Stabilization of G-quadruplex DNA by C-5-methyl-cytosine in bcl-2 promoter: implications for epigenetic regulation.

The C-5-methylation of cytosine in the CpG islands is an important pattern for epigenetic modification of gene, which plays a key role in regulating gene transcription. G-quadruplex is an unusual DNA secondary structure formed in G-rich regions and is identified as a transcription repressor in some oncogenes, such as c-myc and bcl-2. In the present study, the results from CD spectrum and FRET assay showed that the methylation of cytosine in the CpG islands could induce a conformational change of the G-quadruplex in the P1 promoter of bcl-2, and greatly increase the thermal-stability of this DNA oligomer. Moreover, the methylation of cytosine in the G-quadruplex could protect the structure from the disruption by the complementary strand, showing with the increasing ability to arrest the polymerase in PCR stop assay. This data indicated that the stabilization of the G-quadruplex structure in the CpG islands might be involved in the epigenetical transcriptional regulation for specific genes through the C-5-methylation modification pattern.

[Tea polyphenols inhibits the proliferation of prostate cancer DU145 cells].

OBJECTIVE: To investigate the effect of tea polyphenols on the proliferation of human prostate cancer cells and its possible mechanism. METHODS: We cultured androgen-independent prostate cancer DU145 cells in the medium with different concentrations (50, 100, 250 and 500 microg/ml) of tea polyphenols, and those in the normal medium as the control. After 48 hours of culture, we detected the survival rate of the cells by MTT assay and determined the expression of survivin by Western blot and quantitative RT-PCR. RESULTS: At 48 hours, the survival rates of the prostate cancer DU145 cells were 0.97 +/- 0.12, 0.71 +/- 0.07, 0.20 +/- 0.03 and 0.08 +/- 0.01 in the 50, 100, 250 and 500 microg/ml tea polyphenols treatment groups, all significantly reduced as compared with the control group (P < 0.01) except that of the 50 microg/ml group (P = 0.42). Furthermore, the survival rate continued to decrease with the prolonging of time, dropping below 5% at 96 hours except in the 50 microg/ml group. The grey values of the survivin expression in the 100, 250 and 500 microg/ml tea polyphenols groups were 13 425 +/- 34, 2 017 +/- 24 and 1 274 +/- 22, respectively, at 48 hours, significantly lower than 15 075 +/- 48 in the control group (P < 0.01). Moreover, the content of survivin mRNA at 48 hours was markedly lower in the 50, 100, 250 and 500 microg/ml treatment groups (0.74 +/- 0.03, 0.64 +/- 0.02, 0.52 +/- 0.01 and 0.21 +/- 0.02) than in the control (P < 0.01). CONCLUSION: Tea polyphenols can inhibit the proliferation of human prostate cancer DU145 cells, which may be associated with the decreased expression of the survivin gene.

Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A (CHNQD-0803). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a KD value of 4.728 × 10-8 M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition, LPS-stimulated inflammation, TGF-ß-induced fibrosis cell models and the MCD-induced mouse model of NASH. The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition, negatively regulated the NF-κB-TNFα inflammatory axis to suppress inflammation, and ameliorated liver injury and fibrosis. These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00168-z.

MobileSal: Extremely Efficient RGB-D Salient Object Detection.

The high computational cost of neural networks has prevented recent successes in RGB-D salient object detection (SOD) from benefiting real-world applications. Hence, this article introduces a novel network, MobileSal, which focuses on efficient RGB-D SOD using mobile networks for deep feature extraction. However, mobile networks are less powerful in feature representation than cumbersome networks. To this end, we observe that the depth information of color images can strengthen the feature representation related to SOD if leveraged properly. Therefore, we propose an implicit depth restoration (IDR) technique to strengthen the mobile networks' feature representation capability for RGB-D SOD. IDR is only adopted in the training phase and is omitted during testing, so it is computationally free. Besides, we propose compact pyramid refinement (CPR) for efficient multi-level feature aggregation to derive salient objects with clear boundaries. With IDR and CPR incorporated, MobileSal performs favorably against state-of-the-art methods on six challenging RGB-D SOD datasets with much faster speed (450fps for the input size of 320×320) and fewer parameters (6.5M). The code is released at https://mmcheng.net/mobilesal.

Lightweight Salient Object Detection via Hierarchical Visual Perception Learning.

Recently, salient object detection (SOD) has witnessed vast progress with the rapid development of convolutional neural networks (CNNs). However, the improvement of SOD accuracy comes with the increase in network depth and width, resulting in large network size and heavy computational overhead. This prevents state-of-the-art SOD methods from being deployed into practical platforms, especially mobile devices. To promote the deployment of real-world SOD applications, we aim at developing a lightweight SOD model in this article. Our observation comes from that the primate visual system processes visual signals hierarchically with different receptive fields and eccentricities in different visual cortex areas. Inspired by this, we propose a hierarchical visual perception (HVP) module to imitate the primate visual cortex for hierarchical perception learning. With the HVP module incorporated, we design a lightweight SOD network, namely, HVPNet. Extensive experiments on popular benchmarks demonstrate that HVPNet achieves highly competitive accuracy compared with state-of-the-art SOD methods while running at 4.3 frames/s CPU speed and 333.2 frames/s GPU speed with only 1.23M parameters.

Complicated behavior of G-quadruplexes and evaluating G-quadruplexes' ligands in various systems mimicking cellular circumstance.

Environments surrounding G-rich sequences remarkably affect the conformations of these structures. A proper evaluation system mimicking the crowded environment in a cell with macromolecules should be developed to perform structural and functional studies on G-quadruplexes. In this study, the topology and stability of a G-quadruplex formed by human telomeric repeat sequences were investigated in a macromolecule-crowded environment created by polyethylene glycol 200 (PEG200), tumor cell extract, and Xenopus laevis egg extract. The interactions between small molecules and telomeric G-quadruplexes were also evaluated in the different systems. The results suggested that the actual behavior of G-quadruplex structures in cells extract is quite different from that in the PEG crowding system, and proteins or other factors in extracts might play a very important role in G-quadruplex structures.

Enterolacaciamine as a potential O-GlcNAcase activator from the leaves of Enterolobium cyclocarpum.

Enterolacaciamine (1), a new potential O-GlcNAcase activator, along with three known triterpenoid saponins, concinnoside B (2), concinnoside D (3), and julibroside A3 (4) was isolated from the leaves of Enterolobium cyclocarpum. Their structures were elucidated by chemical and spectroscopic methods (UV, MS, 1D and 2D NMR). Their effects on O-GlcNAcase activity were evaluated using O-GlcNAcase enzymatic assay. The results showed that compound 1 could obviously enhance the activity of O-GlcNAcase.