Chronic hepatitis B virus (HBV) infection, a serious public health problem leading to cirrhosis and hepatocellular carcinoma, is currently treated with either pegylated alpha interferon (pegIFN-α) or one of the five nucleos(t)ide analogue viral DNA polymerase inhibitors. However, neither pegIFN-α nor nucleos(t)ide analogues are capable of reliably curing the viral infection. In order to develop novel antiviral drugs against HBV, we established a cell-based screening assay by using an immortalized mouse hepatocyte-derived stable cell line supporting a high level of HBV replication in a tetracycline-inducible manner. Screening of a library consisting of 26,900 small molecules led to the discovery of a series of sulfamoylbenzamide (SBA) derivatives that significantly reduced the amount of cytoplasmic HBV DNA. Structure-activity relationship studies have thus far identified a group of fluorine-substituted SBAs with submicromolar antiviral activity against HBV in human hepatoma cells. Mechanistic analyses reveal that the compounds dose dependently inhibit the formation of pregenomic RNA (pgRNA)-containing nucleocapsids of HBV but not other animal hepadnaviruses, such as woodchuck hepatitis virus (WHV) and duck hepatitis B virus (DHBV). Moreover, heterologous genetic complementation studies of capsid protein, DNA polymerase, and pgRNA between HBV and WHV suggest that HBV capsid protein confers sensitivity to the SBAs. In summary, SBAs represent a novel chemical entity with superior activity and a unique antiviral mechanism and are thus warranted for further development as novel antiviral therapeutics for the treatment of chronic hepatitis B.
The aim of this study was to compare the differences between anterolateral thigh perforator free flaps (ALTFF) and pectoralis major myocutaneous flap (PMMF) for reconstruction in oral cancer patients.
Method and Patients: who received free flap or PMMF reconstruction after ablation surgeries were eligible for the current study. The patients’ demographic data, medical history, and quality of life scores(Medical Outcomes Study-Short Form-36 (MOS SF-36) and the University of Washington Quality of Life (UW-QOL) questionnaires were collected.
Results: 81 of 118 questionnaires were returned (68.64%). There was signiﬁcant differences between two groups in the gender (P<0.005). Patients reconstructed with ALTFF had better appearance domains and better shoulders domains, in addition to better role emotion domains.
Conclusions: Using either PMMF or ALTFF for reconstruction of oral defects after cancer resection signiﬁcantly inﬂuences a patient’s quality of life. Data from this study provide useful information for physicians and patients during their discussion of reconstruction modalities for oral cancers.
Key words:Quality of life, ALTFF,PMMF, oral cancer.
Electron paramagnetic resonance (EPR) at 236.6 GHz and 9.5 GHz probed the tumbling of nitroxide spin probes in the lower stem, the upper loop, and near the bulge of mini c TAR DNA. High frequency 236.6 GHz EPR, not previously applied to spin labeled oligonucleotides, was notably sensitive to fast, anisotropic, hindered local rotational motion of the spin probe, occurring approximately about the NO nitroxide axis. Labels attached to the 2′-amino cytidine sugar in the mini c TAR DNA showed such anisotropic motion, which was faster in the lower stem, a region previously suggested to be partially melted. More flexible labels attached to phosphorothioates at the end of the lower stem tumbled isotropically in mini c TAR DNA, mini TAR RNA, and ψ3 RNA, but at 5 °C the motion became more anisotropic for the labeled RNAs, implying more order within the RNA lower stems. As observed by 9.5 GHz EPR, the slowing of nanosecond motions of large segments of the oligonucleotide was enhanced by increasing the ratio of the nucleocapsid protein NCp7 to mini c TAR DNA from zero to two. The slowing was most significant at labels in the loop and near the bulge. At a 4:1 ratio of NCp7 to mini c TAR DNA all labels reported tumbling times > 5 ns, indicating a condensation of NCp7 and TAR DNA. At the 4:1 ratio, pulse dipolar EPR spectroscopy of bi-labels attached near the 3′ and 5′ terminals showed evidence for an NCp7-induced increase in the 3′ - 5 ′end-to-end distance distribution and a partially melted stem.
