bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mobility group box 1 protein regulates osteoclastogenesis through direct actions on osteocytes and osteoclasts in vitro
Authors: Davis Hannah M. , Valdez Sinai , Gomez Leland , Malicky Peter , White Fletcher A. , Subler Mark A. , Windle Jolene J. , Bidwell Joseph P. , Bruzzaniti Angela , Plotkin Lilian I. 
Published: May 2019

AbstractOld age and Cx43 deletion in osteocytes are associated with increased osteocyte apoptosis and osteoclastogenesis. We previously demonstrated that apoptotic osteocytes release elevated concentrations of the proinflammatory cytokine, high mobility group box 1 protein (HMGB1) and apoptotic osteocyte conditioned media (CM) promotes osteoclast differentiation. Further, prevention of osteocyte apoptosis blocks osteoclast differentiation and attenuates the extracellular release of HMGB1 and RANKL. Moreover, sequestration of HMGB1, in turn, reduces RANKL production/release by MLO‐Y4 osteocytic cells silenced for Cx43 (Cx43def), highlighting the possibility that HMGB1 promotes apoptotic osteocyte‐induced osteoclastogenesis. However, the role of HMGB1 signaling in osteocytes has not been well studied. Further, the mechanisms underlying its release and the receptor(s) responsible for its actions is not clear. We now report that a neutralizing HMGB1 antibody reduces osteoclast formation in RANKL/M‐CSF treated bone marrow cells. In bone marrow macrophages (BMMs), toll‐like receptor 4 (TLR4) inhibition with LPS‐RS, but not receptor for advanced glycation end products (RAGE) inhibition with Azeliragon attenuated osteoclast differentiation. Further, inhibition of RAGE but not of TLR4 in osteoclast precursors reduced osteoclast number, suggesting that HGMB1 produced by osteoclasts directly affects differentiation by activating TLR4 in BMMs and RAGE in preosteoclasts. Our findings also suggest that increased osteoclastogenesis induced by apoptotic osteocytes CM is not mediated through HMGB1/RAGE activation and that direct HMGB1 actions in osteocytes stimulate pro‐osteoclastogenic signal release from Cx43def osteocytes. Based on these findings, we propose that HMGB1 exerts dual effects on osteoclasts, directly by inducing differentiation through TLR4 and RAGE activation and indirectly by increasing pro‐osteoclastogenic cytokine secretion from osteocytes.
Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis
Authors: Li GuoBin , Zhang Lan , Wang DongEn , AIQudsy Luban , Jiang Jean X. , Xu HuiYun , Shang Peng 
Published: May 2019

AbstractThe nature of muscle‐bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)‐6, IL‐7, IL‐15, insulin‐like growth factor‐1, fibroblast growth factor (FGF)‐2, and β‐aminoisobutyric acid and through bone‐derived factors including FGF23, prostaglandin E2, transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone‐muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.
Targeted genomic integration of EGFP under tubulin beta 3 class III promoter and mEos2 under tryptophan hydroxylase 2 promoter does not produce sufficient levels of reporter gene expression
Authors: Menzorov Aleksei G. , Orishchenko Konstantin E. , Fishman Veniamin S. , Shevtsova Anastasia A. , Mungalov Roman V. , Pristyazhnyuk Inna E. , Kizilova Elena A. , Matveeva Natalia M. , Alenina Natalia , Bader Michael , Rubtsov Nikolai B. , Serov Oleg L. 
Published: May 2019

AbstractNeuronal tracing is a modern technology that is based on the expression of fluorescent proteins under the control of cell type–specific promoters. However, random genomic integration of the reporter construct often leads to incorrect spatial and temporal expression of the marker protein. Targeted integration (or knock‐in) of the reporter coding sequence is supposed to provide better expression control by exploiting endogenous regulatory elements. Here we describe the generation of two fluorescent reporter systems: enhanced green fluorescent protein (EGFP) under pan‐neural marker class III β‐tubulin (Tubb3) promoter and mEos2 under serotonergic neuron‐specific tryptophan hydroxylase 2 (Tph2) promoter. Differentiation of Tubb3‐EGFP embryonic stem (ES) cells into neurons revealed that though Tubb3‐positive cells express EGFP, its expression level is not sufficient for the neuronal tracing by routine fluorescent microscopy. Similarly, the expression levels of mEos2‐TPH2 in differentiated ES cells was very low and could be detected only on messenger RNA level using polymerase chain reaction‐based methods. Our data shows that the use of endogenous regulatory elements to control transgene expression is not always beneficial compared with the random genomic integration.
Total flavonoids from the Carya cathayensis Sarg. leaves inhibit HUVEC senescence through the miR‐34a/SIRT1 pathway
Authors: Guo Yan , Xing Liwan , Chen Nipi , Gao Chengxian , Ding Zhishan , Jin Bo 
Published: May 2019

