bluuebunny/crossref_metadata_2025 huggingface dataset:
The Stem Cell Potential and Multipotency of Human Adipose Tissue-Derived Stem Cells Vary by Cell Donor and Are Different from Those of Other Types of Stem Cells
Authors: Yang Hyun Jin , Kim Ki-Joo , Kim Min Kyoung , Lee Su Jin , Ryu Yeon Hee , Seo Bommie F. , Oh Deuk-Young , Ahn Sang-Tae , Lee Hee Young , Rhie Jong Won
Published: June 2015

Human adipose tissue-derived mesenchymal stem cells (AT-MSCs) from various sites are applied in tissue engineering and cell therapy. The condition of AT-MSCs depends on the donor's age, body mass index (BMI), and gender. AT-MSCs from 66 human donors were analyzed, and the cells were sorted according to donor age (10-19 years: n = 1; 20-29 years: n = 5; 30-39 years: n = 12; 40-49 years: n = 22; 50-59 years: n = 12; 60-69 years: n = 9, and 70 years or older: n = 5), BMI (under 25, 25-30, and over 30), and gender (19 males and 48 females). Additionally, AT-MSCs were compared to bone marrow MSCs and chorionic tissue-derived MSCs. We measured the MSC yield, growth rate, colony-forming units, multipotency, and surface antigens. AT-MSC proliferation was greater in cells isolated from individuals aged less than 30 years compared to the proliferation of AT-MSCs from those over 50 years old. BMI was correlated with osteogenic differentiation potency; increased BMI enhanced osteogenesis. Adipogenic differentiation was more strongly induced in cells isolated from donors aged less than 30 years compared to those isolated from other age groups. Also, a BMI above 30 was associated with enhanced adipogenic differentiation compared to cells isolated from individuals with a BMI below 25. Bone marrow MSCs were strongly induced to differentiate along both osteogenic and adipogenic lineages, whereas AT-MSCs predominantly differentiated into the chondrogenic lineage. Therefore, the type of regeneration required and variations among potential donors must be carefully considered when selecting MSCs for use in applied tissue engineering or cell therapy.
Effects of Reinnervation of the Triceps Brachii on Joint Kinematics and Electromyographic Patterns of the Feline Forelimb during Level and Upslope Walking
Authors: Livingston Beven P. , Nichols T. Richard
Published: June 2015

Nerve injury in the hindlimb of the cat results in locomotor changes, yet these findings have not been explored in a more multifunctional forelimb. Kinematics and muscle activity of the shoulder and elbow during level and upslope locomotion following reinnervation of the feline long head of the triceps brachii (TLo) were evaluated (1) during paralysis [none to minimum motor activity (short-term effects)] and (2) after the motor function was recovered but the proprioceptive feedback was permanently disrupted (long-term effects). The step cycle was examined in three walking conditions: level (0%), 25% grade (14° upslope) and 50% grade (26.6° upslope). Measurements were taken prior to and at three time points (2 weeks, 1 month and 12+ months) after transecting and suturing the radial nerve of TLo. There was less of a yield (increased flexion) at the elbow joint and more extensor activity during elbow flexion during stance (E2) as the grade of walking increased. Substantial short-term effects were observed at the elbow joint (increased flexion during E2) as well as increased motor activity by the synergistic elbow extensors, and greater shoulder extension at paw contact, leading to altered interjoint coordination during stance. Forelimb shoulder and elbow kinematics during level and upslope locomotion progressed back to baseline at 12 months. The short-term effects can be explained by both mechanical and neural factors that are altered by the functional elimination of the TLo. Full recovery of the forelimb kinematics during level and upslope walking suggests that the proprioceptive length feedback loss is compensated by other sensory sources or altered central drive.
Progesterone Metabolites as Farnesoid X Receptor Inhibitors
Authors: Abu-Hayyeh Shadi , Williamson Catherine
Published: June 2015

Sulfated progesterone metabolites rise 100-fold in the third trimester of human pregnancy and have been shown to be elevated further in the gestational disorder intrahepatic cholestasis of pregnancy (ICP). Typical concentrations of progesterone sulfates range from 1 to 10 µmol/L in an uncomplicated pregnancy and rise to approximately 40 µmol/L in ICP. At this level they can influence bile acid and lipid metabolism. Studies using human and rodent specimens have shown that sulfated metabolites of progesterone competitively inhibit bile acid homeostasis pathways by functioning as partial agonists of farnesoid X receptor (FXR). This explains the loss of induction of FXR target genes in ICP, and may explain susceptibility to hypercholanaemia and dyslipidaemia in the second half of human pregnancy. Furthermore, progesterone sulfates are competitive inhibitors of biliary influx (NTCP) and efflux (BSEP) transport proteins, actions likely to further exacerbate hypercholanaemia and cholestasis.
Anti-Inflammatory Effect of White Wine in CKD Patients and Healthy Volunteers
Authors: Migliori Massimiliano , Panichi Vincenzo , de la Torre Rafael , Fitó Montserrat , Covas Maribel , Bertelli Alberto , Muñoz-Aguayo Daniel , Scatena Alessia , Paoletti Sabrina , Ronco Claudio
Published: June 2015