EPR; spin label; NCp7; mini c TAR DNA
Glioma pathogenesis related-2 (GLIPR-2) belongs to pathogenesis related-1 (PR-1) family whose function remains unknown. In our previous studies, GLIPR-2 was found to be a novel potent stimulator of epithelial-to-mesenchymal transition (EMT) in renal fibrosis which has been classified as type 2 EMT. However, whether GLIPR-2 could induce type 3 EMT in carcinogenesis needs further investigation. In this study, we showed that GLIPR-2 was expressed in hepatocellular carcinoma (HCC) tissues, hypoxia could upregulate the expression of GLIPR-2 in HepG2 and PLC/PRF/5 cells in vitro, overexpression of this protein promoted migration and invasion via EMT, knockdown of GLIPR-2 attenuated migration and invasion of HepG2 and PLC/PRF/5 cells in hypoxia. Moreover, extracellular signal-regulated kinases 1 and 2 (ERK1/2) are positively regulated by GLIPR-2. Taken together, we provide evidence for a hypoxia/GLIPR-2/EMT/migration and invasion axis in HCC cells and it provides novel insights into the mechanism of migration and invasion of hepatocellular carcinoma cells in hypoxia condition.
To evaluate the feasibility, effectiveness, and safety of reinnervation of the bilateral posterior cricoarytenoid (PCA) muscles using the left phrenic nerve in patients with bilateral vocal fold paralysis.
Forty-four patients with bilateral vocal fold paralysis who underwent reinnervation of the bilateral PCA muscles using the left phrenic nerve were enrolled in this study. Videostroboscopy, perceptual evaluation, acoustic analysis, maximum phonation time, pulmonary function testing, and laryngeal electromyography were performed preoperatively and postoperatively. Patients were followed-up for at least 1 year after surgery.
Videostroboscopy showed that within 1 year after reinnervation, abductive movement could be observed in the left vocal folds of 87% of patients and the right vocal folds of 72% of patients. Abductive excursion on the left side was significantly larger than that on the right side (P < 0.05); most of the vocal function parameters were improved postoperatively compared with the preoperative parameters, albeit without a significant difference (P > 0.05). No patients developed immediate dyspnea after surgery, and the pulmonary function parameters recovered to normal reference value levels within 1 year. Postoperative laryngeal electromyography confirmed successful reinnervation of the bilateral PCA muscles. Eighty-seven percent of patients in this series were decannulated and did not show obvious dyspnea after physical activity. Those who were decannulated after subsequent arytenoidectomy were not included in calculating the success rate of decannulation.
Reinnervation of the bilateral PCA muscles using the left phrenic nerve can restore inspiratory vocal fold abduction to a physiologically satisfactory extent while preserving phonatory function at the preoperative level without evident morbidity.
The reconstruction of mandibular defects after trauma or tumor resection is one of the most challenging problems facing reconstructive surgeons. Although the primary intended outcome of surgery to treat head-and-neck malignancies is still the disease-free survival of the patient, health-related quality of life (HRQOL) is now seen as an essential secondary outcome. This study aims to evaluate HRQOL outcomes in young patients undergoing primary mandible reconstruction with free fibula flap and to collect information about their socio-cultural situation.
The HRQOL outcomes of 25 young patients after primary mandible reconstruction with free fibula flap for mandible malignancies were assessed using the Medical Outcomes Study-Short Form-36 (MOS SF-36) and University of Washington Quality of Life (UW-QOL) questionnaires 12 months postoperatively.
Using the UW-QOL questionnaire, the best-scoring domain was ‘pain’, whereas ‘chewing’ and ‘anxiety’ were given the lowest scores. Using the MOS SF-36 questionnaire, the best-scoring domain was ‘physical functioning’, while ‘bodily pain’ and ‘general health’ also scored well.
Mandible reconstruction with fibula flap will significantly influence a young patient’s HRQOL. Young patients pay more attention to postoperative facial appearance; this should be considered in surgical planning. The socio-cultural data show a fairly low level of education for the majority of patients.