AbstractAging shows a significant relationship with changed vascular structure and function, and advancing age is a major nonmodifiable risk factor in the occurrence of cardiovascular diseases. The senescence of endothelial cells is one of the hallmarks of vascular aging and can induce vascular dysfunction. This study aimed to investigate the effect of total flavonoids (TFs) on human umbilical vein endothelial cells (HUVEC) senescence and identify the potential mechanisms involved. A HUVEC senescence model was induced by angiotensin II. The senescence markers, including senescence‐associated β‐galactosidase (SA‐β‐gal), p53, p21, and stagnate G0/G1, were measured. The effects of TFs on miR‐34/ SIRT1 were examined by quantitative polymerase chain reaction analysis and Western blot analysis. TFs decreased the percentage of SA‐β‐gal‐positive cells and resulted in G0/G1 cell cycle arrest, while the percentage of cells in the S phase increased. Furthermore, TFs reduced miR‐34a expression and increased the expression of SIRT1. After treatment with TFs and a miR‐34a inhibitor, the percentage of SA‐β‐gal‐positive cells and the expression of miR‐34a decreased, and the expression of SIRT1 increased. The TFs inhibited HUVEC senescence, and the mechanism was related to the miR‐34a/Sirtuin1 pathway.
Downregulation of microRNA‐92b‐3p suppresses proliferation, migration, and invasion of gastric cancer SGC‐7901 cells by targeting Homeobox D10
Authors: Li Cheng , Huo Binliang , Wang Yongheng , Cheng Chong 
Published: May 2019

AbstractTo investigate the effect and mechanism of microRNA‐92b‐3p (miR‐92b‐3p) targeting Homeobox D10 (HOXD10) on proliferation, migration, and invasion of gastric cancer, we detected the expression of miR‐92b‐3p and HOXD10 in SGC‐7901 cells. The effects of miR‐92b‐3p or HOXD10 on proliferation, migration, invasion, and matrix metalloproteinase (MMP)‐2/9 expression in SGC‐7901 cells were measured by the Cell Counting Kit‐8 assay, Transwell assay, and Western blot, respectively. The results showed that miR‐92b‐3p expression was increased, and HOXD10 expression was decreased in SGC‐7901 cells, compared with human normal gastric epithelial cells GES‐1. Functional experiments demonstrated that cell proliferation, migration, invasion, and expression of MMP‐2/9 in SGC‐7901 cells were significantly inhibited by miR‐92b‐3p silencing and HOXD10 overexpression. Moreover, HOXD10 was a potential target gene of miR‐92b‐3p as evidenced by the TargetScan software and double luciferase reporter assay. In the rescue experiment, knockdown of HOXD10, accompanied by higher expression of MMP‐2/9, could significantly eliminate the inhibitory effects of miR‐92b‐3p silencing on cell proliferation, migration, and invasion. In conclusion, miR‐92b‐3p is highly expressed in gastric cancer SGC‐7901 cells, and interfering with its expression might inhibit SGC‐7901 cell proliferation, migration, and invasion via downregulating MMP‐2/9 expression and targeting HOXD10.
Serum galectin‐3 concentrations in patients with ankylosing spondylitis
Authors: Cao Ming‐Yu , Wang Jiang , Gao Xiao‐Liang , Hu Ya‐Bin 
Published: May 2019

