Monthly Archives: January 2020

Compared with conventional microscale microbubbles nanobubbles continues to decline achievable

Nanobubbles offer several advantages in targeted gene transfection. For example, nanobubbles are characterized by strong penetrating power and stable performance, which allow them to enter tumor tissues through the tumor vasculature. Therefore, in this study, we combined RNAi technology with nanotechnology by preparing nanobubbles carrying AR small interfering RNA. The physical properties of these bubbles were then assayed. Furthermore, the prepared nanobubbles were used for the siRNA transfection of AIPC cells together with ultrasonic irradiation treatment to induce the release of the siRNA transcripts. The in vitro transfection efficiency was systematically evaluated. Additionally, the anti-tumor efficacy of the nanobubbles was evaluated using imaging studies and a tumor growth inhibition assay in a mouse xenograft prostate cancer model. The results presented here provide experimental support for the use of nanobubbles carrying AR siRNA in combination with ultrasonic irradiation as a potential effective therapy for AIPC. To date, various gene therapy treatments utilizing viral vectors have been proposed. However, the use of viral vectors is a major concern because this vector system is associated with numerous safety concerns, including toxicity, immunogenicity, and tumorigenicity. Thus, the clinical application of viral vectors has been greatly restricted. The construction of an efficient, safe, and controllable in vivo gene delivery system has been a highly debated and challenging endeavor in the gene therapy community. The present study shows that ultrasound-mediated microbubble destruction may have the potential to become a new approach for targeted gene transfection. Other studies have also shown that ultrasound-destructible microbubbles not only enhanced gene transfection efficiency but were also potentially useful as a novel in vivo gene transfection vector for the delivery of any antisense oligonucleotide or DNA fragment. Thus, ultrasounddestructible microbubbles show great promise for clinical applications in the future. Despite this promise, some challenges remain in the application of conventional ultrasound-destructible microbubbles for gene or drug delivery to treat cancer. Most notably, the diameter of conventional ultrasound-destructible microbubbles, which ranges from 1-10 mm, likely prevents the bubbles from passing through the tumor vascular wall into the tumor tissues because the maximum pore size of the tumor vascular wall is 380–780 nm. This size discrepancy can affect the release and transfection of carried genes, ultimately decreasing the anti-tumor efficacy of these micro-scaled, ultrasound-destructible microbubbles. To address this size problem, researchers have proposed that nanobubbles may be a better alternative to conventional microbubbles as a gene or drug carrier for the treatment of tumors. Nanobubbles have a size of less than 1000 nm.

Differentiate into functional odontoblasts in vivo when the tooth encounters external mild stimuli

The reactionary and reparative dentin formed by surviving odontoblasts and newly differentiated odontoblast-like cells protect the pulp from further damage. Our previous study has indicated that stem cells exist in carious pulp and are named carious dental pulp stem cells. CDPSCs displayed an increased proliferative capacity and enhanced alkaline phosphatase activity, mineralization ability, and the expression of osteogenesis/dentinogenesis-related genes compared with DPSCs. Though the biological characteristics of these two stem cells have been well analyzed, the molecular mechanisms responsible for the biological differences between CDPSCs and DPSCs are still unclear. Mass spectroscopy based proteomics is becoming an efficient method characterized by systematic large-scale qualitative and quantitative mapping of the whole proteome of stem cell phenotypes from different niches, allowing for the rapid understanding the mechanisms that control their self-renewal ability, differentiation potential and regeneration capacity. Previous studies compared the protein expression profiles in mesenchymal stem cells derived from human periodontal ligament, dental pulp, dental follicle, and dental papilla to provide a database for proteins commonly or differentially expressed among various dental stem cell populations,. Recently analyzed the proteomic profiling of SHED to reveal the abundantly expressed proteins. In this work, we performed two-dimensional fluorescence difference gel electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry to identify the differentially expressed proteins between DPSCs and CDPSCs and to explore the candidate molecular markers contributing to the regeneration of dental structures in stem cell-based tissue engineering protocols. Recent studies have reported that DPSCs are able to differentiate into various cell types or tissues including osteoblasts, odontoblasts, chondroblasts,, adipocytes, neuronal cells, endothelial cells, melanocytes and cornea. Among these, the most important function of DPSCs is forming odontoblasts, however; the mechanisms that are responsible for DPSCs migration, proliferation, and differentiation when the tooth encounters deep caries are poorly known. Our study revealed that both DPSCs and CDPSCs had fibroblast-like morphology and were shown to be capable of differentiating into various cell types including osteoblasts, adipocytes and chondrocytes. Moreover, CDPSCs had a higher proliferative potential than DPSCs, which was consistent with the previous study. To better understand the molecular mechanisms underlying the changes in DPSCs encountering deep caries, we used 2D-DIGE to identify the proteins differentially expressed between DPSCs and CDPSCs. The comparative narrow range PH analysis showed that most differentially expressed proteins such as carious lesion, attrition and abrasion.