Free fibula flap; Health-related quality of life; Reconstruction
Covalently closed circular DNA (cccDNA) of hepadnaviruses exists as an episomal minichromosome in the nucleus of infected hepatocyte and serves as the transcriptional template for viral mRNA synthesis. Elimination of cccDNA is the prerequisite for either a therapeutic cure or immunological resolution of HBV infection. Although accumulating evidence suggests that inflammatory cytokines-mediated cure of virally infected hepatocytes does occur and plays an essential role in the resolution of an acute HBV infection, the molecular mechanism by which the cytokines eliminate cccDNA and/or suppress its transcription remains elusive. This is largely due to the lack of convenient cell culture systems supporting efficient HBV infection and cccDNA formation to allow detailed molecular analyses. In this study, we took the advantage of a chicken hepatoma cell line that supports tetracycline-inducible duck hepatitis B virus (DHBV) replication and established an experimental condition mimicking the virally infected hepatocytes in which DHBV pregenomic (pg) RNA transcription and DNA replication are solely dependent on cccDNA. This cell culture system allowed us to demonstrate that cccDNA transcription required histone deacetylase activity and IFN-α induced a profound and long-lasting suppression of cccDNA transcription, which required protein synthesis and was associated with the reduction of acetylated histone H3 lysine 9 (H3K9) and 27 (H3K27) in cccDNA minichromosomes. Moreover, IFN-α treatment also induced a delayed response that appeared to accelerate the decay of cccDNA. Our studies have thus shed light on the molecular mechanism by which IFN-α noncytolytically controls hepadnavirus infection.
Hepatitis B virus (HBV) infection affects approximately one-third of the world population and more than 350 million people are chronically infected by the virus, for which the currently available antiviral therapies fail to provide a cure. This is because the HBV DNA polymerase inhibitors have no direct effect on the nuclear form of HBV genome, the covalently closed circular (ccc) DNA. Elimination or transcriptional silencing of cccDNA is the prerequisite for either a therapeutic cure or immunological resolution of HBV infection. However, due to the lack of proper experimental systems, the molecular mechanism of cccDNA biosynthesis, maintenance and transcription regulation remains to be elucidated. We report herein the establishment of a cell-based assay where the replication of duck hepatitis B virus (DHBV), a close relative of HBV, is supported by cccDNA. This experimental system not only allows us to demonstrate the unique property of alpha-interferon suppression of cccDNA transcription, but also shows for the first time that DHBV cccDNA transcription requires histone deacetylase activity. It is conceivable that the principles revealed by studying DHBV cccDNA metabolism and transcription regulation should provide valuable insight in HBV cccDNA biology and clues for the development of therapeutics to control chronic hepatitis B.
Multispectral excitation-resolved fluorescence tomography (MEFT) uses excitation light of different wavelengths to illuminate the fluorophores and obtains the reconstruction image frame which is fluorescence yield at each corresponding wavelength. For structures containing fluorophores of different concentrations, fluorescence yields show different variation trends with the excitation spectrum. In this study, principal component analysis (PCA) is used to analyze the MEFT reconstructed image frames. By taking advantage of the different variation trends of fluorescence yields, PCA can provide a set of principal components (PCs) in which structures containing different concentrations of fluorophores are shown separately. Simulations and experiments are both performed to test the performance of the proposed algorithm. The results suggest that the location and structure of fluorophores with different concentrations can be obtained and the contrast of fluorophores can be improved further by using this algorithm.
(170.3010) Image reconstruction techniques; (170.6960) Tomography; (100.3190) Inverse problems; (170.3880) Medical and biological imaging; (170.3660) Light propagation in tissues; (290.1990) Diffusion; (290.7050) Turbid media
Nasopharyngeal carcinomas of the undifferentiated or lymphoepithelial type are most commonly seen in South East Asians. Identical tumors have also been described at a variety of other sites including lung, skin and salivary gland and have been referred to by a number of names including lymphoepithelial carcinoma (LEC). LECs of major salivary gland are extremely rare. They are particularly common amongst the Inuit populations of the arctic region including Greenland (Denmark), Canada and Alaska, as well as South East Asians. Within the Inuit group, this tumor represents the majority of all salivary gland carcinomas. Amongst primary LEC of major salivary gland, most cases reported in the literature have represented typical nasopharynx-like tumors. Variants of Epstein–Barr Virus (EBV) associated LEC have not been described previously, to the best of our knowledge. In this report, we describe 4 EBV-associated major salivary gland LECs with prominent basaloid morphology, which represent 22 % of a cohort of 18 salivary LECs from an Inuit population in Greenland. The features described in these cases raise a differential diagnosis of other basaloid tumors, particularly in light of the salivary gland location. A basaloid variant of LEC in major salivary gland should be recognized, especially in highly prone populations, to avoid misdiagnosis of other more common salivary tumors.
