r20 (S)-protopanaxatriol improves atherosclerosis by inhibiting low-density lipoprotein receptor degradation in ApoE KO mice.

Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein-cholesterol (LDL-C) is the primary goal in preventing and treating AS. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a crucial role in regulating LDL-C metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20(S) protopanaxatriol (20(S)-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20(S)-PPT were investigated in vivo and in vitro by western blotting, real time-polymerase chain reaction (RT-PCR), Enzyme-linked Immunosorbent Assay (ELISA), immunofluorescence staining, and other assays. The in vitro experiments revealed that 20(S)-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low density lipoprotein receptor (LDLR) protein levels, promoted LDL uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of FoxO3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20(S)-PPT upregulated aortic αSMA expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol fed in ApoE-/- mice (HCF group). Additionally, 20(S)PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the HCF group. The study revealed that 20(S)-PPT inhibited LDLR degradation via PCSK9 to alleviate AS.

Caffeine can alleviate non-alcoholic fatty liver disease by augmenting LDLR expression via targeting EGFR.

Increasing low-density lipoprotein receptor (LDLR) protein levels represents a key strategy for the prevention and treatment. Berberine can reportedly alleviate non-alcoholic fatty liver disease (NAFLD) by increasing the LDLR expression in an ERK1/2 signaling-dependent manner of NAFLD. Studies have shown that caffeine can inhibit fat deposition in the livers of mice; however, caffeine has not been reported to alleviate NAFLD by augmenting the LDLR expression via targeting EGFR. Here, an MTT assay, western blotting, RT-qPCR, immunohistochemistry, and surface plasmon resonance (SPR) analysis were used to investigate the role of caffeine in low-density lipoprotein cholesterol (LDL-C) clearance both in vitro and in vivo. In vitro, we found that caffeine could activate the EGFR-ERK1/2 signaling pathway in HepG2 cells, leading to increased LDLR mRNA and protein expression, and this effect could be inhibited by cetuximab. The SPR assay results have indicated that caffeine may increase the LDLR expression by directly binding to the EGFR extracellular domain and activating the EGFR-ERK1/2 signaling pathway. In vivo, caffeine markedly improved fatty liver and related blood indices in ApoE KO mice with high-fat-diet-induced NAFLD. Consistent with our in vitro results, we found that caffeine could also activate EGFR-ERK1/2 signaling and promote the LDLR expression in ApoE KO mice. In summary, caffeine can enhance the LDLR expression by directly binding to EGFR and activating the EGFR-ERK1/2 signaling pathway. EGFR signaling may represent a novel target for the prevention and treatment of NAFLD.

Research progress of PBX1 in developmental and regenerative medicine.

Pre-B-cell leukemia transcription factor 1 (PBX1) proteins are a subfamily of evolutionarily conserved atypical homeodomain transcription factors belonging to the superfamily of triple amino acid loop extension homeodomain proteins. PBX family members play crucial roles in the regulation of various pathophysiological processes. This article reviews the research progress on PBX1 in terms of structure, developmental function, and regenerative medicine. The potential mechanisms of development and research targets in regenerative medicine are also summarized. It also suggests a possible link between PBX1 in the two domains, which is expected to open up a new field for future exploration of cell homeostasis, as well as the regulation of endogenous danger signals. This would provide a new target for the study of diseases in various systems.

20(S)-Protopanaxadiol decreases atherosclerosis in ApoE KO mice by increasing the levels of LDLR and inhibiting its binding with PCSK9.

Chinese medicinal and edible plants such as Panax notoginseng and ginseng are widely used for the treatment of atherosclerosis (AS). AS is the main pathological basis of cardiac-cerebral vascular disease, which seriously threatens human health and quality of life. Low-density lipoprotein (LDL) is the main pathogenic factor of AS. The LDL receptor (LDLR) is an important protein that functions to mediate the uptake and degradation of plasma LDL. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) can mediate the internalization and degradation of LDLR. So, increasing the LDLR level by inhibiting PCSK9 is an important means of prevention and treatment of AS. In this study, by combining interaction technology (surface plasmon resonance, SPR) of small molecule compounds with membrane receptor proteins, cell experiments, and in vivo experiments, it is proved for the first time that 20(S)-protopanaxadiol (PPD), as a hydrolytic product of Panax notoginseng saponins in the intestinal tract, can bind to the extracellular domain of LDLR and inhibit the role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in mediating LDLR degradation. The results showed that PPD significantly reduced aortic plaques and hepatic steatosis in HFD-fed ApoE KO mice. LDLR protein levels were elevated in the liver tissues isolated from PPD-treated HFD-fed ApoE KO mice and PPD-treated HepG2 cells. Our findings demonstrated that PPD significantly increased LDLR levels and reduced AS in the HFD-fed ApoE KO mice on account of LDLR degradation being inhibited by PPD inhibiting the interaction between PCSK9 and LDLR.

Research in Nonlinearity of Surface Acoustic Wave Devices.