Background: Mediterranean-style diet has been considered for its important beneficial effects on the progression of CV disease. Wine is an important component of the Mediterranean diet, and moderate wine drinkers have lower mortality rates than nondrinkers and heavy drinkers in epidemiologic studies. The beneficial effects of red wine are thought to be dependent on the polyphenol compounds such as resveratrol that exhibit potent antioxidant activity. However, white wine, although lacking polyphenols, contains simple phenols, such as tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), characteristic also of extra-virgin olive oil, which may share similar antioxidant and inflammatory properties. Patients and Methods: The effect of white wine and extra-virgin olive oil on inflammatory markers was evaluated in 10 healthy volunteers and in 10 patients with CKD (chronic kidney disease) K-DOQI stage III-IV in a prospective, single blind, randomized, cross-over trial. After two weeks of wash-out from alcoholic beverages, subjects were randomized to a cross-over design A-B or B-A of a 2-week treatment with white wine (4 ml/kg body weight, 0.48 g/kg of alcohol 12%, corresponding to 2-3 glasses/daily) and extra-virgin olive oil (treatment A) or extra-virgin olive oil alone (treatment B). The two study periods were separated by a two-week wash-out period. At baseline and at the end of each treatment, plasma levels of inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8) concentration were determined. Urinary levels of Tyr, OH-Tyr, and their metabolites were measured at the same time. Results: During combined consumption of white wine and extra-virgin olive oil (treatment A), plasma levels of CRP and IL-6 decreased from 4.1 ± 1.8 to 2.4 ± 1.9 mg/l (p < 0.05) and from 5.3 ± 3.2 to 3.4 ± 2.3 mg/l (p < 0.05) in CKD patients. CRP decreased from 2.6 ± 1.2 to 1.9 ± 0.9 mg/l (p < 0.05), and IL-6 decreased from 2.2 ± 1.8 to 1.7 ± 1.3 mg/l (p = ns) in healthy volunteers. No significant variation versus baseline was observed during treatment B. A significant increase in urinary Tyr and OH-Tyr was observed during treatment A (white wine and extra-virgin olive oil). Conclusions: Plasma markers of chronic inflammation were significantly reduced in CKD patients during the combined consumption of white wine and olive oil, suggesting a possible anti-inflammatory effect of this nutritional intervention.
Dental Shape Variability in Cercopithecoid Primates: A Model for the Taxonomic Attribution of Macaques from Roman Archaeological Contexts
Authors: Delgado Mónica Nova , Gamarra Beatriz , Nadal Jordi , Mercadal Oriol , Olesti Oriol , Guàrdia Jordi , Pérez-Pérez Alejandro , Galbany Jordi
Published: June 2015

Morphometric variation of biological structures has been widely used to determine taxonomic affinities among taxa, and teeth are especially informative for both deep phylogenetic relationships and specific ecological signals. We report 2-dimensional geometric morphometrics (GM) analyses of occlusal crown surfaces of lower molars (M1, n = 141; M2, n = 158) of cercopithecoid primate species. A 12-landmark configuration, including cusp tips and 8 points of the molar crown contour, were used to evaluate patterns of variation in lower molar shape among cercopithecoid primates and to predict the taxonomic attribution of 2 archaeological macaques from Roman time periods. The results showed that the lower molar shape of cercopithecoid primates reflects taxonomic affinities, mostly at a subfamily level and close to a tribe level. Thus, the cusp positions and crown contour were important elements of the pattern related to interspecific variation. Additionally, the archaeological specimens, attributed to Macaca sylvanus based on osteological information, were classified using the GM molar shape variability of the cercopithecoid primates studied. The results suggest that their molar shape resembled both M. sylvanus and M. nemestrina, and species attribution varied depending on the comparative sample used.
Diet1 Is a Regulator of Fibroblast Growth Factor 15/19-Dependent Bile Acid Synthesis
Authors: Reue Karen , Lee Jessica M. , Vergnes Laurent
Published: June 2015

Background: A fascinating aspect of bile acid homeostasis is the coordination between bile acid uptake in intestine and hepatic bile acid synthesis. In response to bile acid uptake in enterocytes, farnesoid X receptor is activated and induces transcription of fibroblast growth factor (FGF)15 in mice, or FGF19 in humans. FGF15/19 is secreted into the enterohepatic circulation, and through activation of hepatic receptors, leads to repression of Cyp7a1, a rate-limiting enzyme for bile acid synthesis. Using a genetic approach, we identified a novel protein, Diet1, as a control point for FGF15/19 production. Key Messages: Mice with a Diet1-null mutation have reduced FGF15 secretion, causing impaired feedback repression of hepatic bile acid synthesis, and increased fecal bile acid excretion. As a result, Diet1-deficient mice constitutively convert cholesterol to bile acids and are resistant to diet-induced hypercholesterolemia and atherosclerosis. Diet1 affects FGF15/19 production at the posttranscriptional level, and the proteins appear to have overlapping subcellular localization in enterocytes. Diet1 appears to be a control point for the production of FGF15/19 in enterocytes, and thus a regulator of bile acid and lipid homeostasis. Studies to evaluate the role of common and rare DIET1 genetic variants in human health and disease are warranted. Conclusions: Further elucidation of the Diet1-FGF15/19 interaction will provide new insights into the intricate regulatory mechanisms underlying bile acid metabolism.
The Effect of CAPE-V Sentences on Cepstral/Spectral Acoustic Measures in Dysphonic Speakers
Authors: Watts Christopher R.
Published: June 2015