EBV; Lymphoepithelial-like; Undifferentiated; Carcinoma; Basaloid
Despite improvements in treatment strategies for head and neck squamous cell carcinoma (HNSCC), outcomes have not significantly improved; highlighting the importance of identifying novel therapeutic approaches to target this disease. To address this challenge, we proceeded to evaluate the role of iron in HNSCC.
Expression levels of iron-related genes were evaluated in HNSCC cell lines using quantitative RT-PCR. Cellular phenotypic effects were assessed using viability (MTS), clonogenic survival, BrdU, and tumor formation assays. The prognostic significance of iron-related proteins was determined using immunohistochemistry.
In a panel of HNSCC cell lines, hemochromatosis (HFE) was one of the most overexpressed genes involved in iron regulation. In vitro knockdown of HFE in HNSCC cell lines significantly decreased hepcidin (HAMP) expression and intracellular iron level. This in turn, resulted in a significant decrease in HNSCC cell viability, clonogenicity, DNA synthesis, and Wnt signalling. These cellular changes were reversed by re-introducing iron back into HNSCC cells after HFE knockdown, indicating that iron was mediating this phenotype. Concordantly, treating HNSCC cells with an iron chelator, ciclopirox olamine (CPX), significantly reduced viability and clonogenic survival. Finally, patients with high HFE expression experienced a reduced survival compared to patients with low HFE expression.
Our data identify HFE as potentially novel prognostic marker in HNSCC that promotes tumour progression via HAMP and elevated intracellular iron levels, leading to increased cellular proliferation and tumour formation. Hence, these findings suggest that iron chelators might have a therapeutic role in HNSCC management.
Lactococcus lactis can undergo respiration when hemin is added to an aerobic culture. The most distinctive feature of lactococcal respiration is that lactate could be consumed in the stationary phase concomitantly with the rapid accumulation of diacetyl and acetoin. However, the enzyme responsible for lactate utilization in this process has not yet been identified. As genes for fermentative NAD-dependent l-lactate dehydrogenase (l-nLDH) and potential electron transport chain (ETC)-related NAD-independent l-LDH (l-iLDH) exist in L. lactis, the activities of these enzymes were measured in this study using crude cell extracts prepared from respiratory and fermentation cultures. Further studies were conducted with purified preparations of recombinant LDH homologous proteins. The results showed that l-iLDH activity was hardly detected in both crude cell extracts and purified l-iLDH homologous protein while l-nLDH activity was very significant. This suggested that l-iLDHs were inactive in lactate utilization. The results of kinetic analyses and the effects of activator, inhibitor, substrate and product concentrations on the reaction equilibrium showed that l-nLDH was much more prone to catalyze the pyruvate reduction reaction but could reverse its role provided that the concentrations of NADH and pyruvate were extremely low while NAD and lactate were abundant. Metabolite analysis in respiratory culture revealed that the cellular status in the stationary phase was beneficial for l-nLDH to catalyze lactate oxidation. The factors accounting for the respiration- and stationary phase-dependent lactate utilization in L. lactis are discussed here.
