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Publication
Journal: The ocular surface
May/17/2020
Abstract
High resolution visualization of the ocular surface and intact eyeball is critical and essential for our understanding and treatment of eye diseases. This study is to achieve this goal using advanced tissue clearing and three-dimensional (3D) imaging technologies.Wild type and fluorescently labeled transgenic mice of Prox-1-GFP (green fluorescent protein) or Thy1-YFP (yellow fluorescent protein) were used in the study. Eyeballs were harvested from normal or a disease model of corneal inflammation. Samples were infused with hydrogel monomers and heated for polymerization. Lipids were removed by electrophoresis. The transparent tissue-hydrogel hybrids of the anterior segments or intact eyeballs with immunolabeling or endogenous fluorescence were imaged by an advanced light sheet fluorescent microscope. High resolution 3D images and videos were captured for a wide array of structures and cell types.Optical transparency was achieved from intact eyeballs of both normal and diseased conditions. A variety of important structures and cell types, such as blood and lymphatic vessels, Schlemm's canal, nerves and endothelial cells, were detected with their natural morphology, location and organizational network.This study provides the first comprehensive and 3D high resolution imaging of the intact eyeball using tissue clearing and advanced light sheet microscopy. Given that the eye is the window of the body, we anticipate this advanced technology will facilitate diverse applications in biomedical research inside and outside the eye.
Publication
Journal: Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine
May/17/2020
Authors
Publication
Journal: Methods in enzymology
May/17/2020
Abstract
Understanding the roles that individual species or communities play within a microbiome is a significant challenge. The complexity and heterogeneity of microbiomes presents a challenge to researchers looking to unravel the function that microbiomes serve within larger environments. While identification of the species and proteins present in a microbiome can be accomplished through genomics approaches, strategies that report on enzyme activity are limited. In this chapter, we describe the application of small molecule chemical probes in the isolation and subsequent characterization of microbiome subpopulations based on enzymatic function. We will cover protocols for labeling microbes with appropriate probes, microbiome sample preparation, and using fluorescence-activated cell sorting to isolate subpopulations based on function. We hope that the strategies outlined here will serve as a resource for researchers studying the functional role that microbiomes play in the gut and soil.
Publication
Journal: Methods in enzymology
May/17/2020
Abstract
Salicyl-AMS (1) is a potent inhibitor of salicylate adenylation enzymes used in bacterial siderophore biosynthesis and a promising lead compound for the treatment of tuberculosis. An optimized, multigram synthesis is presented, which provides salicyl-AMS as its sodium salt (1·Na) in three synthetic steps followed by a two-step salt formation process. The synthesis proceeds in 11.6% overall yield from commercially available adenosine 2',3'-acetonide and provides highly purified material.
Publication
Journal: Methods in enzymology
May/17/2020
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
We present prenatal diagnosis and molecular cytogenetic characterization of Wolf-Hirschhorn syndrome (WHS) in a fetus with facial cleft and preaxial polydactyly.A 37-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age, and the result showed an aberrant chromosome 4 or 46,XX,add(4) (p15.3). The woman consulted our clinics at 22 weeks of gestation and requested for repeat amniocentesis. Prenatal ultrasound revealed intrauterine growth restriction, facial cleft, vermian hypoplasia of cerebellum, micrognathia and absent stomach. Conventional cytogenetic analysis was performed on cultured amniocytes, parental bloods and cord blood. Array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed on the DNAs extracted from uncultured amniocytes and parental bloods. Fluorescence in situ hybridization (FISH) analysis was performed on cultured metaphase amniocytes.aCGH analysis on uncultured amniocytes revealed arr 4p16.3p16.1 (74,447-8,732,731) × 1.0 [GRCh37 (hg19)] with an 8.66-Mb deletion of 4p16.3-p16.1 encompassing 70 [Online Mendelian Inheritance of in Man (OMIM)] genes including ZNF141, FGFRL1, TACC3, LETM1, NSD2 and NELFA. QF-PCR revealed a paternal origin of the distal 4p deletion. Conventional cytogenetic analysis revealed 46,XX,del(4) (p16.1)dn in the fetus. Metaphase FISH analysis confirmed a 4p16 deletion. The parental karyotypes were normal. The pregnancy was subsequently terminated, and a malformed fetus was delivered with typical WHS facial dysmorphism, bilateral cleft lip and palate, and preaxial polydactyly on the right hand.aCGH, QF-PCR and FISH help to delineate the nature of a prenatally defected aberrant chromosome, and the acquired information is useful for genetic counseling.