bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and Management of Paget's Disease of Bone in Adults: A Clinical Guideline
Authors: Ralston Stuart H , Corral-Gudino Luis , Cooper Cyrus , Francis Roger M , Fraser William D , Gennari Luigi , Guañabens Núria , Javaid M Kassim , Layfield Robert , O'Neill Terence W , Russell R Graham G , Stone Michael D , Simpson Keith , Wilkinson Diana , Wills Ruth , Zillikens M Carola , Tuck Stephen P 
Published: February 2019

ABSTRACT

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Dexamethasone downregulates expression of several genes encoding orphan nuclear receptors that are important to steroidogenesis in stallion testes
Authors: Valdez Raul , Cavinder Clay A. , Varner Dickson D. , Welsh Thomas H. , Vogelsang Martha M. , Ing Nancy H. 
Published: February 2019

AbstractGlucocorticoids impair testosterone synthesis by an unknown mechanism. Stallions treated with the synthetic glucocorticoid dexamethasone had testes collected at 6 or 12 hours postinjection. The testicular expression of selected genes encoding nuclear receptors and steroidogenic enzymes was measured. At 6 hours, dexamethasone treatment decreased levels of NR0B2,
NR4A1,
NR5A1, and
NR5A2 messenger RNAs (mRNAs) and
NR5A2 mRNA levels remained depressed at 12 hours. In contrast, dexamethasone increased levels of
NFKBIA mRNA at both time points. At 6 hours, dexamethasone did not alter levels of
NR0B1,
NR2F1,
NR2F2,
NR3C1,
CYP11A1,
CYP17A1,
CYP19A1,
DHCR24,
GSTA3,
HSD3B2,
HSD17B3,
LHCGR, or
STAR mRNAs. In primary cultures of Leydig cells, 10
−9 and 10
−7M dexamethasone decreased levels of
NR4A1 and
NR5A1 mRNAs and increased those of
NFKBIA mRNA. Our discovery that dexamethasone downregulates
NR4A1,
NR5A1, and
NR5A2 genes, known to be important for testicular functions, may be part of the mechanism by which glucocorticoids acutely decreases testosterone.
The effect of N‐acetylcysteine supplementation on the oxidative stress levels, apoptosis, DNA damage, and hematopoietic effect in pesticide‐exposed fish blood
Authors: Ucar Arzu , Özgeriş Fatma Betül , Yeltekin Aslı Çilingir , Parlak Veysel , Alak Gonca , Keleş Mevlüt Sait , Atamanalp Muhammed 
Published: February 2019

AbstractCysteine is important for protein synthesis, detoxification, and diverse metabolic functions. However, cysteine metabolism has been poorly described in fish, and the role of the therapeutic effect in pesticide toxicology on aquatic organisms is unknown. The aim of this study was to determine the effects of regular cysteine treatment on the hematology, biochemistry, apoptosis, oxidative DNA damage, and antioxidant parameters in fish blood after chemical application. Therefore, fish were exposed to cypermethrin for 2 weeks. Then two different concentrations of N‐acetylcysteine (NAC) were applied for a 4‐day treatment period and compared with the group of the self‐healing process. At the end of the treatment, the hematological index, blood biochemical parameters, paraoxonase (PON), arylesterase (ARE), and myeloperoxidase (MPO) activities in the fish blood samples were investigated. With regard to the hematological parameters, statistical differences were obtained except for mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) (P < 0.05). Enzyme activities (ARE, PON, and MPO), as well as some biochemical parameters (creatinin [Cre], alanine amino transferase, total glyceride, alkaline phosphatase, iron, calcium, low density lipoprotein‐cholesterol [LDL‐C], sodium, and potassium), were found to be importantly different among all groups at the
P < 0.05 level, while 8‐hydroxydeoxyguanosine and caspase‐3 levels were determined to be high in the pesticide group but decreased significantly in NAC‐treated groups (
P < 0.05). According to the results of the study, acute cysteine treatment showed an ameliorative effect on the hematological index, biochemical parameters, PON, MPO, and ARE in the blood in the all the treatment group fish. The positive effect of NAC on protein synthesis, detoxification, and diverse metabolic functions against cypermethrin toxicity was more effective in 1.0 mM NAC. NAC has an important therapeutic effect on pesticide‐induced hematoxicity for fish in terms of all the data.
The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide‐induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities
Authors: Taslimi Parham , Kandemir Fatih Mehmet , Demir Yeliz , İleritürk Mustafa , Temel Yusuf , Caglayan Cuneyt , Gulçin İlhami 
Published: February 2019