•LutABC proteins do not participate in lactate oxidation in Lactococcus lactis•Lactococcus lactis has very low NAD-independent lactate dehydrogenase activity•Fructose-1,6-bisphosphate-dependent lactate dehydrogenase can work in reverse in vivo•Metabolite concentrations in the stationary phase are favorable for lactate oxidation•Respiratory metabolism is the basis for continual lactate oxidation in Lactococcus
Lactococcus lactis; Lactate oxidation; Lactate dehydrogenase; Type II IPP isomerase; Proton motive force; ETC, electron transport chain; LDH, lactate dehydrogenase; iLDH, NAD-independent lactate dehydrogenase; nLDH, NAD-dependent lactate dehydrogenase; FBP, fructose 1,6-bisphosphate; PMF, proton motive force; DCPIP, 2,6-dichlorophenolindophenol; IPP, isopentenyl diphosphate
In normal adult brain the microtubule associated protein (MAP) tau contains 2–3 phosphates per mol of the protein and at this level of phosphorylation it is a soluble cytosolic protein. The normal brain tau interacts with tubulin and promotes its assembly into microtubules and stabilizes these fibrils. In Alzheimer disease (AD) brain tau is three to fourfold hyperphosphorylated. The abnormally hyperphosphorylated tau binds to normal tau instead of the tubulin and this binding leads to the formation of tau oligomers. The tau oligomers can be sedimented at 200,000 × g whereas the normal tau under these conditions remains in the supernatant. The abnormally hyperphosphorylated tau is capable of sequestering not only normal tau but also MAP MAP1 and MAP2 and causing disruption of the microtubule network promoted by these proteins. Unlike Aβ and prion protein (PrP) oligomers, tau oligomerization in AD and related tauopathies is hyperphosphorylation-dependent; in vitro dephosphorylation of AD P-tau with protein phosphatase 2A (PP2A) inhibits and rehyperphosphorylation of the PP2A-AD P-tau with more than one combination of tau protein kinases promotes its oligomerization. In physiological assembly conditions the AD P-tau readily self-assembles into paired helical filaments. Missense tau mutations found in frontotemporal dementia apparently lead to tau oligomerization and neurofibrillary pathology by promoting its abnormal hyperphosphorylation. Dysregulation of the alternative splicing of tau that alters the 1:1 ratio of the 3-repeat: 4-repeat taus such as in Down syndrome, Pick disease, and progressive supranuclear palsy leads to the abnormal hyperphosphorylation of tau.
microtubule associated protein tau; abnormal hyperphosphorylation of tau; O-GlcNAcylation of tau; protein phosphatase 2A; alternate splicing of tau; Alzheimer neurofibrillary degeneration; Alzheimer disease; tauopathies
To determine the accuracy of MR imaging with gadoxetic acid disodium (Gd-EOB-DTPA) for the detection of hepatocelluar carcinoma (HCC).
Materials and Methods
A systematic search was performed in PUBMED, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database up to March 2013 to identify studies about evaluation of Gd-EOB-DTPA enhanced MR imaging in patients suspected of having HCC. The data were extracted to perform heterogeneity test and threshold effect test and to calculate sensitivity, specificity, diagnostic odds ratio, predictive value, and areas under summary receiver operating characteristic curve (AUC).
From 601 citations, 10 were included in the meta-analysis. The methodological quality of the 10 studies was good. Overall HCC: There was significant heterogeneity in the pooled analysis (I2 = 69.4%, P = 0.0005), and the pooled weighted values were determined to be sensitivity: 0.91 (95% confidence interval (CI): 0.89, 0. 93); specificity: 0.95 (95% CI: 0.94, 0.96); diagnostic odds ratio: 169.94 (95% CI: 108.84, 265.36); positive likelihood ratio: 15.75 (95% CI: 7.45, 33.31); negative likelihood ratio: 0.10 (95% CI: 0.06, 0.15). The AUC was 0.9778. HCC in cirrhosis: The estimates were to be sensitivity: 0.91 (95% CI: 0.88, 0.93); specificity: 0.93 (95% CI: 0.89, 0.95); diagnostic odds ratio: 234.24 (95% CI: 33.47, 1639.25); positive likelihood ratio: 15.08 (95% CI: 2.20, 103.40); negative likelihood ratio: 0.08 (95% CI: 0.03, 0.21). The AUC was 0.9814. ≤20
mm HCC: The AUC was 0.9936. There was no notable publication bias.
This meta-analysis suggests that MR imaging with Gd-EOB-DTPA has high diagnostic accuracy for the detection of HCC, especially for ≤20 mm HCC. This technique shows good prospect in diagnosis of HCC.