Objective: To investigate the effect of connected speech stimuli from the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) on cepstral/spectral acoustic measurements. Patients and Methods: Recordings from 20 participants seeking treatment for dysphonia were analyzed in this study. The participants read the 6 sentence stimuli from the CAPE-V at a comfortable pitch and loudness. Acoustic measures of cepstral peak prominence (CPP) and its standard deviation, the low-to-high spectral ratio and its standard deviation (LH and LHsd) and the multiparametric measure Cepstral Spectral Index of Dysphonia were acquired from each sentence recording and applied to analyses. Results: A significant main effect for sentence type was present on the measurements of CPP, LH and LHsd. Post hoc pairwise comparisons revealed the most robust effect on CPP from the all-voiced sentence ‘We were away a year ago'. For the measures of LH and LHsd, sentence effects were significant for the majority of comparisons. Conclusion: The connected speech stimuli from the CAPE-V affected cepstral/spectral acoustic measurements differentially. These findings support the rationale for using the various CAPE-V stimuli during clinical assessment, and indicate the need for further investigations to inform clinical practice.
Nuclear Receptors in Acute and Chronic Cholestasis
Authors: Gonzalez-Sanchez Ester , Firrincieli Delphine , Housset Chantal , Chignard Nicolas
Published: June 2015

Background: Nuclear receptors (NRs) form a family of 48 members. NRs control hepatic processes such as bile acid homeostasis, lipid metabolism and mechanisms involved in fibrosis and inflammation. Due to their central role in the regulation of hepatoprotective mechanisms, NRs are promising therapeutic targets in cholestatic disorders. Key Messages: NRs can be classified into five different physiological clusters. NRs from the ‘bile acids and xenobiotic metabolism' and from the ‘lipid metabolism and energy homeostasis' clusters are strongly expressed in the liver. Furthermore, NRs from these clusters, such as farnesoid X receptor α (FXRα), pregnane X receptor (PXR) and peroxisome proliferator-activated receptors (PPARs), have been associated with the pathogenesis and the progression of cholestasis. The latter observation is also true for vitamin D receptor (VDR), which is barely detectable in the whole liver, but has been linked to cholestatic diseases. Involvement of VDR in cholestasis is ascribed to a strong expression in nonparenchymal liver cells, such as biliary epithelial cells, Kupffer cells and hepatic stellate cells. Likewise, NRs from other physiological clusters with low hepatic expression, such as estrogen receptor α (ERα) or reverse-Erb α/β (REV-ERB α/β), may also control pathophysiological processes in cholestasis. Conclusions: In this review, we will describe the impact of individual NRs on cholestasis. We will then discuss the potential role of these transcription factors as therapeutic targets.
Use of Farnesoid X Receptor Agonists to Treat Nonalcoholic Fatty Liver Disease
Authors: Sanyal Arun J.
Published: June 2015

Nonalcoholic fatty liver disease is a common cause of liver related morbidity and mortality. It is closely linked to underlying insulin resistance. It has recently been shown that bile acids modulate insulin signaling and can improve insulin resistance in cell based and animal studies. These effects are mediated in part by activation of farnesoid x receptors by bile acids. In human studies, FXR agonists improve insulin resistance and have recently been shown to improve NAFLD. The basis for the use of FXR agonists for the treatment of NAFLD and early human experience with such agents is reviewed in this paper.
S-777469, a Novel Cannabinoid Type 2 Receptor Agonist, Suppresses Itch-Associated Scratching Behavior in Rodents through Inhibition of Itch Signal Transmission
Authors: Haruna Takayo , Soga Masahiko , Morioka Yasuhide , Hikita Ichiro , Imura Kinichi , Furue Yoko , Yamamoto Mina , Imura Chihiro , Ikeda Minoru , Yamauchi Akira , Deguchi Masashi , Shichijo Michitaka , Arimura Akinori , Yasui Kiyoshi
Published: June 2015

We have previously reported that S-777469 [1-([6-ethyl-1-(4-fluorobenzyl)-5-methyl-2-oxo-1,2-dihydropyridine-3-carbonyl]amino)-cyclohexanecarboxylic acid], a novel cannabinoid type 2 receptor (CB2) agonist, significantly suppressed compound 48/80-induced scratching behavior in mice in a dose-dependent manner when it was administered orally. Here, we demonstrated that the inhibitory effects of S-777469 on compound 48/80-induced scratching behavior are reversed by pretreatment with SR144528, a CB2-selective antagonist. In addition, we investigated the effects of S-777469 on itch-associated scratching behavior induced by several pruritogenic agents in mice and rats. S-777469 significantly suppressed scratching behavior induced by histamine or substance P in mice or by serotonin in rats. In contrast, the H1-antihistamine fexofenadine clearly inhibited histamine-induced scratching behavior but did not affect scratching behavior induced by substance P or serotonin. Moreover, S-777469 significantly inhibited histamine-induced peripheral nerve firing in mice. In conclusion, these results suggest that S-777469 produces its antipruritic effects by inhibiting itch signal transmission through CB2 agonism.
Bonobos Show Limited Social Tolerance in a Group Setting: A Comparison with Chimpanzees and a Test of the Relational Model
Authors: Cronin Katherine A. , De Groot Evelien , Stevens Jeroen M.G.
Published: June 2015