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
Genistein obviously inhibits the migration and invasion of various tumor cells. However, its effects on cervical cancer cells have seldom been referred. We aimed to evaluate the effects of genistein on the proliferation, migration and invasion of cervical cancer HeLa cells, the expressions and phosphorylations of proteins related with FAK-paxillin and MAPKs signaling pathways, as well as the expressions of related key genes.HeLa cells were stimulated with genistein for 24 h and 48 h respectively. After adherence for 2 h, 0 μM, 12.5 μM, 25 μM, 50 μM and 100 μM genistein solutions were added in DMEM. Cell proliferation was tested by the CCK-8 assay. After treatment with 100 μM genistein, the migration ability was detected by the scratch assay. Transwell assay was used to detect cell migration and invasion abilities. Western blot and qRT-PCR were used to detect the expressions of proteins and mRNAs related with FAK-paxillin and MAPKs signaling pathways respectively.The effect of genistein on the proliferation of HeLa cells was proportional to treatment time and drug dose, and the proliferation was inhibited after 24 h and 48 h at 100 μM. After treatment with 100 μM genistein, the scratch migration rate was significantly lower than that of the control group at 24 h and 48 h (P < 0.05). Genistein also inhibited the invasion of tumor cells through the upper chamber and Matrigel. The number of invasive cells was significantly lower than that of the control group (P < 0.05). Genistein significantly inhibited the phosphorylations of FAK, paxillin, p38 and p42/44. Compared to the control group, 100 μM genistein significantly suppressed the mRNA expressions of FAK, paxillin, Snail and twist.Genistein inhibited the migration and invasion of cervical cancer HeLa cells by regulating FAK-paxillin and MAPK signaling pathways in dose-dependent manners.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
Breech presentation is the most common form of malpresentation, and associated with perinatal asphyxia and mortality, and maternal morbidity. Data associated with labor induction in breech presentation are limited. The aim of this study was to compare maternal and fetal complication rates in induced and spontaneous vaginal, and cesarean delivery with breech presentation.Pregnant women with breech presentation were grouped: spontaneous vaginal delivery (Group 1, n = 72) induced or augmented vaginal delivery (Group 2, n = 32), and cesarean delivery (Group 3, n = 253). Fetal complications were as follows: clavicle fracture, femur fracture, humerus fracture, brachial plexus injury, cephalic hematoma, pneumothorax, need for intensive care unit (ICU), and 5th minute APGAR <7. Maternal complications were as follows: vaginal hematoma, deep vaginal laceration, perineal injury (≥3rd degree), decline in hemoglobin level (>2 g/dL), and postpartum endometritis. Data were collected and analyzed retrospectively.The highest fetal complication rate was in Group 2, and the lowest in Group 3 (p = 0.001). Clavicle fracture was significantly less in Group 3 compared with the other groups (p = 0.024). The rate of lower APGAR scores at the 5th minute was similar in all groups. Maternal complications were significantly higher in Group 2 compared with the other groups (p = 0.001). Fetal complications were 5.66-fold higher in Group 1 than in Group 3 (p = 0.002). Fetal and maternal complications were 9.48-fold and 7.48-fold higher, respectively, in Group 2 than in Group 3 (p < 0.001).This study is the first in literature to have investigated and analyzed neonatal complications in breech delivery according to different delivery modes including induced vaginal delivery. Due to possible complications, the risks and benefits of a specific type of delivery should be considered in breech presentation.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
