Miracle-dz/UniFAR-FTUs huggingface dataset:
Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects

Considering the increased interest in cell‐based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti‐apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3‐E1 osteoblastic cells from H2O2‐induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27‐overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4‐week of transplantation, both control cell‐ and Hsp27 overexpressed cell‐transplanted groups showed significantly higher new bone formation in comparison with cell‐free gel‐transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4‐week but did not differentiate into bone‐forming osteoblasts. In conclusion, cell‐containing collagen gel accelerated calvarial bone defect healing in comparison with cell‐free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation‐based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974–1982, 2016. © 2016 Wiley Periodicals, Inc.
Involvement of Transient Receptor Potential Cation Channel Vanilloid 1 (TRPV1) in Myoblast Fusion

The mechanisms that underlie the complex process of muscle regeneration after injury remain unknown. Transient receptor potential cation channel vanilloid 1 (TRPV1) is expressed in several cell types, including skeletal muscle, and is activated by high temperature and by certain molecules secreted during tissue inflammation. Severe inflammation and local temperature perturbations are induced during muscle regeneration, which suggests that TRPV1 might be activated and involved in the process. The aim of this study, was to clarify the role of TRPV1 in the myogenic potential of satellite cells responsible for muscle regeneration. We found that mRNA and protein levels of TRPV1 increased during regeneration after cardiotoxin (CTX)‐induced muscle injury in mice. Using isolated mouse satellite cells (i.e., myoblasts), we observed that activation of TRPV1 by its agonist capsaicin (CAP) augmented myogenin protein levels. Whereas CAP did not alter myoblast proliferation, it facilitated myoblast fusion (evaluated using myonucleii number per myotube and fusion index). In contrast, suppression of TRPV1 by siRNA impaired myoblast fusion. Using mice, we also demonstrated that intramuscular injection of CAP facilitated muscle repair after CTX‐induced muscle injury. Moreover, we showed that these roles of TRPV1 might be mediated by interleukin‐4 and calcium signaling during myoblast fusion. Collectively, these results suggest that TRPV1 underlies normal myogenesis through promotion of myoblast fusion. J. Cell. Physiol. 231: 2275–2285, 2016. © 2016 Wiley Periodicals, Inc.
Acoustic Impedance Measures in the Down's Population

Impedance audiometry has proved to be especially valuable in the auditory evaluation of difficult-to-test children—including those youngsters with Down's syndrome. The impedance technique is extremely sensitive in differentiating between normal and pathologic middle ears. Impedance measurements, especially tympanometry and acoustic reflex testing, may be used prior to traditional audiometric tests so that the clinician will know what type of hearing impairment to anticipate. Some clinicians prefer to perform tympanometry and acoustic reflex measurement following routine audiometry to confirm pure tone results. In either case, acoustic impedance measurements provide important information concerning the otologic status of all pediatric patients. The Down's child certainly has many potential reasons for presenting with conductive-type hearing impairment. Ear symptoms commonly associated with Down's include small pinnae, narrow external auditory canals, abnormal external ear configuration, and a strong tendency to have otitis media (Rigrodsky, Prunty, and Glovsky, 1961). In addition, it has been suggested that the Down's child may be more susceptible to upper respiratory tract infections than the normal child because of peculiar skull development, which can adversely affect proper drainage of the sinuses and middle-ear spaces (Mclntire, Menolascino, and Wiley, 1965). Thus, with the numerous difficulties that may be encountered when performing routine audiometry with mentally retarded children, impedance measurements often confirm or rule out the presence of conductive-type hearing disorder.
Skin Metabolite, Farnesyl Pyrophosphate, Regulates Epidermal Response to Inflammation, Oxidative Stress, and Migration

