COX-2 Inhibitor Nimesulide Analogs are Aromatase Suppressors in Breast Cancer Cells

Cyclooxygenase-2 (COX-2) inhibitor nimesulide derivatives compounds A and B decreased aromatase activity in breast cancer cells via a novel mechanism different to aromatase inhibitors (AIs), and were defined as “aromatase suppressors”. Breast carcinoma cells (MCF-7aro and T47Daro) transfected with aromatase full gene were used to explore the mechanisms of the two compounds. They dose and time-dependently suppressed aromatase activity in MCF-7aro and T47Daro cells in the nanomole range. However, they neither directly inhibited aromatase, nor improved aromatase degradation even at much higher concentrations. They could also suppress androgen stimulated cell growth, but did not affect estrogen enhanced cell proliferation. These results suggest that compounds A and B selectively interfere with aromatase in breast cancer cells, but not estrogen receptor (ER) downstream to disrupt androgen mediated cell growth. Interestingly, compound B effectively inhibited LTED (long-term estrogen deprived MCF-7aro cell) cell growth, which is a model for AIs resistance, with an IC50 of 4.68 ± 0.54 μM. The results indicate that compound B could potentially overcome AI resistance in breast cancer cell and could be used as a lead to design more potent derivatives

Growth Factor Signaling Enhances Aromatase Activity of Breast Cancer Cells Via Post-Transcriptional Mechanisms

It has been demonstrated that growth factors produced by breast cancer cells stimulate aromatase expression in both breast cancer and adjacent adipose fibroblasts and stromal cells. However, whether these growth factors affect aromatase activity by other mechanisms still remain unclear. In the current study, MCF-7aro and T47Daro aromatase transfected breast carcinoma cells were used to explore the mechanisms of post-transcriptional regulation of aromatase activity by growth factor pathways. Our study reveals that PI3K/Akt and MAPK inhibitors suppressed aromatase activity in MCF-7aro cells. However, PI3K/Akt pathway inhibitors stimulated aromatase activity in T47Daro cells. This is due to enhanced MAPK phosphorylation as compensation after the PI3K/Akt pathway has been blocked. IGF-1 treatment increased aromatase activity in both breast cancer cell lines. In addition, LTEDaro cells (long-term estrogen deprived MCF-7aro cells) which have enhanced MAPK activity, show higher aromatase activity compared to parental MCF-7aro cells, but the aromatase protein level remains the same. These results suggest that aromatase activity could be enhanced by growth factor signaling pathways via post-transcriptional mechanisms

Growth Factor Signaling Enhances Aromatase Activity of Breast Cancer Cells Via Post-Transcriptional Mechanisms

It has been demonstrated that growth factors produced by breast cancer cells stimulate aromatase expression in both breast cancer and adjacent adipose fibroblasts and stromal cells. However, whether these growth factors affect aromatase activity by other mechanisms still remain unclear. In the current study, MCF-7aro and T47Daro aromatase transfected breast carcinoma cells were used to explore the mechanisms of post-transcriptional regulation of aromatase activity by growth factor pathways. Our study reveals that PI3K/Akt and MAPK inhibitors suppressed aromatase activity in MCF-7aro cells. However, PI3K/Akt pathway inhibitors stimulated aromatase activity in T47Daro cells. This is due to enhanced MAPK phosphorylation as compensation after the PI3K/Akt pathway has been blocked. IGF-1 treatment increased aromatase activity in both breast cancer cell lines. In addition, LTEDaro cells (long-term estrogen deprived MCF-7aro cells) which have enhanced MAPK activity, show higher aromatase activity compared to parental MCF-7aro cells, but the aromatase protein level remains the same. These results suggest that aromatase activity could be enhanced by growth factor signaling pathways via post-transcriptional mechanisms

Heat shock transcription factor 1 preserves cardiac angiogenesis and adaptation during pressure overload

To examine how heat shock transcription factor 1 (HSF1) protects against maladaptive hypertrophy during pressure overload, we subjected HSF1 transgenic (TG), knockout (KO) and wild type (WT) mice to a constriction of transverse aorta (TAC), and found that cardiac hypertrophy, functions and angiogenesis were well preserved in TG mice but were decreased in KO mice compared to WT ones at 4 weeks, which was related to HIF-1 and p53 expression. Inhibition of angiogenesis suppressed cardiac adaptation in TG mice while overexpression of angiogenesis factors improved maladaptive hypertrophy in KO mice. In vitro formation of vasculatures by microvascular endothelial cells was higher in TG mice but lower in KO mice than in WT ones. A siRNA of p53 but not a HIF-1 gene significantly reversed maladaptive hypertrophy in KO mice whereas a siRNA of HIF-1 but not a p53 gene induced maladaptive hypertrophy in TG mice. Heart microRNA analysis showed that miR-378 and miR-379 were differently changed among the three mice after TAC, and miR-378 or siRNA of miR-379 could maintain cardiac adaptation in WT mice. These results indicate that HSF1 preserves cardiac adaptation during pressure overload through p53-HIF-1-associated angiogenesis, which is controlled by miR-378 and miR-379

