WhaTech | Report explores the oral cancer rapid test kit market WhaTech Oral cancer is one of the largest group of cancers, which comes under category of Head and Neck cancer. It includes lips, tongue, throat, sinuses, and floor of the mouth. About 90% of the oral cancers are squamous cell carcinoma (OSCC). According to ... |
Festuca arundinacea and F. pratensis are the models in forage grasses to recognize the molecular basis of drought, salt and frost tolerance, respectively. Transcription profiles of plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) aquaporin genes were obtained for leaves of Festuca species treated with different abiotic stimuli. F. arundinacea plants were exposed to drought and salt stress, whereas F. pratensis plants were cold-hardened. Changes in genes expression measured with use of real time qRT-PCR method were compared between two genotypes characterized with a significantly different level of each stress tolerance. Under drought the transcript level of PIP1;2 and TIP1;1 aquaporin decreased in both analyzed F. arundinacea genotypes, whereas for PIP2;1 only in a high drought tolerant plant. A salt treatment caused a reduction of PIP1;2 transcript level in a high salt tolerant genotype and an increase of TIP1;1 transcript abundance in both F. arundinacea genotypes, but it did not influence the expression of PIP2;1 aquaporin. During cold-hardening a decrease of PIP1;2, PIP2;1, and TIP1;1 aquaporin transcripts was observed, both in high and low frost tolerant genotypes. The obtained results revealed that the selected genotypes responded in a different way to abiotic stresses application. A reduced level of PIP1;2 transcript in F. arundinacea low drought tolerant genotype corresponded with a faster water loss and a lowering of photosynthesis efficiency and gas exchange during drought conditions. In F. pratensis, cold acclimation was associated with a lower level of aquaporin transcripts in both high and low frost tolerant genotypes. This is the first report on aquaporin transcriptional profiling under abiotic stress condition in forage grasses.
Sigmodontinae rodents constitute the second-largest subfamily among mammals. Alongside the taxonomic diversity, they are also ecologically diverse, exhibiting a wide array of locomotion modes, with semifossorial, terrestrial, semiaquatic, scansorial, arboreal, and saltatorial forms. To understand the ecomorphologic aspects that allow these rodents to display such locomotion diversity, we analyzed 35 qualitative characters of the appendicular skeleton (humerus, ulna, radius, scapula, femur, tibia, ilium, ischium and pubis) in 795 specimens belonging to 64 species, 34 genera and 10 tribes, representing all locomotion modes assigned to this subfamily. We performed a statistical analysis based upon the coefficient of trait differentiation to test the congruence of character states and the different locomotion modes. We also mapped characters states in a molecular phylogeny in order to reconstruct ancestral states and to evaluate how appendicular characters evolved within main lineages of Sigmodontinae radiation under a phylogenetic framework. The statistical analyses revealed six characters related to specific locomotion modes, except terrestrial. The mapping and parsimony ancestral states reconstruction identified two characters with phylogenetical signal and eight characters that are exclusively or more frequently recorded in certain modes of locomotion, four of them also detected by the statistical analysis. Notwithstanding the documented morphological variation, few changes characterize the transition to each of the locomotion modes, at least regarding the appendicular skeleton. This finding corroborates previous results that showed that sigmodontines exhibit an all-purpose appendicular morphology that allows them to use and explore a great variety of habitats.
Accurate identification of abnormalities in the mouse embryo depends not only on comparisons with appropriate, developmental stage-matched controls, but also on an appreciation of the range of anatomical variation that can be expected during normal development. Here we present a morphological, topological and metric analysis of the heart and arteries of mouse embryos harvested on embryonic day (E)14.5, based on digital volume data of whole embryos analysed by high-resolution episcopic microscopy (HREM). By comparing data from 206 genetically normal embryos, we have analysed the range and frequency of normal anatomical variations in the heart and major arteries across Theiler stages S21–S23. Using this, we have identified abnormalities in these structures among 298 embryos from mutant mouse lines carrying embryonic lethal gene mutations produced for the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme. We present examples of both commonly occurring abnormal phenotypes and novel pathologies that most likely alter haemodynamics in these genetically altered mouse embryos. Our findings offer a reference baseline for identifying accurately abnormalities of the heart and arteries in embryos that have largely completed organogenesis.
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter-regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase-2 (MMP-2) during periodontitis, in vivo and in vitro. In a Mif-knockout (KO) mouse model of ligature-induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin-6 (IL-6), MIF, MMP-2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL-6 and MMP-2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor-alpha (TNF-α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild-type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL-6 concentrations. Systemic GC levels were reduced in WT and Mif-KO mice during inflammation, with overall lower concentrations in Mif-KO mice. In vivo and in vitro, MMP-2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP-2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP-2. Our findings further suggest that MIF may regulate systemic GC levels.
