bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTPH1 immunohistochemical expression and promoter methylation in breast cancer patients from India: A retrospective study
Authors: Venkatesh Thejaswini , Shetty Abhishek , Chakraborti Shrijeet , Suresh Padmanaban S. 
Published: September 2018

AbstractProtein Tyrosine Phosphatase H1/Protein Tyrosine Phosphatase Non receptor Type 3 (PTPH1/PTPN3) is upregulated and/or mutated in glioma, ovarian, gastric, and colorectal cancers. Previous studies have documented that PTPH1‐associated breast cancers exhibit enhanced sensitivity to tamoxifen and tyrosine kinase inhibitors through dephosphorylation of ER and epidermal growth factor receptor, respectively. Owing to the key role that PTPH1 plays as a biomarker in predicting the response of chemotherapeutic drugs and lack of studies on Indian breast cancer patients, the present study investigated PTPH1 protein expression and its relationship to clinical features, ER/PR/HER2/neu statuses, and methylation of promoter in breast cancer tissues (n = 67) among Indian population by immunohistochemistry and methylation specific polymerase chain reaction. PTPH1 expression was upregulated in 58.21% (39/67) and downregulated in the rest of tumor specimens, and it correlated with ER, PR, and HER2/neu statuses with p values of <0.0001, 0.0113, and 0.0448, respectively. Additionally, we found that the 2 kb region upstream of PTPH1 gene harbored CpG sites within, and was ubiquitously methylated in breast cancer (n = 13), colon cancer tissue (n = 1), uterine cancer tissue (n = 1), normal breast tissue (n = 1) in addition to Hela and MCF7 cell lines. In conclusion, our data showed a strong correlation of the PTPH1 status with the ER and ubiquitous nature of PTPH1 promoter methylation at specific CpG sites irrespective of cancer types and protein expression. Our findings underscore the clinical relevance of PTPH1 expression in Indian patients and warrant additional studies to explore the importance of ubiquitously methylated promoter at specific CpG sites in upstream of the PTPH1 gene.
Biocompatibility of alumina‐based biomaterials–A review
Authors: Rahmati Maryam , Mozafari Masoud 
Published: September 2018

AbstractIn today's medicine world, alumina‐based biomaterials owing to their excellent biomechanical, and biocompatibility properties play a key role in biomedical engineering. However, the literature still suffers from not having a valid database regarding the protein adsorption and subsequently cell responses to these surfaces. Proteins by adsorption on biomaterials surfaces start interpreting the construction and also arranging the biomaterials surfaces into a biological language. Hence, the main concentration of this review is on the protein adsorption and subsequently cell responses to alumina’s surface, which has a wide range biomedical applications, especially in dentistry and orthopedic applications. In the presented review article, the general principles of foreign body response mechanisms, and also the role of adsorbed proteins as key players in starting interactions between cells and alumina‐based biomaterials will be discussed in detail. In addition, the essential physicochemical, and mechanical properties of alumina surfaces which significantly impact on proteins and cells responses as well as the recent studies that have focused on the biocompatibility of alumina will be given. An in depth understanding of how the immune system interacts with the surface of alumina could prove the pivotal importance of the biocompatibility of alumina on its success in tissue engineering after implantation in body.
Resveratrol ameliorates podocyte damage in diabetic mice via SIRT1/PGC‐1α mediated attenuation of mitochondrial oxidative stress
Authors: Zhang Tao , Chi Yanqing , Kang Yingli , Lu Hua , Niu Honglin , Liu Wei , Li Ying 
Published: September 2018

