Month: January 2020

Allows them to access the inside of tumor tissues and achieve real target imaging and treatment. Based on the results of this study, the ultrasound-destructible nanobubbles carrying AR siRNA that we prepared could not only enhance the imaging effect of transplanted tumor, but also distribute more widely in the tumor, compared with the control microbubbles. In other normal tissues and organs, such as the liver and the kidney, nanobubbles had longer imaging duration than microbubbles while there was no obvious different distribution between them. Additionally, recent studies have shown that nanobubbles under ultrasonic irradiation can also enhance gene transfection efficiency. Therefore, in theory, nanobubbles show great potential for gene therapy. The difficulty of developing nanobubbles with a high carrying capacity for highly stable drugs and genes prevents the application of ultrasound-destructible nanobubbles as a drug or gene transfection vector. Currently, electrostatic binding and biotin/avidin binding are the two main methods of combining genes with microbubbles. Electrostatic binding is not suitable for wide use due to its instability and low encapsulation rate. Biotin/avidin binding, although stable, cannot be used for nanobubbles because of the large molecular weight of biotin/avidin, which can result in a significant increase in bubble size. Some researchers have utilized the PLL method, which can be regarded as an improved method of electrostatic binding. PLL contains a polycation chain with a positively charged surface, and the prepared nanobubbles have a negatively charged surface. After PLL binding via static electricity, the surface of the nanobubble has a positive charge and can combine with the negatively charged siRNA via electrostatic adsorption. In this study, nanobubbles carrying AR siRNA were prepared based on the above mechanism. Nanobubbles with an average size of 609.5 nm exhibited stable binding to siRNA, as indicated by the finding that the loading capability of the carried nucleic acids remained high after repeated washes with PBS. These results suggest that PLL is an effective method for preparing nanobubbles carrying nucleic acids. Currently, however, the application of nanobubbles carrying genes to inhibit tumor growth remains in the exploratory stage. Many key issues, such as the preparation method, stability, penetration capability, in vivo imaging properties, and transfection efficiency of nanobubbles, still need to be systematically investigated. Therefore, when accompanied by ultrasonic irradiation, these bubbles facilitated a high transfection efficiency in AIPC cells, providing evidence that ultrasound-destructible nanobubbles may represent a viable option for gene therapy delivery to tumors in vivo. Many studies have also shown that the intensity and duration of ultrasonic irradiation and the concentration of microbubbles can inhibit cell growth and even cause cell death.

We investigated the low-dose effects of CYP exposure during the perinatal stage and found impaired testicular development and steroidogenesis in the male offspring. The male-o-female ratio, BW, and TW were decreased at PD21.5. The structure of the seminiferous epithelium layer was also changed. The expression levels of steroidogenesis genes and hormone receptors were altered after CYP exposure both in vivo and in vitro. The mitosis and meiosis markers were also changed. The serum T levels were decreased, and E2 levels were increased. Androgen is a prerequisite for normal spermatogenesis and development, and the binding of androgen to the AR plays an important role in the induction of the male external genitalia during embryonic differentiation and spermatogenesis. In fetal and neonatal testes, AR expression is restricted to the interstitial compartment. Merlet et al. observed testicular dysgenesis during the embryonic period of gender differentiation in AR knockout mice. Thus, perinatal CYP exposure may affect the precursors of adult Leydig cells. Star and 3b-HSD were downregulated significantly in the CYP groups; in addition, in these groups, the T level was reduced, and the Cyp19a1 and E2 levels were increased. Moreover, the AR hormone receptor was downregulated, and ERa was upregulated. An imbalance of androgenic and estrogenic signals may lead to serious structural abnormalities. Previous results have demonstrated that mice overexpressing human aromatase possess a multitude of structural and functional alterations in the reproductive organs, and a decreased male-to-female ratio may arise from this overexpression. Taken together, the current results indicate that the inhibition of the androgenic signal during the prenatal and neonatal periods impairs the ability of Leydig cells to produce T in favor of E2 due to the overexpression of aromatase. The apoptosis of spermatogonia and spermatocytes occurs in the mitotic phase. Studies have also found that deltamethrin and diethylstilboestrol induce a greater degree of apoptosis in adult male testes. In this study, we found much greater apoptosis of germ cells in the CYP groups. Sufficient T plays a vital role in the inhibition of germ cell apoptosis. Reduced T levels lead to the separation of germ cells from the epithelium of the seminiferous tubules. In the present study, we found that the serum T levels were decreased significantly by maternal CYP exposure, which will weaken their ability to maintain spermatogenesis. Studies on bisphenol A and hexachlorocyclohexane have demonstrated that EDCs can affect mitosis and meiosis, and we also found that the expression of mitosis and meiosis marker genes was altered. The levels of Nanos3, which is important for maintaining undifferentiated spermatogonia, and the cell cycle regulator Cyclin D2 were evaluated. We found that the expression of these two genes was decreased in the CYP groups at PD21.5 and PD45.5.