| The Daily Nonpareil | Editorial: The faces of courage The Daily Nonpareil Mark Engelke, a Glenwood resident and father of five who was diagnosed with cancer in the tonsils and lymph nodes, always managed to find the silver lining in his diagnosis. An outdoorsman, Engelke took a boat ride to clear his head after hearing the ... and more » |
| Medical panel encourages HPV vaccine Gainesville Times Greene said she has seen in her work as a dentist that HPV causes head and neck cancers in areas such as the larynx, tonsils and tongue. "I've been out of school for over 12 years now and I've really seen a drastic, drastic difference in increase of ... |
| Medical panel encourages HPV vaccine Gainesville Times Greene said she has seen in her work as a dentist that HPV causes head and neck cancers in areas such as the larynx, tonsils and tongue. "I've been out of school for over 12 years now and I've really seen a drastic, drastic difference in increase of ... |
Previous study has revealed that H19 expression is required for efficient tumor growth induced by BCR-ABL in chronic myeloid leukemia (CML). Herein, we further determined H19 expression and its clinical implication in patients with CML. H19 expression and methylation were detected by real-time quantitative PCR and real-time quantitative methylation-specific PCR, and then clinical implication of H19 expression was further analyzed. H19 expression was significantly up-regulated in CML patients (P < 0.001). H19 expression with an area under receiver operating characteristic curve value of 0.824 might serve as a promising biomarker in distinguishing CML patients from controls. The patients with high H19 expression had a tendency of higher white blood cells and BCR-ABL transcript than those with low H19 expression. H19 overexpression occurred with the higher frequency in blast crisis stage (11/11, 100%), lower in accelerated phase (3/5, 60%) and chronic phase (42/62, 66%) stages. Moreover, paired patients during disease progression with increased BCR-ABL transcript also showed a significant upregulation of H19 expression. Meanwhile, H19 expression was decreased in follow-up patients who achieved complete molecular remission after tyrosine kinase inhibitors-based therapy. Epigenetic studies showed that H19 differentially methylated region/imprinting control region (DMR/ICR) was hypomethylated and associated with H19 expression in CML patients. Moreover, demethylation of H19 DMR/ICR reactivated H19 expression in K562 cells. Collectively, H19 overexpression, a frequent event in CML, was associated with higher BCR-ABL transcript involving in disease progression. Moreover, H19 DMR/ICR hypomethylation in CML may be one of the mechanisms mediating H19 overexpression. This article is protected by copyright. All rights reserved
Mesenchymal stem cells (MSCs) are widely used in modern medicine for which understanding the mechanisms controlling their differentiation is fundamental. Ion channels offer novel insights to this process because of their role in modulating membrane potential and intracellular milieu. Here, we evaluate the contribution of calcium-activated potassium (KCa) channels to the three main components of MSC differentiation: initiation, proliferation and migration. First, we demonstrate the importance of the membrane potential (Vm) and the apparent association of hyperpolarization with differentiation. Of KCa subtypes, most evidence points to activity of big-conductance channels in inducing initiation. On the other hand, intermediate-conductance currents have been shown to promote progression through the cell cycle. Whilst there is no information on the role of KCa channels in migration of MSCs, work from other stem cells and cancer cells suggest that intermediate-conductance and to a lesser extent big-conductance channels drive migration. In all cases, these effects depend on species, tissue origin and lineage. Finally, we present a conceptual model that demonstrates how KCa activity could influence differentiation by regulating Vm and intracellular Ca2+ oscillations. We conclude that KCa channels have significant involvement in MSC differentiation and could potentially enable novel tissue engineering approaches and therapies. This article is protected by copyright. All rights reserved
Glioma is the most common type of primary brain tumor and has an undesirable prognosis. Autophagy plays an important role in cancer therapy, but it's effect is still not definite. P53 is an important tumor suppressor gene and protein that is closely to autophagy. Our aim was to study the effect of β-asarone on inhibiting cell proliferation in human glioma U251 cells and to detect the effect of the inhibition on autophagy through the P53 signal pathway. For cell growth, the cells were divided into four groups: the model, β-asarone, temozolomide (TMZ) and co-administration groups. For cell autoghapy and the P53 pathway, the cells were divided into six groups: the model, β-asarone, 3MA, Rapa, Pifithrin-µ and NSC groups. The counting Kit-8 assay and flow cytometry (FCM) were then used to measure the cell proliferation and cycle. Electron microscopy was used to observe autophagosome formation. Cell immunohistochemistry/-immunofluorescence, FCM and western blot (WB) were used to examine the expression of Beclin-1 and P53. The levels of P53 and GAPDH mRNA were detected by RT-PCR. Using WB, we determined autophagy-related proteins Beclin-1, LC3-aaa/aaa and P62 and those of the P53 pathway-related proteins P53, Bcl-2, mTOR, P-mTOR, AMPK, P-AMPK and GAPDH. We got the results that β-asarone changed the cellular morphology, inhibited cell proliferation and enhanced the expression of P53, LC3-aaa/aaa, Beclin-1, AMPK and pAMPK while inhibiting the expression of P62, Bcl-2, mTOR and pmTOR. All the data suggested that β-asarone could reduce the cell proliferation and promote autophagy possible via the P53 pathway in U251 cells. This article is protected by copyright. All rights reserved
Medial artery calcification, a hallmark of type 2 diabetes mellitus and chronic kidney disease (CKD), is known as an independent risk factor for cardiovascular mortality and morbidity. Hyperphosphatemia associated with CKD is a strong stimulator of vascular calcification but the molecular mechanisms regulating this process remain not fully understood. We showed that calcification was induced after exposing Sprague-Dawley rat aortic explants to high inorganic phosphate level (Pi, 6 mM) as examined by Alizarin red and Von Kossa staining. This calcification was associated with high Tissue-Nonspecific Alkaline Phosphatase (TNAP) activity, vascular smooth muscle cells de-differentiation, manifested by downregulation of smooth muscle 22 alpha (SM22α) protein expression which was assessed by immunoblot analysis, immunofluorescence, and trans-differentiation into osteo-chondrocyte-like cells revealed by upregulation of Runt related transcription factor 2 (Runx2), TNAP, osteocalcin, and osteopontin mRNA levels which were determined by quantitative real-time PCR. To unravel the possible mechanism(s) involved in this process, microRNA (miR) expression profile, which was assessed using TLDA technique and thereafter confirmed by individual qRT-PCR, revealed differential expression 10 miRs, five at day 3 and 5 at day 6 post Pi treatment versus control untreated aortas. At day 3, miR-200c, -155, 322 were upregulated and miR-708 and 331 were downregulated. After 6 days of treatment, miR-328, -546, -301a were upregulated whilst miR-409 and miR-542 were downregulated. Our results indicate that high Pi levels trigger aortic calcification and modulation of certain miRs. These observations suggest that mechanisms regulating aortic calcification might involve miRs, which warrant further investigations in future studies. This article is protected by copyright. All rights reserved
Endothelial cell myofibroblast transition (EndoMT) is found during the process of bleomycin (BLM)-induced pulmonary fibrosis in rats, and plays a very important role in sustaining inflammation and collagen secretion. Moreover, some studies have suggested that the Notch1 signaling pathway may be involved in the expression of Î ± -smooth muscle actin (Î ± -SMA) in pulmonary microvascular endothelial cells (PMVECs), a protein marker of EndoMT. Therefore, we aimed to investigate the expression level of Î ± -SMA and Notch1-related signaling molecules in PMVECs from BLM-induced rats and determine the relationship between the Notch1 signaling pathway and the expression of Î ± -SMA in PMVECs. We found that the expression levels of Î ± -SMA, Notch1, and Jagged1 were upregulated, while the expression levels of Dll4 were downregulated. Furthermore, there was a positive correlation between the expression of Jagged1 and the Î ± -SMA proteins in PMVECs, and NF-ΰB was downregulated by decreasing the expression of Jagged1. In conclusion, the Jagged1/Notch1 signaling pathway is activated in PMVECs during the pathogenesis of BLM-induced pulmonary fibrosis in rats, and it may induce Î ± -SMA expression via a non-canonical pathway involving NF-ΰB as the target molecule. The precise mechanism and the molecules involved in this signaling pathway need to be further elucidated. This article is protected by copyright. All rights reserved
For over 35 years, research has examined frontal alpha EEG asymmetry, discussed in terms of relative left frontal activity (rLFA) in the present review, as a concurrent and prospective marker of affective processing and psychopathology. Because rLFA may index (a) neural correlates of frontal asymmetry, or (b) psychological constructs to which frontal asymmetry relates, rLFA can advance our understanding of both neural and psychological models of emotion and psychopathology. In order to improve such understanding, the specific role of rLFA in extending or challenging existing theory must be clear to researchers and readers alike. In particular, in 2004, Coan and Allen argued that examination of rLFA as a mediator or moderator may improve our theoretical understanding of rLFA. Despite being a commonly cited paper in the field, most rLFA research today still fails to acknowledge the statistical role of rLFA in the research. The aim of the present paper is to (a) convince the reader of the importance of distinguishing rLFA as a predictor, outcome, mediator, or moderator in order to conduct theory-driven research, and (b) highlight some of the major advances in rLFA literature since the review by Coan and Allen (2004) in the framework of mediators and moderators. We selected a broad range of search terms to capture relevant rLFA research and included only those studies utilizing established methods for rLFA measurement.