Clarity ChatGPT: An Interactive and Adaptive Processing System for Image Restoration and Enhancement

The generalization capability of existing image restoration and enhancement (IRE) methods is constrained by the limited pre-trained datasets, making it difficult to handle agnostic inputs such as different degradation levels and scenarios beyond their design scopes. Moreover, they are not equipped with interactive mechanisms to consider user preferences or feedback, and their end-to-end settings cannot provide users with more choices. Faced with the above-mentioned IRE method's limited performance and insufficient interactivity, we try to solve it from the engineering and system framework levels. Specifically, we propose Clarity ChatGPT-a transformative system that combines the conversational intelligence of ChatGPT with multiple IRE methods. Clarity ChatGPT can automatically detect image degradation types and select appropriate IRE methods to restore images, or iteratively generate satisfactory results based on user feedback. Its innovative features include a CLIP-powered detector for accurate degradation classification, no-reference image quality evaluation for performance evaluation, region-specific processing for precise enhancements, and advanced fusion techniques for optimal restoration results. Clarity ChatGPT marks a significant advancement in integrating language and vision, enhancing image-text interactions, and providing a robust, high-performance IRE solution. Our case studies demonstrate that Clarity ChatGPT effectively improves the generalization and interaction capabilities in the IRE, and also fills the gap in the low-level domain of the existing vision-language model

Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. Objective: Trinucleotide GGC repeat expansion in the 5’UTR of the NOTCH2NLC gene has been recognized as the pathogenesis of neuronal intranuclear inclusion disease (NIID). Previous studies have described that some NIID patients showed clinical and pathological similarities with multiple system atrophy (MSA). This study aimed to address the possibility that GGC repeat expansion in NOTCH2NLC might be associated with some cases diagnosed as MSA. Methods: A total of 189 patients with probable or possible MSA were recruited to screen for GGC repeat expansion in NOTCH2NLC by repeat-primed PCR (RP-PCR). In addition, long-read sequencing (LRS) was performed for all patients with RP-PCR-positive expansion, five patients with RP-PCR-negative expansion, and five controls on the Nanopore platform. Skin biopsies were performed on two patients with GGC expansion. Results: Five of 189 patients (2.6%) were found to have GGC expansion in NOTCH2NLC. LRS results identified that the five patients had GGC expansion between 101 and 266, but five patients with RP-PCR-negative expansion and five controls had GGC expansion between 8 and 29. Besides the typical symptoms and signs of MSA, patients with GGC expansion might have longer disease duration, severe urinary retention, and prominent cognitive impairment. In the skin samples from the patients with GGC expansion, typical p62-postive but alpha-synuclein-negative intranuclear inclusions were found in fibroblasts, adipocyte and ductal epithelial cells of sweat glands. Conclusion: Trinucleotide GGC repeat expansion in NOTCH2NLC could be observed in patients with clinically diagnosed MSA. Adult-onset NIID should be considered as a differential diagnosis of MSA

Review of research on evaluating the ecological security of cultivated land

Cultivated land provides fundamental land-related resources, and its ecological security is, thus, an important means of protecting it. The ecological security of cultivated land has emerged as an important and challenging area of research in recent years. In this study, we summarize the progress in research on the evaluation of the ecological security of cultivated land through visual analysis. We review the concepts, characteristics, driving factors, scales and methods of evaluation, technologies, and simulations used in the relevant literature. The results show that while the relevant concept has been preliminarily established, research on the ecological security of cultivated land remains in its infancy, and comprehensive work on the subject is lacking. The Prevalent research has mainly focused on analyzing the current situation, but lacks a dynamic analysis of the driving mechanism of the ecological security of cultivated land based on simulations. This has made it difficult to understand the spatiotemporal mechanism of the ecological security of cultivated land. Future research in the area should discuss the complex driving mechanism of interactions between the social economy system and the ecological system and focus on an integrated model to assess its dynamic spatial and multi-scale characteristics of ecological security of cultivated land because this can inform the theory of protecting cultivated land and the design of plans for land use to mitigate global climate change