bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senescence and odontoblastic differentiation of dental pulp cells
Authors: Nozu Aoi , Hamano Sayuri , Tomokiyo Atsushi , Hasegawa Daigaku , Sugii Hideki , Yoshida Shinichiro , Mitarai Hiromi , Taniguchi Shuntaro , Wada Naohisa , Maeda Hidefumi 
Published: August 2018

Cellular senescence has been suggested to be involved in physiological changes of cytokine production. Previous studies showed that the concentration of tumor necrosis factor‐α (TNF‐α) is higher in the blood of aged people compared with that of young people. So far, the precise effects of TNF‐α on the odontoblastic differentiation of pulp cells have been controversial. Therefore, we aimed to clarify how this cytokine affected pulp cells during aging. Human dental pulp cells (HDPCs) were cultured until reaching the plateau of their growth, and the cells were isolated at actively (young HDPCs; yHDPCs) or inactively (senescent HDPCs; sHDPCs) proliferating stages. sHDPCs expressed senescence‐related molecules while yHDPCs did not. When these HDPCs were cultured in an odontoblast‐inductive medium, both young and senescent cells showed mineralization, but mineralization in sHDPCs was lower compared with yHDPCs. However, the administration of TNF‐α to this culture medium altered these responses: yHDPCs showed downregulated mineralization, while sHDPCs exhibited significantly increased mineralization. Furthermore, the expression of tumor necrosis factor receptor 1 (TNFR1), a receptor of TNF‐α, was significantly upregulated in sHDPCs compared with yHDPCs. Downregulation of TNFR1 expression led to decreased mineralization of TNF‐α‐treated sHDPCs, whereas restored the reduction in TNF‐α‐treated yHDPCs. These results suggested that sHDPCs preserved the odontoblastic differentiation capacity and TNF‐α promoted odontoblastic differentiation of HDPCs with the progress of their population doublings through increased expression of TNFR1. Thus, TNF‐α might exert a different effect on the odontoblastic differentiation of HDPCs depending on their proliferating activity. In addition, the calcification of pulp chamber with age may be related with increased reactivity of pulp cells to TNF‐α.
Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats
Authors: Jiang Run‐Hao , Wu Chen‐Jiang , Xu Xiao‐Quan , Lu Shan‐Shan , Zu Qing‐Quan , Zhao Lin‐Bo , Wang Jun , Liu Sheng , Shi Hai‐Bin 
Published: August 2018

In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label‐free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label‐free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.
Hyaluronidase2 (Hyal2) modulates low shear stress‐induced glycocalyx impairment via the LKB1/AMPK/NADPH oxidase‐dependent pathway
Authors: Yang Hongfeng , Zhu Linlin , Chao Yuelin , Gu Yue , Kong Xiangquan , Chen Mingxing , Ye Peng , Luo Jie , Chen Shaoliang 
Published: August 2018

The endothelium glycocalyx layer (ECL), presents on the apical surface of endothelial cells, creates a barrier between circulating blood and the vessel wall. Low shear stress (LSS) may accelerate the degradation of the glycocalyx via hyaluronidase2 (Hyal2) and then alter the cell polarity. Yet the liver kinase B1 (LKB1) signaling pathway plays an important role in regulating cell polarity. However, the relationship between LKB1 and glycocalyx during LSS is not clear. In the current study, we demonstrate that LSS attenuates LKB1 and AMP‐activated protein kinase activation as well as activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47phox) and Hyal2 in the human umbilical vein endothelial cell (HUVEC). Pretreatment with 5‐Aminoimidazole‐4‐carboxamide1‐β‐D‐ribofuranoside (AICAR), or diphenyleneiodonium (DPI chloride) and transfection with LKB1 overexpression vector and p47phox small interfering RNA downregulated LSS‐induced Hyal2 activation. By coimmunoprecipitation, we discovered the existence of p47phox/Hyal2 complex. LSS induced the dissociation of p47phox/Hyal2 complex, which was inhibited by LKB1 overexpression and AICAR. Furthermore, knockdown of Hyal2 performed a positive feedback on LKB1 activity. In addition, we also show that LSS enhanced LKB1 translocation from the cytosol to the nucleus. Taken together, these data indicate that Hyal2 regulates LSS‐induced injury of the glycocalyx via LKB1/AMPK/NADPH oxidase signaling cascades.
Cellular senescence: Molecular mechanisms and pathogenicity
Authors: Wei Wenqiang , Ji Shaoping 
Published: August 2018