In cued task switching, performance relies on proactive and reactive control processes. Proactive control is evident in the reduction in switch cost under conditions that promote advance preparation. However, the residual switch cost that remains under conditions of optimal proactive control indicates that, on switch trials, the target continues to elicit interference that is resolved using reactive control. We examined whether posttarget interference varies as a function of trial-by-trial variability in preparation. We investigated target congruence effects on behavior and target-locked ERPs extracted across the response time (RT) distribution, using orthogonal polynomial trend analysis (OPTA). Early N2, late N2, and P3b amplitudes were differentially modulated across the RT distribution. There was a large congruence effect on late N2 and P3b, which increased with RT for P3b amplitude, but did not vary with trial type. This suggests that target properties impact switch and repeat trials equally and do not contribute to residual switch cost. P3b amplitude was larger, and latency later, for switch than repeat trials, and this difference became larger with increasing RT, consistent with sustained carryover effects on highly prepared switch trials. These results suggest that slower, less prepared responses are associated with greater target-related interference during target identification and processing, as well as slower, more difficult decision processes. They also suggest that neither general nor switch-specific preparation can ameliorate the effects of target-driven interference. These findings highlight the theoretical advances achieved by integrating RT distribution analyses with ERP and OPTA to examine trial-by-trial variability in performance and brain function.
Publication date: Available online 3 August 2017
Source:Cryobiology
Author(s): Franco Lugnani, Enric Gunther, Pedro Torrecillas, Carlos Galacho, Adolfo Jiménez Garrido, Paul Mikus, Nina Klein, Michael K. Stehling, Matteo Macchioro, Liel Rubinsky, Narayan Raju, Boris Rubinsky
We report results from an acute, single case study in the pig liver on the effects of a tissue ablation protocol (we named cryoelectrolysis) in which 10 min of cryosurgery, with a commercial cryosurgical probe, are delivered after 10 min of electrolysis generated by a current of about 60 mA. The histological appearance of tissue treated with cryoelectrolysis is compared with the appearance of tissue treated with 10 min of cryosurgery alone and with 10 min of electrolysis alone. Histology done after 3 h survival shows that the mixed rim of live and dead cells found around the ablated lesion in both cryosurgery and electrolytic ablation is replaced by a sharp margin between life and dead cells in cryoelectrolysis. The appearance of the dead cells in each, cryoelectrolysis, cryosurgery and electrolytic ablation is different. Obviously, this is an acute study and the results are only relevant to the conditions of this study. There is no doubt that additional acute and chronic studies are needed to strengthen and expand the findings of this study.
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Although it has been recently shown that type 2 diabetics have an increased risk of hip fracture, the effects of exercise therapy to prevent this have not been clarified. We examined whether a treadmill running exercise contributes to the bone mineral density (BMD) and bone microarchitecture of the femur and what kind of exercise intensity and duration are optimum in type 2 diabetes mellitus using KK-Ay diabetic mice. The mice were divided into two running groups, one fast speed and short duration (FS), the other slow speed and long duration (SL), and a group of controls with no running (CO). The running exercise was started when the mice were 8 weeks of age, and continued once a day 5 days per week for 10 weeks. Ten weeks after the start of the running exercise, the BMD of the proximal region and mid-diaphysis in the SL were significantly higher in comparison with that in the CO, whereas there was no difference in bone microarchitecture among the three groups. Blood glucose, insulin levels, and visceral fat contents in the SL were significantly lower than those in the CO and FS. Bone resorption protein and C-reactive protein levels in the SL were significantly lower than those in the CO. These results suggest that slow, long duration loading is better for both bone and glycemic control than fast, short duration loading in type 2 diabetes.
Afforestation is conducive to soil carbon (C) sequestration in semi-arid regions. However, little is known about the effects of afforestation on sequestrations of total and labile soil organic carbon (SOC) fractions in semi-arid sandy lands. In the present study, we examined the effects of Caragana microphylla Lam. plantations with different ages (12- and 25-year-old) on sequestrations of total SOC as well as labile SOC fractions such as light fraction organic carbon (LFOC) and microbial biomass carbon (MBC). The analyzed samples were taken from soil depths of 0–5 and 5–15 cm under two shrub-related scenarios: under shrubs and between shrubs with moving sand dunes as control sites in the Horqin Sandy Land of northern China. The results showed that the concentrations and storages of total SOC at soil depths of 0–5 and 5–15 cm were higher in 12- and 25-year-old C. microphylla plantations than in moving sand dunes (i.e., control sites), with the highest value observed under shrubs in 25-year-old C. microphylla plantations. Furthermore, the concentrations and storages of LFOC and MBC showed similar patterns with those of total SOC at the same soil depth. The 12-year-old C. microphylla plantations had higher percentages of LFOC concentration to SOC concentration and MBC concentration to SOC concentration than the 25-year-old C. microphylla plantations and moving sand dunes at both soil depths. A significant positive correlation existed among SOC, LFOC and MBC, implying that restoring the total and labile SOC fractions is possible by afforestation with C. microphylla shrubs in the Horqin Sandy Land. At soil depth of 0–15 cm, the accumulation rate of total SOC under shrubs was higher in young C. microphylla plantations (18.53 g C/(m2•a); 0–12 years) than in old C. microphylla plantations (16.24 g C/(m2•a); 12–25 years), and the accumulation rates of LFOC and MBC under shrubs and between shrubs were also higher in young C. microphylla plantations than in old C. microphylla plantations. It can be concluded that the establishment of C. microphylla in the Horqin Sandy Land may be a good mitigation strategy for SOC sequestration in the surface soils.