We present perinatal cytogenetic discrepancy in a fetus with low-level mosaicism for trisomy 21 and a favorable outcome.A 40-year-old woman underwent amniocentesis at 19 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+21[7]/46,XY[14]. She underwent cordocentesis 21 weeks of gestation, and the karyotype of cord blood was 47,XY,+21[13]/46,XY[38]. The prenatal ultrasound findings were unremarkable. After genetic counseling of a favorable outcome of low-level mosaic trisomy 21 at amniocentesis, the parents decided to continue the pregnancy, and a 3128-g phenotypically normal male baby was delivered at 38 weeks of gestation without phenotypic features of Down syndrome. Postnatal cytogenetic analysis of cord blood revealed a karyotype of 47,XY,+21[3]/46,XY[47]. The placenta had a karyotype of 47,XY,+21[8]/46,XY[32], and the umbilical cord had a karyotype of 47,XY,+21[5]/46,XY[35]. Array comparative genomic hybridization analysis on the DNA extracted from cord blood revealed no genomic imbalance. Polymorphic DNA marker analysis excluded uniparental disomy 21. Interphase fluorescence in situ hybridization analysis on urinary cells revealed trisomy 21 signals in 2/102 (1.96%) cells compared with 2/103 (1.94%) cells in normal control.The cells of abnormal cell line in prenatally detected mosaic trisomy 21 may decrease in number or disappear in various tissues as the fetus grows, and there exists perinatal cytogenetic discrepancy in mosaic trisomy 21 detected at prenatal diagnosis.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
We present prenatal diagnosis and molecular cytogenetic characterization of a de novo interchromosomal insertion of ins(1; 8)(p22.1; q22q23) at amniocentesis.A 34-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Conventional cytogenetic analysis revealed a chromosome 1p22.1 interstitial duplication and a chromosome 8q22-q23 interstitial deletion. The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) analysis using the DNA extracted from cultured amniocytes revealed no genomic imbalance. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes showed an interchromosomal insertion of ins(1; 8)(p22.1; q22q23) or ins(1; 8) (1pter→1p22.1::8q23→8q22::1p22.1→1qter; 8pter→8q22::8q23→8qter). The long arm of chromosome 8 between bands 8q22 and 8q23 had been directly inserted into the short arm of chromosome 1 at band 1p22.1. The karyotype was 46,XY,ins(1; 8)(p22.1; q22q23) or 46,XY,ins(1; 8)(1pter→1p22.1::8q23→8q22::1p22.1→1qter; 8pter→8q22::8q23→8qter). After genetic counseling, the parents decided to continue the pregnancy. A phenotypically normal male baby was delivered at term.FISH and aCGH are useful for genetic counseling and molecular cytogenetic characterization of a de novo interchromosomal insertion detected by amniocentesis.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
The possible mechanism of preeclampsia is investigated in this study to facilitate the exploration of the future remediation of this disease by analysing the changes of IL-17 and IL-35 in peripheral blood and placental tissue of pregnant women with preeclampsia (PE).The study was conducted using 45 healthy pregnant women as the control group and 90 pregnant women in the preeclampsia group, including 45 cases with severe preeclampsia and 45 cases with mild preeclampsia. All of 135 pregnant women underwent caesarean delivery. IL-17 and IL-35 concentrations in the serum were measured by ELISA, and IL-17 and IL-35 expression in placental specimens was detected by immunohistochemistry.There were no statistically significant differences in age among the three study groups. Serum IL-17 levels were significantly higher in PE patients than in healthy pregnant women (P < 0.01). The ratio of positive staining for IL-17 was markedly higher in mild PE tissues (84.44%; 38/45) and severe PE tissues (86.67%; 39/45) than in healthy pregnant tissues (35.56%; 16/45) (P < 0.01). The strong positive rates for IL-17 were markedly higher in mild PE tissues (48.89%; 22/45) and severe PE tissues (68.89%; 31/45) than in healthy pregnant tissues (13.33%; 6/45) (P < 0.01). No differences between mild PE tissues and severe PE tissues were noted in both positive case rates and strong positive rates. Consistent with this finding, the ratio of strong positive staining for IL-35 was higher in healthy pregnant tissues (66.67%; 30/45) than in mild PE tissues (33.11%; 14/45) and severe PE tissues (26.67%; 12/45) (P < 0.01).The abnormal increase in serum and placental of IL-17 has an association with the formation and development of PE. IL-35 expression is significantly lower in severe PE placenta tissue and serum compared with normal pregnant women. These results suggested that IL-17/IL-35 imbalance may play a role in the pathophysiology of PE.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
