐coding single‐stranded RNAs, which play significant roles in the regulation of a myriad of biological processes. Overwhelmingly increasing high‐impact research has also deepened our understanding about the central role of miRNAs in cancer development, metastatic spread, and development of resistance against various drugs. Recent studies have identified miRNAs that regulate RNA expression/processing and posttranscriptional expression of important oncogenes and tumor suppressors. Rapidly emerging experimentally verified data have started to shed light on the significance of miRNAs as biomarkers for diagnostic, prognostic, and monitoring purposes. Next‐generation sequencing and DNA microarray technologies have helped us tremendously in the identification of miRNA and mRNA signatures in different cancers and their subtypes on a genome‐wide scale. It is being increasing realized that miRNAs have diametrically opposite roles in different cancers. miR‐410 is context‐dependently involved in positive and negative regulation of cancers. miR‐410 negatively regulates BAK1, CETN3, and BRD7 to promote cancer. However, miR‐410 effectively targetes c‐MET, AGTR1, and SNAIL to suppress cancer. In this review, we will comprehensively summarize most recent evidence available related to the “split personality” of miR‐410 in different cancers.
Emerging themes of regulation of oncogenic proteins by Solanum nigrum and its bioactive molecules in different cancers
Authors: Butt Ghazala , Romero Mirna Azalea , Tahir Fatima , Farooqi Ammad Ahmad 
Published: August 2018

AbstractResearch over the decades has sequentially and systematically provided a near‐complete resolution of multifaceted and therapeutically challenging nature of cancer. Drug discovery from plants has enjoyed a renaissance in the past few years. Natural products have provided many of the lead structures, which are currently being used as templates for the design and synthesis of novel compounds with biologically enhanced properties. With the maturity and diversification of technologies, there is a growing need to design high‐throughput functional assays for the evaluation of the myriad of compounds being catalogued. This review sheds light on the tumor suppressive properties of Solanum nigrum and its bioactive ingredients. Several worthy of mention include uttroside B, solanine, solamargine, and physalins, which have been tested for efficacy in cancer cell lines and xenografted mice. We have summarized the most recent findings related to S. nigrum‐mediated regulation of intracellular protein network in different cancers. α‐Solanine, an active component of S. nigrum, is involved in the regulation of microRNA‐21 (miRNA‐21) (oncogenic) and miRNA‐138 (tumor suppressor) in prostate cancer. However, this is the only available evidence that gives us a clue related to the tumor suppressive effects exerted by components of S. nigrum at a posttranscriptional level. More interestingly, S. nigrum and its components exerted inhibitory effects on different pathways including PI3K/AKT, JAK‐STAT, VEGF/VEGFR, and matrix metalloproteinases in different cancers. We also provide an overview of new tools, methodologies, and approaches, which will allow researchers to extract as much information as possible out of the tremendous data sets currently being generated. The use of computational tools will be helpful in processing structurally complex natural products and also in prediction of their macromolecular targets.
Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes
Authors: Nojehdehi Shahrzad , Soudi Sara , Hesampour Ardeshir , Rasouli Shima , Soleimani Masoud , Hashemi Seyed Mahmoud 
Published: August 2018

AbstractExosomes derived from adipose tissue‐derived mesenchymal stem cells (AD‐MSCs) have immunomodulatory effects of T‐cell inflammatory response and reduction of clinical symptoms on streptozotocin‐induced of the type‐1 diabetes mellitus (T1DM). Beside control group and untreated T1DM mice, a group of T1DM mice was treated with intraperitoneal injections of characterized exosomes derived from autologous AD‐MSCs. Body weight and blood glucose levels were measured during the procedure. Histopathology and immunohistochemistry were used for evaluation of pancreatic islets using hemotoxylin and eosin (H&E) staining and anti‐insulin antibody. Isolated splenic mononuclear cells (MNCs) were subjected to splenocytes proliferation assay using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, immunophenotyping of regulatory T cells and cytokines. A significant increase in the levels of interleukin‐4 (IL‐4), IL‐10, and transforming growth factor‐β, and a decrease in the levels of IL‐17 and interferon‐γ in concordance with the significant increase in the Treg cell ratio in splenic MNCs (P < 0.05) was shown in T1DM mice treated with AD‐MSC's exosomes as compared to T1DM untreated mice. This amelioration of autoimmune reaction after treatment of T1DM mice with the AD‐MSC exosomes was confirmed with a significant increase in islets using H&E staining and Immunohistochemistry analyses. As expected, body weight, blood glucose levels in a survival of T1DM mice treated with AD‐MSC's exosomes were maintained stable in comparison to untreated T1DM mice. It can be concluded that AD‐MSC's exosomes exert ameliorative effects on autoimmune T1DM through increasing regulatory T‐cell population and their products without a change in the proliferation index of lymphocytes, which makes them more effective and practical candidates.
Dynamic thiol/disulfide homeostasis in patients with lichen planus
Authors: Kalkan Göknur , Emre Selma , Alisik Murat , Aktaş Akın , Baran Pervin 
Published: August 2018