Endometriosis: The presence of tissue that normally grows inside the uterus (womb) in an abnormal anatomical location. Endometriosis is very common and may not produce symptoms, or it may lead to painful menstruation. It has also been associated with infertility. Endometriosis occurs most commonly within the Fallopian tubes and on the outside of the tubes and ovaries, the outer surface of the uterus and intestines, and anywhere on the surface of the pelvic cavity. It can also be found, less often, on the surface of the liver, in old surgery scars or, very rarely, in the lung or brain.
Endometriosis occurs in the reproductive years. The average age at diagnosis is 25-30.Endometriosis may be suspected by during a physical examination; it is confirmed by surgery, usually laparoscopy; available treatments include medication for pain, hormone therapy, and surgery.
Common Misspellings: andrometriosis, endometreosis, endometrisis, edometriosis, indometriosis
Rejuvenation Research , Vol. 0, No. 0.
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| Medical panel encourages HPV vaccine Gainesville Times Greene said she has seen in her work as a dentist that HPV causes head and neck cancers in areas such as the larynx, tonsils and tongue. "I've been out of school for over 12 years now and I've really seen a drastic, drastic difference in increase of ... |
| Jerry Kelly says results are misleading: He's playing poorly Minneapolis Star Tribune He classifies himself as a "10 out of 10" sports fan, is a diligent spokesman for colon cancer screening research and started a fundraising page to help a former PGA Tour rules official with cancer. Never one to hold his tongue, Kelly is also quick to ... and more » |
Tissue Engineering Part A , Vol. 0, No. 0.
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Thyroid Aug 2017, Vol. 27, No. 8: 1107-1107.
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Lewis-Sumner syndrome (LSS) is a rare disease characterized by asymmetrical and multifocal mononeuropathy commonly located in the upper limbs. Some rare cases affecting cranial nerve have been described, but LSS is unknown to affect especially laryngeal nerves. This paper presents the first case of unilateral vocal fold paresis caused by an LSS in a 59-year-old man complaining of dysphonia, breathy voice, and vocal fatigue. Epidemiology, clinical features, diagnosis, and treatment will be described.
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Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF-1–mediated myotube hypertrophy in vitro. Primary skeletal myotubes were treated with IGF-1 (50 ng/ml) with or without 0.5 µM/L CX-5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre-rRNA expression (–64 ± 5% vs. IGF-1; P < 0.001) and total RNA content (–16 ± 2% vs. IGF-1; P < 0.001) in IGF-1-treated myotubes. IGF-1-mediated increases in myotube diameter (1.27 ± 0.09-fold, P < 0.05 vs. control) and total protein (+20 ± 2%; P < 0.001 vs. control) were not prevented by CX treatment. Suppression of rRNA synthesis during IGF-1 treatment did not prevent early increases in AKT (+203 ± 39% vs. CX; P < 0.001) and p70 S6K1 (269 ± 41% vs. CX; P < 0.001) phosphorylation. Despite robust inhibition of the dynamic ribosomal biogenesis response to IGF-1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF-1-induced myotube hypertrophy in vitro.—Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-1–mediated hypertrophy of human primary myotubes.
Bisphenol A (BPA) can disrupt glucose homeostasis and impair pancreatic islet function; however, the mechanisms behind these effects are poorly understood. Male mice (4 wk old) were treated with BPA (50 or 500 μg/kg/day) for 8 wk. Whole-body glucose homeostasis, pancreatic islet morphology and function, and miR-338-mediated molecular signal transduction analyses were examined. We showed that BPA treatment led to a disruption of glucose tolerance and a compensatory increase of pancreatic islets insulin secretion and pancreatic and duodenal homeobox 1 (Pdx1) expression in mice. Inhibition of Pdx1 reduced glucose-stimulated insulin secretion and ATP production in the islets of BPA-exposed mice. Based on primary pancreatic islets, we also confirmed that miR-338 regulated Pdx1 and thus contributed to BPA-induced insulin secretory dysfunction from compensation to decompensation. Short-term BPA exposure downregulated miR-338 through activation of G protein-coupled estrogen receptor 1 (Gpr30), whereas long-term BPA exposure upregulated miR-338 through suppression of glucagon-like peptide 1 receptor (Glp1r). Taken together, our results reveal a molecular mechanism, whereby BPA regulates Gpr30/Glp1r to mediate the expression of miR-338, which acts to control Pdx1-dependent insulin secretion. The Gpr30/Glp1r-miR-338-Pdx1 axis should be represented as a novel mechanism by which BPA induces insulin secretory dysfunction in pancreatic islets.—Wei, J., Ding, D., Wang, T., Liu, Q., Lin, Y. MiR-338 controls BPA-triggered pancreatic islets insulin secretory dysfunction from compensation to decompensation by targeting Pdx-1.
Telemedicine and e-Health , Vol. 0, No. 0.
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We thank Persson and Ueki1 for commenting on our recent article on eosinophil extracellular trap (EET) formation in nasal polyp tissues.2 Although we agree with some of their comments, we would like to point out the following.
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We read with great interest the study by Fitzpatrick et al,1 showing how, in preschool children with persistent asthma, the type 2 inflammation biomarkers (ie, aeroallergen sensitization and/or increased blood eosinophilic counts) are strong predictors of a positive therapeutic response to daily inhaled corticosteroid treatment. To our knowledge, Fitzpatrick et al's study is the first to extrapolate and clearly identify a particular phenotype of persistent eosinophilic asthma, without pneumoallergen sensitization.
