The Effect of Nano Albumin Combined with Paclitaxel on Drug Resistance of Breast Cancer Through Regulating ATP Binding Cassette Subfamily B Member 1 (ABCB1)

The paclitaxel is a common-used chemotherapy drug and its combination with nano albumin reduces drug side effect. However, whether nab-paclitaxel affects drug resistance of breast cancer remains unclear. This study intends to discuss the mechanism of drug resistance induced by nab-paclitaxel. The drug resistance of MCF-7/nab-paclitaxel in MCF-7 cell and cell proliferation was detected by MTT along with analysis of ABCB1 expression, cell cycle, and apoptosis. There was stronger drug resistance of nab-paclitaxel in the MCF-7/nab-paclitaxel cell group through be adopted with different concentration of nab-paclitaxel at the 0th hour, 24th hour and 48th hour. There was remarkable abnormal expression of the ABCB1 in the MCF-7/nab-paclitaxel cell group. The si-ABCB1 could release the quantity of the MCF-7/nab-paclitaxel cell blocked at S period. And the si-ABCB1 could reduce the expression of cyclin D1 and CDK2 in the MCF-7/nab-paclitaxel cell notably. But the expression level of p21 was increased when there was high concentration of si-ABCB1. The si-ABCB1 could increase the quantity of the MCF-7/nab-paclitaxel cell at the later period of cell apoptosis notably. The rat’s tumor growth was delayed obviously at the MCF-7/nabpaclitaxel cell group treated by si-ABCB1. But the inhibiting effect of the MCF-7/nab-paclitaxel cell on tumor growth was less. There was stronger drug resistance of cell for the nano albumin combined with paclitaxel. The function of cell proliferation in breast cancer was restrained by the nano albumin combined with paclitaxel mainly through inducing the expression of ABCB1, adjusting the growth of cell cycle and the expression of P21/BCL-2 protein.

TMEM8C-mediated fusion is regionalized and regulated by NOTCH signalling during foetal myogenesis

The location and regulation of fusion events within skeletal muscles during development remain unknown. Using the fusion marker myomaker (Mymk), named TMEM8C in chicken, as a readout of fusion, we identified a co-segregation of TMEM8C-positive cells and MYOG-positive cells in single-cell RNA-sequencing datasets of limbs from chicken embryos. We found that TMEM8C transcripts, MYOG transcripts and the fusion-competent MYOG-positive cells were preferentially regionalized in central regions of foetal muscles. We also identified a similar regionalization for the NOTCH ligand JAGGED2 along with an absence of NOTCH activity in TMEM8C+ fusion-competent myocytes. NOTCH function in myoblast fusion had not been addressed so far. We analysed the consequences of NOTCH inhibition for TMEM8C expression and myoblast fusion during foetal myogenesis in chicken embryos. NOTCH inhibition increased myoblast fusion and TMEM8C expression and released the HEYL transcriptional repressor from the TMEM8C regulatory regions. These results identify a regionalization of TMEM8C-dependent fusion and a molecular mechanism underlying the fusion-inhibiting effect of NOTCH in foetal myogenesis. The modulation of NOTCH activity in the fusion zone could regulate the flux of fusion events.

Micro Characterization of Hot-Rolled Plate of Nb-Bearing Grain-Oriented Silicon Steel

In this study, niobium was added into grain-oriented silicon steels, four Nb-bearing hot-rolled bands with Nb content range from 0–0.025 wt% were prepared and a detailed study of the micro characterization (microstructure, texture and precipitates) of hot-rolled bands was carried out by various analysis methods, such as EBSD and TEM. The results indicate that the precipitates in Nb-free steel are MnS and AlN; however, in the Nb-bearing steel they are MnS, AlN and Nb(C, N). The precipitates are finer and more dispersed in Nb-bearing steel, and a stronger pining force was obtained, which contributes to the finer microstructure and less recrystallization fractions of the hot-rolled bands. A larger volume fraction and stronger intensity of Goss texture is presented in steel with 0.025 wt% Nb due to the effective inhibiting effect. However, it has little effect on the changes of microstructure and texture when the Nb content is more than 0.009 wt%.

Lowland amphibians - recalculation of data on effects of diluted thyroxine

Our previous paper described methodological problems and a generally acceptable pooling method for metamorphosis experiments and application of that method to the results of multicentre experiments performed over the course of two decades (1990 - 2010) on highland amphibians (Rana temporaria) treated with a homeopathically prepared high dilution of thyroxine (“30x”). Differences between treatment groups thus calculated were in line with those obtained with other pooling methods: Thyroxine 30x does slow down metamorphosis in highland amphibians. This follow up paper provides a broader background on metamorphosis physiology and describes application of the pooling method to experiments with Rana temporaria from lowland biotopes both with a moderate dilution of thyroxine (“8x”) and with 30x. Analogously prepared water was used for control (water 8x or 30x). Development was, again as above, monitored by documenting the number of animals that had entered the 4-legged stage. Experiments were carried out between 1990 and 2000 by different researchers independently and in blind. As it is well known, metamorphosis can be speeded up by thyroxine 10-8 mol/l; interestingly, thyroxine 8x may produce a reverse, i.e. inhibiting effect (p < 0.01). In contrast to the inhibiting effect of thyroxine 30x on highland larvae (see above), 2-legged lowland larvae did not react to thyroxine 30x (p > 0.05). However, an inhibiting effect on lowland larvae was found when animals were treated from the spawn stage on (p < 0.01).