To evaluate clinical and pregnancy outcomes of double and single blastocyst transfers related with morphological grades in vitrified-warmed embryo transfer.In a retrospective cohort analysis, data were assessed from women who underwent vitrified-warmed blastocyst transfers (VBT) at CHA Gangnam Medical Center between 2014 and 2015. All VBT cycles were categorized into three groups according to blastocyst quality: GG (double good blastocysts transfer), GP (one good and one poor blastocyst transfer), and GS (single good blastocyst transfer). Blastocysts were graded morphologically and ⩾3BB grade was considered good quality.There were 628 transfers in group GG, 401 transfers in group GP, and 277 transfers in group GS. Both clinical pregnancy rate (CPR) and live birth rate (LBR) were the highest in group GG (CPR 65.9%, LBR 55.3%, p < 0.001), but not significantly different between group GP and GS. Multiple pregnancy rates increased significantly in the following order: GS (1.4%), GP (13.5%), and GG (25.6%). Single LBR was the highest in group GS (38.6%, p < 0.001).As an effective VBT, especially for reducing multiple pregnancy and increasing single live birth, single good blastocyst transfer may be recommended rather than any double blastocyst transfer methods. Moreover, transferring a good and a poor blastocyst simultaneously should be avoided.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
The purpose of this study was to define the pregnancy and oncologic outcomes after fertility-sparing treatment of atypical hyperplasia (AH)/endometrial intraepithelial neoplasia (EIN) and early-stage endometrioid endometrial cancer (EEC).The retrospective cohort study included patients who had applied to Başkent University's Ankara Hospital between January 2007 and October 2018 with either AH/EIN (n: 27; Group A) or EEC (n: 30; Group B), and who had the desire to preserve their fertility. The medical records of all patients included in the study were reviewed retrospectively from the hospital records.There were 2 (7.4%) and 5 (16.7%) recurrences, whereby one patient from Group A and two patients from Group B underwent staging surgery. In Group A, 8 patients attempted pregnancy after their treatment and 4 of them (50%) became pregnant, while 3 of them (37.5%) had a live birth. In Group B, there were 17 patients who wanted to become pregnant following treatment of the disease; 8 of them (47%) became pregnant after treatment, 5 of them (16.6%) had a live birth, 1 experienced intrauterine exitus (at 21st gestational week, 350 g), and 2 currently have ongoing pregnancies.Hysteroscopic resection of visible lesions and full endometrial curettage prior to hormonal therapy as a fertility-preserving approach for women of reproductive age with endometrial malignancies can achieve promising oncologic and obstetric responses.
Publication
Journal: Taiwanese journal of obstetrics & gynecology
May/17/2020
Abstract
Lymph node (LN) metastasis is among the important prognostic factors for survival in endometrial cancer (EC). This study aimed to evaluate the occurrence of lymphatic complications following lymphadenectomy in patients with EC.EC patients were retrospectively evaluated. Lower extremity lymphedema (LEL) and pelvic lymphocele (PL) were evaluated according to the International Society of Lymphology guidelines and the National Cancer Institute Common Terminology Criteria for Adverse Events, respectively.A total of 289 patients were enrolled. Surgery was performed via laparotomy and laparoscopy in 200 (69.2%) and 89 (30.8%) patients, respectively. LEL and PL occurred in 43 (14.9%) and 33 (11.4%) patients, respectively. In multivariate logistic regression analysis, circumflex iliac node (CIN) removal (odds ratio [OR]: 3.22; 95% CI: 1.43-7.98; P = 0.004) was an independent risk factor for LEL, while the surgical approach (OR: 4.46; 95% CI: 1.13-29.9; P = 0.004) was an independent risk factor for PL.CIN dissection was a significant risk factor for LEL, while laparotomy was an independent risk factor for PL compared to laparoscopy in EC patients. This suggests that laparoscopic surgery combined with sentinel lymph node navigation surgery will prevent lymphatic complications in low-risk EC patients.