Moreover, we recently demonstrated that S. mansoni infection elicited the accumulation of unique CD4 + T cell populations exhibiting unconventional cytokine profiles in the liver, but not in the spleen, of mice infected during the transition phase, the period between early Th1- and late Th2-superior phases. These hepatic T cell populations produced the combinations of cytokines; IFN-c+IL-4 and IFN-c+IL-13. Furthermore, some of the unique populations simultaneously secreted IFN-c, IL4, and IL-13. We explored the previously unresolved molecular machineries underlying the accumulation of MCPHT cell populations in the liver during the transition phase of S. mansoni infection. The data presented here suggest that IL-18 induced during S. mansoni infection acts as a factor associated with the expansion of MCPHT cells. S. mansoni infection stimulated the elevation of IL18 levels not only in the sera but also in the liver during the transition phase, when the expansion of MCPHT cell populations and oviposition of the trematode begin. IL-18-deficient mice displayed severely impaired expansion of c4 and c13 cells in the liver during S. mansoni infection. Furthermore, expression of IL18R was observed in approximately half of both c4 and c13 cells. It is noteworthy that MCPHT cell populations were induced in IL-18KO mice at four weeks PI. The subsequent increase of these MCPHT cells was not induced in the IL-18KO mice, and this resulted in a considerable reduction in the proportions and the absolute numbers of c4 and c13 cells in IL-18KO mice compared to WT control mice at 6 weeks PI. This suggests that IL-18 is indispensable for the expansion, but not required for the generation, of c4 and c13 cells in the liver during S. mansoni infection. The determinant of the generation of MCPHT cells induced following S. mansoni infection are unknown. One possible candidate is an adolescent worm product. Indeed, soluble worm antigen preparation has been shown to endow conventional hepatic T cells with the capacity to produce large amounts of IL-4 and IL-13. SWAP consists of several components including not only T cell antigens but also factors that stimulate, or are targeted by innate immunity. It is probable that SWAP produced by immature and mature worms differs in its composition. Hence, the cytokine profiles of Th1 cells generated during the early phase of S. mansoni infection, when the antigens are presented by Kupffer cells affected by immature worm’s SWAP, may be converted into those of the MCPHT cells described here, induced during the transition phase, when the Kupffer cells influenced by mature worm’s SWAP present antigens. As the kinetics of the induction of MCPHT cells and fluke oviposition seem to be identical, the other possible candidate for the determinant of the generation MCPHT cells is soluble egg antigen, particularly omega-1, which is a glycosylated T2 RNase and most abundantly present in SEA.