Corporate Financialization, Financing Constraints, and Environmental Investment

This paper took non-financial listed companies on A-shares from 2014 to 2018 as samples to empirically test the relationship between corporate financialization, financing constraints, and environmental investment. The empirical results showed that the degree of corporate financialization is negatively related to environmental investment, and the negative relationship between long-term financial assets and environmental investment is more significant. Financialization has a “crowding out” effect on environmental investment when the firm is a non-state enterprise or a small-scale enterprise. Financialization has a “reservoir” effect on environmental investment when it is subject to less financing constraints. Further analysis revealed that both long-term and short-term financial assets have an inhibiting effect on environmental investment when environmental regulations are stringent. This paper provides a theoretical reference for companies to make investment decisions on financial assets and to improve their ability on environmental investment and green sustainability.

Sitagliptin Attenuates Porphyromonas Gingivalis Virulence and Inflammatory Response in Macrophage on Titanium

BackgroundIn peri-implantitis, porphyromonas gingivalis and macrophage play central roles. The aim of this study was to detect the attenuating effect of an anti-diabetic drug sitagliptin on porphyromonas gingivalis virulence and inflammatory response in macrophage on titanium discs. Materials and methodsPorphyromonas gingivalis and macrophage were cultured on titanium discs. Antibacterial and antibiofilm activities of sitagliptin were assessed and the morphology of porphyromonas gingivalis were observed by SEM. Bacterial early adhesion, aggregation, hemagglutination, hemolysis and porphyromonas gingivalis virulence factors mRNA expression were assessed to preliminarily investigate the mechanisms of action. Flow cytometry assay, qRT-PCR and Western Blot were used to assess the anti-inflammatory effect of sitagliptin on porphyromonas gingivalis lipopolysaccharide-stimulated macrophage. ResultsThe present study demonstrated the inhibiting effect of sitagliptin on the growth, biofilm, phenotypic behavior and virulence factors of porphyromonas gingivalis and the protective effect on the porphyromonas gingivalis lipopolysaccharide-induced polarization in macrophage. And we also confirmed the anti-inflammatory effect of sitagliptin on the secretion of inflammation-related factors in macrophage by inhibiting the MAPK and AKT signaling pathways. ConclusionsSitagliptin possesses the attenuating effect on porphyromonas gingivalis virulence and inflammatory response in porphyromonas gingivalis lipopolysaccharide-stimulated macrophage on titanium.

Prestimulation of wheat seedlings with gibberellic acid followed by application of an agitated high dilution of the same hormone

Background In previous multicentre studies, the influence of a homeopathic ultra-high dilution of gibberellic acid on wheat growth was scrutinized. Data showed that this test dilution slowed down stalk growth when experiments were performed in the autumn season. Aim To test the hypothesis that pretreatment of grains with high concentrations of gibberellic acid would enhance the growth-inhibiting effect of the ultra-high dilution of the plant hormone Methods Grains of winter wheat (Triticum aestivum, 500 or 1000 per group) were pretreated with (non-agitated) gibberellic acid 10-5, 10-4 and 10-3 or with water (“W”) for control prior to treatment with G30x or W30x. Grains were observed under the influence of extremely diluted gibberellic acid (10-30) prepared by stepwise dilution and agitation according to a protocol derived from homeopathy (“G30x”). Analogously prepared water was used for control (“W30x”). Seedlings were allowed to develop under standardized conditions for 7 days; plants were harvested and stalk lengths were measured. Results Of the four pretreatment variants under study, Ge-3 yielded most growth, followed by Ge-4 , Ge-5 and finally W. This outcome was modulated by the application of G30x and W30x in that the inhibition obtained with G30x as compared to W30x was the greater the lower the pretreatment concentration of G had been. The hypothesis that pretreatment of grains with high concentrations of gibberellic acid would enhance the growth inhibiting effect of G30x had to be rejected. Rather, G30x slowed down stalk growth most in the W group with p < 0.001, only moderately in the Ge-5 and Ge-4 group and not at all in the Ge-3 group.