AbstractChrysin (CH) or 5,7‐dihydroxyflavone is a flavonoid present in various plants, bee propolis, and honey. Cyclophosphamide (CYP) is a chemotherapeutic drug, which is extensively used in the treatment of multiple human malignancies. In our study, we aimed to investigate the effects of CYP and CH on some metabolic enzymes including carbonic anhydrase, aldose reductase, paraoxonase‐1, α‐glycosidase, acetylcholinesterase, and butyrylcholinesterase enzyme activities in the brain, heart, testis, liver, and kidney tissues of rats. Thirty‐five adult male Wistar rats were used. The animals were pretreated with CH (25 and 50 mg/kg b.w.) for seven days before administering a single dose of CYP (200 mg/kg b.w.) on the seventh day. In all the tissues, the treatment of CH significantly regulated these enzyme activities in CYP‐induced rats. These results showed that CH exhibited an ameliorative effect against CYP‐induced brain, heart, liver, testis, and kidney toxicity.
RNA‐Seq analysis of differentially expressed genes relevant to mismatch repair in aging hematopoietic stem‐progenitor cells
Authors: Lian Xiaolan , Dong Yongpin , Zhao Mingyi , Liang Yajie , Jiang Weiwei , Li Wenfang , Zhang Lina 
Published: February 2019

AbstractWe used RNA‐sequencing (RNA‐Seq) technology and an old hematopoietic stem and progenitor cells (HSPCs) model in vitro to analyze differential expressions of mismatch repair (MMR)‐related genes in aged HSPCs, so as to explore the mechanism of DNA MMR injury in hematopoietic stem cells (HSC) aging. In this study, by combining RNA‐seq data and National Center for Biotechnology Information database, we focus on six widely reported MMR genes MSH2, MSH3, MSH6, MLH1, PMS1, PMS2, and five MMR genes with closer ties to HSC aging Pcna, Exo1, Rpa1, Rpa2, and Rpa3 according to the genes functional classification and the related signaling pathway. It is concluded that MMR is closely related to HSC aging. This study provides experimental evidence for future researching MMR in HSC aging.
NOS1‐derived nitric oxide facilitates macrophage uptake of low‐density lipoprotein
Authors: Roy Anjali , Banerjee Sreeparna , Saqib Uzma , Baig Mirza S. 
Published: February 2019

AbstractFoam cell formation is a hallmark event during atherosclerosis. The current paradigm is that lipid uptake by a scavenger receptor in macrophages initiates necrosis core formation that characterizes atherosclerosis. We report that NOS1‐derived nitric oxide (NO) facilitates low‐density lipoprotein (LDL) uptake by macrophages independent of the inflammatory response. LDL uptake could be dramatically suppressed by NOS1 specific inhibitor 1‐(2‐trifluoromethylphenyl) imidazole (TRIM). Importantly, the notion that NOS1 can mediate uptake of lipoproteins suggests that the foam cell formation is regulated by NOS1‐derived NO‐mediated mechanism. This is a novel study involving NOS1 as a critical player of foam cell formation and reveals much about the key molecular proteins involved in atherosclerosis. Targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages and hence dampening the atherosclerosis progression.
Umbilical cord blood mesenchymal stem cells application in hematopoietic stem cells expansion on nanofiber three‐dimensional scaffold
Authors: Darvish Maryam , Payandeh Zahra , Soleimanifar Fatemeh , Taheri Behnaz , Soleimani Masoud , Islami Maryam 
Published: February 2019