AbstractObjectiveThe aim of our study was to assess potential correlations between serum galectin‐3 concentrations and Ankylosing Spondylitis Disease Activity (ASDAS) index in patients with ankylosing spondylitis (AS).MethodsA total of 112 patients with AS were included, and 130 healthy subjects were considered as controls. We collected the detailed medical history, and ASDAS index was used to assess the disease severity in patients with AS.ResultsThe serum galectin concentrations were higher in AS patients compared to the health groups (14.1 ± 9.6 vs 9.2 ± 3.7, P < 0.001). The correlation analysis showed that serum galectin concentrations were significantly positively correlated with C‐reactive protein and erythrocyte sedimentation rate (r = 0.369, P < 0.001; r = 0.240, P = 0.011). In addition, the positively correlation of serum galectin‐3 with global pain index (r = 0.238, P = 0.011) was observed in AS patients. A significant positively correlation between serum galectin and ASDAS index in AS patients was found (r = 0.367; P < 0.001). In multiple linear regression analysis, the results indicated that increased serum galectin still was correlated with ASDAS index (r = 0.322, P < 0.001) in patients with AS.ConclusionsSerum galectin concentrations were found to be correlated with ASDAS index in patients with AS.
Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities
Authors: Paterek Aleksandra , Mackiewicz Urszula , Mączewski Michał 
Published: May 2019

AbstractIron is a key micronutrient for the human body and participates in biological processes, such as oxygen transport, storage, and utilization. Iron homeostasis plays a crucial role in the function of the heart and both iron deficiency and iron overload are harmful to the heart, which is partly mediated by increased oxidative stress. Iron enters the cardiomyocyte through the classic pathway, by binding to the transferrin 1 receptor (TfR1), but also through other routes: T‐type calcium channel (TTCC), divalent metal transporter 1 (DMT1), L‐type calcium channel (LTCC), Zrt‐, Irt‐like Proteins (ZIP) 8 and 14. Only one protein, ferroportin (FPN), extrudes iron from cardiomyocytes. Intracellular iron is utilized, stored bound to cytoplasmic ferritin or imported by mitochondria. This cardiomyocyte iron homeostasis is controlled by iron regulatory proteins (IRP). When the cellular iron level is low, expression of IRPs increases and they reduce expression of FPN, inhibiting iron efflux, reduce ferritin expression, inhibiting iron storage and augment expression of TfR1, increasing cellular iron availability. Such cellular iron homeostasis explains why the heart is very susceptible to iron overload: while cardiomyocytes possess redundant iron importing mechanisms, they are equipped with only one iron exporting protein, ferroportin. Furthermore, abnormalities of iron homeostasis have been found in heart failure and coronary artery disease, however, no clear picture is emerging yet in this area. If we better understand iron homeostasis in the cardiomyocyte, we may be able to develop better therapies for a variety of heart diseases to which abnormalities of iron homeostasis may contribute.
Impact of different ectopic fat depots on cardiovascular and metabolic diseases
Authors: Ferrara Daniele , Montecucco Fabrizio , Dallegri Franco , Carbone Federico 
Published: May 2019

AbstractA growing body of evidence is pointing out the pathophysiological role of fat accumulation in different organs. Ectopic fat depots within heart, liver, skeletal muscle, kidney, and pancreas as well as around blood vessels might be more associated to cardiometabolic risk than classical variables, such as body mass index. Among different mechanisms, lipid metabolism appears to be particularly influenced by ectopic fat depots. Indeed, intracellular accumulation of nonesterified fatty acids, and triglycerides promotes endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, and altered membrane composition/function, finally promoting inflammatory response and cell death. The dysfunctional adipose tissue was shown to induce both local and systemic effects, with relevant clinical consequences. Epicardial fat and myocardial steatosis have been associated with the development of atrial fibrillation and ventricular dysfunction. Similarly perivascular adipose tissue appears to trigger atherosclerosis and hypertension. Nonalcoholic fatty liver disease has been recognized both as the hepatic manifestation of metabolic syndrome and as a cardiovascular (CV) risk factor. Importantly, the renal sinus fat emerged as a potential player in kidney dysfunction. Finally, both skeletal muscle and pancreatic fat depots have been indicated as potential endocrine modulators of insulin resistance. Considering the global rise in the prevalence of obesity, the understanding of mechanisms underlying ectopic fat accumulation represents an urgent need, with potential clinical implications for CV risk stratification. Here, we attempt to update the current knowledge of the different ectopic fat depots, focusing on underlying mechanisms and potential clinical implications.
Epithelial–mesenchymal transition in the formation of hypertrophic scars and keloids
Authors: Yuan Feng‐Lai , Sun Zi‐Li , Feng Yi , Liu Si‐Yu , Du Yong , Yu Shun , Yang Ming‐Lie , Lv Guo‐Zhong 
Published: May 2019

AbstractAbnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients. Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial–mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids.
The immunoreceptor CD300a controls the intensity of inflammation and dysfunction in a model of Ag-induced arthritis in mice
Authors: Valiate Bruno V S , Alvarez Rodrigo U , Karra Laila , Queiroz-Júnior Celso M , Amaral Flavio A , Levi-Schaffer Francesca , Teixeira Mauro M 
Published: May 2019

Abstract
CD300a is an inhibitory immunoreceptor expressed in lymphoid and myeloid cells. This study evaluates whether CD300a plays a role in the control of joint inflammation in a model of Ag-induced arthritis (AIA) in mice. CD300a was found to be expressed mostly on neutrophils and its expression was enhanced on neutrophils that migrated to the inflamed synovial cavity. Joint inflammation, as characterized by neutrophil accumulation, was significantly greater in CD300a KO (CD300a−/−) mice subjected to AIA, as compared to WT mice. This was associated with joint dysfunction, as measured by lower mechanical nociception threshold. There was greater production of the chemokine CXCL1 and the cytokine IL-6 in joints of CD300a−/− mice. In vitro, Mϕs from CD300a−/− mice released higher concentrations of CXCL1 and IL-6 in response to LPS. Splenocytes from immunized CD300a−/− mice produced increased levels of IFN-γ and IL-17 and lower levels of IL-10 when challenged with Ag than cells from WT mice. Neutrophils lacking the CD300a gene had greater chemotactic activity in response to fMLP, CXCL1, and LTB4 than WT neutrophils. In conclusion, these results reveal that the absence of CD300a promotes exacerbation of inflammation in a model of Ag-induced arthritis, suggesting that CD300a is an important receptor for negatively controlling the inflammatory response in this model. Mechanistically, CD300a seems to regulate the activity of various immune cells types involved in the process, including neutrophils, Mϕs, and lymphocytes.
Drought leads to reproductive quiescence in smooth‐billed anis: Phenotypic evidence for opportunistic breeding and reproductive readiness
Authors: Morais Mychel Raony Paiva Teixeira , Teófilo Tiago da Silva , Azevedo Bruna K. G. , Cavalcanti Diogo Manuel Lopes Paiva , Fontenele‐Neto José Domingues 
Published: May 2019

AbstractPrevious studies have suggested that the smooth‐billed ani (Crotophaga ani, Linnaeus, 1758) breeds opportunistically following unpredictable rainfall in drought areas. To obtain proof of this phenomenon, the present study described and compared reproductive morphology and cell proliferation in the gonads of free‐living smooth‐billed anis during a wet season (April to June 2012) and the following dry season (July to September 2012) in a semiarid area using light and electron microscopy (transmission and scanning) and the AgNOR method. The morphological findings indicated distinct levels of reproductive activity related to seasonal changes. Morphological and morphometric analyses of the gonads confirmed intense gametogenic activity during the wet season, whereas gonadal involution occurred after rainfall ceased. The sizes of the testes and ovaries were significantly reduced compared to those in the wet season. The volumetric fraction of the seminiferous tubules in the testis decreased considerably, and no preovulatory follicles were detected in the ovary in the dry season. Moreover, the AgNOR count in the gonads revealed a significant decline in cell recruitment for gametogenesis after rainfall ceased. The histological findings indicated partial gonadal activation throughout the dry season. The analysis of the seminiferous epithelium confirmed the early testicular recrudescence phase, and sporadic postovulatory follicles indicated random ovulation during this time. The excurrent ducts and the oviduct also underwent remarkable involution in the dry season. Taken together, these findings confirm opportunistic breeding by smooth‐billed anis in a semiarid habitat and suggest that gonadal recrudescence has been established as a reproductive strategy to cope with unexpected precipitation events.
Yield parameters and antioxidant compounds of tomato fruit: the role of plant defence inducers with or without Cucumber mosaic virus infection
Authors: Rendina Nunzia , Nuzzaci Maria , Sofo Adriano , Campiglia Pietro , Scopa Antonio , Sommella Eduardo , Pepe Giacomo , De Nisco Mauro , Basilicata Manuela Giovanna , Manfra Michele 
Published: May 2019

