Source:Autoimmunity Reviews
Author(s): Manuele Furnari, Vincenzo Savarino, Edoardo Savarino
http://ift.tt/2cqQIr7
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Publication date: Available online 22 September 2016
Source:Trends in Cell Biology
Author(s): Dae In Kim, Kyle J. Roux
There are inherent limitations with traditional methods to study protein behavior or to determine the constituency of proteins in discrete subcellular compartments. In response to these limitations, several methods have recently been developed that use proximity-dependent labeling. By fusing proteins to enzymes that generate reactive molecules, most commonly biotin, proximate proteins are covalently labeled to enable their isolation and identification. In this review we describe current methods for proximity-dependent labeling in living cells and discuss their applications and future use in the study of protein behavior.
http://ift.tt/2cWVqAM
FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation. Thirty-two Cushing's syndrome patients and 32 matched controls underwent memory tests, 3-Tesla MRI of the brain, and DNA extraction from total leukocytes. DNA samples were bisulfite treated, PCR amplified, and pyrosequenced to assess a total of 41CpG-dinucleotides in the introns 1, 2, 5, and 7 of FKBP5. Significantly lower intronic FKBP5 DNA methylation in CS patients compared to controls was observed in ten CpG-dinucleotides. DNA methylation at these CpGs correlated with left and right HV (Intron-2-Region-2-CpG-3: LHV, r = 0.73, p = 0.02; RHV, r = 0.58, p = 0.03). Cured and active CS patients showed both lower methylation of intron 2 (92.37, 91.8, and 93.34 %, respectively, p = 0.03 for both) and of intron 7 (77.08, 73.74, and 79.71 %, respectively, p = 0.02 and p < 0.01) than controls. Twenty-two subjects had the CC genotype, 34 had the TC genotype, and eight had the TT genotype. Lower average DNA methylation in intron 7 was observed in the TT subjects compared to CC (72.5vs. 79.5 %, p = 0.02) and to TC (72.5 vs. 79.0 %, p = 0.03). Our data demonstrate, for the first time, a reduction of intronic DNA methylation of FKBP5 in CS patients.
|
Publication date: Available online 23 September 2016
Source:Journal of Proteomics
Author(s): Christopher A Toth, Zsuzsanna Kuklenyik, Jeffrey I Jones, Bryan A Parks, Michael S Gardner, David M Schieltz, Jon C Rees, Michael L Andrews, Lisa G McWilliams, James L Pirkle, John R Barr
Apolipoproteins measured in plasma or serum are potential biomarkers for assessing metabolic irregularities that are associated with the development of cardiovascular disease (CVD). LC-MS/MS allows quantitative measurement of multiple apolipoproteins in the same sample run. However, the accuracy and precision of the LC-MS/MS measurement depends on the reproducibility of the enzymatic protein digestion step. With the application of an immobilized enzyme reactor (IMER), the reproducibility of the trypsin digestion can be controlled with high precision via flow rate, column volume and temperature. In this report, we demonstrate the application of an integrated IMER-LC-MS/MS platform for the simultaneous quantitative analysis of eight apolipoproteins. Using a dilution series of a characterized serum pool as calibrator, the method was validated by repeated analysis of pooled sera and individual serum samples with a wide range of lipid profiles, all showing intra-assay CV<4.4% and inter-assay CV<8%. In addition, the method was compared with traditional homogeneous digestion coupled LC-MS/MS for the quantification of apoA-I and apoB-100. Applied in large scale human population studies, this method can serve the translation of a wider panel of apolipoprotein biomarkers from research to clinical application.SignificanceCurrently, the translation of apolipoprotein biomarkers to clinical application is impaired because of the high cost of large cohort studies using traditional single-analyte immunoassays. The application of on-line tryptic digestion coupled with LC-MS/MS analysis is an effective way to address this problem. In this work we demonstrate a high throughput, multiplexed, automated proteomics workflow for the simultaneous analysis of multiple proteins.