Cellular senescence is the arrest of normal cell division. Oncogenic genes and oxidative stress, which cause genomic DNA damage and generation of reactive oxygen species, lead to cellular senescence. The senescence‐associated secretory phenotype is a distinct feature of senescence. Senescence is normally involved in the embryonic development. Senescent cells can communicate with immune cells to invoke an immune response. Senescence emerges during the aging process in several tissues and organs. In fact, increasing evidence shows that cellular senescence is implicated in aging‐related diseases, such as nonalcoholic fatty liver disease, obesity and diabetes, pulmonary hypertension, and tumorigenesis. Cellular senescence can also be induced by microbial infection. During cellular senescence, several signaling pathways, including those of p53, nuclear factor‐κB (NF‐κB), mammalian target of rapamycin, and transforming growth factor‐beta, play important roles. Accumulation of senescent cells can trigger chronic inflammation, which may contribute to the pathological changes in the elderly. Given the variety of deleterious effects caused by cellular senescence in humans, strategies have been proposed to control senescence. In this review, we will focus on recent studies to provide a brief introduction to cellular senescence, including associated signaling pathways and pathology.
Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties
Authors: Hatamipour Mahdi , Ramezani Mahin , Tabassi Sayyed Abolghasem Sajadi , Johnston Thomas P. , Ramezani Mahnaz , Sahebkar Amirhosein 
Published: August 2018

The eradication of cancer in a patient remains an elusive challenge despite advances in early detection and diagnosis, chemo‐ and immunotherapy, pinpoint radiation treatments, and expert surgical intervention. Although significant gains have been made in our understanding of cancer cell biology, a definite cure for most cancers does not exist at present. Thus, it is not surprising that the research and medical communities continue to explore the importance and therapeutic potential of natural products in their multimodality cancer treatment approach. Curcuminoids found in turmeric are one such class of natural products that have been extensively investigated for their potential to halt the progression of cancer cell proliferation and, more important, to stop metastasis from occurring. In this review, we examine one curcuminoid (demethoxycurcumin [DMC]) largely because of its increased stability and better aqueous solubility at physiological pH, unlike the more well‐known curcuminoid (curcumin), which is largely unabsorbed after oral ingestion. The present review will focus on the signaling pathways that DMC utilizes to modulate the growth, invasion, and metastasis of cancer cells in an effort to provide enhanced mechanistic insight into DMC’s action as it pertains to brain, ovarian, breast, lung, skin, and prostate cancer. Additionally, this review will attempt to provide an overview of DMC’s mechanism of action by modulating apoptosis, cell cycle, angiogenesis, metastasis, and chemosensitivity. Lastly, it is hoped that increased understanding will be gained concerning DMC’s interactive role with microRNA‐551a, 5′ adenosine monophosphate‐activated protein kinase, nuclear factor‐κB, Wnt inhibitory factor‐1, and heat shock protein 70 to affect the progression of cancer.
Anemia in celiac disease is multifactorial in etiology: A prospective study from India
Authors: Berry Neha , Basha Jahangeer , Varma Neelam , Varma Subhash , Prasad Kaushal Kishor , Vaiphei Kim , Dhaka Narendra , Sinha Saroj K , Kochhar Rakesh 
Published: August 2018