Publication
Journal: Infectious disorders drug targets
May/17/2020
Abstract
<AbstractText>Cryptococcal meningitis is a dreaded complication in HIV infected patients. It was associated with high mortality and morbidity before the advent of Highly Active Anti-Retroviral Therapy. A study was planned in our institute to evaluate the clinical profile, laboratory findings, and prognostic factors for survival in these patients.</AbstractText><AbstractText>A prospective hospital-based observational study, conducted in the Department of Medicine at a tertiary care centre in western Rajasthan.</AbstractText><AbstractText>HIV infected patients presenting with clinical features of meningitis, and positive CSF culture for Cryptococcus were included in our study. All cases underwent detailed clinical history, physical examinations and relevant laboratory investigations including CD4 count and CSF examination.</AbstractText><AbstractText>48 HIV infected cryptococcal meningitis patients were analysed, and the most common presenting clinical features were headache (85.42%), and fever (72.92%), followed by neck stiffness (62.50%). CSF examination was also done for Cryptococcal Antigen test which was reactive in all cases (100%), and India ink staining was positive in 43 cases (89.58%). Significant fatal outcome was associated with patients presenting with altered sensorium, loss of consciousness, cranial nerve palsy and CD4 cell count of less than 100. Similarly, on laboratory and imaging diagnosis, cryptococcal antigen test (>3+reactive), fundus examination (papilloedema) and abnormal CT/MRI brain imaging were associated with poor survival.</AbstractText><AbstractText>Cryptococcal meningitis is a potentially lethal infection in immunocompromised individuals and should be diagnosed early with high clinical suspicion as around 10% of the cases may not be detected on India ink staining and a large proportion (75%) of cases may have normal imaging at initial evaluation. Early diagnosis, watchful eye on prognostic factors and treatment is vital to improve outcome in these patients.</AbstractText>
Publication
Journal: Chemical biology & drug design
May/17/2020
Abstract
The emergence of New Delhi metal beta-lactamase (NDM-1) -producing bacteria and their worldwide spread pose great challenges for the treatment of drug-resistant bacterial infections. These bacteria can hydrolyze most β-lactam antibacterials. Unfortunately, there are no clinically useful NDM-1 inhibitors. In the current work, we manually collected NDM-1 inhibitors reported in the past decade and established the first NDM-1 inhibitor database. Four machine learning models were constructed using the structural and property characteristics of the collected compounds as input training set to discover potential NDM-1 inhibitors. In order to distinguish between high active inhibitors and putative positive drugs, a three-classification strategy was introduced in our study. In detail, the commonly used positive and negative divisions are converted into strongly active, weakly active and inactive. The accuracy of the best prediction model designed based on this strategy reached 90.5%, compared with 69.14% achieved by the traditional docking-based virtual screening method. Consequently, the best model was used to virtually screen a natural product library. The safety of the selected compounds was analyzed by the ADMET prediction model based on machine learning. Seven novel NDM-1 inhibitors were identified, which will provide valuable clues for the discovery of NDM-1 inhibitors.
Publication
Journal: Journal of biomedical materials research. Part A
May/17/2020
Abstract
Neurons of the central nervous system do not regenerate spontaneously after injury. As such, biofunctional tissue scaffolds have been explored to provide a growth-promoting environment to enhance neural regeneration. In this regard, aligned electrospun fibers have proven invaluable for regeneration by offering guidance for axons to cross the injury site. However, a high fiber density could potentially limit axonal ingrowth into the scaffold. Here, we explore which fiber density provides the optimal environment for neurons to regenerate. By changing fiber electrospinning time, we generated scaffolds with different fiber densities and implanted these in a rat model of spinal cord injury (SCI). We found that neurons were able to grow efficiently into scaffolds with high fiber density, even if the gaps between fiber bundles were very small (< 1 μm). Scaffolds with high fiber density showed good host-implant integration. Cell infiltration was not affected by fiber density. Efficient blood vessel ingrowth likely requires larger gaps between fibers or faster degrading fibers. We conclude that scaffolds with high fiber densities, and thus a large number of small gaps in between fiber bundles, provide the preferred environment for nerve regeneration after SCI. This article is protected by copyright. All rights reserved.
Publication
Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
May/17/2020
Abstract
In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future.