ObjectiveLichen planus (LP) is an autoimmune inflammatory disease of the mucocutaneous tissue, whose exact pathological course remains unclear. Abnormal thiol/disulfide homeostasis has been postulated to be responsible for a number of diseases predominated by chronic inflammation. To be able to contribute complicated and unclear pathogenesis of LP, we aimed to investigate dynamic thiol/disulfide homeostasis in patients with LP, using an original automated method developed by Erel and Neselioglu in this study.MethodsThe study group consisted of 81 unrelated patients with LP and 80 unrelated healthy controls with no LP lesions in their personal history or on clinical examination. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically.ResultsNative thiol and total thiol levels were found as significantly higher in patients with LP than the control group (P = 0.026 and 0.035, respectively). There was no significant difference between the disulfide levels of the patients with LP and the control group.ConclusionsWe provide evidence that that thiol/disulphide homeostasis impaired in favor of thiol levels in LP patients compared to the control group based on the data of our study. To the best of our knowledge, the present study is the first examination on the correlation between thiol and disulfide homeostasis in patients with LP.
Postnatal deletion of Alk5 gene in meniscal cartilage accelerates age‐dependent meniscal degeneration in mice
Authors: Wang Quan , Tan Qiaoyan , Xu Wei , Kuang Liang , Zhang Bin , Wang Zuqiang , Ni Zhenhong , Su Nan , Jin Min , Li Can , Jiang Wanling , Huang Junlan , Li Fangfang , Zhu Ying , Chen Hangang , Du Xiaolan , Chen Di , Deng Chuxia , Qi Huabing , Xie Yangli , Chen Lin 
Published: August 2018

Activation of transforming growth factor‐β (TGF‐β) signaling has been used to enhance healing of meniscal degeneration in several models. However, the exact role and molecular mechanism of TGF‐β signaling in meniscus maintenance and degeneration are still not understood due to the absence of in vivo evidence. In this study, we found that the expression of activin receptor‐like kinases 5 (ALK5) in the meniscus was decreased with the progression of age and/or osteoarthritis induced meniscal degeneration. Col2α1 positive cells were found to be specifically distributed in the superficial and inner zones of the anterior horn, as well as the inner zone of the posterior horn in mice, indicating that Col2α1‐CreERT2 mice can be a used for studying gene function in menisci. Furthermore, we deleted Alk5 in Col2α1 positive cells in meniscus by administering tamoxifen. Alterations in the menisci structure were evaluated histologically. The expression levels of genes and proteins associated with meniscus homeostasis and TGF‐β signaling were analyzed by quantitative real‐time PCR analysis (qRT‐PCR) and immunohistochemistry (IHC). Our results revealed severe and progressive meniscal degeneration phenotype in 3‐ and 6‐month‐old Alk5 cKO mice compared with Cre‐negative control, including aberrantly increased hypertrophic meniscal cells, severe fibrillation, and structure disruption of meniscus. qRT‐PCR and IHC results showed that disruption of anabolic and catabolic homeostasis of chondrocytes may contribute to the meniscal degeneration phenotype observed in Alk5 cKO mice. Thus, TGF‐β/ALK5 signaling plays a chondro‐protective role in menisci homeostasis, in part, by inhibiting matrix degradation and maintaining extracellular matrix proteins levels in meniscal tissues.
In vivo study: Th1–Th17 reduction in pristane‐induced systemic lupus erythematosus mice after treatment with tolerogenicLactobacillusprobiotics
Authors: Mardani Fatemeh , Mahmoudi Mahmoud , Esmaeili Seyed‐Alireza , Khorasani Sahar , Tabasi Nafiseh , Rastin Maryam 
Published: August 2018