AbstractExcessive generation of mitochondrial reactive oxygen species (ROS) is considered to be initiating event in the development of diabetic nephropathy (DN). Mitochondrial biosynthesis mediated by coactivator PGC‐1α and its downstream transcription factors NRF1 and TFAM may be a key target in maintaining mitochondrial function. Resveratrol (RESV), a natural polyphenolic antioxidant, is a potent SIRT1 agonist. In this study we established diabetes mouse and podocyte exposed to high glucose as in vivo and in vitro models to investigate the efficacy and mechanism of RESV on renoprotection. We found that RESV alleviated proteinuria of diabetic mice, decreased malondialdehyde content while increased Mn‐SOD activity in renal cortex, inhibited the apoptosis of glomerular podocytes and renal tubular epithelial cells, ameliorated pathological manifestations, and restored the expression of SIRT1 and PGC‐1α in renal tissues of DN mice. In podocytes exposed to high glucose, RESV inhibited excessive ROS production and apoptosis. In addition, RESV decreased mitochondrial ROS production, improved respiratory chain complex I and III activity, elevated mitochondrial membrane potential, and inhibited the release of Cyto C and Diablo in the mitochondria into the cytoplasm. Taken together, our findings suggest that RESV ameliorates podocyte damage in diabetic mice via SIRT1/PGC‐1α mediated attenuation of mitochondrial oxidative stress.
Effect of microfragmented adipose tissue on osteoarthritic synovial macrophage factors
Authors: Paolella Francesca , Manferdini Cristina , Gabusi Elena , Gambari Laura , Filardo Giuseppe , Kon Elizaveta , Mariani Erminia , Lisignoli Gina 
Published: September 2018

AbstractCell‐based therapies using adipose‐derived mesenchymal stromal cells (ADMSCs) have shown promising results for the treatment of osteoarthritis (OA). In fact, ADMSCs are now indicated as one of the most powerful cell sources through their immunomodulatory and anti‐inflammatory activities. Recently, an innovative one‐step closed device was developed to obtain microfragmented adipose tissue (MF) to avoid the need for good manufacturing practices for ADMSCs expansion while maintaining their regenerative potential. The aim of this study was to assess the mechanisms of action of MF and ADMSCs from MF (MF‐ADMSCs) on an inflammatory cell model of OA synoviocytes. We found that MF produced low levels of inflammatory factors such as interleukin 6 (IL‐6), CC‐chemokine ligand 5/receptor‐activated normal T‐cell expressed and secreted (CCL5/RANTES), CC‐chemokine ligand 2/monocyte chemoattractant protein‐1 (CCL2/MCP‐1), and CC‐chemokine ligand 3/macrophage inflammatory protein‐1α (CCL3/MIP‐1α), and a higher level only of CXC‐chemokine ligand 8/interleukin 8 compared with MF‐ADMSCs. Matrix metalloproteinase 9 (MMP‐9) degradative factor but released a lower level of its inhibitor tissue inhibitor of the metalloproteinase (TIMP‐1). MF in coculture with synoviocytes significantly induced both the metabolic activity and the release of IL‐6. In contrast, MF, not MF‐ADMSCs, partially decreased CCL5/RANTES. Moreover, MF reduced the release of both macrophage‐specific chemokines (CCL2/MCP‐1 and CCL3/MIP‐1α) and degradative marker MMP‐9. Interestingly, MF increased TIMP‐1 (the MMP‐9 inhibitor) and down‐modulated toll‐like receptor (TLR4) receptor and key molecules of NFκB pathways.These data evidenced different effects of MF versus MF‐ADMSCs on inflamed synoviocytes. MF reduced typical macrophages markers and its potentiality by switching off macrophages activity was strictly dependent on TLR4 and NFκB signaling.
Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis
Authors: Wang Jin‐Cheng , Xia An‐Liang , Xu Yong , Lu Xiao‐Jie 
Published: September 2018

AbstractPortal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.
The phosphorylation of Tudor‐SN mediated by JNK is involved in the regulation of milk protein synthesis induced by prolactin in BMECs
Authors: Zhang Sen , Qi Hao , Wen Xue‐Peng , Li Ping , Gao Xue‐Jun , Ao Jin‐Xia 
Published: September 2018

