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1.

Background

Gliadins are involved in gluten-related disorders and are responsible for the alteration of the cellular redox balance. It is not clear if the gliadin-related oxidative stress can induce DNA damage in enterocytes.

Aim

To investigate any possible genotoxicity caused by gliadin and to assess its relationship with oxidative stress in vitro and ex vivo.

Methods

Caco-2 cells were exposed for 6–12–24?h to increasing concentrations (250?μg/mL–1000?μg/mL) of digested gliadin. We investigated: cytotoxicity, oxidative balance (reactive oxygen species, ROS), DNA damage (comet assay and γ-H2AX detection), transglutaminase type 2 (TG2) activity and annexin V expression. H2AX and 8-OHG immunohistochemistry has been evaluated on duodenal biopsies of celiac subjects and controls.

Results

Gliadin induced a significant increase (+50%) of ROS after 12?h of exposition starting with a 500?μg/mL dose of gliadin. Comet assay and γ-H2AX demonstrated DNA damage, evident at the gliadin concentration of 500?μg/mL after 24?h. TG2 activity increased in chromatin and cytoskeleton cellular compartments at different gliadin doses (250/500/1000?μg/mL). The γ-H2AX and 8-OHG immunohistochemistry was altered in the duodenal biopsies of celiac patients.

Conclusions

Gliadin induces cellular oxidative stress, DNA damage and pro-apoptotic stimulation in Caco-2 cells and in the duodenal mucosa of celiac patients.  相似文献   
2.
Coagulase-negative Staphylococcus (CNS) strains are frequently associated with bacteremia and hospital-acquired infections. 293 CNS strains were isolated from 744 samples from a dialysis center in S. M. de Tucumán, Argentina, from hemocultures, catheters and urine and identified as S. epidermidis, S. haemolyticus, S. saprophyticus, S. hominis and S. cohnii. 13 antibiotics were tested for antibacterial resistance. 75% of S. saprophyticus, 66% of S. epidermidis and 57% of S. haemolyticus was resistant to erythromycin and 50% of S. haemolyticus was resistant to ciprofloxacin. OXA resistance was found in 43% of S. haemolyticus. Presence of PBP 2a in OXA-R strains was confirmed with the modified agglutination assay (MRSA) and presence of the mecA gene. 15 strains with intermediate halos for vancomycin and teicoplanin showed a MIC in solid and liquid medium 相似文献   
3.
AIM:To investigate the weight loss and glycemic control status[blood glucose,hemoglobin A1c(HbA1c)and hypoglycaemic treatment].METHODS:The primary risk factor for type 2 diabetes is obesity,and 90%of all patients with type 2 diabetes are overweight or obese.Although a remarkable effect of bariatric surgery is the profound and durable resolution of type 2 diabetes clinical manifestations,little is known about the difference among various weight loss surgical procedures on diabetes remission.Data from patients referred during a 3-year period(from January2009 to December 2011)to the University of Naples"FedericoⅡ"diagnosed with obesity and diabetes were retrieved from a prospective database.The patients were split into two groups according to the surgical intervention performed[sleeve gastrectomy(SG)and mini-gastric bypass(MGB)].Weight loss and glycemic control status(blood glucose,HbA1c and hypoglycaemic treatment)were evaluated.RESULTS:A total of 53 subjects who underwent sleeve gastrectomy or mini-gastric bypass for obesity and diabetes were screened for the inclusion in this study.Of these,4 subjects were excluded because of surgical complications,7 subjects were omitted because young surgeons conducted the operations and 11 subjects were removed because of the lack of follow-up.Thirtyone obese patients were recruited for this study.A total of 15 subjects underwent SG(48.4%),and 16underwent MGB(51.6%).After adjusting for various clinical and demographic characteristics in a multivariate logistic regression analysis,high hemoglobin A1c was determined to be a negative predictor of diabetes remission at 12 mo(OR=0.366,95%CI:0.152-0.884).Using the same regression model,MGB showed a clear trend toward higher diabetes remission rates relative to SG(OR=3.780,95%CI:0.961-14.872).CONCLUSION:Although our results are encouraging regarding the effectiveness of mini-gastric bypass on diabetes remission,further studies are needed to provide definitive conclusions in selecting the ideal procedure for diabetes remission.  相似文献   
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The incidence of involved intramammary lymph node (intra‐MLN) with breast carcinoma (BC) is rare. Its clinical significance and impact on the clinical decision making is unclear. A total of 113 BC cases with at least one positive intra‐MLN were collected from 11 academic institutions. The inclusion criteria were subsequent axillary lymph node dissection, and the availability of information on T‐stage, size of node metastasis, extranodal extension status, biomarkers status, and clinical follow‐up. Stage 4 cases and/or neo‐adjuvant treated patients were excluded. AJCC TN‐stage was calculated twice, with and without intra‐MLN. Five‐year overall survival (OS) and relapse (local and/or distant)‐free survival (RFS) were calculated and correlated with the clinicopathologic variables. Excluding intra‐MLN, TN‐stage correlated with OS (P = .016) but not with RFS (P = .19). However, when intra‐MLN was included, TN‐stage correlated with both OS (P < .001) and RFS (P = .016). In the multivariate analysis, when intra‐MLN was excluded, only radiation therapy (RT) correlated with RFS (HR = 0.19, 95% CI: 0.054‐0.66, P = .009). However, when intra‐MLN was included in the TN‐stage both RT (HR = 0.13, 95% CI: 0.04‐0.45, P = .001) and TN‐stage 3 (HR = 8.92, 95% CI: 1.47‐54, P = .017) correlated with RFS. Tumor multifocality was the only variable correlated with OS when the intra‐MLN involvement was excluded. When intra‐MLN was included, multifocality became insignificant but TN‐stage 3 correlated with OS (HR = 8.59, 95% CI: 1.06‐69.71, P = .044). Positive intra‐MLN is an independent factor in predicting both RFS and OS.  相似文献   
7.
The egg development of the freshwater crayfish (Pacifastacus leniusculus Dana) under laboratory conditions is studied in this work from spawning to hatching. The sequence of its development is presented here, and the chronology of the different embryonic phases is established at one specific temperature (15.5 degrees +/- 1 degree C).  相似文献   
8.