Publication date: Available online 23 September 2016
Source:Journal of Proteomics
Author(s): Xia Yang, Zichang Zhang, Tao Gu, Mingchao Dong, Qiong Peng, Lianyang Bai, Yongfeng Li
Barnyardgrass (Echinochloa crus-galli) is one of the top 15 herbicide-resistant weeds around the world that interferes with rice growth, resulting in major losses of rice yield. Thus, multi-herbicide resistance in barnyardgrass presents a major threat, with the underlying mechanisms that contribute to resistance requiring elucidation. In an attempt to characterize this multi-herbicide resistance at the proteomic level, comparative analysis of resistant and susceptible barnyardgrasses was performed using iTRAQ, both with and without quinclorac, bispyribac-sodium and penoxsulam herbicidal treatment. A total of 1342 protein species were identified from 2248 unique peptides by searching the UniProt database and conducting data analysis. Approximately 904 protein species with 4774 Gene Ontology (GO) terms were grouped into the categories of biological process, cellular component and molecular function. Among these, 688 protein species were annotated into 1583 KEGG pathways, with 980 protein species relating to metabolism and 93 relating to environmental information processing. A total of 292 protein species showed more than a 1.2-fold change in abundance in the resistant biotype relative to the susceptible biotype. Furthermore, herbicide treatment resulted in 157 protein species that showed more than a 1.2-fold change in the resistant biotype. Moreover, physiological analyses demonstrated an ecological fitness cost in the resistant biotype.SignificanceWhile some studies have shown a fitness cost to be associated with an altered ecological interaction, our understanding of the fitness costs associated with herbicide resistance are limited. Herein, physiological and proteomic analysis demonstrates herbicide resistance associated ecological fitness cost and potential mechanisms of herbicide-resistance in resistant biotypes of E. crus-galli. The results presented herein have revealed differences in ecological adaptation between resistant and susceptible biotypes in E. crus-galli and provide a fundamental basis enabling the development of new strategies for weed control. Lastly, this is the first large-scale proteomics study to examine herbicide stress responses in different barnyardgrass biotypes.
Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Elena Stoffel, Kathleen A. Cooney
http://ift.tt/2cqJ5kl
Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Iva Petrovchich, James M. Ford
Gastric cancer ranks as the 3rd leading cause of cancer mortality worldwide and confers a 5-year survival of 20%. While most gastric cancers are sporadic, ~1-3% can be attributed to inherited cancer predisposition syndromes. Germline E-cadherin/CDH1 mutations have been identified in families with an autosomal dominant inherited predisposition to diffuse gastric cancer. The cumulative risk of gastric cancer for CDH1 mutation carriers by age 80 years is reportedly 70% for men and 56% for women. Female mutation carriers also have an estimated 42% risk for developing lobular breast cancer by age 80 years. However, most individuals meeting clinical criteria for hereditary diffuse gastric cancer syndrome (HDGC) do not have a germline CDH1 mutation, and germline CDH1 mutation carriers do not all exhibit similar clinical outcomes in terms of age of diagnosis or cancer types. E-cadherin (CDH1) as the one known causative gene for HDGC accounts for only 40% of cases, leaving 60% with an unknown genetic diagnosis. In addition to HDGC, we will review other genetic syndromes with elevated gastric cancer risk, as well as newly implicated alterations in other genes (CTNNA1, DOT1L, FBXO24, PRSS1, MAP3K6, MSR1, and INSR) that may affect gastric cancer susceptibility and age-specific penetrance.
http://ift.tt/2dgcc03
Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Laura S. Schmidt, W. Marston Linehan
Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes.
http://ift.tt/2cqIkYE
Publication date: Available online 22 September 2016
Source:Seminars in Oncology
Author(s): Gloria M. Petersen
Familial pancreatic cancer (FPC) includes those kindreds that contain at least two first degree relatives with pancreatic ductal adenocarcinoma. At least twelve known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the foremost being BRCA2 and CDKN2A. Research into the identification of mutations in known cancer predisposition genes and through next generation sequencing has revealed extensive heterogeneity. The development of genetic panel testing has enabled genetic risk assessment and predisposition testing to be routinely offered. Precision oncology has opened the possibility of "incidental" germline mutations that may have implications for family members. However, in both cases, evidence-based recommendations for managing patients and at-risk family members in light of genetic status remain emergent, with current practice based upon expert opinion.