AbstractUmbilical cord blood (UCB) hematopoietic stem cells (HSCs) transplantation (HSCTs) is considered as a therapeutic strategy for malignant and nonmalignant hematologic disorders. Nevertheless, the low number of HSCs obtained from each unit of UCB can be a major challenge for using these cells in adults. In addition, UCB is a rich source of mesenchymal stem cells (MSCs) creating hopes for nonaggressive and painless treatment in tissue engineering compared with bone marrow MSCs. This study was designed to evaluate the effects of UCB‐MSCs application in UCB‐HSCs expansion on the nanoscaffold that mimics the cell's natural niche. To achieve this goal, after flow cytometry confirmation of isolated HSCs from UCB, they were expanded on three‐dimensional (3D) poly‐l‐lactic acid (PLLA) scaffolds fabricated by electrospinning and two‐dimensional (2D)‐culture systems, such as (1) HSCs‐MSCs culturing on the scaffold, (2) HSCs culturing on the scaffold, (3) HSCs‐MSCs culturing on 2D, and (4) HSCs culturing on 2D. After 7 days, real‐time polymerase chain reaction (PCR) was performed to evaluate the CXCR4 gene expression in the mentioned groups. Moreover, for the next validation, the number of total HSCs, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl tetrazolium bromide assay, scanning electron microscopy imaging, and colony‐forming unit assay were evaluated as well. The results of the study indicated that UCB‐MSCs interaction with HSCs in 3D‐culture systems led to the highest expansion of UCB‐HSCs on day 7. Flow cytometry results showed the highest purity of HSCs cocultured with MSCs. Real‐time PCR showed a significant increase in gene expression of CXCR4 in the mentioned group. The highest viability and clonogenicity were detected in the mentioned group too. Considered together, our results suggest that UCB‐HSCs and MSCs coculturing on PLLA scaffold could provide a proper microenvironment that efficiently promotes UCB‐HSCs expansion and UCB‐MSCs can also be considered as a promising candidate for UCB‐HSCTs.
A20 overexpression exerts protective effects on podocyte injury in lupus nephritis by downregulating UCH‐L1
Authors: Sun Ling , Zou Lu‐Xi , Han Yu‐Chen , Wu Ling , Chen Ting , Zhu Dong‐Dong , Hu Po 
Published: February 2019

AbstractLupus nephritis (LN), an autoimmune kidney disease caused by systemic lupus erythematosus (SLE), is the inflammation of the kidney. Although the treatment of LN is still a therapeutic challenge for many practitioners, the present study aims to provide a new insight for the treatment and management. The study aims to explore the effect of A20 on LN in relation to the nuclear factor‐kappa B (NF‐κB) signaling pathway. MRL/lpr mice were used as the LN mouse model. Next, A20, UCH‐L1, and NF‐κB expression in LN patients and MRL/lpr mice was determined. A20 was upregulated in podocytes to assess biological functions of A20 in LN. Furthermore, to further investigate the pivotal role of the NF‐κB pathway in LN, the NF‐κB pathway was blocked in podocytes. Next, UCH‐L1 was downregulated in MRL/lpr mice to assess biological functions of UCH‐L1 in LN. A20 was downregulated, whereas UCH‐L1 was upregulated in LN. Overexpressed A20 declined NF‐κB, UCH‐L1 expression, and the extent of p65 phosphorylation. A20 overexpression or UCH‐L1 inhibition increased expression of synaptoporin and nephrin but decreased desmin expression and ubiquitin accumulation level in podocytes. Moreover, A20 overexpression or UCH‐L1 inhibition increased the podocyte number but decreased protein level of cleaved caspase‐3, podocyte lesion improvement, decreased foot process width, glomerulus basement membrane, and foot process fusion rate. In addition, urine protein, blood urea nitrogen, serum creatinine, and ds‐DNA antibody levels decreased with elevated A20 or depleted UCH‐L1. Collectively, it could be concluded that A20 protects against podocyte injury in LN via UCH‐L1 by inactivating the NF‐κB signaling pathway.
Vitamin D levels reverberate in monocytes modulation in hemodialysis patients
Authors: Almeida A. C. S. F. , Siqueira M. C. , Bonan N. B. , Dambiski A. , Bertuzzo G. , Moreno‐Amaral A N. , Barreto F. C. 
Published: February 2019