Social tolerance is a core aspect of primate social relationships with implications for the evolution of cooperation, prosociality and social learning. We measured the social tolerance of bonobos in an experiment recently validated with chimpanzees to allow for a comparative assessment of group-level tolerance, and found that the bonobo group studied here exhibited lower social tolerance on average than chimpanzees in this paradigm. Furthermore, following the Relational Model of de Waal, we investigated whether bonobos responded to an increased potential for social conflict with tolerance, conflict avoidance or conflict escalation, and found that only behaviours indicative of conflict escalation differed across conditions. Taken together, these findings contribute to the current debate over the level of social tolerance of bonobos and lend support to the position that the social tolerance of bonobos may not be notably high compared with other primates.
Calcium Sensing Receptor Regulating Smooth Muscle Cells Proliferation Through Initiating Cystathionine-Gamma-Lyase/Hydrogen Sulfide Pathway in Diabetic Rat
Authors: Zhong Xin , Wang Yuwen , Wu Jichao , Sun Aili , Yang Fan , Zheng Dan , Li Ting , Dong Shiyun , Zhao Yajun , Yang Guangdong , Xu Changqing , Sun Dianjun , Lu Fanghao , Zhang Weihua
Published: June 2015

Aims: Hydrogen sulfide (H2S) inhibits the proliferation of vascular smooth muscle cells (VSMCs). However, how cystathionine-gamma-lyase (CSE), a major enzyme that produces H2S, is regulated remains unknown. Whether calcium-sensing receptor (CaSR) inhibits the proliferation of VSMCs by regulating the endogenous CSE/H2S pathway in diabetic rat has not been previously investigated. Methods and Results: The morphological and ultrastructure alterations were tested by transmission electron microscopy, changes in the H2S concentration and the relaxation of the mesenteric secondary artery loop of diabetic rats were determined by Multiskan spectrum microplate spectrophotometer and isometric force transducer. Additionally, the expression levels of CaSR, CSE and Cyclin D1 in the mesenteric arteries of rats were examined by western blotting. The intracellular calcium concentration, the expression of p-CaMK II (phospho-calmodulin kinases II), CSE activity, the concentration of endogenous H2S and the proliferation of cultured VSMCs from rat thoracic aortas were measured by using confocal microscope, western blotting, microplate spectrophotometer, MTT and BrdU, respectively. The VSMC layer thickened, the H2S concentration dropped, the relaxation of the mesenteric secondary artery rings weakened, and the expression of CaSR and CSE decreased whereas the expression of Cyclin D1 increased in diabetic rats compared with the control group. The [Ca2+]i of VSMCs increased upon treatment with CaSR agonists (10 µM Calindol and 2.5 mM CaCl2), while it decreased upon administration of calhex231, U73122 and 2-APB. The expression of p-CaMK II and CSE increased upon treatment with CaSR agonists in VSMCs. CSE activity and the endogenous H2S concentration decreased in response to high glucose, while it increased with treatment of CaSR agonists. The proliferation rate increased in response to high glucose, and CaSR agonists or NaHS significantly reversed the proliferation of VSMCs caused by high glucose. Conclusions: Our results demonstrated that CaSR regulated the endogenous CSE/H2S pathway to inhibit the proliferation of VSMCs in both diabetic and high glucose models.
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Authors: Li Yu-jie , Jiang Qin , Cao Guo-fan , Yao Jin , Yan Biao
Published: June 2015

Autophagy is an important intracellular degradative process that delivers cytoplasmic proteins to lysosome for degradation. Dysfunction of autophagy is implicated in several human diseases, such as neurodegenerative diseases, infectious diseases, and cancers. Autophagy-related proteins are constitutively expressed in the eye. Increasing studies have revealed that abnormal autophagy is an important pathological feature of several ocular diseases. Pharmacological manipulation of autophagy may provide an alternative therapeutic target for some ocular diseases. In this manuscript, we reviewed the relevant progress about the role of autophagy in the pathogenesis of ocular diseases.
Tumor-Suppressing Effect of MiR-4458 on Human Hepatocellular Carcinoma
Authors: Tang Dan , Sun Baomu , Yu Hongyu , Yang Zhengde , Zhu Liang
Published: June 2015

Background: Besides multiple genetic and epigenetic changes of protein coding genes in hepatocellular carcinoma (HCC), growing evidence indicate that deregulation of miRNAs contribute to HCC development by influencing cell growth, apoptosis, migration, or invasion. IKBKE is amplified and over-expressed in a large percentage of human breast tumors and identified as an oncogene of human breast tumor. Microarray analysis showed that miR-4458 was down-regulated in HCC tissues. Methods: The level of miR-4458 was up-regulated by miR-4458 mimics transfection, or down-regulated by miR-4458 ASO transfection. Cell proliferation was assayed by MTT analysis. MiRNAs and mRNA expression were assayed by qRT-PCR. These potential targeted genes of miR-4458 were predicted by bioinformatic algorithms. Dual luciferase reporter assay system was used to analyze the interaction between miR-4458 and IKBKE. IKBKE protein level was assayed by Western blot. The role of miR-4458 or IKBKE in the survival of HCC patients were revealed by Kaplan-Meier plot of overall survival. Results: Lower miR-4458 expression level or higher IKBKE level in HCC tissues correlated with worse prognosis of HCC patients. Overexpression of miR-4458 inhibited the HCC cells growth and vice versa. MiR-4458 played its role via targeting 3'UTR of IKBKE. Conclusions: MiR-4458 or IKBKE may be potential predictors of HCC prognosis. Restoration of miR-4458 or inhibition of IKBKE could be a prospective therapeutic approach for HCC.
Endothelial Cells Regulate Cardiac Myocyte Reorganisation Through β1-Integrin Signalling
Authors: Zhang Yu , Li Hai , Wei Renyue , Ma Jing , Zhao Yanhua , Lian Zhengxing , Liu Zhonghua
Published: June 2015