Several previous studies have reported the coexistence of Th2-immune conditions in the livers

Here we term these cells “Multiple CytokineProducing Hepatic T Cells”. In the liver, unique and organ-specific immune systems, composed of specialized cells such as Kupffer cells, NK cells, or NKT cells, are present, showing an immunological environment unlike that of any other immune competent organs or tissues. Constitutive exposure of large amounts of both enteric and systemic blood-borne antigens does not induce intense activation of the hepatic immune system, indicating the existence of strict regulation machineries in the liver. Upon the disruption of these regulatory machineries by infection with some pathogens such as the hepatitis B virus, runaway immune reactions are induced in the liver, resulting in fulminant hepatitis. The molecular mechanisms underlying such phenomena remain to be elucidated. Schistosome infection begins with direct penetration of the host skin by the cercariae. Subsequently, the schistosomes invade blood vessels and reach the hepatic portal vein, where they mature, mate, and produce eggs. Oviposition in S. mansoni starts 4–6 weeks after the initial cercarial infection. Approximately 300 eggs a day are laid by one female fluke, and many of them enter the liver via the blood. Antigens derived from both the worms and the eggs accumulate in the liver. Fibrotic granulomatous disorders in the liver are the most significant and serious etiology of S. mansoni infection, although chronic inflammatory lesions are sometimes observed in several other organs. In a S. mansoni-infected host, Th1- and Th2-related responses are evoked during different infectious periods. In the early phase, Th1-related responses are induced. As oviposition begins, the Th1 components are gradually down-regulated, and Th2 reactions become dominant in the late phase. Several previous reports indicate that the immunological balances between Th1 and Th2 responses in S. mansoni-infected hosts have implications for severity of pathology. Intriguingly, the MCPHT cells that we recently reported were found to expand during the period between Th1- and Th2-dominant phases, which we term the “transition phase”. Here, we show that IL-18 contributes to the expansion of MCPHT cells that are induced during S. mansoni infection. Levels of IL-18 in the liver and sera are elevated during the transition phase of the infection, when a significant expansion of MCPHT cells occurs. IL-18-deficient mice displayed severely impaired expansion of MCPHT cells during S. mansoni infection. Therefore, our present studies suggest that IL-18 induced during S. mansoni infection play a role for the expansion of MCPHT cells within the liver of the host. It is thought that Th1- and Th2-responses are incompatible in one immunological circumstance, and that single T cells are ordinarily incapable of producing IFN-c and IL-4, the most typical Th1- and Th2-related cytokines respectively, simultaneously.