AbstractBackgroundPatients with chronic kidney disease (CKD) have a severe vitamin D deficiency and increasing epidemiological data suggesting that this deficiency may play a role in overall morbidity and mortality associated with CKD. It is known that vitamin D regulates the immune system, however, in dialysis patients this deficiency and the modulation of proinflammatory cells is unclear. Among these, monocytes arouse interest considering they constitutively express vitamin D receptors.AimThis study aimed the evaluation of monocytic profile in CKD patients according to vitamin D levels.MethodsPatients in hemodialysis (HD) were divided into two groups, regarding vitamin D levels: Group 1, vitamin D <26 ng/ml (n = 15) and Group 2, vitamin D ≥26 ng/ml (n = 18). Whole blood was collected aiming evaluation of (a) monocytic populations through CD14 and CD16 expression, (b) reactive oxygen species (ROS) generation, and (c) apoptosis.ResultsWe observed that in Group 1, when compared to Group 2, there was a significant increase in intermediate monocytes (CD14++CD16
+; 34.7 ± 31.6 vs. 12.1 ± 6.3; p = 0.006, respectively) and decrease in classical ones (CD14
++CD16
−; 45.3 ± 31.8 vs. 70.4 ± 25.1; p = 0.017, respectively). There was no difference between groups regarding nonclassical monocytes (CD14
+CD16
++), as well as to apoptosis and to ROS generation.ConclusionThis study suggests that HD patients with lower vitamin D levels might have an intensified inflammatory outline as intermediate monocytes with an inflammatory pattern are increased in this population, when compared with patients with higher levels of vitamin D.
Identification of the molecular subgroups in coronary artery disease by gene expression profiles
Authors: Peng Xiao‐Yan , Wang Yong , Hu Haibo , Zhang Xian‐Jin , Li Qi 
Published: February 2019

AbstractCoronary artery disease (CAD) is the most common type of cardiovascular disease and becomes a leading cause of death worldwide. Aiming to uncover the underlying molecular features for different types of CAD, we classified 352 CAD cases into three subgroups based on gene expression profiles, which were retrieved from the Gene Expression Omnibus database. Also, these subgroups present different expression patterns and clinical characteristics. To uncover the transcriptomic differences between the subgroups, weighted gene co‐expression analysis (WGCNA) was used and identified six subgroup‐specific WGCNA modules. Characterization of the WCGNA modules revealed that lipid metabolism pathways, specifically upregulated in subgroup I, might be an indicator of increased severity. Moreover, subgroup II was considered as an early‐stage of CAD because of normal‐like gene expression patterns. In contrast, the mammalian target of rapamycin signaling pathway was significantly upregulated in subgroup III. Although subgroups II and III did not have a significant prognostic difference, their intrinsic biological characteristics were highly different, suggesting that the transcriptome classification may represent risk factors of both age and the intrinsic biological characteristics. In conclusion, the transcriptome classification of CAD cases revealed that cases from different subgroups may have their unique gene expression patterns, indicating that patients in each subgroup should receive more personalized treatment.
Targeting autophagy in cardiac ischemia/reperfusion injury: A novel therapeutic strategy
Authors: Aghaei Mehrdad , Motallebnezhad Morteza , Ghorghanlu Sajjad , Jabbari Ali , Enayati Ayesheh , Rajaei Maryam , Pourabouk Mona , Moradi Alireza , Alizadeh Ali Mohammad , Khori Vahid 
Published: February 2019

AbstractAcute myocardial infarction (AMI) is one of the leading causes of morbidity worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species, and so forth. One of the processes that gets activated in response to I/R injury is autophagy. Indeed, autophagy acts as a “double‐edged sword” in the pathology of myocardial I/R injury and there is a controversy about autophagy being beneficial or detrimental. On the basis of the autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy.
Adipose‐derived exosomes: A novel adipokine in obesity‐associated diabetes
Authors: Zhang Bo , Yang Yang , Xiang Lin , Zhao Zhihe , Ye Rui 
Published: February 2019