http://ift.tt/2dgcXGi
The concept of subclinical cortisol excess and importantly its relevance remains a controversial issue in Endocrinology 1, 2. Preclinical Cushing's syndrome 3, subclinical Cushing's syndrome or subclinical hypercortisolism 2, recently rebadged in the European Society of Endocrinology Guidelines as "autonomous cortisol secretion" 4, is an example where a universally agreed upon definition (and name) has proven to be elusive. It has even been suggested that the syndrome is often an artefact of currently available tests of hypothalamic-pituitary-adrenal axis function 5, 6.
This article is protected by copyright. All rights reserved.
Increasing evidence suggests photo-protection by oral supplementation with ß-carotene and lycopene.
We examined the capacity of lycopene rich tomato nutrient complex (TNC) and lutein, to protect against UVA/B- and UVA1 radiation at a molecular level.
In a placebo-controlled, double blinded, randomized cross over study two actives containing either TNC or lutein were assessed for their capacity to decrease the expression of UVA1 radiation-inducible genes including heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-1 (MMP-1). 65 healthy volunteers were allocated to 4 treatment groups and subjected to a 2-weeks wash-out phase, followed by two 12-weeks treatment phases separated by another 2-weeks wash-out. Volunteers started either with active and switched then to placebo or vice versa. At the beginning and at the end of each treatment phase skin was irradiated and 24 hours later biopsies were taken from untreated, UVB/A- and UVA1 irradiated skin for subsequent RT-PCR analysis of gene expression. Moreover, blood samples were taken after the wash out and the treatment phases for assessment of carotenoids.
TNC completely inhibited UVA1 as well as UVA/B induced upregulation of HO-1, ICAM-1 and MMP1 mRNA no matter of sequence (ANOVA, p<0.05). In contrast, lutein provided complete protection if it was taken in the first period, but showed significantly smaller effects in the second sequence compared to TNC.
Assuming the role of these genes as indicators of oxidative stress, photo-dermatoses and photo-aging these results might indicate that TNC and lutein could protect against solar radiation-induced health damage.
This article is protected by copyright. All rights reserved.
Related Articles |
Occult Langerhans Cell Histiocytosis Presenting with Papillary Thyroid Carcinoma, a Thickened Pituitary Stalk and Diabetes Insipidus.
Case Rep Endocrinol. 2016;2016:5191903
Authors: Gordon MS, Gordon MB
Abstract
Etiologies of a thickened stalk include inflammatory, neoplastic, and idiopathic origins, and the underlying diagnosis may remain occult. We report a patient with a thickened pituitary stalk (TPS) and papillary thyroid carcinoma (PTC) whose diagnosis remained obscure until a skin lesion appeared. The patient presented with PTC, status postthyroidectomy, and I(131) therapy. PTC molecular testing revealed BRAF mutant (V600E, GTC>GAG). She had a 5-year history of polyuria/polydipsia. Overnight dehydration study confirmed diabetes insipidus (DI). MRI revealed TPS with loss of the posterior pituitary bright spot. Evaluation showed hypogonadotropic hypogonadism and low IGF-1. Chest X-ray and ACE levels were normal. Radiographs to evaluate for extrapituitary sites of Langerhans Cell Histiocytosis (LCH) were unremarkable. Germinoma studies were negative: normal serum and CSF beta-hCG, alpha-fetoprotein, and CEA. Three years later, the patient developed vulvar labial lesions followed by inguinal region skin lesions, biopsy of which revealed LCH. Reanalysis of thyroid pathology was consistent with concurrent LCH, PTC, and Hashimoto's thyroiditis within the thyroid. This case illustrates that one must be vigilant for extrapituitary manifestations of systemic diseases to diagnose the etiology of TPS. An activating mutation of the protooncogene BRAF is a potential unifying etiology of both PTC and LCH.