AbstractTudor staphylococcal nuclease (Tudor‐SN) is a multifunctional protein involved in a variety of cellular processes and plays a critical role in the regulation of gene expression. Recently, Tudor‐SN was found to be upregulated in mammary epithelial cells during lactation in response to prolactin, which further to regulate milk protein synthesis. However, the detailed regulatory mechanism of Tudor‐SN to milk protein still remains to be elucidated. In our study, we observed that the levels of Tudor‐SN and phosphor‐Tudor‐SN (Thr103) were both enhanced upon prolactin stimulation. Immunofluorescence assays demonstrated that prolactin treatment facilitated the nuclear transport of Tudor‐SN. Further study revealed that the phosphorylation of Tudor‐SN was depended on activated JNK. Coimmunoprecipitation assays disclosed that Tudor‐SN might be phosphorylated directly by JNK. Using gene mutation assays, we further discovered that mutation of Thr to Ala at site of 103 prevented the nuclear transport of Tudor‐SN. Thus, these results suggested the essential mechanism of the activated Tudor‐SN in milk protein regulation in response to prolactin, which may provide some new sights into improve milk protein production.
Isometric growth in the world's largest bony fishes (genus Mola)? Morphological insights from fisheries bycatch data
Authors: Phillips Natasha D. , Kubicek Lukas , Payne Nicholas L. , Harrod Chris , Eagling Lawrence E. , Carson Carol D. , Cappanera Valentina , Houghton Jonathan D.R. 
Published: September 2018

AbstractFor teleost fishes, the relationship between morphometric traits can provide significant insight into species life history, however gathering such data for noncommercial species can prove challenging. Here, we use data collected opportunistically from fisheries bycatch and stranding events to assess growth scaling over orders of magnitude in the ocean sunfish (genus Mola). Intriguingly, the confidence intervals for the relationship between length and mass suggests that isometric scaling is likely, a growth pattern rarely observed in fishes owing to the scaling of supportive structures. These data also enabled assessment of geometric morphometrics, which indicated that Mola sp shape varies subtly but significantly ontogenetically, with increased fin area comparative to body area as fish increase in size. More practically, total length emerged as an effective predictor for a range of morphological traits, including mass, fin lengths and surface area, which can provide vital baseline data for fisheries modeling and management.
Interreader agreement of PI‐RADS v. 2 in assessing prostate cancer with multiparametric MRI: A study using whole‐mount histology as the standard of reference
Authors: Girometti Rossano , Giannarini Gianluca , Greco Franco , Isola Miriam , Cereser Lorenzo , Como Giuseppe , Sioletic Stefano , Pizzolitto Stefano , Crestani Alessandro , Ficarra Vincenzo , Zuiani Chiara 
Published: September 2018

BackgroundMost studies assessing interreader agreement of Prostate Imaging Reporting and Data System v. 2 (PI‐RADS v2) have used biopsy as the standard of reference, thus carrying the risk of not definitively noting all existent cancers.PurposeTo evaluate the interreader agreement in assessing prostate cancer (PCa) of PI‐RADS v2, using whole‐mount histology as the standard of reference.Study TypeMonocentric prospective cohort study.PopulationIn all, 48 patients with biopsy‐proven PCa referred for radical prostatectomy, undergoing staging multiparametric magnetic resonance imaging (mpMRI) between May 2016 to February 2017.Field Strength/Sequence3.0T system using high‐resolution T2‐weighted imaging, diffusion‐weighted imaging (echo‐planar imaging with maximum b‐value 2000 sec/mm2), and dynamic contrast‐enhanced imaging (T1‐weighted high resolution isotropic volume examination; THRIVE)AssessmentThree radiologists blinded to final histology (2–8 years of experience) analyzed mpMRI images independently, scoring imaging findings in accordance with PI‐RADS v2. On a per‐lesion basis, we calculated overall and pairwise interreader agreement in assigning PI‐RADS categories, as well as assessing malignancy with categories ≥3 or ≥4, and stage ≥pT3.Statistical TestsCohen's kappa analysis of agreement.ResultsOn 71 lesions found on histology, there was moderate agreement in assigning PI‐RADS categories to all cancers (k = 0.53) and clinically significant cancers (csPCa) (k = 0.47). Assessing csPCa with PI‐RADS ≥4 cutoff provided higher agreement than PI‐RADS ≥3 cutoff (k = 0.63 vs. 0.57). Interreader agreement was higher between more experienced readers, with the most experienced one achieving the highest cancer detection rate (0.73 for csPCa using category ≥4). There was substantial agreement in assessing stage ≥pT3 (k = 0.72).Data ConclusionWe found moderate to substantial agreement in assigning the PI‐RADS v2 categories and assessing the spectrum of cancers found on whole‐mount histology, with category 4 as the most reproducible cutoff for csPCa. Readers' experience influenced interreader agreement and cancer detection rate.Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;49:546–555.
CDC42 regulates the expression of superficial zone molecules in part through the actin cytoskeleton and myocardin‐related transcription factor‐A
Authors: Delve Elizabeth , Parreno Justin , Co Vivian , Wu Po‐Han , Chong Jasmine , Di Scipio Matteo , Kandel Rita A. 
Published: September 2018