AbstractDysfunction of the adipose tissue is a central driver for obesity‐associated diabetes. It is characterized by dysregulated adipokine secretion, which contributes to insulin resistance of key metabolic tissues, including the liver, skeletal muscles, and fat itself. The inter‐organ cross talk between the adipose tissue and the other organs as well as the intra‐organ cross talk between adipocytes and macrophages within the adipose tissue, traditionally mediated by hormones, was recently evidenced to be regulated by adipose‐derived exosomes. Exosomes are nano‐sized membrane‐bound vesicles secreted by the donor cells to modify intercellular communication by translating constituent nucleic acids and proteins to the target cells. Herein, we reviewed the latest progress in understanding the role of adipose‐derived exosomes in the development of insulin resistance, a key mechanism that underpins diabetes and diabetic complications, with a special focus on the role of exosomal miRNAs (micro RNAs) and proteins, and discusses the potential implications of targeting adipose tissue‐derived exosomes for diabetic therapeutics.
S100A6 activates EGFR and its downstream signaling in HaCaT keratinocytes
Authors: Graczyk‐Jarzynka Agnieszka , Sobiak Barbara , Mlącki Michał , Wilanowski Tomasz , Leśniak Wiesława 
Published: February 2019

AbstractEpidermal growth factor receptor (EGFR) is a central transmitter of mitogenic signals in epithelial cells; enhanced EGFR activity is observed in many tumors of epithelial origin. S100A6 is a small calcium‐binding protein, characteristic mainly of epithelial cells and fibroblasts, strongly implicated in cell proliferation and upregulated in tumors. In this study, using biochemical assays along with immunohistochemical and immunocytochemical analysis of organotypic and standard cultures of HaCaT keratinocytes with S100A6 overexpression or knock‐down, we have examined the effect of S100A6 on EGFR activity and downstream signaling. We found that HaCaT cells overexpressing S100A6 had enhanced EGFR, phospho EGFR, and phospho extracellular signal‐regulated kinase 1/2 (pERK1/2) staining intensity and level coupled to higher signal transducer and activator of transcription 3 (STAT3) activity. Conversely, S100A6 knockdown cells had impaired EGFR signaling that could be enhanced by addition of recombinant S100A6 to the culture media. Altogether the results show that S100A6 may exert its proproliferative effects through activating EGFR.
Less is more or more is less: Implications of glucose metabolism in the regulation of the reproductive potential and total lifespan of the Saccharomyces cerevisiae yeast
Authors: Maslanka Roman , Zadrag‐Tecza Renata 
Published: February 2019

AbstractCarbohydrates are dietary nutrients that have an influence on cells physiology, cell reproductive capacity and, consequently, the lifespan of organisms. They are used in cellular processes after conversion to glucose, which is the primary source of energy and carbon skeleton for biosynthetic processes. Studies of the influence of glucose on cellular parameters and lifespan of organisms are primarily concerned with the effect of low glucose concentration defined as calorie restriction conditions. However, the effect of high glucose concentration on cell physiology is also very important. Thus, a comparative analysis of the effects of low and high glucose concentration conditions on cell efficiency was proposed with regard to reproductive capacity and total lifespan of the cell. Glucose concentration determines the type of metabolism and biosynthetic capabilities, which in turn, through the regulation on the cell size, may affect the reproductive capacity of cells. This study was conducted on yeast cells of wild‐type and mutant strains Δgpa2 and Δgpr1 with glucose signalling pathway impairment. Such an experimental model enabled testing both the role of glucose concentration in the regulation of metabolic changes and the extent to which these changes depend on the extracellular or intracellular glucose concentrations. It has been shown here that calorie/glucose excess connected with changes in cell metabolic fluxes increases biosynthetic capabilities of yeast cells. This leads to an increase in cell dry weight accompanied by the increase in cell size and a simultaneous decrease in the reproductive potential and the overall length of cell life.