Background and AimsAnemia is one of the most common extraintestinal manifestations of celiac disease (CD), with iron deficiency anemia (IDA) being the predominant cause. However, anemia in CD can have varied etiologies, including mixed nutritional deficiency. We aimed to study the prevalence and etiology of anemia in CD in a north Indian population.MethodsIn this prospective observational study, consecutive patients with documented CD between January 2012 and December 2013 were included, and all patients underwent detailed clinical assessment; hematological investigations including iron profile, serum folate, and vitamin B12 levels; and esophageoduodenoscopy with duodenal biopsies for histopathological examination. Prevalence of anemia and different deficiencies were calculated, and a correlation between hematological parameters and histological findings was found.ResultsOf the 103 patients studied, anemia was detected in 96 patients, giving a prevalence of 93.2% with a baseline hemoglobin of 8.94 ± 2.54 g/dL. Overall, iron deficiency was seen in 84 (81.5%) patients, followed by vitamin B12 deficiency in 14 (13.6%) and folate deficiency in 11 (10.7%) patients; 17 (16.5%) patients had anemia due to mixed nutritional deficiencies, and 4 (3.9%) patients had anemia of chronic disease. The mean hemoglobin and median ferritin levels were significantly lower in patients with severe villous atrophy compared to those with mild atrophy.ConclusionAnemia in patients with CD is multifactorial. Even though iron deficiency is the most common cause, other nutrient deficiencies should always be explored.
Transduction efficacy and retrograde movement of a lentiviral vector pseudotyped by modified rabies glycoprotein throughout the trisynaptic circuit of the rat hippocampus
Authors: Farzaneh Mostafa , Sayyah Mohammad , Eshraghi Hamid Reza , Panahi Negar , Delavar Hadi Mirzapour , Pourbadie Hamid Gholami 
Published: August 2018

AbstractBackgroundThe trisynaptic circuit (entorhinal cortex–dentate gyrus–CA3–CA1) is a key unidirectional network in the hippocampus. Damage to the hippocampus interrupts this circuit and causes neurological disorders. Efficient delivery of therapeutic genes into this network is of great interest with respect to treating trisynaptic circuit pathologies.MethodsWe generated a lentivector system pseudotyped by a variant of rabies glycoprotein, FUG‐B2. The efficiency of the vector in the retrograde transduction of the rat hippocampal neurons (i.e. the entorhinal cortex from the dentate gyrus, the dentate gyrus from CA3, and CA3 from CA1) was examined by direct injection of the vector into the dentate gyrus, CA3 and CA1. To distinguish transduction of the neuronal and glial cells, as well as selective retrograde gene transfer, double‐staining of the green fluorescent protein (GFP) expressing cells with the specific neuron biomarker NeuN (neuronal nuclear protein) and the specific glia biomarker GFAP (glial fibrillary acidic protein) was performed across the network.ResultsThe transgene was successfully introduced into the circuit. More than 80% of the neuronal and glial cells at the injection sites preserved GFP expression during the 2‐month period after vector injection. Importantly, GFP was expressed selectively in almost 80.0% of the presynaptic neuronal cells by retrograde axonal transport of the vector.ConclusionsThe FUG‐B2‐based vector system can efficiently introduce the transgene into the rat hippocampal neurons both directly and indirectly through retrograde monosynaptic movement. This efficient and long‐lasting gene delivery might provide a tool for treating neurological disorders originating in hippocampal circuits.
Simultaneous study of mechanobiology and calcium dynamics on hESC‐derived cardiomyocytes clusters
Authors: Caluori Guido , Pribyl Jan , Cmiel Vratislav , Pesl Martin , Potocnak Tomas , Provaznik Ivo , Skladal Petr , Rotrekl Vladimir 
Published: August 2018