ABSTRACTOsteoarthritis (OA) is a degenerative disease that initially manifests as loss of the superficial zone (SZ) of articular cartilage. SZ chondrocytes (SZC) differ in morphology from other chondrocytes as they are elongated and oriented parallel to the tissue surface. Proteoglycan 4 (PRG4) and tenascin C (TNC) are molecules expressed by SZC, which have been shown to be chondroprotective. Identification of the signalling pathway(s) regulating expression of SZ molecules may lead to a therapeutic target that can be used to delay or prevent the onset of OA. The hypothesis of this study is that expression of SZ molecules are regulated in part, by the CDC42‐actin‐myocardin‐related transcription factor‐A (MRTF‐A) signaling pathway. SZC from bovine metacarpal‐phalangeal joints were isolated and grown in monolayer culture. Each target in the CDC42‐actin‐MRTF‐A pathway was inhibited and the effect on cell shape, actin cytoskeleton status, and expression of PRG4 and TNC were determined. Treatment with the CDC42 inhibitor ML141 decreased PRG4 and TNC expression, and correlated with increased cell circularity and G‐/F‐actin ratio. PRG4 and TNC expression were differentially regulated by actin depolymerizing agents, latrunculin B and cytochalasin D. Chemical inhibition of MRTF‐A resulted in decreased expression of both PRG4 and TNC; however, specific knockdown by small interfering RNA only decreased expression of TNC indicating that TNC, but not PRG4, is regulated by MRTF‐A. Although PRG4 and TNC expression are both regulated by CDC42 and actin, it appears to occur through different downstream signaling pathways. Further study is required to elucidate the pathway regulating PRG4. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2421–2430, 2018.
Adherent agarose mold cultures: An in vitro platform for multi‐factorial assessment of passaged chondrocyte redifferentiation
Authors: Parreno Justin , Bianchi Vanessa J. , Sermer Corey , Regmi Suresh C. , Backstein David , Schmidt Tannin A. , Kandel Rita A. 
Published: September 2018

ABSTRACTGenerating the best possible bioengineered cartilage from passaged chondrocytes requires culture condition optimization. In this study, the use of adherent agarose mold (adAM) cultures to support redifferentiation of passaged twice (P2) chondrocytes and serve as a scalable platform to assess the effect of growth factor combinations on proteoglycan accumulation by cells was examined. By 2 days in adAM culture, bovine P2 cells were partially redifferentiated as demonstrated by regression of actin‐based dedifferentiation signalling and fibroblast matrix and contractile gene expression. By day 10, aggrecan and type II collagen gene expression were significantly increased in adAM cultured cells. At day 20, a continuous layer of cartilage tissue was observed. There was no evidence of tissue contraction by P2 cells in adAM cultures. The matrix properties of the resultant tissue as well as proteoglycan 4 (PRG4) secreted by the cells were dependent on the initial cell seeding density. AdAM cultures were scalable and culture within small 3 mm diameter adAM allowed for multi‐factorial assessment of growth factors on proteoglycan accumulation by human P2 chondrocytes. Although there was a patient specific response in proteoglycan accumulation to the various cocktail combinations, the cocktail consisting of 2 ng/ml TGFβ1, 10 ng/ml FGF2, and 250 ng/ml FGF18 resulted in a consistent increase in alcian blue tissue staining. Additional studies will be required to identify the optimal conditions to bioengineer articular cartilage tissue for clinical use. However, the results to date suggest that adAM cultures may be suitable to use for high throughput assessment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2392–2405, 2018.
Asymmetry between the superior and inferior endplates is a risk factor for lumbar disc degeneration
Authors: Wang Yitao , Wang Hongli , Lv Feizhou , Ma Xiaosheng , Xia Xinlei , Jiang Jianyuan 
Published: September 2018