The present study aimed to identify the molecular pathological changes of the nasopharyngeal carcinoma (NPC) epithelial CNE3 cell line, which has been used in experimental studies for 20 years in a culture environment. The pathological type of NPC and the presence of the Epstein-Barr virus (EBV) were identified. CNE3 short tandem repeats (STRs) were amplified, analyzed and compared using metastatic carcinoma tissue from primary NPC. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to identify the immunophenotype and EBV-encoded small RNA (EBER) expression in nude mice transplanted CNE3 tumor cells. Polymerase chain reaction (PCR) and DNA sequencing were used to identify the EBV oncogene, BamH1-A right frame 1 (BARF1) and electron microscopy was used to analyze the organization of the ultrastructure. CNE3 was not cross-contaminated by other human cell lines and the EBV was no longer present in the CNE3 cells. The pathological type of CNE3 was transformed from an undifferentiated non-keratinizing carcinoma with focal adenocarcinoma differentiation into a poorly-differentiated adenocarcinoma. In conclusion, this knowledge on the molecular pathological changes of CNE3 may aid in the development of new research approaches for NPC.
nasopharyngeal carcinoma; CNE3; molecular pathology
Protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) are major components of insulin-AKT signaling that plays crucial roles in various types of tissue. Recent studies found that these two kinases are modified posttranslationally by O-GlcNAcylation. Here, we demonstrate that O-GlcNAcylation regulated phosphorylation/activation of AKT and GSK-3β in different manners in kidney HEK-293FT cells, but did not affect these two kinases in hepatic HepG2 cells. In neuronal cells, O-GlcNAcylation regulated phosphorylation of AKT negatively, but had no effect on GSK-3β. These results suggest protein-specific and cell type–specific regulation of AKT and GSK-3β by O-GlcNAcylation. Therefore, studies on the roles of AKT and GSK-3β O-GlcNAcylation should be done in a tissue- and cell type–specific manner.
AKT; GSK-3β; O-GlcNAcylation; phosphorylation; cell types
The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.
Adult human brain expresses six isoforms of tau protein as a result of alternative splicing. Alternative splicing of exon 10 (E10) leads to tau isoforms containing either three (3R) or four (4R) microtubule-binding repeats. Imbalance in the 3R-tau/4R-tau ratio causes neurofibrillary degeneration and dementia. Here, we demonstrated that the dual-specificity tyrosine phosphorylation–regulated kinase 1A (Dyrk1A) interacted with the splicing factor 9G8 and phosphorylated it at several serine residues. Dyrk1A itself promoted tau E10 inclusion, whereas 9G8 inhibited E10 inclusion, and these actions were variable depending on the cell types. Co-expression of Dyrk1A and 9G8 led to their translocation from the nucleus to the cytoplasm and suppressed their ability to regulate tau exon 10 splicing. This action is probably due to their interaction-induced translocation from the nucleus, where the regulation of tau E10 splicing occurs, to the cytoplasm. These findings provide novel insights into the molecular mechanism of the regulation of tau E10 splicing and further our understanding of the neurodegeneration caused by dysregulation of tau E10 splicing.
Tau; alternative splicing; 9G8; Dyrk1A; neurodegeneration
Bulimia nervosa (BN) has been characterized as similar to an addiction, though the empirical support for this characterization is limited. This study utilized PET imaging to determine whether abnormalities in brain dopamine (DA) similar to those described in substance use disorders occur in BN.
PET imaging with [11C]raclopride, pre/post methylphenidate administration, to assess dopamine type 2 (D2) receptor binding (BPND) and striatal DA release (ΔBPND).
There was a trend towards lower D2 receptor BPND in two striatal subregions in the patient group compared to the control group. DA release in the putamen in the patient group was significantly reduced and, overall, there was a trend towards a difference in striatal DA release. Striatal DA release was significantly associated with the frequency of binge eating.
These data suggest that BN is characterized by abnormalities in brain DA that resemble, in some ways, those described in addictive disorders.