AbstractCalcium ions act like ubiquitous second messengers in a wide amount of cellular processes. In cardiac myocytes, Ca2+ handling regulates the mechanical contraction necessary to the heart pump function. The field of intracellular and intercellular Ca2+ handling, employing in vitro models of cardiomyocytes, has become a cornerstone to understand the role and adaptation of calcium signalling in healthy and diseased hearts. Comprehensive in vitro systems and cell‐based biosensors are powerful tools to enrich and speed up cardiac phenotypic and drug response evaluation.We have implemented a combined setup to measure contractility and calcium waves in human embryonic stem cells‐derived cardiomyocyte 3D clusters, obtained from embryoid body differentiation. A combination of atomic force microscopy to monitor cardiac contractility, and sensitive fast scientific complementary metal‐oxide‐semiconductor camera for epifluorescence video recording, provided correlated signals in real time. To speed up the integrated data processing, we tested several post‐processing algorithms, to improve the automatic detection of relevant functional parameters. The validation of our proposed method was assessed by caffeine stimulation (10mM) and detection/characterization of the induced cardiac response.We successfully report the first simultaneous recording of cardiac contractility and calcium waves on the described cardiac 3D models. The drug stimulation confirmed the automatic detection capabilities of the used algorithms, measuring expected physiological response, such as elongation of contraction time and Ca2+ cytosolic persistence, increased calcium basal fluorescence, and transient peaks. These results contribute to the implementation of novel, integrated, high‐information, and reliable experimental systems for cardiac models and drug evaluation.
Microstructural and Neurochemical Changes in the Rat Brain After Diffuse Axonal Injury
Authors: Chen Xiran , Chen Yanzi , Xu Yuan , Gao Qilu , Shen Zhiwei , Zheng Wenbin 
Published: August 2018

BackgroundDiffuse axonal injury (DAI) is one of the devastating types of traumatic brain injury, but is difficult to detect on conventional imaging in its early stages.PurposeTo test the technical feasibility and diagnostic value of diffusion kurtosis imaging (DKI) and glutamate chemical exchange saturation transfer (GluCEST) imaging in the brain after DAI.Study TypeProspective.Animal ModelSixty Sprague‐Dawley rats. The DAI model was induced by using the impact acceleration model of Marmarou et al with modified settings.Field Strength/SequenceA 7.0T animal MR scanner with a fast spin‐echo sequence (T2‐weighted imaging), fast spin‐echo multislice sequence (DKI), echo planar imaging in the signal of the chemical exchange saturation transfer sequence (CEST), and point‐resolved spectroscopy sequence (hydrogenproton magnetic resonance spectroscopy, 1H‐MRS).AssessmentBrain MRI scanned before and 2 hours after injury. DKI images were processed with MatLab and MRIcro software, GluCEST images were processed using software routines written in MatLab, and spectroscopic data were postprocessed with LCModel.Statistical TestsThe parameters of these techniques were assessed using the independent sample t‐test and Pearson correlation.ResultsMean kurtosis and mean diffusivity values were significantly higher than controls in the parietal lobe, hippocampus, and thalamus (P <  0.01). However, fractional anisotropy was lower only in the parietal lobe, with no detectable changes in the hippocampus and thalamus. GluCEST values of the parietal lobe, hippocampus, and thalamus were significantly higher than controls in DAI rats (P <  0.01). This change was further validated through 1H‐MRS. A positive correlation was observed between glutamate (Glu) and glutamate compound (Glx) concentrations and GluCEST values (Glu: R2 = 0.589, Glx: R2 = 0.878).Data ConclusionDKI and GluCEST might be acceptably sensitive for tracking microstructural and neurochemical changes in the brain following DAI.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;49:1069–1077.
Distribution of hepatitis C genotypes in Uttar Pradesh, India; rare genotype 4 detected
Authors: Prakash Shantanu , Shukla Suruchi , Ramakrishna Vangala , Jain Amita 
Published: August 2018

