A higher Angiogenin expression is associated with a non-nuclear Maspin location in laryngeal carcinoma

Objectives. In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC). Methods. Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes. Results. On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression 655.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression 655.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041). Conclusion. Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC

Prognostic significance of serine-phosphorylated STAT3 expression in pT1-T2 oral tongue carcinoma

Objectives. Phosphorylated (activated) STAT3 (pSTAT3) is a regulator of numerous genes that play an essential part in the onset, development and progression of cancer; it is involved in cell proliferation and preventing apoptosis, and in invasion, angiogenesis, and the evasion of immune surveillance. This study aimed mainly to investigate the potential prognostic role of pSTAT3 expression in oral tongue squamous cell carcinoma (SCC). Methods. Phospho-ser727 STAT3 immunolabeling was correlated with prognostic parameters in 34 consecutive cases of pT1\u2013T2 tongue SCCs undergoing primary surgery. Computer-based image analysis was used for the immunohistochemical reactions analysis. Results. Statistical analysis showed a difference in disease-free survival (DFS) when patients were stratified by pN status (P=0.031). Most tumors had variable degrees (mean\ub1SD, 80.7%\ub123.8%) of intense nuclear immunoreaction to pSTAT3. Our findings rule out any significant association of serine-phosphorylated nuclear STAT3 expression with tumor stage, grade, lymph node metastasis, recurrence rate, or DFS. Conclusion. In spite of these results, it is worth further investigating the role of pSTAT3 (serine-and tyrosine-pSTAT3) in oral tongue SCC in larger series because preclinical models are increasingly showing that several anticancer strategies would benefit from STAT3 phosphorylation inhibition

Neuron Compatibility and Antioxidant Activity of Barium Titanate and Lithium Niobate Nanoparticles

The biocompatibility and the antioxidant activity of barium titanate (BaTiO3) and lithium niobate (LiNbO3) were investigated on a neuronal cell line, the PC12, to explore the possibility of using piezoelectric nanoparticles in the treatment of inner ear diseases, avoiding damage to neurons, the most delicate and sensitive human cells. The cytocompatibility of the compounds was verified by analysing cell viability, cell morphology, apoptotic markers, oxidative stress and neurite outgrowth. The results showed that BaTiO3 and LiNbO3 nanoparticles do not affect the viability, morphological features, cytochrome c distribution and production of reactive oxygen species (ROS) by PC12 cells, and stimulate neurite branching. These data suggest the biocompatibility of BaTiO3 and LiNbO3 nanoparticles, and that they could be suitable candidates to improve the efficiency of new implantable hearing devices without damaging the neuronal cells

Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation

SummaryRandom autosomal monoallelic gene expression refers to the transcription of a gene from one of two homologous alleles. We assessed the dynamics of monoallelic expression during development through an allele-specific RNA-sequencing screen in clonal populations of hybrid mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). We identified 67 and 376 inheritable autosomal random monoallelically expressed genes in ESCs and NPCs, respectively, a 5.6-fold increase upon differentiation. Although DNA methylation and nuclear positioning did not distinguish the active and inactive alleles, specific histone modifications were differentially enriched between the two alleles. Interestingly, expression levels of 8% of the monoallelically expressed genes remained similar between monoallelic and biallelic clones. These results support a model in which random monoallelic expression occurs stochastically during differentiation and, for some genes, is compensated for by the cell to maintain the required transcriptional output of these genes

DNA methylation-based measures of biological age: meta-analysis predicting time to death.

Estimates of biological age based on DNA methylation patterns, often referred to as epigenetic age , DNAm age , have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10-9), independent of chronological age, even after adjusting for additional risk factors (p\u3c5.4x10-4), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5x10-43). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality

Cortical gamma-synchrony measured with magnetoencephalography is a marker of clinical status and predicts clinical outcome in stroke survivors.

Background: The outcome of stroke survivors is difficult to anticipate. While the extent of the anatomical brain lesion is only poorly correlated with the prognosis, functional measures of cortical synchrony, brain networks and cortical plasticity seem to be good predictors of clinical recovery. In this field, gamma (>30 Hz) cortical synchrony is an ideal marker of brain function, as it plays a crucial role for the integration of information, it is an indirect marker of Glutamate/GABA balance and it directly estimates the reserve of parvalbulin-positive neurons, key players in synaptic plasticity. In this study we measured gamma synchronization driven by external auditory stimulation with magnetoencephalography and tested whether it was predictive of the clinical outcome in stroke survivors undergoing intensive rehabilitation in a tertiary rehabilitation center. Material and methods: Eleven stroke survivors undergoing intensive rehabilitation were prospectively recruited. Gamma synchrony was measured non-invasively within one month from stroke onset with magnetoencephalography, both at rest and during entrainment with external 40 Hz amplitude modulated binaural sounds. Lesion location and volume were quantitatively assessed through a high-resolution anatomical MRI. Barthel index (BI) and Functional Independence Measure (FIM) scales were measured at the beginning and at the end of the admission to the rehabilitation unit. Results: The spatial distribution of cortical gamma synchrony was altered, and the physiological right hemispheric dominance observed in healthy controls was attenuated or lost. Entrained gamma synchronization (but not resting state gamma synchrony) showed a very high correlation with the clinical status at both admission and discharge (both BI and FIM). Neither clinical status nor gamma synchrony showed a correlation with lesion volume. Conclusions: Cortical gamma synchrony related to auditory entrainment can be reliably measured in stroke patients. Gamma synchrony is strongly associated with the clinical outcome of stroke survivors undergoing rehabilitation

Variation in VKORC1 is associated with vascular dementia

BACKGROUND: The genetic variant rs9923231 (VKORC1) is associated with differences in the coagulation of blood and consequentially with sensitivity to the drug warfarin. Variation in VKORC1 has been linked in a gene-based test to dementia/Alzheimer’s disease in the parents of participants, with suggestive evidence for an association for rs9923231 (p = 1.8×10(–7)), which was included in the genome-wide significant KAT8 locus. OBJECTIVE: Our study aimed to investigate whether the relationship between rs9923231 and dementia persists only for certain dementia sub-types, and if those taking warfarin are at greater risk. METHODS: We used logistic regression and data from 238,195 participants from UK Biobank to examine the relationship between VKORC1, risk of dementia, and the interplay with warfarin use. RESULTS: Parental history of dementia, APOE variant, atrial fibrillation, diabetes, hypertension, and hypercholesterolemia all had strong associations with vascular dementia (p < 4.6×10(–6)). The T-allele in rs9923231 was linked to a lower warfarin dose (β(perT - allele) = –0.29, p < 2×10(–16)) and risk of vascular dementia (OR = 1.17, p = 0.010), but not other dementia sub-types. However, the risk of vascular dementia was not affected by warfarin use in carriers of the T-allele. CONCLUSION: Our study reports for the first time an association between rs9923231 and vascular dementia, but further research is warranted to explore potential mechanisms and specify the relationship between rs9923231 and features of vascular dementia