Background: In normal hearts, capillaries are densely distributed throughout the myocardial tissue, and the cross-talk between myocytes and capillary endothelial cells plays a pivotal role in regulating cardiac development, maturation and function. Although previous studies have suggested a role for the endothelium in the organisation of nearby cardiomyocytes, the underlying mechanism has yet to be illustrated. Methods and Results: Using a transwell coculture system, we studied the paracrine effect of endothelial cells on cardiomyocytes and found that the regulation of cardiomyocyte spatial reorganisation and cytoskeletal dynamics by endothelial cells was coupled with β1-integrin induction. To determine the role of β1-integrin in this process, we preincubated myocytes with a β1-integrin function-blocking antibody before coculture. β1-integrin blockage abolished myocyte chemotactic activity and inhibited microtubule extension and stress fibre assembly. We further evaluated the therapeutic potential of combined endothelial cell-cardiac myocyte transplantation against ischemic cardiomyopathy in an acute myocardial infarction (AMI) mouse model. The results showed that myocytes and endothelial cells synergistically promoted ischemic myocardial repair, as evidenced by the robust engraftment and migration of implanted cells within the infarcted area, as well as the stimulation of angiogenesis, the attenuation of scar tissue and the improvement of cardiac function. Conclusion: Our study demonstrated the necessity of β1-integrin in the interactions between cardiomyocytes and endothelial cells and presented a novel combined transplantation approach that might hold promise for treating ischemic cardiomyopathy.
Wear Particles Promote Reactive Oxygen Species-Mediated Inflammation via the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Pathway in Macrophages Surrounding Loosened Implants
Authors: Chen Weishen , Li Ziqing , Guo Ying , Zhou Yuhuan , Zhang Ziji , Zhang Yangchun , Luo Guotian , Yang Xing , Liao Weiming , Li Chaohong , Chen Lingwu , Sheng Puyi
Published: June 2015

Background/Aims: Prosthesis loosening is closely associated with chronic inflammatory cytokine secretion by macrophages, which are activated by wear particles or inflammatory stimulants such as lipopolysaccharide (LPS). Reactive oxygen species (ROS) are critical regulators of inflammation, but their enzymatic sources in response to wear particles and their effects on peri-implant LPS-tolerance remain unclear. Methods: Three ROS-related enzymes—nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1 and -2 and catalase—were investigated in interface membrane tissues and in titanium (Ti) particle-stimulated macrophages in vitro. The generation of ROS and downstream inflammatory effects were measured with or without pre-incubation with apocynin, an NOX inhibitor. Results: Pre-exposure to Ti particles attenuated NF-κB activation in LPS-stimulated macrophages, indicating that wear particles suppress immune response, which may lead to chronic inflammation. NOX-1 and -2 were highly expressed in aseptically loosened interface membranes and in macrophages stimulated with Ti particles; the particles induced a moderate amount of ROS generation, NF-κB activation, and TNF-a secretion in macrophages, and these effects were suppressed by apocynin. Conclusion: Wear particles induce ROS generation through the NOX signaling pathway, resulting in persistent inflammation and delayed loosening. Thus, the suppression of NOX activity may be a useful strategy for preventing prosthesis loosening.
Downregulation of lncRNA TUG1 Affects Apoptosis and Insulin Secretion in Mouse Pancreatic β Cells
Authors: Yin Dan-dan , Zhang Er-bao , You Liang-hui , Wang Ning , Wang Lin-tao , Jin Fei-yan , Zhu Ya-nan , Cao Li-hua , Yuan Qing-xin , De Wei , Tang Wei
Published: June 2015

Background: Increasing evidence indicates that long noncoding RNAs (IncRNAs) perform specific biological functions in diverse processes. Recent studies have reported that IncRNAs may be involved in β cell function. The aim of this study was to characterize the role of IncRNA TUG1 in mouse pancreatic β cell functioning both in vitro and in vivo. Methods: qRT-PCR analyses were performed to detect the expression of lncRNA TUG1 in different tissues. RNAi, MTT, TUNEL and Annexin V-FITC assays and western blot, GSIS, ELISA and immunochemistry analyses were performed to detect the effect of lncRNA TUG1 on cell apoptosis and insulin secretion in vitro and in vivo. Results: lncRNA TUG1 was highly expressed in pancreatic tissue compared with other organ tissues, and expression was dynamically regulated by glucose in Nit-1 cells. Knockdown of lncRNA TUG1 expression resulted in an increased apoptosis ratio and decreased insulin secretion in β cells both in vitro and in vivo . Immunochemistry analyses suggested decreased relative islet area after treatment with lncRNA TUG1 siRNA. Conclusion: Downregulation of lncRNA TUG1 expression affected apoptosis and insulin secretion in pancreatic β cells in vitro and in vivo. lncRNA TUG1 may represent a factor that regulates the function of pancreatic β cells.
CYP2J2 and EETs Protect Against Lung Ischemia/Reperfusion Injury via Anti-Inflammatory Effects in Vivo and in Vitro
Authors: Chen Wenshu , Yang Shijiang , Ping Wei , Fu Xiangning , Xu Qinzi , Wang Jianing
Published: June 2015