Bulimia nervosa; eating disorders; PET imaging; dopamine; addictions; reward
A near-infrared (NIR) hyperspectral imaging system was developed in this study. NIR hyperspectral imaging combined with multivariate data analysis was applied to identify rice seed cultivars. Spectral data was exacted from hyperspectral images. Along with Partial Least Squares Discriminant Analysis (PLS-DA), Soft Independent Modeling of Class Analogy (SIMCA), K-Nearest Neighbor Algorithm (KNN) and Support Vector Machine (SVM), a novel machine learning algorithm called Random Forest (RF) was applied in this study. Spectra from 1,039 nm to 1,612 nm were used as full spectra to build classification models. PLS-DA and KNN models obtained over 80% classification accuracy, and SIMCA, SVM and RF models obtained 100% classification accuracy in both the calibration and prediction set. Twelve optimal wavelengths were selected by weighted regression coefficients of the PLS-DA model. Based on optimal wavelengths, PLS-DA, KNN, SVM and RF models were built. All optimal wavelengths-based models (except PLS-DA) produced classification rates over 80%. The performances of full spectra-based models were better than optimal wavelengths-based models. The overall results indicated that hyperspectral imaging could be used for rice seed cultivar identification, and RF is an effective classification technique.
rice seed cultivar; hyperspectral imaging; random forest (RF); weighted regression coefficients (BW)
Health care workers (HCWs) are at risk of latent tuberculosis infection (LTBI). In China, tuberculosis (TB) is a major public health problem, but the prevalence of LTBI in HCWs especially in the hospital for pulmonary diseases has not been assessed enough. The aim of this study was to determine the prevalence and putative risk factors of LTBI among HCWs in a chest hospital and a TB research institute in China.
A cross-sectional study was conducted among HCWs in China in 2012. LTBI was assessed by T-SPOT.TB, and information on HCWs was collected using a standardised questionnaire. Risk factors for LTBI were analyzed by univariate and multivariate regression. The overall prevalence of LTBI among HCWs was 33.6%. Analyzed by job category, the highest prevalence was found among laboratory staff (43.4%). In the different workplaces, the proportion of LTBI was significantly higher among the high risk workplaces (37.4%) compared to the low risk workplaces. The duration of employment had a significant impact on the prevalence of LTBI. Positive T-SPOT.TB test results accounted for 17.6%, 16.8%, 23.5%, 41.8% and 41.6% in groups of ≤2, 3–5, 6–10, 11–20, and >20 working years respectively. In multivariate analysis, job categories (Laboratory staff [2.76 (95% CI: 1.36; 5.60)], technician staff [2.02 (95% CI: 1.12; 3.64)]); working duration as a HCW for 11 to 20 years [3.57 (95% CI: 1.46; 8.71)], and 20 years above [3.41 (95% CI: 1.28; 9.11)]; and the history of household TB contact [2.47 (95% CI: 1.15; 5.33)] were associated with increased risk of LTBI.
Prevalence of LTBI estimated by T-SPOT.TB is high among Chinese HCWs and working duration, job category and the history of household TB contact were associated with increased risk. These data highlight adequate infection control measures should be undertaken.
ω-3 fatty acids have potential anticancer effects, and consuming food rich in ω-3 fatty acids reduces the human renal cell carcinoma (RCC) risk. However, the direct effect of ω-3 fatty acids on RCC in vitro is unknown. In the present study, the effects of α-linolenic acid (ALA), an ω-3 fatty acid, were observed on cell proliferation in the RCC cell line OS-RC-2. The activity and gene expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) and cyclooxygenase-2 (COX-2) in the OS-RC-2 cells were measured by ELISA and real-time RT-PCR, respectively, following ALA treatment. ALA (20–80 μM) dose-dependently suppressed the proliferation of the OS-RC-2 cells. PPAR-γ activity and gene expression were significantly increased by ALA at 20 and 40 μM. COX-2 activity and gene expression levels were significantly decreased by ALA from 20 μM. Use of purely the PPAR-γ agonist, rosiglitazone, decreased the proliferation of the OS-RC-2 cells, while ALA induced further suppression of cell proliferation in the presence of rosiglitazone. The COX-2 inhibitor N-(3-Pyridyl)indomethacinamide induced further suppression of cell proliferation in the presence of rosiglitazone. N-(3-Pyridyl)indomethacinamide also suppressed the proliferation of the OS-RC-2 cells. In the presence of N-(3-Pyridyl)indomethacinamide, ALA and rosiglitazone further inhibited OS-RC-2 cell proliferation. In conclusion, ALA inhibits the cell proliferation of the OS-RC-2 human RCC cell line. PPAR-γ activation and COX-2 inhibition serve as two signaling pathways for the inhibitory effects of ALA on RCC cell proliferation.