Droplet evaporation method applied to test the efficacy of Zincum metallicum 30c on stressed and non-stressed wheat seeds

Background: The droplet evaporation method (DEM) has been recently proposed as a possible tool to test the efficacy of ultra high dilutions (UHDs) [1]. Here we applied the same methodology consisting in the evaporation of droplets from leakages obtained by placing wheat seeds in UHDs to test whether DEM patterns vary in function of the tested treatment: Zincum metallicum 30c (ZM), lactose 30c as dynamized control (L), and unsuccussed, undiluted water as negative control (C). Since our previous study [1] showed that there is a significant increase in the UHD action in the stressed model, with respect to the non-stressed one, also in the present experiment we tested ZM, L and C on both stressed (s-seeds) and non-stressed wheat seeds (ns-seeds). Aims: The aim of the experiment was to test whether treatments ZM, L, and C applied on ns- and s-seeds influence the DEM pattern characteristics. Materials and methods: Whole, undamaged wheat seeds (Triticum aestivum cv. Inallettabile, harvesting year 2010) were used for the experiment, following the experimental protocol described in [1]. The distinction between s- and ns-seeds is based upon different storing conditions from the harvest until the analysis day: the ns-seeds were kept in controlled conditions at 5°C and in the dark, whereas the s-seeds were kept in lab at varying temperature, humidity and light conditions. As far as treatment preparation is concerned, ZM and L were obtained from triturations 3c (received from the Federal University of Rio de Janeiro) by vertical mechanical succussions and following dilutions; negative control (C) was ultra-pure water from the same water batch used for dilutions. The experiment was repeated on 6 days within one month; each seed lot (ns- and s-seeds) was analyzed on 3 different days (s-seeds on 10th, 11th and 24th February 2014 and ns-seeds on 12th, 26th February and 3th March 2014), with three treatment-replicates for ZM and L and two for C, three repetitions for each treatment-replicate and 5 droplets per repetition (360 patterns for each seed lot). The complexity degree of polycrystalline structures obtained from the evaporating droplets was measured by means of the ImageJ software [2] by calculating their local connected fractal dimensions (LCFD). The data on moon phase, moon position and moon distance from Earth at the beginning of each evaporation process were collected from the online tool virtuelles Telescope [3]. All data were processed by a three-way ANOVA at a significance level of p ≤ 0.05. Correlations between the moon data and LCFD were evaluated by r Pearson coefficient. Results: The effect of the treatment on LCFD values of DEM patterns was significant only in the stressed model: ZM showed a crystallization inhibiting action vs. C on all 3 analysis days, whereas a significant difference between ZM and L could be observed only on first and third analysis day (Fig 1a). ANOVA analysis showed that the overall LCFD means for the s-seed lot differed significantly between each other: 1.33 (a) for C, 1.26 (b) for L, and 1.19 (c) for ZM. Moreover, the LCFD values of both seed lots showed a strong day factor influence. A possible explanation of this finding might be the influence of the moon (position, phase, and distance from Earth) on the crystallization process: strong correlation between the LCFD of the patterns and moon data were found (r values were from -0.72 to -0.97). Figure 1: Graphical representation of the mean local connected fractal dimension values (LCFD) of droplet evaporation patterns obtained from stressed and non-stressed wheat seeds following treatments with Zincum metallicum 30c (ZM), lactose 30c (L), and unsuccussed/undiluted water (C). Discussion: The present study confirms a pre-sensitization effect towards UHD action in stressed models: a significant inhibiting effect of ZM 30c was found in all experimentation day. Furthermore, the strong correlations observed between the LCFD values and moon data indicate that the complexity of polycrystalline structures from evaporating droplets of wheat seed leakages might be affected by tidal forces. Since DEM needs to be standardized, these correlations can be considered only simultaneous and not causal, however their strength gives good reasons for further studies. Conclusions: The results of the present pilot-study seem to encourage further DEM experiments on s-seeds following UHD treatments. For further confirmation of the inhibiting effect of ZM on s-seeds, germination tests should be planned. Finally, the performance of DEM experimentations during days and hours with equal tidal influence on gravity might be helpful for the reduction of the day factor. Keywords:Ultra high dilutions, droplet evaporation method, patterns, Zincum metallicum

Highland amphibians and extremely diluted thyroxine: pre-experiment storage at low temperature

Introduction: In the course of more than two decades of experimental work on a model with amphibians and extremely diluted thyroxine, one experiment in particular, investigating the effect of an ultra-high dilution of thyroxine (T30x) v analogously prepared water (W30x) in amphibians from highland biotopes, was found to be reproducible. A total of 22 experimental runs were performed between 1990 and 2011, 15 by the initial researchers and 7 by altogether 5 independent researchers (1-5). In most of these (the sole exception being two performed and reported by the initial team) a trend was found of T30x-animals developing more slowly than W30x-animals. Pooled T30x values obtained by the initial team were 10.1% lower than W30x values (100%) (p < 0.01), and pooled T30x values from the 5 independent researchers were 12.4% lower (p < 0.01). The purpose of this study was to test the hypothesis that storing the animals at 4°C prior to the experiment does not influence (i.e. inhibit) the effect of T30x. Cooling here seemed to be a promising means of facilitating the transport of the highland larvae to laboratories and of synchronizing experiments. Methods: The original protocol was followed, but animals were stored at 4°C for several days prior to the experiment. Results: In contrast to the majority of previous experiments, no clear trend was found of T30x values being different from W30x values, i.e. of animals developing more slowly under the influence of T30x (p > 0.05). Conclusion: This experiment failed to reproduce the previously observed inhibiting effect of ultra-high diluted thyroxine on highland amphibians. The hypothesis that storage of the animals at 4°C does not influence the effect of T30x could not be proven; in contrast, it may be that this intermediate cooling down of the larvae is responsible for the failure of the replication.