PMID: 27656301 [PubMed]
OBJECTIVE: We analyzed the effects of intensive and mitigatory blood glucose control strategy on elderly people with type 2 diabetes mellitus (T2DM) combined with Alzheimer disease (AD).
PATIENTS AND METHODS: We enrolled 90 elderly patients with T2DM combined with AD to participate in this study. They were randomly divided into 3 groups: the control group, the strength group and the mitigation group with 30 cases in each group. In the control group, patients were only treated with diet and exercise while in the strength group patients were treated with oral hypoglycemic medications, subcutaneous insulin infusion or continuous infusion by micropump. Blood glucose level in the strength group patients was stabilized within 1 month (pre-meal ≤7.0 mmol/L, 2 hours post-meal glucose ≤12.0 mmol/L and glycosylated hemoglobin or HbA1c ≤7.0%). Personalized treatment programs were adopted for the mitigation group and the objective was to control the pre-meal blood glucose at ≤ 10.0 mmol/L (within 3 to 6 months) and also to control 2 hours post-meal blood glucose at ≤20.0 mmol/L (within 3 to 6 months). We compared the occurrence rate of diabetic complications, occurrence rate of new-onset dementia and progressive rate of dementia.
RESULTS: Our results showed that target glucose rate in the mitigation group was significantly higher than that in the strength group. The occurrence rate of diabetic complications in the mitigation group was significantly lower than that observed in the other two groups. Occurrence rate of diabetic hyperosmolar coma was significantly higher in the control group, the occurrence rate of hypoglycemia was meaningfully lower in the strength group and the occurrence rate of new-onset target-organ injury was considerably higher in the mitigation group. The occurrence rate of new-onset dementia and progressive rate of dementia in mitigation group was significantly lower than those in other two groups. Comparison between the control group and the strength group did not reveal any statistical significance (p>0.05). In the meantime, the survival time in mitigation group was significantly longer.
CONCLUSIONS: Elderly patients with T2DM combined with AD may benefit more from the moderate control of blood glucose and a proper increase of the target value.
L'articolo Effect of different blood glucose intervention plans on elderly people with type 2 diabetes mellitus combined with dementia sembra essere il primo su European Review.
The objective of the study was to investigate the relationship between pH-neutralization, hydrophilicity, and free hygroscopic expansion stress of self-adhesive resin cements (SARCs) after storage in artificial saliva.
The SARCs RelyX Unicem Automix 2 (RX2, 3 M ESPE), iCEM (iCEM, Heraeus) and Maxcem Elite (MCE, Kerr) were under investigation in this study. Cylinders (height × diameter, 6 × 4mm) were prepared from each material and stored in artificial saliva (7d at 37 °C). Cylinder height was measured at baseline and after 7 days. After storage, the compression modulus was measured to calculate the free hygroscopic expansion stress. For pH-neutralization and hydrophilicity assessment, disks (height × diameter, 1 × 1.5 mm) were prepared, covered with electrolyte, and monitored over 24 h at 37 °C. Hydrophilicity was assessed using the static sessile drop technique at baseline and at different time intervals up to 24 h. Data were analyzed using one-way ANOVA and post hoc Student-Newman-Keuls test (S-N-K, α = 0.05).
After 24 h, RX2 (pH24h 4.68) had a significantly higher (p < 0.05) pH-value than MCE (pH24h 4.2) and iCEM (pH24h 3.23). iCEM showed the significantly highest hydrophilicity (p < 0.05) after 24 h (θ24h 85.02°), while MCE resulted lower (θ24h 113.01°) in comparison with RX2 (θ24h 108.11°). The resulting hygroscopic expansion stress of iCEM (29.15 MPa) was significantly higher (p < 0.05) compared to RX2 (14.5 MPa) and MCE (21.02 MPa).
The material with lowest pH-neutralization capacity displayed higher hydrophilicity after 24 h and higher hygroscopic expansion stress after 7 days compared to those with high pH-neutralization.