renal cell carcinoma; α-linolenic acid; peroxisome proliferator-activated receptor-γ; cyclooxygenase-2; cell proliferation
Many head-and-neck cancer survivors treated with radiotherapy suffer from permanent impairment of their salivary gland function, for which few effective prevention or treatment options are available. This study explores the potential of transient activation of Wnt/β-catenin signaling in preventing radiation damage to salivary glands in a preclinical model.
Methods and Materials
Wnt reporter transgenic mice were exposed to 15 Gy single dose radiation in head and neck area to evaluate the effects of radiation on Wnt activity in salivary gland. Transient Wnt1 over-expression in basal epithelia was induced in inducible Wnt1 transgenic mice before, in together with, after or without local radiation, then saliva flow rate, histology, apoptosis, proliferation, stem cell activity and mRNA expression were evaluated.
Radiation damage did not significantly affect activity of Wnt/β-catenin pathway as physical damage did. Transient expression of Wnt1 in basal epithelia significantly activated Wnt/β-catenin pathway in submandibular glands of male mice but not in those of females. Concurrent transient activation of Wnt pathway prevented chronic salivary gland dysfunction following radiation by suppressing apoptosis and preserving functional salivary stem/progenitor cells. In contrast, Wnt activation 3 days before or after irradiation did not show significant beneficial effects mainly due to failure to inhibit acute apoptosis after radiation. Excessive Wnt activation before radiation failed to inhibit apoptosis likely due to extensive induction of mitosis and up-regulation of proapoptosis gene Puma, while that after radiation might miss the critical treatment window.
These results suggest that concurrent transient activation of Wnt/β-catenin pathway could prevent radiation-induced salivary gland dysfunction.
Salivary gland; Xerostomia; Radiation; Wnt/β-catenin pathway; Stem cells
Fluorescence molecular tomography (FMT) with early-photons can improve the spatial resolution and fidelity of the reconstructed results. However, its computing scale is always large which limits its applications. In this paper, we introduced an acceleration strategy for the early-photon FMT with graphics processing units (GPUs). According to the procedure, the whole solution of FMT was divided into several modules and the time consumption for each module is studied. In this strategy, two most time consuming modules (Gd and W modules) were accelerated with GPU, respectively, while the other modules remained coded in the Matlab. Several simulation studies with a heterogeneous digital mouse atlas were performed to confirm the performance of the acceleration strategy. The results confirmed the feasibility of the strategy and showed that the processing speed was improved significantly.
Casticin, a polymethoxyflavone, is reported to have anticancer activities. The aim of the present study was to examine the molecular mechanisms by which casticin induces apoptosis in ovarian cancer cells. The human ovarian cancer cell lines SKOV3 and A2780 were cultured in vitro. Various molecular techniques, including histone/DNA enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR), western blot analysis and gene transfection, were used to assess the expression of FOXO3a and forkhead box protein M1 (FoxM1) in casticin-treated ovarian cancer cell lines. Casticin-induced apoptotic cell death was accompanied by the activation of transcription factor FOXO3a, with a concomitant decrease in the expression levels of FoxM1 and its downstream target factors, namely survivin and polo-like kinase 1 (PLK1), and an increase in p27KIP1. A small inhibitory RNA (siRNA) knockout of FoxM1 potentiated casticin-induced apoptosis in ovarian cancer cells. Silencing FOXO3a expression using siRNA increased FoxM1 expression levels and clearly attenuated the induction of apoptosis by casticin treatment. These results show that casticin-induced apoptosis in ovarian cancer may be caused by the activation of FOXO3a, leading to FoxM1 inhibition.
ovarian cancer; casticin; FOXO3a; forkhead box protein M1; apoptosis