Background: Injurious inflammatory response is critical to the development of lung ischemia/reperfusion injury (LIRI). The cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert an anti-inflammatory effect on the cardiovascular system. We therefore cytochrome hypothesized that CYP2J2 overexpression and pretreatment with exogenous EETs may have the potential to reduce LIRI. Methods: A rat model was used to mimic the condition of LIRI by clamping the left pulmonary hilum for 60 minutes, followed by reperfusion for 2 hours. Moreover, we developed a cell model using human pulmonary artery endothelial cells by anoxia for 8 hours, followed by reoxygenation for 16 hours to determine the anti-inflammatory effect and mechanism of CYP2J2 overexpression and exogenous 11,12-EET. Results: Lung ischemia/reperfusion increased lung wet/dry and lung weight/body weight ratios, protein concentration in bronchoalveolar lavage fluid and concentrations of pro-inflammatory, including mediators in serum IL-1ß, IL-8, TNF-a, sP- and sE-selectin, and decreased concentration of anti-inflammatory mediator IL-10. Ischemia/reperfusion also leaded to pulmonary edema and inflammation under light microscopy. Furthermore, activation of NF-γB p65 and degradation of IγBa were remarkably increased in ischemia/reperfusion lung tissues. While CYP2J2 overexpression significantly inhibited the above effects (p<0.05). In vitro data further confirmed the anti-inflammatory effect of CYP2J2 overexpression and 11,12-EET, an effect that may probably be mediated by PPARγ activation. Conclusion: CYP2J2 overexpression and administration of exogenous EETs can protect against LIRI via anti-inflammatory effects. This can be a novel potential strategy for prevention and treatment of LIRI.
Normative Data and Dialectical Effects on Nasalance in Flemish Adults
Authors: D''haeseleer Evelien , Bettens Kim , De Mets Sarah , De Moor Valerie , Van Lierde Kristiane
Published: June 2015

Objective: The purpose of this study was to investigate the impact of dialect and gender and to obtain normative nasalance values for Flemish adults as measured with the Nasometer II. Subjects and Methods: One hundred and sixty-four adult subjects from the five regions in Flanders corresponding to different dialects were included in the study. The group consisted of 71 adult men and 93 adult women with a mean age of 43 years and an age range between 20 and 82 years (SD 16). Nasalance scores of connected speech using an oral, an oronasal and a nasal text were measured with the Nasometer II model 6450. Results: The nasalance scores for the oral, oronasal and nasal texts are provided in this study. No significant differences were found across the five dialects and between men and women. Conclusion: This study provides new Flemish normative data as measured with the Nasometer II model 6450. The results of this study are very important for clinical purposes and for future Flemish studies collecting nasalance scores of subjects with different dialects.
Low Socioeconomic Status Is an Independent Risk Factor for Ischemic Stroke: A Case-Control Study in North Indian Population
Authors: Kumar Amit , Prasad Manya , Kathuria Prachi , Nair Pallavi , Pandit Awadh Kishor , Sahu Jitendra K. , Prasad Kameshwar
Published: June 2015

Background: Stroke is a multifactorial disease and is influenced by complex environmental interactions. The contribution of various risk factors to the burden of stroke worldwide is not well known, particularly in developing countries. The present case-control study is aimed at exploring the association between a low socioeconomic status and the risk of ischemic stroke among the North Indian population. Methods: The study design was a hospital-based, case-control study. Age- and sex-matched controls were included. The demographic characteristics and risk factor variables were documented by means of a personal interview through a standardized case record form. The household asset index for determining the socioeconomic status (HAISS) was used for the assessment of the socioeconomic status of the population. HAISS was validated with the widely used Kuppuswamy scale for measurement of socioeconomic status. The multivariable logistic regression model was used to estimate the odds ratio associated with stroke. Results: In all, 224 ischemic stroke patients and 224 controls were recruited between February 2009 and February 2012. The mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The low economic status was independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.8; 95% CI 1.2-6.3). Conclusion: Our findings suggest that there is a significant association between a low socioeconomic status and the risk of ischemic stroke risk in North Indian population. Well-designed studies embedded with long-term prospective cohorts are required for confirming the results.
Lymphoproliferative Disorders in Patients with Chronic Myeloid Leukemia: A Single-Center Case Series
Authors: Alshehry Nawal F. , Al-Huneini Mohammed , Lipton Jeffrey H. , Michelis Fotios V.
Published: June 2015