AimThe worldwide prevalence of hepatitis C virus infection (HCV) is nearly 150 to 170 million cases. The prevalence of HCV infection in India is estimated to be around 1%. In India HCV genotype (GT)3 is the predominant GT followed by GT1. Our study aims to establish the prevalent GTs/subtypes of HCV circulating in Uttar Pradesh, North India, as reported from a tertiary care hospital.MethodsThe study was a retrospective observational analysis of consecutive 404 HCV RNA positive cases referred to our hospital from September 2014 to April 2017, and was approved by an institutional ethics committee. Written informed consent was taken from each participant. Clinical and demographic details of these patients were recorded using predesigned questionnaires. All the laboratory testing was carried out on a stored serum sample of enrolled cases. Genotyping of all 404 strains was done by Sanger’s sequencing of the core region. The phylogenetic analysis of 179 HCV strains with a high‐quality sequencing data was performed.ResultsThe distributions of prevalent GTs/subtypes as noted in the current study were (
n [%]): GT1a, 101 (25%); GT1b, 12 (2.9%); GT1c, 1 (0.25%); GT3a, 275 (68.07%); GT3b, 9 (2.2%); GT3g, 2 (0.49%); GT3i, 3 (0.74%); and GT4a, 1 (0.24%). HCV GTs GT2, GT5, and GT6 were not detected from our region. Sequence analysis showed high genotypic variability in HCV GT3. Phylogenetic analysis showed that HCV GT3 and GT1 circulating in our region were related to Indian strains reported earlier.ConclusionsHCV GTs 3a and 1a are the commonest circulating GTs in Uttar Pradesh, India.
EEG discrimination of perceptually similar tastes
Authors: Andersen Camilla Arndal , Kring Marianne Leonard , Andersen Rasmus Holm , Larsen Ole Næsbye , Kjær Troels Wesenberg , Kidmose Ulla , Møller Stine , Kidmose Preben 
Published: August 2018

AbstractPerceptually similar stimuli, despite not being consciously distinguishable, may result in distinct cortical brain activations. Hypothesizing that perceptually similar tastes are discriminable by electroencephalography (EEG), we recorded 22 human participants’ response to equally intense sweet‐tasting stimuli: caloric sucrose, low‐caloric aspartame, and a low‐caloric mixture of aspartame and acesulfame K. Time‐resolved multivariate pattern analysis of the 128‐channel EEG was used to discriminate the taste responses at single‐trial level. Supplementing the EEG study, we also performed a behavioral study to assess the participants’ perceptual ability to discriminate the taste stimuli by a triangle test of all three taste pair combinations. The three taste stimuli were found to be perceptually similar or identical in the behavioral study, yet discriminable from 0.08 to 0.18 s by EEG analysis. Comparing the participants’ responses in the EEG and behavioral study, we found that brain responses to perceptually similar tastes are discriminable, and we also found evidence suggesting that perceptually identical tastes are discriminable by the brain. Moreover, discriminability of brain responses was related to individual participants’ perceptual ability to discriminate the tastes. We did not observe a relation between brain response discriminability and calorie content of the taste stimuli. Thus, besides demonstrating discriminability of perceptually similar and identical tastes with EEG, we also provide the first proof of a functional relation between brain response and perception of taste stimuli at individual level.
Impact of Feeding on Resting Metabolic Rate and Gas Exchange in Critically Ill Patients
Authors: Frankenfield David C. 
Published: August 2018

AbstractBackgroundFeeding is understood to alter gas exchange and resting metabolic rate (RMR) in critically ill patients, but there are limited data describing such changes.MethodsA large collection of RMR measurements and energy intake was assembled in mechanically ventilated and critically ill patients. The data were used to explore differences in RMR, respiratory quotient (RQ), and carbon dioxide production (V̇co2) related to feeding state.ResultsA total of 708 RMR measurements were available. No significant thermogenic effect of feeding could be appreciated. When controlled for body weight, the difference was 4.2% (1946 ± 400 kcal/d for unfed vs 2028 ± 341 kcal/d for fed patients; P = .299), and this small difference was fully eliminated when body temperature was also controlled for. RQ increased as carbohydrate and energy intake increased, but there was much variation in the relationship. Among 215 overfed patients, only 22 had RQ ≥1.0, and among 9 patients whose carbohydrate intake alone exceeded RMR, only 4 had an RQ ≥1.0. V̇co2 was influenced mainly by the volume of oxygen consumed and to a lesser degree by carbohydrate intake.ConclusionsNo appreciable thermogenic effect of feeding occurs in continuously fed critically ill patients. This factor does not need to be considered in the assessment of resting energy needs. RQ is not a reliable indicator of overfeeding, and the ability of carbohydrate intake to alter V̇co2 is small, although not absent.