The hypermethylome detected in melanomas that represents better prognoses markedly decreased. The decrease in the methylation levels occurred gradually, as the continuous Breslow thickness variables allowed us to distinguish more than two groups among primary melanomas and to map the progress of demethylation during distinct stages. The genes involved in demethylation partially overlap among clinical subgroups: five genes were found to be commonly demethylated in large, nodular subtype, ulcerated and metastatic melanomas. The SEPT9 gene is an ovarian tumour suppressor playing a role in cell cycle control ; IL8 gene expression is elevated in metastatic melanomas and can increase the level of MMP2 ; SLC22A18 has been reported to be down-regulated due to promoter hypermethylation in gliomas ; MMP14 has not been found to play a role in melanoma progression thus far. Among the aforementioned clinical groups, the largest similarity has been detected between the demethylated genes associated with Breslow thickness and ulceration. The histologic subtype represents the most unique methylation pattern, comprising 30 differentially methylated genes between superficial and nodular melanomas. Our results contrast those of studies describing the hypermethylation patterns of specific genes as tumour progression-related markers based on single gene approaches. However, Conway et al. supported the claim that a covalent change from cytosine to 5methylcytosine in the promoter region occurs as an early aberration event in melanomas. Notwithstanding, their results highlighted not only the hypermethylated but also the demethylated genes in heterogeneous melanomas compared to naevi. This group reported a lack of similarity – involving only two genes, namely, RUNX3 and SYK – with the previously published data. In addition to the common mutations, specific patterns of CN alterations have been reported in melanomas characteristic of unfavourable clinical outcomes. Furthermore, it has become obvious that BRAFV600E mutated melanomas display distinct patterns for CN changes, providing the first line of evidence in support of Knudson’s two-hit hypothesis. However, none of the published studies attempted to evaluate the relationship between CN alterations and DNA methylation in melanomas. Our group performed a Tiling Array CGH, and, apart from highlighting common CN losses and amplification in the subgroups of primary melanomas, we demonstrated that 6q12– 6q25.1 comprises a remarkable CN loss, harbouring two hypermethylated genes on 6q23, EYA4 and MYB1. This result was measured and verified quantitatively and provides evidence for Knudson’s two-hit hypothesis at the level of CN loss and DNA hypermethylation. Notably, MYB1 is an important discriminator between melanomas and naevi, as validated by FISH in 123 melanomas and 110 naevi. The copy number deletion of MYB1 is currently used in the diagnosis of melanoma.

This still needs to be demonstrated. Although personality traits characterize individuals, attending physicians do not function as individuals only they work in teams within departments, delivering specialized patient care and medical training. The clinical specialty establishes a specific professional context, not only for the nature of patient care that varies across specialties, but also for interpersonal behaviors towards and interactions with patients. In addition, teaching performance of attending physicians is differently evaluated across specialties. What works for one specialty, does not necessarily work for another specialty. This is in line with Nettle’s cost-benefit trade-off model, which states that costs and benefits of personality traits depend on the context in which they are expressed. Subsequently, a certain personality trait could be beneficial for the teaching of residents within one specialty, but could come with costs within another specialty. Still, specialty dependent effects of personality on teaching performance of attending physicians are unexplored. Overall, since previous research suggests that personality traits could affect teaching performance in non-clinical settings, there is a critical need for examining these in residency training. Moreover, the little existing research done in clinical teaching settings used qualitative methods only, making it nearly impossible to make inferences based on quantitative evidence. Moreover, nothing is known about differences between specialties in terms of plausible links between personality traits and teaching performance. Therefore, the objective of this study is to examine the relationship of personality traits with teaching performance of attending physicians within and across surgical and non-surgical specialties. We hypothesize that conscientiousness, extraversion, emotional stability, agreeableness, and openness all positively affect teaching performance. Since the differences between surgical and non-surgical specialties on this matter had not been documented in the literature, we had no specific expectations, electing for an explorative approach to this issue. Attending physicians self-reported their personality traits using the shortened version of the Big Five Inventory, as an additional and optional questionnaire attached to SETQ. The BFI-10 measures personality in five domains according to the Five Factor Model: conscientiousness, extraversion, emotional stability, agreeableness and openness. Attending physicians could selfreport their personality scales on a 5-point scale. Taking into account BFI authors’ recommendations, we added an extra item for the subscale agreeableness in order to safeguard internal consistency for this subscale, as it showed less internal consistency than the other personality subscales. This way, our BFI contained eleven items, instead of ten.