ABSTRACTEndplate pathology plays an important role in the development of lumbar disc degeneration. Previous research paid little attention to differences between the superior and inferior endplates as a possible risk factor for disc degeneration. The purpose of this study was to test the hypothesis that asymmetry between the superior and inferior endplates is a risk factor for the development of lumbar disc degeneration. A total of 134 patients with lumbar disc herniation (LDH) and 100 healthy adults (“Controls”) underwent magnetic resonance imaging scans. Each disc was categorized as non‐degenerated (Pfirrmann grades I–II) or degenerated (Pfirrmann grades III–V) and get the following three groups: “Degenerated LDH” discs (n = 145), “Non‐degenerated LDH” discs (n = 525) and “Non‐degenerated Control” discs (n = 500). On mid‐sagittal image, the lumbar endplate morphology could be categorized into three types: Flat, concave, and irregular. Superior and inferior endplates of a given disc were “symmetric” if both were of the same type, and “asymmetric” if they were of different types. The proportion of asymmetric endplates at L4–5 was higher in the “Degenerated LDH” discs group (47%) than in the “Non‐degenerated LDH” discs group (21%) or “Non‐degenerated Control” discs group (7%) (p < 0.05). At L5‐S1 the proportions were 73%, 55%, and 38% (p < 0.05). Asymmetry of superior and inferior endplates in the mid‐sagittal plane is a risk factor for lumbar disc degeneration. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2469–2475, 2018.
Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50
Authors: Weinmann Daniela , Mueller Monika , Walzer Sonja M. , Hobusch Gerhard M. , Lass Richard , Gahleitner Claudia , Viernstein Helmut , Windhager Reinhard , Toegel Stefan 
Published: September 2018

ABSTRACTThis study aimed to evaluate the chondroprotective and anti‐inflammatory activity of brazilin in human osteoarthritic (OA) cartilage and chondrocytes with particular focus on the nuclear factor‐kappa B (NF‐κB) pathway. Therefore, brazilin was isolated from Caesalpinia sappan and identified using high performance liquid chromatography (HPLC). The effect of brazilin was assessed in cartilage explants treated with 10 ng/ml interleukin (IL)‐1β and 10 ng/ml tumor necrosis factor (TNF)‐α using histological and biochemical glycosaminoglycan (GAG) analyses and in primary chondrocytes treated with 10 ng/ml IL‐1β using RT‐qPCR, ELISA, and Western blot. The involvement of NF‐κB signaling was examined using a human NF‐κB signaling array and in silico pathway analysis. Brazilin was found to reduce the GAG loss from cartilage explants stimulated with IL‐1β and TNF‐α. NF‐κB pathway analysis in chondrocytes revealed NFKB1/p50 as a central player regulating the anti‐inflammatory activities of brazilin. Brazilin suppressed the IL‐1β‐mediated up‐regulation of OA markers and the induction of NFKB1/p50 in chondrocytes. In conclusion, brazilin effectively attenuates catabolic processes in human OA cartilage and chondrocytes—at least in part due to the inhibition of NFKB1/p50—which indicates a chondroprotective potential of brazilin in OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2431–2438, 2018.
High glucose‐induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells
Authors: Jiang Zengxin , Lu Wei , Zeng Qingmin , Li Defang , Ding Lei , Wu Jingping 
Published: September 2018

ABSTRACTDiabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high‐glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha‐lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase‐3, cleaved caspase‐9, Bcl‐2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose‐ and time‐dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase‐3, cleaved caspase‐9, Bax, and cytochrome c but decreased the level of the anti‐apoptotic protein Bcl‐2. ALA inhibited the expression of cleaved caspase‐3, cleaved caspase‐9, Bax, and cytochrome c but enhanced the expression of Bcl‐2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose‐induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose‐ and time‐dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2476–2483, 2018.