Uncontrolled inflammation in systemic lupus erythematosus (SLE) could cause dysfunction in multiple organs. T helper 17 (Th17) cells are a main branch of inflammatory responses in the pathogenesis of SLE, and by producing interleukin 17 (IL‐17), represent a major functional tool in the progression of inflammation. Animal models provide a special field for better studies of the pathogenesis of diseases. Tolergenic probiotics could decrease inflammation in autoimmune diseases by modulating the immune system and maintaining homeostasis. The aim of this project was to evaluate the effects ofLactobacillus rhamnosusandLactobacillus delbrueckiion Th17 cells and their related mediators in a pristane‐induced BALB/c mice model of SLE. The mice were divided into pretreatment groups, which received probiotics or prednisolone at Day 0, and treatment groups, which received probiotics and prednisolone 2 months after injection. The presence of antinuclear antibody (ANA), anti‐double‐stranded DNA (anti‐dsDNA), and anti‐ribonucleoprotein (anti‐RNP) and lipogranuloma was evaluated; also, the population of Th1–Th17 cells as well as interferon γ (IFN‐γ), IL‐17, and IL‐10 levels, and the expression of RAR‐related orphan related receptor gamma (RORγt) and IL‐17 were determined. We observed that probiotics and prednisolone could delay SLE in pretreatment and treatment mice groups, with a reduction in ANA, anti‐dsDNA, anti‐RNP, and mass of lipogranuloma. Probiotics and prednisolone decreased the population of Th1–Th17 cells and reduced IFN‐γ and IL‐17 as inflammatory cytokines in the pretreatment and treatment groups in comparison with SLE‐induced mice. Our results indicated that, due to their anti‐inflammatory properties and reduction of Th17, Th1, and cytotoxic T lymphocyte (CTL) cells, the use of these probiotics could probably represent a new tool for the better management of SLE.
Long noncoding RNA GAS5 regulates the proliferation, migration, and invasion of glioma cells by negatively regulating miR‐18a‐5p
Authors: Liu Qian , Yu Wei , Zhu Shujuan , Cheng Ke , Xu Hong , Lv Yalan , Long Xuan , Ma Lan , Huang Juan , Sun Shanquan , Wang Kejian 
Published: August 2018

IntentionLong noncoding RNAs, transcribed from a recently discovered class of noncoding genes, may play a critical role in regulating cellular processes, such as cell proliferation and apoptosis, as well as in cancer progression and metastasis. We previously detected the induction of growth arrest–specific 5 (GAS5) during glioma cell death. However, the function and underlying mechanism of GAS5 in human gliomas remain to be elucidated.MethodsCell proliferation was detected using CellTiter 96® AQueous Non‐Radioactive Cell Proliferation Assay (MTS) and tumorigenicity assay in nude mice. Wound‐healing assay and transwell assay were utilized to examine the effects of GAS5 expression on glioma cells migration and invasion. In situ hybridization (ISH) was performed to evaluate GAS5 and microRNA (miR)‐18a‐5p levels in tissue microarrays. The relationship between GAS5 and miR‐18a‐5p was evaluated by quantitative reverse‐transcription polymerase chain reaction and RNA precipitation.ResultsIn this study, we demonstrated that overexpression of GAS5 inhibits malignant phenotypes in glioma cells, including proliferation, migration, and invasion, whereas GAS5 knockdown enhances these phenotypes. We further observed Argonaute 2–dependent reciprocal repression between GAS5 and miR‐18a‐5p in glioma cells. Downregulation of GAS5 and upregulation of miR‐18a‐5p were observed in glioma tissue microarrays relative to normal brain tissue by ISH. By deletion analysis, we identified one miR‐18a‐5p‐binding site within exon 2 of GAS5 that is partially responsible for the tumor‐suppressor functions of GAS5.ConclusionTaken together, our findings suggest that GAS5 is a tumor suppressor in human gliomas that acts in part by repressing miR‐18a‐5p.
Keratins and epidermolysis bullosa simplex
Authors: Khani Pouria , Ghazi Farideh , Zekri Ali , Nasri Farzad , Behrangi Elham , Aghdam Arad Mobasher , Mirzaei Hamed 
Published: August 2018

Keratin intermediate filaments play an important role in maintaining the integrity of the skin structure. Understanding the importance of this subject is possible with the investigation of keratin defects in epidermolysis bullosa simplex (EBS). Nowadays, in addition to clinical criteria, new molecular diagnostic methods, such as next generation sequencing, can help to distinguish the subgroups of EBS more precisely. Because the most important and most commonly occurring molecular defects in these patients are the defects of keratins 5 and14 (KRT5 and KRT14), comprehending the nature structure of these proteins and their involved processes can be very effective in understanding the pathophysiology of this disease and providing new and effective therapeutic platforms to treat it. Here, we summarized the various aspects of the presence of KRT5 and KRT14 in the epidermis, their relation to the incidence and severity of EBS phenotypes, and the processes with which these proteins can affect them.