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Longo et al1 raise an interesting issue regarding the differentiation of eosinophilic asthma that may be nonatopic in nature. As indicated in our study, the likelihood of a favorable response to daily inhaled corticosteroid therapy in young children with emerging asthma was associated with either a blood eosinophil count of greater than or equal to 300 cells/mm3 or allergic sensitization as defined by multiallergen testing.2 The combination of these 2 features enhanced the likelihood of a favorable response as compared with our other 2 treatment strategies, either daily oral montelukast or inhaled corticosteroid administered with albuterol at the time of symptoms.
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We read with interest the report by Gevaert et al1 on eosinophils in nasal polyps. For decades the senior authors of this article1 have championed roles of eosinophil death through apoptosis. They now report that apoptosis was practically absent in the highly eosinophilic polyps. This concession needs underscoring because it agrees with reports questioning the importance of eosinophil apoptosis in human diseased airway tissues in vivo.2,3 Regarding eosinophil death through lysis, Gevaert et al1 assert "that cell lysis did not occur under the conditions of EET formation." This arguably is a misleading statement.
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Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive demyelinating form of CMT characterized by a severe distal motor and sensory neuropathy. NDRG1 is the causative gene for CMT4D. To date, only four mutations in NDRG1 — c.442C>T (p.Arg148*), c.739delC (p.His247Thrfs*74), c.538-1G>A, and duplication of exons 6–8 — have been described in CMT4D patients. Here, using targeted next-generation sequencing (NGS) examination, we identified for the first time two homozygous missense variants in NDRG1, c.437T>C (p.Leu146Pro) and c.701G>A (p.Arg234Gln), in two Chinese CMT families with consanguineous histories. Further functional studies were performed to characterize the biological effects of these variants. Cell culture transfection studies showed that mutant NDRG1 carrying p.Leu146Pro, p.Arg148*, or p.Arg234Gln variant degraded faster than wild-type NDRG1, resulting in lower protein levels. Live cell confocal microscopy and co-immunoprecipitation analysis indicated that these variants did not disrupt the interaction between NDRG1 and Rab4a protein. However, NDRG1-knockdown cells expressing mutant NDRG1 displayed enlarged Rab4a-positive compartments. Moreover, mutant NDRG1 could not enhance the uptake of DiI-LDL or increase the fraction of LDLR on the cell surface. Taken together, our study described two missense mutations in NDRG1 and emphasized the important role of NDRG1 in intracellular protein trafficking.
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Publication date: Available online 3 August 2017
Source:Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Author(s): Michele Machado Vidor, Gabriela Salatino Liedke, Mathias Pante Fontana, Heraldo Luis Dias da Silveira, Nadia Assein Arus, André Lemos, Mariana Boessio Vizzotto
ObjectiveTo evaluate the accuracy of CBCT images for bone/implant interface diagnosis in comparison to periapical radiographs.Study DesignTitanium implants were inserted in 74 bovine rib blocks in intimate contact to the bone walls, and with a gap of 0.125 mm (simulating a failure in the osseointegration process). Periapical radiographs were taken with conventional film, and CBCT scans were acquired with i-CAT (0.2mm and 0.125mm voxel) and Kodak (0.2mm and 0.076mm voxel) units. Three examiners evaluated the images using a 5-point scale. Diagnostic accuracy was analyzed through sensitivity, specificity, and the area under the ROC curve (AUC) with 95% confidence intervals (CI). Intra- and inter-examiner agreements were analyzed through Kendall's concordance test.ResultsIntra- and inter-examiner agreements showed satisfactory results. The greatest accuracy was observed with conventional radiographs (AUC = 0.963 / CI 95% = 0.891-0.993). I-CAT 0.125mm images showed good accuracy (AUC = 0.885 / CI 95% = 0.790-0.947), with no significant difference compared to conventional radiography. Kodak images had high specificity and low sensitivity, presenting more false-negative results.ConclusionConventional radiographs showed the highest accuracy for bone/implant interface diagnosis. However, CBCT scans (i-CAT 0.125 mm voxel), if available or if performed for pre-surgical assessment of another implant site, may provide similar accuracy.
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Upon liver injury, excessive deposition of collagen from activated hepatic stellate cells (HSCs) is a leading cause of liver fibrosis. An understanding of the mechanism by which collagen biosynthesis is regulated in HSCs will provide important clues for practical anti-fibrotic therapy. Endoplasmic reticulum oxidase 1α (ERO1α) functions as an oxidative enzyme of protein disulfide isomerase, which forms intra-molecular disulfide bonds of membrane and secreted proteins. However, the role of ERO1α in HSCs remains unclear. Here, we show that ERO1α was expressed and mainly localized in the endoplasmic reticulum in human HSCs. When HSCs were transfected with ERO1α siRNA or ERO1α shRNA-expressing plasmid, expression of ERO1α was completely silenced. Silencing of ERO1α expression in HSCs markedly suppressed their proliferation but did not induce apoptosis, which was accompanied by impaired secretion of collagen type 1. Silencing of ERO1α expression induced impaired disulfide bond formation and inhibited autophagy via activation of the Akt/mammalian target of rapamycin signaling pathway, resulting in intracellular accumulation of collagen type 1 in HSCs. Furthermore, silencing of ERO1α expression also promoted proteasome-dependent degradation of membrane type 1-matrix metalloproteinase (MT1-MMP), which stimulates cell proliferation through cleavage of secreted collagens. The inhibition of HSC proliferation was reversed by treatment with MT1-MMP-cleaved collagen type 1. The results suggest that ERO1α plays a crucial role in HSC proliferation via posttranslational modification of collagen and MT1-MMP and therefore may be a suitable therapeutic target for managing liver fibrosis.