Lymphoproliferative disorders presenting simultaneously with or subsequent to the occurrence of chronic myeloid leukemia (CML) have rarely been reported. Herein, we report 8 cases of a variety of lymphoproliferative conditions associated with CML at different times during the course of the disease. All 8 patients were treated with tyrosine kinase inhibitors at some point during the course of their illness. The literature regarding the uncommon association of these apparently unrelated disorders is reviewed as well as the possible underlying mechanisms that could be associated with this phenomenon.
Interaural Level Difference Cues Determine Sound Source Localization by Single-Sided Deaf Patients Fit with a Cochlear Implant
Authors: Dorman Michael F. , Zeitler Daniel , Cook Sarah J. , Loiselle Louise , Yost William A. , Wanna George B. , Gifford Rene H.
Published: June 2015

In this report, we used filtered noise bands to constrain listeners' access to interaural level differences (ILDs) and interaural time differences (ITDs) in a sound source localization task. The samples of interest were listeners with single-sided deafness (SSD) who had been fit with a cochlear implant in the deafened ear (SSD-CI). The comparison samples included listeners with normal hearing and bimodal hearing, i.e. with a cochlear implant in 1 ear and low-frequency acoustic hearing in the other ear. The results indicated that (i) sound source localization was better in the SSD-CI condition than in the SSD condition, (ii) SSD-CI patients rely on ILD cues for sound source localization, (iii) SSD-CI patients show functional localization abilities within 1-3 months after device activation and (iv) SSD-CI patients show better sound source localization than bimodal CI patients but, on average, poorer localization than normal-hearing listeners. One SSD-CI patient showed a level of localization within normal limits. We provide an account for the relative localization abilities of the groups by reference to the differences in access to ILD cues.
Atrial Fibrillation: Recent Advances in Understanding the Role of MicroRNAs in Atrial Remodeling with an Electrophysiological Overview
Authors: Poudel Pradeep , Xu Yanmin , Cui Zhanqian , Sharma Deepak , Tian Bing , Paudel Sudarshan
Published: June 2015

Atrial fibrillation (AF) is a highly prevalent condition associated with pronounced cardiovascular-related morbidity, mortality and socioeconomic burden. It accounts for more hospitalization days than does any other arrhythmia. This article reviews the basic electrophysiology of AF, electrical and structural remodeling in AF and recent advances in understanding the molecular mechanisms of AF in relation to specific microRNAs. This paper also reviews the potential role of microRNAs as novel therapeutic targets as well as biomarkers in the management of AF. AF shows characteristics typical of altered electrophysiology that promote ectopic activity and facilitate reentry, thereby contributing to the progression from short paroxysmal AF to a persistent, permanent form via atrial remodeling, even in the absence of progressive underlying heart disease. MicroRNAs have been suggested to influence the development of AF by regulating gene expression at the post-transcriptional level. Increasing evidence has identified various microRNA modifications and their impacts on AF initiation and maintenance through electrical and structural remodeling. The discovery of specific microRNAs as novel therapeutic targets and some experimental evidence implicating microRNAs as potential molecular diagnostic markers have had a significant impact on the diagnosis and management of AF and demand further research.
Association between Dairy Intake and Caries among Children and Adolescents. Results from the Danish EYHS Follow-Up Study
Authors: Lempert Susanne M. , Christensen Lisa B. , Froberg Karsten , Raymond Kyle , Heitmann Berit L.
Published: June 2015

The aim of this paper was to investigate associations between the intake of dairy products and the development in caries (DMFS, decayed, missing and filled surfaces) among children/adolescents over a period of 3 and 6 years, and to investigate whether dairy intake protects against caries incidence. A total of 68.9% of the children were caries free at the age of 9 compared with 34.0% of the adolescents at the age of 15 (measured as DMFS = 0). A larger percentage of children/adolescents with a dairy intake above the mean were caries free compared with the group of children/adolescents with an intake below the mean (72.8 vs. 65.8% at age 9 and 41.1 vs. 30.7% at age 15). The results from the generalized estimation equation showed that dairy and milk intake, as well as intakes of components of dairy such as dairy calcium, whey and casein, was generally inversely associated with childhood/adolescent caries experience (measured as DMFS). With regard to caries incidence, the same inverse association was found for incidence over a period of 3 years and for incidence over 6 years, but the results were only statistically significant for the 3-year incidence and for the unadjusted models of the 6-year incidence. This study found that previous dairy intake, as well as milk intake or intake of dairy components, may be a predictor of future risk of caries measured by the DMFS count level. This relationship was inverse, meaning that a high intake of dairy products was associated with less future caries development. However, more studies on larger cohorts are needed to confirm these findings.
Atypical Fibroxanthoma of the Conjunctiva in Xeroderma Pigmentosum
Authors: Shalabi Nabeel , Galor Anat , Dubovy Sander R. , Thompson Jordan , Bermudez-Magner J. Antonio , Karp Carol L.
Published: June 2015