Skin produces cholesterol and a wide array of sterols and non‐sterol mevalonate metabolites, including isoprenoid derivative farnesyl pyrophosphate (FPP). To characterize FPP action in epidermis, we generated transcriptional profiles of primary human keratinocytes treated with zaragozic acid (ZGA), a squalene synthase inhibitor that blocks conversion of FPP to squalene resulting in endogenous accumulation of FPP. The elevated levels of intracellular FPP resulted in regulation of epidermal differentiation and adherens junction signaling, insulin growth factor (IGF) signaling, oxidative stress response and interferon (IFN) signaling. Immunosuppressive properties of FPP were evidenced by STAT‐1 downregulation and prominent suppression of its nuclear translocation by IFNγ. Furthermore, FPP profoundly downregulated genes involved in epidermal differentiation of keratinocytes in vitro and in human skin ex vivo. Elevated levels of FPP resulted in induction of cytoprotective transcriptional factor Nrf2 and its target genes. We have previously shown that FPP functions as ligand for the glucocorticoid receptor (GR), one of the major regulator of epidermal homeostasis. Comparative microarray analyses show significant but not complete overlap between FPP and glucocorticoid regulated genes, suggesting that FPP may have wider transcriptional impact. This was further supported by co‐transfection and chromatin immunoprecipitation experiments where we show that upon binding to GR, FPP recruits β‐catenin and, unlike glucocorticoids, recruits co‐repressor GRIP1 to suppress keratin 6 gene. These findings have many clinical implications related to epidermal lipid metabolism, response to glucocorticoid therapy as well as pleiotropic effects of cholesterol lowering therapeutics, statins. J. Cell. Physiol. 231: 2452–2463, 2016. © 2016 Wiley Periodicals, Inc.
Apigenin Reduces Survival of Choriocarcinoma Cells by Inducing Apoptosis via the PI3K/AKT and ERK1/2 MAPK Pathways

Apigenin is a flavonoid found in parsley, onions, oranges, tea, chamomile, wheat, and sprouts. It has a variety of biological properties including anti‐oxidant, anti‐mutagenic, anti‐carcinogenic, anti‐inflammatory, anti‐proliferative, and anti‐spasmodic effects. Based on epidemiological and case‐control studies, apigenin is regarded as a novel chemotherapeutic agent against various cancer types. However, little is known about the effects of apigenin on choriocarcinoma cells. Therefore, we investigated the anti‐cancer effects of apigenin on choriocarcinoma cells (JAR and JEG3) in the present study. Apigenin reduced viability and migratory properties, increased apoptosis, and suppressed mitochondrial membrane potential in both the JAR and JEG3 cells. In addition, apigenin predominantly decreased phosphorylation of AKT, P70RSK, and S6 whereas the phosphorylation of ERK1/2 and P90RSK was increased by apigenin treatment of JAR and JEG3 cells in a dose‐dependent manner. Moreover, treatment of JAR and JEG3 cells with both apigenin and pharmacological inhibitors of PI3K/AKT (LY294002) and ERK1/2 (U0126) revealed synergistic anti‐proliferative effects. Collectively, these results indicated that the apigenin is an invaluable chemopreventive agent that inhibits progression and metastasis of choriocarcinoma cells through regulation of PI3K/AKT and ERK1/2 MAPK signal transduction mechanism. J. Cell. Physiol. 231: 2690–2699, 2016. © 2016 Wiley Periodicals, Inc.
Intricate Functions of Matrix Metalloproteinases in Physiological and Pathological Conditions

Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryological development to apoptosis. The activity of MMPs is controlled at three different stages: (1) transcription; (2) zymogen activation; and (3) inhibition of active forms by tissue inhibitor metalloproteinases (TIMPs). They can collectively degrade any component of ECM and basement membrane, and their excessive activity has been linked to numerous pathologies mainly including, but not limited to, tumor invasion and metastasis. The lack of information about several MMPs and the steady stream of new discoveries suggest that there is much more to be studied in this field. In particular, there is a need for controlling their expression in disease states. Various studies over the past 30 years have found that each MMP has a specific mode of activation, action, and inhibition. Drugs specifically targeting individual MMPs could revolutionize the treatment of a great number of health conditions and tremendously reduce their burden. In this review article, we have summarized the recent advances in understanding the role of MMPs in physiological and pathological conditions. J. Cell. Physiol. 231: 2599–2621, 2016. © 2016 Wiley Periodicals, Inc.
Dose and energy dependence of mechanical properties of focused electron-beam-induced pillar deposits from Cu(C5HF6O2)2