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Rufomycin is a circular heptapeptide with anti-mycobacterial activity and is produced by Streptomyces atratus ATCC 14046. Its structure contains three non-proteinogenic amino acids, N-dimethylallyltryptophan, trans-2-crotylglycine, and 3-nitrotyrosine (3NTyr). Although the rufomycin structure was already reported in the 1960s, its biosynthesis, including 3-NTyr generation, remains unclear. To elucidate the rufomycin biosynthetic pathway, we assembled a draft genome sequence of S. atratus and identified the rufomycin biosynthetic gene cluster (ruf cluster), consisting of 20 ORFs (rufA-rufT). We found a putative heptamodular nonribosomal peptide synthetase encoded by rufT, a putative tryptophan N-dimethylallyltransferase by rufP, and a putative trimodular type I polyketide synthase by rufEF. Moreover, the ruf cluster contains an apparent operon harboring putative cytochrome P450 (rufO) and nitric oxide synthase (rufN) genes. A similar operon, txtDE, is responsible for the formation of 4-nitrotryptophan in thaxtomin biosynthesis; the cytochrome P450 TxtE catalyzes the 4-nitration of Trp. Therefore, we hypothesized that RufO should catalyze the Tyr 3-nitration. Disruption of rufO abolished rufomycin production by S. atratus, which was restored when 3NTyr was added to the culture medium of the disruptant. Recombinant RufO protein exhibited Tyr 3-nitration activity both in vitro and in vivo. Spectroscopic analysis further revealed that RufO recognizes Tyr as the substrate with a dissociation constant of ~ 0.1 μM. These results indicate that RufO is an unprecedented cytochrome P450 that catalyzes Tyr nitration. Taken together with the results of an in silico analysis of the ruf cluster, we propose a rufomycin biosynthetic pathway in S. atratus.
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The faith community provides an important access point for practice focused on population health at a time when health issues such as obesity and overweight are affecting large number of Americans. The purpose of this study was to examine faith community nurses' self-efficacy perceptions following a nutrition educational intervention. A convenience sample of 92 faith community nurses were randomly assigned to experimental and control groups. The t-distribution analysis revealed significant differences between the nutrition knowledge self-efficacy (p = .016) and nutrition counseling self-efficacy (p = .010) post-test scores for the experimental and control groups. This type of educational intervention provides a model to be used with faith community nurses as they integrate faith and health in this setting.
Religious conversion is an important phenomenon in contemporary religious climate, but existing psychology research work is mostly based on quantitative methods. In an attempt to contribute to this field, the present study proposes a qualitative exploration of religious conversion. The in-depth interview of a French woman is examined in order to investigate her experience of religious conversion, 40 years prior. The interview was analysed using interpretative phenomenological analysis, with the purpose of revealing how the participant experienced the process of religious conversion, what was its impact on her life, identity and personality and how she coped with this impact. The four emerging themes were: conflicted relationship with Judaism, the pursuit of a spiritual quest, changes after conversion and life after conversion. These themes painted the image of a powerful spiritual transformation, a profound and dynamic lifelong process, integrating concepts and practices, life changes and developments. The findings are explained with the help of available literature.
In order to provide adequate health care, it is important to be well aware of the views and attitudes of the health seeker regarding health, illness and medicine. In the Belgian context, the views of Muslim women, particularly of middle-aged and elderly Moroccan women, have been understudied. The aim of this article is twofold. First, we seek to bring forward the attitudes and beliefs of middle-aged and elderly Moroccan Muslim women living in Antwerp (Belgium) towards health, illness and medicine. Second, we seek to explore which role religion plays in their views and attitudes regarding health, illness and medicine. Qualitative empirical research was conducted with a sample of middle-aged and elderly Moroccan Muslim women living in Antwerp (Belgium) (n = 30) and with experts in the field (n = 15). In-depth interviews and participant observations were conducted to reveal their perceptions regarding health, illness and medicine. This study reveals that religion plays a crucial role in how Muslim women perceive and deal with illness. Theological considerations that centre on God's omnipotence, the belief in the afterlife and religious virtues take up a central position. A holistic approach is adopted in the search for healing, i.e. an interplay between calling upon medicine and turning to God. Religious beliefs seem to be a powerful source in coping with illness.
The objective of this study was to evaluate the biomechanical properties of dentin and the microtensile bond strength (μTBS) performed before or after radiotherapy (RT).
Dentin chemical composition (infrared spectroscopy—FTIR), SEM images, and mechanical properties (Vickers microhardness—VHN and elastic modulus—E) were evaluated comparing no irradiated and irradiate dentin (n = 5). RT was defined by application of 72 Gy (1.8 Gy daily, 5 days per week, during 8 weeks) with sample immersed in distilled water. μTBS evaluated three groups (n = 10): NI—no irradiated; IB—irradiation before restoration; and IA—irradiation after restoration. Resin-dentin sticks (1.0 mm2) were obtained and submitted to μTBS. Analysis of the bonding interface was made by confocal microscopy.
After RT, percentage ratio of FTIR analysis showed increased absorption for all bands. SEM image showed a disorganized dentin structure. Two-way ANOVA showed increased VHN (p = 0.005) and decreased E (p < 0.001). For μTBS, one-way ANOVA and Duncan test showed significant differences among groups (p = 0.018). IB group presented the lowest bond strength values.
RT alters the absorption bands and SEM images showed a disorganization of the dentin structure. Mechanical properties were changed with increased VHN and decreased E. μTBS was affected by the radiotherapy and restoration period (before or after).
RT causes changes that contribute to increased risk of tooth decay. Restorative treatments can be performed using adhesive procedures, but it is preferable to be performed before of the irradiation protocol, to guarantee better adhesive properties to restoration.
| Polymer coatings test for cancer, prevent infections, detect bacterial contamination plastemart.com A range of polymer coatings are available in the form of lubrications, anti-microbial liquids, water repellent polymers. Each variant is used for different applications. Besides sanitation, the other concerns about coatings are allergenic substances ... |
IL-4 and IL-13 are major T helper cell (Th) 2 cytokines implicated in the pathogenesis of several lung diseases, including pulmonary fibrosis. In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared to saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline were attenuated in mice deficient in either IL-13 or IL-4Rα-driven signaling compared to wild-type mice treated with bleomycin. Further, our results demonstrated that IL-13- and IL-4Rα-driven signaling are involved in excessive migration of macrophages and fibroblasts. Notably, our findings demonstrated that IL-13-driven migration involves increased pFAK signaling and F-actin polymerization. Importantly, in vivo findings demonstrated that IL-13 augments MMP2 and MMP9 activity that has also been shown to increase migration and invasiveness of fibroblasts in the lungs during bleomycin-induced pulmonary fibrosis. Together, our findings demonstrate a pathogenic role for Th2-cytokine signaling that includes excessive migration and protease activity involved in severe fibrotic lung disease.