Publication
Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
May/17/2020
Abstract
The role of DCST1-AS1 has been investigated in several types of cancer, while the role of DCST1-AS1 in glioblastoma (GBM) is unclear. This study aimed to investigate the role of DCST1-AS1 in GBM.GBM and paired non-tumor tissues were collected from 62 GBM patients. Expression levels of DCST1-AS1 and miR-29b in paired tissue samples were determined by RT-qPCR. The role of DCST1-AS1 in regulating the methylation of miR-29b was assessed by methylation-specific PCR (MSP). Cell proliferation was analyzed by cell proliferation assay.It was observed that the upregulation of DCST1-AS1 in GBM predicted poor survival. MiR-29b was downregulated in GBM and inversely correlated with the expression of DCST1-AS1. In GBM cells, overexpression of DCST1-AS1 resulted in the downregulation of miR-29b and the increased methylation level of miR-29b gene. Overexpression of DCST1-AS1 resulted in increased cell proliferation. Moreover, Overexpression of DCST1-AS1 significantly reversed the inhibitory effects of miR-29b on cancer cell proliferation.DCST1-AS1 may downregulate miR-29b through methylation in GBM to promote cancer cell proliferation.
Authors
Publication
Journal: Journal of Crohn's & colitis
May/17/2020
Publication
Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May/17/2020
Abstract
Fyn kinase in the dorsomedial striatum (DMS) of rodents has a central role in mechanisms underlying excessive alcohol intake. The DMS comprises medium spiny neurons (MSNs) that project directly (dMSNs) or indirectly (iMSNs) to the substantia nigra. Here, we examined the cell-type specificity of Fyn's actions on alcohol use. First, we knocked down Fyn selectively in DMS dMSNs or iMSNs of mice and measured the level of alcohol consumption. We found that downregulation of Fyn in dMSNs, but not in iMSNs, reduces excessive alcohol but not saccharin intake. D1Rs are coupled to Gαs/olf, which activate cAMP signaling. To examine whether Fyn's actions are mediated through cAMP signaling, DMS dMSNs were infected with GαsDREADD, and the activation of Fyn signaling was measured following CNO treatment. We found that remote stimulation of cAMP signaling in DMS dMSNs activates Fyn and promotes the phosphorylation of the Fyn substrate, GluN2B. In contract, remote activation of GαsDREADD in DLS dMSNs did not alter Fyn signaling. We then tested whether activation of GαsDREADD in DMS dMSNs or iMSNs alters alcohol intake and observed that CNO-dependent activation of GαsDREADD in DMS dMSNs but not iMSNs increases alcohol but not saccharin intake. Finally, we examined the contribution of Fyn to GαsDREADD-dependent increase in alcohol intake, and found that systemic administration of the Fyn inhibitor, AZD0503 blocks GαsDREADD-dependent increase in alcohol consumption. Our results suggest that the cAMP-Fyn axis in the DMS dMSNs is a molecular transducer of mechanisms underlying the development of excessive alcohol consumption.
Publication
Journal: Cancer biomarkers : section A of Disease markers
May/17/2020
Abstract
EGFR-mutant lung cancer inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).To investigate the clinical relevance of microRNAs (miRNAs) in TKI therapy response and resistance.We performed a miRNA PCR array analysis and used The Cancer Genome Atlas (TCGA) database to identify potential miRNAs related to EGFR TKIs resistance. We then correlated miRNA expression in 70 surgical and 50 malignant pleural effusion specimens with patient outcomes in those with non-small cell lung carcinoma. Molecular manipulation was performed in EGFR mutant lung cancer cells to assess the effect of miR-200c-3p on cell migratory ability and EGFR-TKI sensitivity.We identified miR-200c-3p and miR-203a-3p as potential EGFR TKI resistance regulators via their modulation of epithelial-to-mesenchymal transition (EMT). MiR-200c-3p and miR-203a-3p were down-regulated in EGFR TKI-resistant cell lines. Progression-free survival (PFS) with EGFR-TKI treatment of patients with high miR-200c-3p expression, but not miR-203a-3p, in the specimens was significantly longer than that of patients with low expression. MiR-200c-3p overexpression inhibited the EMT process in EGFR TKI resistance cell lines and promoted cell death. MiR-200c-3p silencing in EGFR TKI sensitive cell lines increased drug resistance.MiR-200c-3p plays a role in sensitivity to EGFR TKIs via modulating EMT process.