AbstractBACKGROUNDThe production of fruit and vegetables rich in health‐promoting components in an eco‐friendly context represents the winning answer to the world population demand for food. In this study, the effects of different treatments on the yield and fruit chemical characteristics of tomato (Solanum lycopersicum L.) are reported. The treatments included three inducers of plant defence responses (chitosan, Trichoderma harzianum T‐22 and Bacillus subtilis QST713) applied alone or before Cucumber mosaic virus infection. Fruit production and antioxidant compounds were investigated by ultrahigh‐performance liquid chromatography (UHPLC) and liquid chromatography–tandem mass spectrometry (LC–MS/MS).RESULTSCompared to control fruit harvested from untreated and healthy plants, treatment with QST713 increased the fruit number. Furthermore, plant treatments with T22, QST713 and chitosan alone enhanced fruit carotenoids (lutein and β‐carotene), ascorbic acid and phenolic acids (caffeoyl glucoside and p‐coumaroyl glucoside). In parallel, compared to fruit harvested from only CMV‐infected plants, treatments with T22, QST713 and chitosan before CMV enhanced fruit ascorbic acid and flavonoids (quercetin 3‐O‐xylosyl‐rutinoside and rutin).CONCLUSIONAntioxidant compounds of tomato fruit can increase with the application of the plant defence inducers, thus protecting both the consumer and plant health. © 2019 Society of Chemical Industry
The assessment of the visual discomfort caused by vergence‐accommodation conflicts based on EEG
Authors: Zheng Yawen , Zhao Xiaojie , Yao Li 
Published: May 2019

AbstractStereoscopic displays have gained much popularity, while visual discomfort during watching stereoscopic displays is becoming an increasing concern. Vergence‐accommodation conflicts are one of factors inducing visual discomfort. How to properly assess the visual discomfort by vergence‐accommodation conflicts has been the focus of researchers. Compared with previous studies, this paper aims to address two problems: (1) designing an elaborate experiment to induce visual discomfort without interference of the long performance time and (2) objectively selecting fewer electrodes and extracting electroencephalogram (EEG) features much related to visual discomfort. The results show that, better than previous experimental paradigm, the designed experimental paradigm not only causes the visual discomfort properly but also shortens the performance time to less than an hour. Moreover, for the proposed model, the visual discomfort can be evaluated well based only on six selected electrodes or even better than previous models relying on much more electrodes.
Surgical technique in stapedotomy hearing outcome and complications
Authors: Pauli Nina , Strömbäck Karin , Lundman Lars , Dahlin‐Redfors Ylva 
Published: May 2019

Objectives/HypothesisThe aim of this study was to investigate different stapes surgery techniques in relation to hearing outcome and risk for complications such as tinnitus, hearing deterioration, dizziness, and taste disturbance.Study DesignRetrospective database review.MethodsThe study was based on data from the Swedish Quality Register for Otosclerosis Surgery (SQOS). Two study protocols were completed by the surgeon, and a questionnaire was distributed to each patient 1 year after surgery. A total of 832 patients operated on during 2013 to 2016 were included. Pure‐tone audiometry was performed preoperatively and 1 year after surgery.ResultsThere was no significant difference in postoperative high‐frequency hearing thresholds among the subgroups at the 1‐year follow‐up. The CO2 + drill laser group had the best hearing outcome according to the following criteria: air‐bone gap closure ≤10 dB, air‐conduction improvement >20 dB, and bone conduction not worsened >5 dB. The overall complication rate was low in all analyzed groups. The most commonly reported symptom after surgery was newly developed or worsened tinnitus (6%). Subjective hearing 1 year after surgery was reported to be better or much better in 91% of the patients.ConclusionsThe combination of a drill and CO2 laser or a drill and potassium‐titanyl‐phosphate laser resulted in the best hearing outcome in this study from the SQOS. There were no major differences in high‐frequency hearing outcome when comparing the different surgical techniques. Complications from surgery were rare, and patient satisfaction was very high 1 year after the operation.Level of EvidenceNALaryngoscope, 130:790–796, 2020