Background: Atypical fibroxanthoma (AFX) is a pleomorphic tumor that most commonly presents in the elderly and arises on sun-exposed skin. Methods: We report a case of a 24-year-old white male with xeroderma pigmentosum (XP), who developed an AFX of the conjunctiva, and review the literature. Results: The patient presented with a rapidly growing conjunctival mass which was surgically excised and found to be AFX. The patient has done well with no recurrence. A review of the literature was performed, and we found that only one other case has been published so far. Conclusion: Patients with XP may present with unusual tumors, including nonepithelial soft-tissue tumors. AFX is a rapidly growing tumor which may rarely present on the ocular surface.
Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients
Authors: Wang Zhaolu , Wong Adrian , Liu Wenyan , Yang Jie , Chu Winnie C.W. , Au Lisa , Lau Alexander , Chan Anne , Xiong Yunyun , Soo Yannie , Leung Thomas , Wong Lawrence K.S. , Mok Vincent C.T.
Published: June 2015

Background: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). Methods: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. Results: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). Conclusion: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.
A Cluster Randomized Controlled Trial of Nonpharmacological Interventions for Old-Old Subjects with a Clinical Dementia Rating of 0.5: The Kurihara Project
Authors: Nakatsuka Masahiro , Nakamura Kei , Hamanosono Ryo , Takahashi Yumi , Kasai Mari , Sato Yuko , Suto Teiko , Nagatomi Ryoichi , Meguro Kenichi
Published: June 2015

Background: Evidence as to the benefits of nonpharmacological interventions for the boundary state between normal aging and dementia [mild cognitive impairment or a Clinical Dementia Rating (CDR) of 0.5] remains weak due to a lack of positive controls. Aims: To directly compare the effects of cognitive interventions (CI), physical activities (PA) and a group reminiscence approach (GRA), we conducted a pilot study on the basis of a cluster randomized controlled trial design. Method: A total of 127 participants aged >74 years with a CDR of 0.5 were cluster randomized into three groups for CI, PA and GRA. The intervention lasted 12 weeks and consisted of weekly group sessions and home assignments. Mini-Mental State Examination (MMSE), Trail Making Test part A (TMT-A), word fluency (WF), 6-meter walk time and Quality of Life (QOL) Face Scale scores were evaluated as primary outcomes. Results: Methodology-related benefits of CI and PA were found for MMSE scores and walk time, respectively. TMT-A, WF and QOL Face Scale scores improved irrespective of the methodologies used. Conclusions: Our findings suggest that CI and PA may be beneficial to cognitive and physical abilities, respectively. Executive functions and QOL may improve irrespective of the intervention methodologies used.
Vitamin D3 Treatment Decreases Frequencies of CD16-Positive and TNF-α-Secreting Monocytes in Asthmatic Patients
Authors: Grubczak Kamil , Lipinska Danuta , Eljaszewicz Andrzej , Singh Paulina , Radzikowska Urszula , Miklasz Paula , Dabrowska Milena , Jablonska Ewa , Bodzenta-Lukaszyk Anna , Moniuszko Marcin
Published: June 2015

Background: Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties. Methods: Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry. Results: We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects. Conclusions: This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC.
Repigmentierung ausgedehnter inflammatorischer Vitiligo mit erhabenem Saum durch frühzeitige und aggressive Behandlung
Authors: Gunasekera Nicole , Murphy George F. , Sheth Vaneeta M.
Published: June 2015

Die inflammatorische Vitiligo mit erhabenem Saum (inflammatory vitiligo with raised borders; IVRB) ist ein seltener Subtyp der Vitiligo, der durch einen erhabenen, erythematösen, die depigmentierten Flecken umgebenden Rand definiert ist. Die Ätiologie ist weitgehend ungeklärt; in der Literatur gibt es nur wenige Berichte über erfolgreiche Behandlungen. Wir berichten über den Fall eines 38-jährigen Patienten südasiatischer Abstammung, der sich mit kleinen und größeren diffusen, über große Teile der Körperoberfläche disseminierten depigmentierten Flecken mit blau-grauem Rand vorstellte. Die Lichtmikroskopie ergab den Befund einer inflammatorischen Vitiligo. Der Patient wurde mit 2 Zyklen oralem Prednison und einer Ganzkörper-UV-Fototherapie mit Schmalband-UV-B-Strahlung behandelt, wodurch die Ausbreitung der Krankheit aufgehalten und eine weitgehende Repigmentierung erreicht wurde. Unsere Beobachtungen deuten darauf hin, dass eine frühzeitige und aggressive Behandlung bei IVRB zu signifikanter und schneller Besserung führen kann.
Initiation of Renal Replacement Therapy in the Intensive Care Unit in Vicenza (IRRIV) Score
Authors: Zaragoza Jose J. , Villa Gianluca , Garzotto Francesco , Sharma Aashish , Lorenzin Anna , Ribeiro Leonardo , Lu Renhua , Bellomo Rinaldo , Ronco Claudio ,   NEFROINT investigators
Published: June 2015

Introduction: One of the top research priorities in acute kidney injury is related to the timing of renal replacement therapy (RRT) initiation. The purpose was to develop an index that might serve as a standardized concept of timing of initiation of RRT. Methods: A previously described database was used. We applied a multivariable Cox regression model with backward selection to characterize parameters present in those patients who received RRT compared with those who did not receive RRT. Results: We studied 590 patients. We identified independent risk factors for RRT and a risk score was devised. The Area Under the Curve of the receiver operating characteristic curve was 0.81 (95% CI 0.74-0.86) for predicting the need for RRT. Conclusions: We have developed a simple Score (IRRIV Score) to identify patients at high risk of requiring RRT. This score may serve as a standardized definition of the timing of initiation of RRT.