Publication
Journal: JMIR medical education
May/17/2020
Abstract
Medical students commonly refer to Wikipedia.org as their preferred online resource for medical information. The quality and readability of articles about common vascular disorders on Wikipedia has not been evaluated or compared against a standard textbook of surgery.Aims of this study are to: (1) Compare the quality of Wikipedia.org articles to equivalent chapters in a standard undergraduate medical textbook of surgery; (2) Identify any errors of omission in either resource; (3) Compare the readability of both resources using validated ease-of-reading and grade-level tools.Using the Medical Council of Canada's Objectives of the Qualification Examination, eight fundamental topics of vascular surgery were chosen. These topics were located on Wikipedia.org through its native search engine, and equivalent chapters were marked in Schwartz Principles of Surgery 9th edition. Two medical learners assessed these passages on their original platforms and independently compared Wikipedia.org and Schwartz Principles of Surgery in terms of readability, quality, and errors of omission. Readability was evaluated using multiple validated scoring systems to asses for reading ease and grade level of the articles. Quality was evaluated using the DISCERN questionnaire, and errors of omission were evaluated using a standardized scoring system designed by the authors.The articles from Wikipedia have an average Flesch Reading Ease score of 30.5 (Interquartile range; IQR 13.6) compared to Schwartz with a score of 20.2 (IQR 8.4), which suggests that Wikipedia is significantly easier to read (p = 0.032). The average calculated grade levels of the Wikipedia articles by all grade level indices was 14.2 (IQR 1.6), while Schwartz had an average grade level of 15.9 (IQR 0.9), with p = 0.019. The quality of the text was also assessed using the DISCERN tool, which resulted in average scores of 52.9 (IQR 15.9) for Wikipedia and 71.4 (IQR 3.3) for Schwartz, suggesting that Schwartz has higher quality compared to Wikipedia (p = 0.002). Finally, Wikipedia articles scored an average of 12.5 (IQR 8.5) on the errors of omission scale, while Schwartz scored an average of 21.3 (IQR 1.4), suggesting that there were fewer errors of omission in the surgical textbook (p = 0.008).Online resources are increasingly easier to access but can vary in quality. Based on this comparison, the authors of this study recommend the use of vascular surgery textbooks as a primary source of learning material due to greater consistency in quality and fewer errors of omission. Wikipedia can be a useful resource for quick reference, particularly due to its ease of reading, but its vascular surgery articles require further development.
Publication
Journal: Cancer biomarkers : section A of Disease markers
May/17/2020
Abstract
PTEN exerts tumor suppressor role through inhibiting PI3K/AKT signaling. DJ-1 plays an oncogenic role through negatively regulation of PTEN expression. Curcumin (Cur) is a phenolic compound extracted from a variety of plant roots, with multiple anti-tumor pharmacological effects. This study aims to investigate whether Cur plays a role in the regulation of DJ-1-PENT/PI3K/AKT signaling as well as the proliferation and apoptosis of hepatocellular carcinoma cells. Normal human hepatocyte HL-7702 and hepatocellular carcinoma cell lines SMMC-7721 and HepG2 were cultured followed by analysis of the expression of DJ-1 and PTEN. SMMC-7721 and HepG2 cells were treated with different concentrations of Cur (0, 5, 10 μM) followed by measuring cell proliferation by CCK-8, caspase-3 activity as well as DJ-1 expression by western blot. In addition, SMMC-7721 or HepG2 cells were divided into two groups: Cur+pcDNA3.1-Blank and Cur+pcDNA3.1-DJ-1 for analysis of the expression of DJ-1, PTEN and p-AKT, cell apoptosis and proliferation. Compared with HL-7702, SMMC-7721 and HepG2 cells displayed significantly higher DJ-1 expression and lower PTEN expression. Cur treatment significantly inhibited proliferation of SMMC-7721 and HepG2 cells, increased caspase-3 activity and downregulated DJ-1 expression. Transfection of pcDNA3.1-DJ-1 significantly increased DJ-1 and p-AKT expression, promoted cell proliferation, but decreased PTEN expression and cell apoptosis. In conclusion, Cur inhibits proliferation of hepatocellular carcinoma cells and PTEN/PI3K/AKT signaling pathway via the reduction of DJ-1 expression, which provides new insights to the anticancer effects of curcumin in hepatocellular carcinoma.
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