The cystic fibrosis transmembrane conductance regulator (CFTR) and the amiloride-sensitive epithelial sodium channels (ENaC) are located in the apical membranes of airway and alveolar epithelial cells. These transporters play an important role in the regulation of lung fluid balance across airway and alveolar epithelia by being the conduits for chloride (Cl-) and bicarbonate (HCO3-) secretion and sodium (Na+) ion absorption, respectively. The functional role of these channels in the respiratory tract is to maintain the optimum volume and ionic composition of the bronchial pericilary fluid (PCL) and alveolar lining fluid (ALF) layers. The PCL is required for proper mucociliary clearance of pathogens and debris and the ALF is necessary for surfactant homeostasis and optimum gas exchange. Dysregulation of ion transport may lead to mucus accumulation, bacterial infections, inflammation, as well as pulmonary edema and compromised respiratory function. Influenza (or flu) in mammals is caused by influenza A and B viruses. Symptoms include dry cough, sore throat and is often followed by secondary bacterial infections, accumulation of fluid in the alveolar spaces and acute lung injury. The underlying mechanisms of flu symptoms are not fully understood. This review summarizes our present knowledge of how influenza virus infections alter airway and alveolar epithelial cell CFTR and ENaC function in vivo and in vitro and the role of these changes in influenza pathogenesis.
Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher. We hypothesized that PDGFRα and Ras-related C3 botulinum toxin substrate 1(Rac1) are required for mechanosensitive myofibroblast migration. Spreading of PDGFRα-deficient lung fibroblasts was insensitive to increased rigidity, and their migration was not reduced by Rac1-guanine exchange factor (GEF)-inhibition. PDGFRα-expressing fibroblasts migrated towards stiffer regions within 2-dimensional substrates by increasing migrational persistence (durotaxis). Using a Förster resonance energy transfer (FRET) biosensor for Rac1-GTP, we observed that PDGFRα was required for fibroblast Rac1-responsiveness to stiffness within a 3-dimensional collagen substrate, which by itself increased Rac1-FRET. Rho-GTPase stabilized whereas Rac1-GTPase increased the turnover of focal adhesions. Under conditions which increased Rac1-GTP, PDGFRα signaled through both phosphoinositide-3-kiase (PIK) or Src to engage the Rac1 guanine-exchange factors (GEF)s dedicator of cytokinesis-1 (Dock180) and p21-activated-kinase interacting exchange factor-β (βPIX). In cooperation with collagen fibers, these signaling pathways may guide fibroblasts toward the more rigid alveolar entry ring during secondary septation. Because emphysema and interstitial fibrosis disrupt the parenchymal mechanical continuum, understanding how mechanical factors regulate fibroblast migration could elicit strategies for alveolar repair and regeneration.
Tissue matrix remodeling and fibrosis leading to loss of pulmonary arterial and right ventricular compliance are important features of both experimental and clinical pulmonary hypertension (PH). We have previously reported that transglutaminase 2 (TG2) is involved in PH development while others have shown it to be a crosslinking enzyme that participates in remodeling of extracellular matrix in fibrotic diseases in general. In the present studies, we used a mouse model of experimental PH (Sugen 5416 and hypoxia; SuHypoxia) and cultured primary human cardiac and pulmonary artery adventitial fibroblasts to evaluate the relationship of TG2 to the processes of fibrosis, protein crosslinking, extracellular matrix collagen accumulation and fibroblast to myofibroblast transformation. We report here that TG2 expression, activity as measured by serotonylated fibronectin and protein crosslinking activity along with fibrogenic markers are significantly elevated in lungs and right ventricles of SuHypoxic mice with PH. Similarly, TG2 expression and activity, protein crosslinking activity and fibrogenic markers are significantly increased in cultured cardiac and pulmonary artery adventitial fibroblasts in response to hypoxia exposure. Pharmacological inhibition of TG2 activity with ERW1041E significantly reduced hypoxia-induced crosslinking activity and synthesis of collagen 1 and α-smooth muscle actin in both the in vivo and in vitro studies. TG2 siRNA had a similar effect in vitro. Our results suggest that TG2 plays an important role in hypoxia-induced pulmonary and right ventricular tissue matrix remodeling in the development of PH.
A key physiological feature of Acute Respiratory Distress Syndrome (ARDS) is inflammation. Toll-like receptor (TLR) signaling is required to combat the infection that underlies many ARDS cases but also contributes to pathological inflammation. Several TLR signaling pathway genes encoding positive effectors of inflammation also produce alternatively spliced mRNAs encoding negative regulators of inflammation. An imbalance between these isoforms could contribute to pathological inflammation and disease severity. To determine if splicing in TLR pathways is altered in ARDS patients, we monitored alternative splicing of MyD88 and IRAK1, two genes that function in multiple TLR pathways. The MyD88 and IRAK1 genes produce long pro-inflammatory mRNAs (MyD88L and IRAK1) and shorter anti-inflammatory mRNAs (MyD88S and IRAK1c). We quantified mRNA encoding inflammatory cytokines and MyD88 and IRAK1 isoforms in peripheral blood mononuclear cells (PBMCs) from 104 ARDS patients and 30 healthy control subjects. We found that MyD88 pre-mRNA splicing is altered in ARDS patients in a pro-inflammatory direction. We also observed altered MyD88 isoform levels in a second critically ill patient cohort, suggesting that these changes may not be unique to ARDS. Early in ARDS, PBMC IRAK1c levels were associated with patient survival. Despite the similarities in MyD88 and IRAK1 alternative splicing observed in previous in vitro studies, there were differences in how MyD88 and IRAK1 alternative splicing was altered in ARDS patients. We conclude that pre-mRNA splicing of TLR signaling genes is altered in ARDS patients, and further investigation of altered splicing may lead to novel prognostic and therapeutic approaches.
Chronic asthma patients experience difficulties even years after the inciting allergen. Although studies in small animal asthma models have enormously advanced progress in uncovering the mechanisms of inception and development of the disease, little is known about the processes involved in the persistence of asthma symptoms in the absence of allergen exposure. Long term asthma mouse models have so far been scarce or not been able to reproduce the findings in patients. Here we used a common ovalbumin induced acute allergic airway inflammation mouse model to study lung function and remodeling after a four months recovery period. We show by x-ray based lung function measurements that the recovered mice continue to show impaired lung function by displaying significant air-trapping compared to controls. High resolution synchrotron phase contrast computed tomography of structural alterations and diaphragm motion analysis suggest that these changes in pulmonary function are due to a pronounced loss in lung elasticity. Histology of lung sections confirmed that this is most likely caused by a decrease in elastic fibers, indicating that remodelling can develop or persist independently of acute inflammation and is closely related to a loss in lung function. Our findings demonstrate that this x-ray based imaging platform has the potential to comprehensively and non-invasively unravel long term effects in preclinical mouse models of AAI and thus benefits our understanding of chronic asthma.