Remnant hydrophilicity due to low pH-neutralization of SARCs could lead to cement interface stress build-up and long-term failure of silicate ceramic restorations.
The aim of this study was to evaluate the acidogenicity of dual-species biofilms of bifidobacteria and Streptococcus mutans.
The following strains were tested: Bifidobacterium dentium DSM20436, Parascardovia denticolens DSM10105, and Scardovia inopinata DSM10107. Streptococcus mutans UA159 and Lactobacillus acidophilus ATCC4356 were used as control. Bifidobacteria were studied planktonically as they were not able to form monospecies biofilm, they were grown in biofilms associated with S. mutans. Endogenous polysaccharide reserves of cultures at log phase were depleted. Standardized suspensions of the microorganisms were incubated in growth media supplemented with 10 mM glucose, lactose, raffinose, glucose, or xylitol. S. mutans biofilms were grown on glass cover slips for 24 h to which bifidobacteria were added. After 24 h, the dual-species biofilms were exposed to the same carbon sources, and after 3 h, the pH of spent culture media and concentrations of organic acids were measured. Statistical analyses were carried out using ANOVA and Tukey's test (α = 0.05).
A higher pH drop was observed when S. mutans was associated with P. denticolens or S. inopinata, in either planktonic or biofilm cultures, than with S. mutans alone. Bifidobacteria showed a higher pH drop in the presence of raffinose than S. mutans or L. acidophilus.
Dual-species biofilms of bifidobacteria and S. mutans produced more acid and greater pH drops than biofilms of S. mutans alone.
New insights on the complex process of caries pathogenicity contribute to the establishment of preventive and therapeutic measures, in particular in specific cases, such as in early childhood caries.
This study assessed the outcome measures of single-visit root canal retreatments and frequency of periapical complications considering preoperative, intraoperative and postoperative factors.
Between November 2011 and December 2012, in 173 patients, a total of 234 endodontically treated teeth were retreated in a single appointment by one experienced endodontist. Five teeth were extracted and 119 teeth were lost to follow-up yielding to 110 teeth (47 %) to be examined by two calibrated examiners for the outcome of healing (periapical index score-PAI ≤2; no signs or symptoms) or non-healing (presence of apical periodontitis-PAI >2; signs or symptoms). Preoperative, intraoperative and postoperative factors were evaluated for their association with the outcome. Data were analysed using Fisher's exact and Fisher-Freeman Halton tests for bivariate analysis to identify potential outcome predictors. Logistic regression models were used for multivariate analysis to determine significant outcome predictors.
Mean observation time was 29 months. Follow-up assessment revealed 100 teeth (90.9 %) as healed and 10 teeth (9.1 %) non-healed. Age, gender, tooth type and preoperative (pain, periodontal defects, root filling density and length), intraoperative (sealer extrusion) and postoperative (type of coronal restorations) factors did not significantly affect the outcome (p > 0.05). Preoperative periradicular lesions with diameters less than 5 mm presented significantly better outcome than larger lesions (p < 0.05; odds ratio (OD) 6; 95 % CI 1.45–24.85). Logistic regression model showed an increased risk of non-healing for the parameter of preoperative periradicular lesions with diameters larger than 5 mm (OD 6.42; 95 % CI 1.51–27.27).
Single-appointment root canal retreatments presented a favourable success rate. Only preoperative lesion size had a significant effect on the outcome where the lesions smaller than 5 mm performed significantly better healing.
Single-appointment root canal retreatments could be considered as a viable treatment option for orthograde retreatment cases with periradicular lesion size smaller than 5 mm.
Publication date: Available online 22 September 2016
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): M. Mayoral, P. Paredes, B. Domènech, P. Fusté, S. Vidal-Sicart, A. Tapias, A. Torné, J. Pahisa, J. Ordi, F. Pons, F. Lomeña
ObjectiveDefinitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference.Material and methodsA prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results.ResultsIn the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found.ConclusionsPET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes.
http://ift.tt/2cqpJMa
|
|
|
|
@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }
|
|
|
@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }
|
|
|