Bending and vibration tests performed inside a scanning electron microscope were used to mechanically characterize high aspect pillars grown by focused electron-beam- (FEB) induced deposition from the precursor Cu(C5HF6O2)2. Supported by finite element (FE) analysis the Young’s modulus was determined from load–deflection measurements using cantilever-based force sensing and the material density from additional resonance vibration analysis. The pillar material consisted of a carbonaceous (C-, O-, F-, H-containing) matrix which embeds 5–10 at. % Cu deposited at 5 and 20 keV primary electron energy and 100 pA beam current, depending on primary electron energy. The Young’s moduli of the FEB deposits increased from 17 ± 6 to 25 ± 8 GPa with increasing electron dose. The density of the carbonaceous matrix shows a dependence on the primary electron energy: 1.2 ± 0.3 g cm−3 (5 keV) and 2.2 ± 0.5 g cm−3 (20 keV). At a given primary energy a correlation with the irradiation dose is found. Quality factors determined from the phase relation at resonance of the fundamental pillar vibration mode were in the range of 150–600 and correlated to the deposited irradiation energy.
Teachers' Perceptions of the Role and Effectiveness of Occupational Therapists in Schools

Teachers' expectations from occupational therapists working with exceptional children in two Ontario public school boards were explored in this study. Information was obtained through a questionnaire distributed to all teachers (N = 143) who had worked with occupational therapists and personal interviews conducted with 10 of these teachers. Findings suggested that all teachers believed that there was an important role for occupational therapists in the school system. They defined this role as offering programming suggestions, consulting with school personnel, providing and adapting equipment, liaising with school, home and community, assessing, and following-up school-aged children. Teachers also suggested that occupational therapists further define their roles and responsibilities in school, for themselves, and for school personnel. Finally, teachers suggested that occupational therapists must continue to support and share their knowledge about children with special needs with teachers by providing more demonstration, and modeling of suggested occupational therapy programmes and by working with exceptional students inside the classroom, rather than outside, whenever possible.
Congress report of the 2014 American Academy of Neurology annual meeting

The 66th American Academy of Neurology (AAN) annual meeting (Fig. 1) was held in Philadelphia, Pennsylvania, USA, between 26 April and 3 May 2014. Philadelphia, also known as Philly and The City of Brotherly Love, is the sixth largest megalopolis in the USA. Philadelphia is also the home of The Philadelphia Museum of Art, which is known to most Japanese people for its sweeping front steps in the Oscar winning film “Rocky”. Other famous landmarks and organizations in Philadelphia include the Liberty Bell and the Philadelphia Orchestra, whose conductor laureate is Charles Dutoit, the music director of the NHK Symphony in Tokyo from 1998 to 2003.
Effect of Streptozotocin Induced Maternal Diabetes on Fetal Skeletal Development in the Rat

Abstract Alizarin red‐S stained skeletons of the fetuses of the streptozotocin induced (on days 2, 6 and 8 of gestation) diabetic and insulin and buffer treated control rats were examined on day 20 of gestation for malformations and hypoplasia. Hypoplasia of both the neurocranial and viscerocranial bones was significant in all 3 diabetic groups. Insulin treatment had a remarkable rescue effect on fetuses of the day 8 group; a moderately similar response was found in others. Inhibition of ossification of the scapula, humerus, radius and ulna was relatively less remarkable when compared to that of the homologous bones of the hind‐limbs. However the metacarpals were affected more than the metatarsals. Day 6 of gestation was particularly susceptible for retardation of sternal ossification. Agenesis, hemi‐ and double hemivertebrae were also observed in a few cases. Reduction in caudal sacral and coccygeal vertebral development was remarkable. Incidence of the 14th rib was highest in the day 6 group and insulin administration significantly reduced this abnormality. Meticulous metabolic control had beneficial effect over the growth retarding effects of maternal diabetes but did not completely prevent the malformations.
State of the art in microRNA as diagnostic and therapeutic biomarkers in chronic lymphocytic leukemia