Healthcare workers experienced high degree of stress during COVID-19. Purpose of the present article is to compare mental health (depressive and Post-Traumatic-Stress-Disorders—PTSD—symptoms) and epigenetics aspects (degree of methylation of stress-related genes) in front-line healthcare professionals versus healthcare working in non-COVID-19 wards. Sixty-eight healthcare workers were included in the study: 39 were working in COVID-19 wards (cases) and 29 in non-COVID wards (controls). From all participants, demographic and clinical information were collected by an ad-hoc questionnaire. Depressive and PTSD symptoms were evaluated by the Patient Health Questionnaire-9 (PHQ-9) and the Impact of Event Scale—Revised (IES-R), respectively. Methylation analyses of 9 promoter/regulatory regions of genes known to be implicated in depression/PTSD (ADCYAP1, BDNF, CRHR1, DRD2, IGF2, LSD1/KDM1A, NR3C1, OXTR, SLC6A4) were performed on DNA from blood samples by the MassARRAY EpiTYPER platform, with MassCleave settings. Controls showed more frequent lifetime history of anxiety/depression with respect to cases (χ2 = 5.72, p = 0.03). On the contrary, cases versus controls presented higher PHQ-9 (t = 2.13, p = 0.04), PHQ-9 sleep item (t = 2.26, p = 0.03), IES-R total (t = 2.17, p = 0.03), IES-R intrusion (t = 2.46, p = 0.02), IES-R avoidance (t = 1.99, p = 0.05) mean total scores. Methylation levels at CRHR1, DRD2 and LSD1 genes was significantly higher in cases with respect to controls (p < 0.01, p = 0.03 and p = 0.03, respectively). Frontline health professionals experienced more negative effects on mental health during COVID-19 pandemic than non-frontline healthcare workers. Methylation levels were increased in genes regulating HPA axis (CRHR1) and dopamine neurotransmission (DRD2 and LSD1), thus supporting the involvement of these biological processes in depression/PTSD and indicating that methylation of these genes can be modulated by stress conditions, such as working as healthcare front-line during COVID-19 pandemic.

  相似文献   
9.
The coexistence of mesothelioma and other primary malignancies has been previously reported in literature, but the finding of a pleural mesothelioma with a synchronous peritoneal mesothelioma has not been reported so far. We report a case of a 58-years-old woman that came to our attention for the incidental finding of an inguinal mass. Fine-needle biopsies of the mass and a thoracoscopy with pleural biopsies were performed, after imaging studies showed pleural thickenings suspicious for malignancy. Histological morphology and growth pattern were similar in both cases. Both tumors stained for calretinin, but only the pleural mesothelioma showed positivity for Wilms-Tumor 1 antibody. We tried to demonstrate with molecular biology techniques whether they were synchronous or one was the metastasis of the other, but our studies did not give informative results. The prognosis in this case is poor, and after 6 months the patient is still following a chemotherapy regimen, which is the only practicable approach given the extent of the disease.  相似文献   
10.
Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel. It is also frequently part of topical analgesic drugs available in a pharmacy, although its mechanism of action is still unknown. Compelling evidence indicates that voltage-gated Na+ channels are critical for experiencing pain sensation. We tested the hypothesis that menthol may block voltage-gated Na+ channels in dorsal root ganglion (DRG) neurons. By use of a patch clamp, we evaluated the effects of menthol application on tetrodotoxin (TTX)-resistant Nav1.8 and Nav1.9 channel subtypes in DRG neurons, and on TTX-sensitive Na+ channels in immortalized DRG neuron-derived F11 cells. The results indicate that menthol inhibits Na+ channels in a concentration-, voltage-, and frequency-dependent manner. Menthol promoted fast and slow inactivation states, causing use-dependent depression of Na+ channel activity. In current clamp recordings, menthol inhibited firing at high-frequency stimulation with minimal effects on normal neuronal activity. We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na+ channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na+ channels, indicating a role for Na+ channel blockade in the efficacy of menthol as topical analgesic compound.  相似文献   
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