Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.
Oral squamous cell carcinoma (OSCC) is one of the most common malignances. In epithelial-mesenchymal transition (EMT), epithelial cells switch to mesenchymal-like cells exhibiting high mobility. This migratory phenotype is significant during tumor invasion and metastasis. Objective: The aim of this study is to evaluate the expression of the EMT markers E-cadherin, N-cadherin and vimentin in OSCC.Material and Methods : Immunohistochemical detection of E-cadherin, N-cadherin and vimentin was performed on 20 OSCC samples. Differences in the expression of each protein at the invasive front (IF) and in the central/superficial areas (CSA) of the tumor were assessed. Differences in the expression of each protein at the IF of both histologically high- and low-invasive OSCCs were evaluated. Associations among expression of proteins at the IF were assessed. Correlations between the expression levels of each protein at the IF and the tumor stage and clinical nodal status were also evaluated.Results : Reduced expression of E-cadherin was detected in 15 samples (75%). E-cadherin expression was reduced at the IF when compared to the CSA and in high-invasive tumors when compared to low-invasive tumors. All samples were negative for N-cadherin, even though one sample showed an inconspicuous expression. Positive expression of vimentin was observed in 6 samples (30%). Nevertheless, there was no difference in vimentin expression between the IF and the CSA regions or between the low- and high-invasive tumors. Furthermore, no association was observed among protein expression levels at the IF. Finally, no correlations were observed between each protein’s expression levels and tumor stage or clinical nodal status.Conclusions : Reduced E-cadherin expression at the IF and its association with histological invasiveness suggest that this protein is a noteworthy EMT marker in OSCC. Although vimentin was also detected as an EMT marker, its expression was neither limited to the IF nor was it related to histological invasiveness.
Although different nanosized materials, including quantum dots (QDs), are intended to be used for biomedical applications, their interactions with microvessels and their inflammatory potential are largely unknown. In this in vivo study we report that leukocyte recruitment is modulated in the presence of quantum dots. We found that the surface chemistry of QDs strongly affects their localization in postcapillary venules, their uptake by perivascular macrophages, and their potential to modify steps of leukocyte recruitment.
In OSCC, higher laminin-5 γ2 expression is associated with high-intensity tumor budding and with higher density of stromal myofibroblasts, suggesting that this expression is related to the establishment of an invasive phenotype of neoplastic cells and a permissive environment for tumor invasion in this neoplasia.
A influência de modificação química (por tratamento ácido seguido de funcionalização com trietilenotetramina, TETA) sobre a superfície de nanotubos de carbono de paredes múltiplas (MWCNT) foi estudada qualitativa e quantitativamente. A análise termogravimétrica (TGA) mostrou que, no caso do nanotubo funcionalizado com amina, 29% de perda de massa pode ser atribuída a -C(=O)TETA e grupos funcionais residuais que contêm oxigênio. A espectroscopia de fotoelétrons excitados por raios X (XPS) foi utilizada para observar as funções aminadas e oxigenadas ligadas covalentemente à superfície do nanotubo. As imagens de microscopia de força elétrica (EFM) indicaram que, à medida que se modifica a química superficial dos nanotubos em presença de ar, estes mostram respostas diferentes em função do potencial da ponta. Deslocamentos nos sinais de fase de EFM decrescem quando se modifica a superfície dos tubos com grupos funcionais contendo oxigênio e amina. Em atmosfera seca e inerte de N 2 , as três diferentes superfícies mostraram a mesma resposta à EFM. Além disso, o caráter hidrofílico dos "buckypapers" cresceu na ordem MWCNT < MWCNT-aminado < MWCNT-oxidado.The influence of chemical modification by acid treatment followed by triethylenetetramine (TETA) functionalization on the surface of multi-walled carbon nanotubes (MWCNT) was evaluated, both qualitative and quantitatively. Thermogravimetric analysis (TGA) showed that, in the case of amine-functionalized nanotubes, 29% of mass loss can be attributed to -C(=O)TETA and residual oxygen-containing functional groups. X-ray photoelectron spectroscopy (XPS) was used to observe the oxygenated and aminated functions covalently linked to the nanotube surface. Electric force microscopy (EFM) images indicated that the nanotubes with diverse surface chemistry showed distinct responses to the tip potential in the presence of air. Shifts in EFM phase images decreased when the nanotube surface was modified with oxygen and amine-containing functional groups. In dry and inert N 2 atmosphere, however, the three different surfaces showed the same response to EFM. In addition, the hydrophilic character of the buckypapers increased in the order MWCNT < aminated-MWCNT < oxidized-MWCNT.Keywords: multi-walled carbon nanotubes, triethylenetetramine, surface chemical modification, spectroscopic characterization, electric force microscopy IntroductionAn important historical reference about carbon nanotube (CNT) synthesis is the work of Oberlin et al. in 1976. 1 However, it was not until Iijima's work, in 1991, 2 that CNTs emerged as a key material in the field of nanotechnology due to their extraordinary thermal, electrical and mechanical properties.2-4 However, low dispersibility in organic and inorganic solvents, combined with poor chemical compatibility, has become a major issue. 5,6 Functionalization or chemical modification of CNT, that is, the covalent attachment of atoms or molecules to the surface, has been used to introduce chemical specificity and processability in different environments...
Maternal PA appears to be safe for both mother and fetus, and additional studies are needed to confirm the real influence of this practice in the offspring, as well as the perpetuation and transfer of these features between generations.
The behavior of quantum dots (QDs) in the microvasculature and their impact on inflammatory reactions under pathophysiological conditions are still largely unknown. Therefore, we designed this study to investigate the fate and effects of surface-modified QDs in postischemic skeletal and heart muscle. Under these pathophysiological conditions, amine-modified QDs, but not carboxyl-QDs, were strongly associated with the vessel wall of postcapillary venules and amplified ischemia-reperfusion-elicited leukocyte transmigration. Importantly, strong association of amine-QDs with microvessel walls was also present in the postischemic myocardium. As shown by electron microscopy and verified by FACS analyses, amine-modified QDs, but not carboxyl-QDs, were associated with endogenous microparticles. At microvessel walls, these aggregates were attached to endothelial cells. Taken together, we found that both the surface chemistry of QDs and the underlying tissue conditions (i.e., ischemia-reperfusion) strongly determine their uptake by endothelial cells in microvessels, their association to endogenous microparticles, as well as their potential to modify inflammatory processes. Thus, this study strongly corroborates the view that the surface chemistry of nanomaterials and the physiological state of the tissue are crucial for the behavior of nanomaterials in vivo.
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