Early diagnostic is one of the most important steps in cancer therapy which helps to design and choose a better therapeutic approach. The finding of biomarkers in various levels including genomics, transcriptomics, and proteomics levels could provide better treatment for various cancers such as chronic lymphocytic leukemia (CLL). The CLL is the one of main lymphoid malignancies which is specified by aggregation of mature B lymphocytes. Among different biomarkers (e.g., CD38, chromosomes abnormalities, ZAP‐70, TP53, and microRNA [miRNA]), miRNAs have appeared as new diagnostic and therapeutic biomarkers in patients with the CLL disease. Multiple lines of evidence indicated that deregulation of miRNAs could be associated with pathological events which are present in the CLL. These molecules have an effect on a variety of targets such as Bcl2, c‐fos, c‐Myc, TP53, TCL1, and STAT3 which play critical roles in the CLL pathogenesis. It has been shown that expression of miRNAs could lead to the activation of B cells and B cell antigen receptor (BCR). Moreover, exosomes containing miRNAs are one of the other molecules which could contribute to BCR stimulation and progression of CLL cells. Hence, miRNAs and exosomes released from CLL cells could be used as potential diagnostic and therapeutic biomarkers for CLL. This critical review focuses on a very important aspect of CLL based on biomarker discovery covers the pros and cons of using miRNAs as important diagnostics and therapeutics biomarkers for this deadly disease.
Serotonin transporter protects the placental cells against apoptosis in caspase 3‐independent pathway

Serotonin (5‐HT) and its specific transporter, SERT play important roles in pregnancy. Using placentas dissected from 18d gestational SERT‐knock out (KO), peripheral 5‐HT (TPH1)‐KO, and wild‐type (WT) mice, we explored the role of 5‐HT and SERT in placental functions in detail. An abnormal thick band of fibrosis and necrosis under the giant cell layer in SERT‐KO placentas appeared only moderately in TPH1‐KO and minimally present in WT placentas. The majority of the changes were located at the junctional zone of the placentas in SERT. The etiology of these findings was tested with TUNEL assays. The placentas from SERT‐KO and TPH1‐KO showed 49‐ and 8‐fold increase in TUNEL‐positive cells without a concurrent change in the DNA repair or cell proliferation compared to WT placentas. While the proliferation rate in the embryos of TPH1‐KO mice was 16‐fold lower than the rate in gestational age matched embryos of WT or SERT‐KO mice. These findings highlight an important role of continuous 5‐HT signaling on trophoblast cell viability. SERT may contribute to protecting trophoblast cells against cell death via terminating the 5‐HT signaling which changes cell death ratio in trophoblast as well as proliferation rate in embryos. However, the cell death in SERT‐KO placentas is in caspase 3‐independent pathway.
Gastro‐oesophageal reflux disease in primary care: an international study of different treatment strategies with omeprazole

Objective To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms. Design Randomized, double-blind, parallel-group, placebo-controlled comparison. Subjects Patients were recruited using a symptom-based questionnaire for diagnosis of gastro-oesophageal reflux disease. Interventions After endoscopy, patients without endoscopie oesophagitis were randomized to omeprazole 20 mg (Ome20), omeprazole 10 mg (Ome10) or placebo once daily for 4 weeks (n = 261) and those with oesophagitis (except circumferential/ulcerative) were randomized to receive either Ome20 or Ome10 once daily for 4 weeks (n = 277). Patients not symptom-free at 4 weeks received open treatment with Ome20 once daily for a further 4 weeks. Those symptom-free at 4–8 weeks were followed up for 6 months off treatment, to see whether their symptoms recurred. Main outcome measure Complete upper Gl symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopie oesophagitis. Results Forty one percent of all patients on Ome20 and 35% on Ome10 reported complete relief from upper Gl symptoms during week 4, whilst 73% of the patients on Ome20 and 62% on Ome10 obtained sufficient control. Complete relief during week 4 was reported by 19% of endoscopy-negative patients on placebo, and sufficient control by 35%. Endoscopie healing at 4 weeks occurred in 76% of oesophagitis patients on Ome20 and in 56% on Ome10. After 6 months off treatment, 90% of patients with oesophagitis and 75% of endoscopy-negative patients reported symptomatic relapse. Conclusion Both 10 mg and 20 mg of omeprazole gave effective relief of symptoms, although 20 mg gave superior healing in patients with oesophagitis. After cessation of treatment, symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients.
Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury

Irisin, a newly identified hormone, is critical to modulating body metabolism, thermogenesis and reducing oxidative stresses. However, whether irisin protects the heart against myocardial ischemia and reperfusion (I/R) injury remains unknown. In this study, we determine the effect of irisin on myocardial I/R injury in the Langendorff perfused heart and cultured myocytes. Adult C57/BL6 mice were treated with irisin (100 mg/kg) or vehicle for 30 min to elicit preconditioning. The isolated hearts were subjected to 30 min ischemia followed by 30 min reperfusion. Left ventricular function was measured and infarction size were determined using by tetrazolium staining. Western blot was employed to determine myocardial SOD‐1, active‐caspase 3, annexin V, p38, and phospho‐p38. H9c2 cardiomyoblasts were exposed to hypoxia and reoxygenation for assessment of the effects of irisin on mitochondrial respiration and mitochondrial permeability transition pore (mPTP). Irisin treatment produced remarkable improvements in ventricular functional recovery, as evident by the increase in RPP and attenuation in LVEDP. As compared to the vehicle treatment, irisin resulted in a marked reduction of myocardial infarct size. Notably, irisin treatment increased SOD‐1 and p38 phosphorylation, but suppressed levels of active‐caspase 3, cleaved PARP, and annexin V. In cardiomyoblasts exposed to hypoxia/reoxygenation, irisin treatment significantly attenuated hypoxia/reoxygenation (H/R), as indicated by the reduction of lactate dehydrogenase (LDH) leakage and apoptotic cardiomyocytes. Furthermore, irisin treatments suppressed the opening of mPTP, mitochondrial swelling, and protected mitochondria function. Our results indicate that irisin serves as a novel approach to eliciting cardioprotection, which is associated with the improvement of mitochondrial function.
MAPK3/1 participates in the activation of primordial follicles through mTORC1‐KITL signaling

The majority of ovarian primordial follicles are preserved in a dormant state to maintain the female reproductive lifespan, and only a few primordial follicles are activated to enter the growing follicle pool in each wave. Recent studies have shown that primordial follicular activation depends on mammalian target of rapamycin complex 1 (mTORC1)‐KIT ligand (KITL) signaling in pre‐granulosa cells and its receptor (KIT)‐phosphoinositol 3 kinase (PI3K) signaling in oocytes. However, the upstream regulator of mTORC1 signaling is unclear. The results of the present study showed that the phosphorylated mitogen‐activated protein kinase3/1 (MAPK3/1) protein is expressed in some primordial follicles and all growing follicles. Culture of 3 days post‐parturition (dpp) ovaries with the MAPK3/1 signaling inhibitor U0126 significantly reduced the number of activated follicles and was accompanied by dramatically reduced granulosa cell proliferation and increased oocyte apoptosis. Western blot and immunofluorescence analyses showed that U0126 significantly decreased the phosphorylation levels of Tsc2, S6K1, and rpS6 and the expression of KITL, indicating that U0126 inhibits mTORC1‐KITL signaling. Furthermore, U0126 decreased the phosphorylation levels of Akt, resulting in a decreased number of oocytes with Foxo3 nuclear export. To further investigate MAPK3/1 signaling in primordial follicle activation, we used phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor bpV(HOpic) to promote primordial follicle activation. In this model, U0126 also inhibited the activation of primordial follicles and mTORC1 signaling. Thus, these results suggest that MAPK3/1 participates in primordial follicle activation through mTORC1‐KITL signaling.