The ASPM protein only detected in advanced staged primary melanomas

Notably, the altered genomic regions encompass, which harbours the DNMT1 gene, which plays a role in the establishment and regulation of tissue-specific patterns of methylated cytosine residues. The DNA CN alterations of DNMT1 in advanced stages primary melanomas raise crucial questions: Is demethylation, contributing to clinical outcomes, only a passive consequence of CN loss? Or do CN alterations – as was demonstrated in the context of epigenetic mechanisms and the BRAFV600E mutation – directly control the DNA methylation changes to influence the gene expression patterns of given molecules? Regardless of the reason for changes in methylation, we obtained better insight into how gene expression levels are regulated by DNA methylation: demethylation was associated with increased mRNA levels, whereas hypermethylation was associated with decreased levels. In summary, we demonstrated the strong influence of DNA methylation changes on melanoma progression. However, hypermethylation, which has been greatly emphasised in the literature, appears to represent more complexity both in melanoma initiation and progression. Additionally, the inhibition of promoter hypermethylation might represent the most promising therapeutic target for the treatment of melanoma, and several types of DNMT inhibitors are currently being developed. Considering the dual role of DNA methylation, further efforts are needed to investigate the importance of such drugs in melanoma treatment. Approximately 225,000 new cases of ovarian cancer were diagnosed in 2008 worldwide, comprising 4% of all female cancers. The majority of ovarian cancers are epithelial, frequently present at advanced stages and are associated with high mortality rates. Therefore, investigating the function and expression of potential prognostic proteins is essential for the advancement of our understanding of the molecular pathogenesis of epithelial ovarian cancer. This is especially desirable with regards to the identification of diagnostic biomarkers for patient management. The MCPH1 and MCPH5 genes encode Microcephalin and the abnormal spindle-like microcephaly-associated protein respectively. MCPH1 and MCPH5 are two of ten microcephaly genes identified, which are implicated in autosomal recessive primary microcephaly. Microcephaly is characterized by reduced foetal brain growth resulting from mitotic defects during embryonic brain development. Microcephalin is a nuclear and cytoplasmic protein consisting of 835 amino acids. The protein contains three BRCA1 C-terminus domains, one N-terminally located and two in the Cterminus. Microcephalin is involved in DNA damage response with a further role as a regulator of chromosome condensation preventing cells from entering mitosis before DNA replication is completed. Microcephalin is also known as BRIT1, which was initially identified as a transcriptional repressor of human telomerase reverse transcriptase, the catalytic subunit of human telomerase.

Reporting of personality traits was anonymous and given that this reporting is not part of the documented performance evaluation

We expected little socially desirable reporting. Nonetheless, future research could enhance neutral phrasing of personality items, as neutral phrasing has been shown to decrease the degree of socially desirable answers. Another point of self-reported personality traits is that they might have provided other information about personality traits than observer-reports would have. Indeed, it has been shown that self-reported and observer-reported personality traits each have unique variance. Yet, self- and observer-rated personality traits also showed to have a high degree of construct overlap and self-reported personality traits appeared to provide valid information about the person, predictive for various consequences. Both self- and observer-reported measures deliver valuable information about personality traits, However, both selfand observer-reports of personality are indirect measures, and cannot be directly observed. The conclusions drawn from our results should be interpreted accordingly. Up till date, self-reported personality traits in relation to teaching performance are less common in research than otherreported personality traits. Therefore, this study on selfreported personality traits, which also shows associations with teaching performance, makes an original contribution to current knowledge on this topic. The reported positive effects of extraversion are consistent with previous research. This study adds knowledge on the specific teaching skills involved – namely, provision of a motivating learning climate, communication of learning goals, provision of constructive feedback, and adequate evaluation of residents. Possibly, the positive evaluation of extraverted attending physicians reflects residents’ appreciation of those attending physicians who are best able to adjust to the demands of modern health care and residency training, which stresses typical extraversion related competencies, such as communication and collaboration. In line with expectations, conscientiousness turned out to be a positive trait for some specific teaching skills, i.e. the creation of a motivating learning climate and communication of learning goals. In general, conscientious people tend to be active learners, which may be instrumental or even contagious in terms of teaching residents to be active learners as well. Indeed, residents in this study find that conscientious attending physicians motivate them to study further, keep up with the literature, actively participate in discussions and prioritize learning goals. In addition, we found that attending physicians who reported higher levels of conscientiousness, were perceived as more adequate in evaluating the knowledge and skills of residents, however, this only applied to non-surgical attending physicians. An explanation for this finding could be found in the fact that nonsurgical residents find evaluation a more important teaching.