Publication date: Available online 3 August 2017
Source:Cancer Cell
Author(s): Gulfem Dilek Guler, Charles Albert Tindell, Robert Pitti, Catherine Wilson, Katrina Nichols, Tommy KaiWai Cheung, Hyo-Jin Kim, Matthew Wongchenko, Yibing Yan, Benjamin Haley, Trinna Cuellar, Joshua Webster, Navneet Alag, Ganapati Hegde, Erica Jackson, Tracy Leah Nance, Paul Garrett Giresi, Kuan-Bei Chen, Jinfeng Liu, Suchit Jhunjhunwala, Jeff Settleman, Jean-Philippe Stephan, David Arnott, Marie Classon
Maintenance of phenotypic heterogeneity within cell populations is an evolutionarily conserved mechanism that underlies population survival upon stressful exposures. We show that the genomes of a cancer cell subpopulation that survives treatment with otherwise lethal drugs, the drug-tolerant persisters (DTPs), exhibit a repressed chromatin state characterized by increased methylation of histone H3 lysines 9 and 27 (H3K9 and H3K27). We also show that survival of DTPs is, in part, maintained by regulators of H3K9me3-mediated heterochromatin formation and that the observed increase in H3K9me3 in DTPs is most prominent over long interspersed repeat element 1 (LINE-1). Disruption of the repressive chromatin over LINE-1 elements in DTPs results in DTP ablation, which is partially rescued by reducing LINE-1 expression or function.
Non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is a malignancy whose incidents is rapidly increasing. However, the mechanisms that drive development of HCC in a steatotic microenvironment remain unknown. Here we report that the obesity-associated protein JCAD is expressed at significantly higher levels in human NASH-HCC specimens compared to peri-carcinoma specimens. High JCAD expression was verified in multiple hepatoma cell lines. Forced overexpression of JCAD in hepatoma cells promoted tumor growth and proliferation; whereas JCAD silencing yielded opposite effects. JCAD interacted with the kinase domain of the tumor suppressor kinase LATS2, a core component of the Hippo signaling pathway. JCAD overexpression inhibited the ability of LATS2 to phosphorylate YAP in this pathway, in turn upregulating CCND1 and GLI2 to promote hepatoma cell proliferation. JCAD was induced by fatty acid overload in hepatic cells and was highly expressed in a mouse model of NASH-precarcinoma lesions, where the ratio of phospho-YAP to YAP was decreased. In human NASH-HCC specimens, JCAD expression and YAP phosphorylation patterns paralleled with the mouse model. Our findings illuminate a new role for JCAD and its critical interplay in the Hippo signaling cascade during the transition of NASH to HCC, with potential implications for therapeutic development in this setting.
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It has been estimated that >1,000 genetic loci have yet to be identified for breast cancer risk. Here we report the first study utilizing targeted next-generation sequencing to identify single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Targeted sequencing of 283 genes was performed in 240 women with early-onset breast cancer (≤ 40 years) or a family history of breast and/or ovarian cancer. Common coding variants with minor allele frequencies (MAF) >1% that were identified were presumed initially to be SNPs, but further database inspections revealed variants had MAF of ≤1% in the general population. Through prioritization and stringent selection criteria, we selected 24 SNPs for further genotyping in 1,516 breast cancer cases and 1,189 non-cancer controls. Overall, we identified the JAK2 SNP rs56118985 to be significantly associated with overall breast cancer risk. Subtype analysis performed for patient subgroups defined by ER, PR and HER2 status suggested additional associations of the NOTCH3 SNP rs200504060 and the HIF1A SNP rs142179458 with breast cancer risk. In silico analysis indicated that coding amino acids encoded at these three SNP sites were conserved evolutionarily and associated with decreased protein stability, suggesting a likely impact on protein function. Our results offer proof of concept for identifying novel cancer risk loci from next-generation sequencing data, with iterative data analysis from targeted, whole-exome or whole-genome sequencing a wellspring to identify new SNPs associated with cancer risk.
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Gilomas with mutant p53 occurring in 30% of giloma patients exhibit therapeutic resistance and poor outcomes. In this study, we identify a novel mechanism through which mutant p53 drives cancer cell survival and malignant growth. We documented overexpression of the zinc finger protein ZDHHC5 in glioma compared to normal brain tissue and that this event to be tightly correlated with p53 mutations. Mechanistic investigations revealed that mutant p53 transcriptionally upregulated ZDHHC5 along with the nuclear transcription factor NF-Y. These events contributed to the development of glioma by promoting the self-renewal capacity and tumorigenicity of glioma stem-like cells, by altering the palmitoylation and phosphorylation status of the tumor suppressor EZH2. Taken together, our work highlighted ZDHHC5 as a candidate therapeutic target for management of p53-mutated gliomas.
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While the development of evidence-based air quality standards for airborne particulate matter (PM) for Europe and North America is well-documented, the standard-setting processes in other regions are less well characterized. Many Pacific Rim economies suffer from severe and worsening air pollution. Particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) is associated with acute and chronic health effects and is a widely used air quality indicator. This paper reports on PM regulation in selected Pacific Rim economies, focusing on PM2.5, and provides recommendations on air quality regulation to economies without current standards Through workshops held by the Association of Pacific Rim Universities (APRU) Global Health Program, experts in air pollution from eight universities in eight Pacific Rim economies characterized current PM2.5 standards and monitoring in their economies, and then collaboratively created recommendations. A great diversity of air pollution exposures exists in the Pacific Rim. While some economies experience low levels of exposure, others have PM levels that are among the highest in the world. The health effects of air pollution are a concern everywhere, but few economies carry out in-depth, local impact assessments and comprehensive air quality monitoring to provide evidence for guidelines and standards. The development of regulations and policies addressing PM2.5 pollution is urgently needed in many Pacific Rim economies. The international literature provides a robust guide to local risks and should be used, in combination with country-specific population-directed air monitoring, to guide decisions on policies addressing this important global health problem.
The modeling of genetic interactions within a cell is crucial for a basic understanding of physiology and for applied areas such as drug design. Interactions in gene regulatory networks (GRNs) include effects ...
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