Surface acoustic wave (SAW) devices are one of the indispensable components in the radio frequency (RF) front-end of mobile phones. With the development of mobile communication technology, the requirements for linear specification of devices are more and more strict. Nonlinear distortions of SAW devices have a serious influence on the application of mobile RF modules. To satisfy the strict requirement of linearity of communication system, it is necessary to understand the generation mechanism of nonlinearity and study the accurate modeling, appropriate measurement methods, and nonlinear response elimination technology. In this paper, we summarize the research progress on the nonlinearity of SAW devices in recent years from four aspects: the generation mechanism, simulation methods, measurement system, and suppression technology. The nonlinear harmonics with the nonlinear Mason equivalent circuit model are simulated. Furthermore, harmonics and intermodulation signals of SAW filters are tested by the authors. Thanks to these research studies, it is of great significance to the development of future RF front-end modules with high linear SAW devices.

A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.

PURPOSE: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data. METHODS: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model. RESULTS: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P<0.05). Stratified analysis results further confirmed this model performed well. By analyzing the validation group, the results of receiver operating characteristic (ROC) curve analysis and survival analysis further validated this model. CONCLUSION: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC.

Caffeine inhibits the anticancer activity of paclitaxel via down-regulation of α-tubulin acetylation.

Caffeine (1,3,7-trimethylxanthine) is a xanthine alkaloid found in a number of dietary products consumed worldwide, such as coffee, tea, and soft beverages, and is known to act as a modifying agent for cytotoxic chemotherapeutic drugs. Studies have shown that caffeine reduces the cytotoxic effects of paclitaxel and inhibits paclitaxel-induced apoptosis; however, the underlying mechanism remains unclear. Here, we investigated whether caffeine inhibits the antitumor activity of paclitaxel via down-regulation of α-tubulin acetylation. In vitro studies, involving MTT assay, wound-healing assay, cell apoptosis assay, and western blotting analysis of A549 and HeLa cells, were performed. A549 and HeLa cell-based xenografts were established, and western blotting and immunohistochemical staining were performed for in vivo studies. The results showed that caffeine promoted the growth of cancer cells treated with paclitaxel. Additionally, caffeine enhanced migration ability, inhibited apoptosis, and decreased the acetylation of α-tubulin in paclitaxel-treated cancer cells. Furthermore, caffeine decreased the inhibitory effect of paclitaxel on tumor growth through down-regulation of α-tubulin acetylation in vivo. Taken together, these findings demonstrate that caffeine inhibits the anticancer activity of paclitaxel via down-regulation of α-tubulin acetylation, suggesting that patients receiving treatment with taxanes, such as paclitaxel, should avoid consuming caffeinated beverages or foods.

Tripterygium wilfordii polyglycosidium ameliorates pouchitis induced by dextran sulfate sodium in rats.

BACKGROUND: The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii polyglycosidium (TWP) to rats with dextran sulfate sodium (DSS)-induced pouchitis and its possible mechanism. METHODS: Sprague-Dawley rats underwent surgery of ileal pouch anal anastomosis (IPAA) and pouchitis was induced by DSS. Rats were randomly divided into no intervention (NI), normal saline (NS) and TWP groups. Rats were lavaged with normal saline (3ml/day in NS group) or TWP (12mg/kg/day in TWP group) for 7days. General conditions of animals and histopathological examinations were evaluated. Interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor (TNF)-α mRNA expression was measured. Levels of occludin and Zo-1 proteins were measured by immunohistochemistry. In addition, ALT and AST were assessed. RESULTS: TWP significantly attenuated the symptoms of pouchitis characterized by body weight loss, diarrhea, and bloody stool. Furthermore, TWP diminished histological damage compared with other groups. There was a significant reduction in levels of IL-1ß, IL-6, and TNF-α, as well as an increase in IL-10 in the TWP group. The expression of tight junction proteins occludin and Zo-1 were increased in the TWP group. There were no statistical differences in serum ALT and AST among the three groups. CONCLUSIONS: TWP significantly ameliorated pouchitis and inhibited the production of IL-1ß, IL-6, and TNF-α as well as increased the levels of IL-10, occludin, and Zo-1 protein in rats. These findings suggest TWP might be a potential therapeutic agent for patients with pouchitis.

Fecal microbiota in pouchitis and ulcerative colitis.

AIM: To investigate the changes in microbiota in feces of patients with ulcerative colitis (UC) and pouchitis using genomic technology. METHODS: Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis (IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16S rRNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16S rRNA gene. RESULTS: Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups (P < 0.001) and IPAA groups (P < 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC (r = -6.591, P < 0.01), was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and pouchitis. CONCLUSION: Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis.

Structure of phonon focusing patterns in tetragonal crystals.

A set of critical conditions for the characteristic caustic points in the phonon focusing patterns in tetragonal crystals is formulated. A caustic line segment in the focusing pattern is generally associated with either a fold or a cusp on the wave surface. Most of the caustic lines are symmetrical with respect to the principal symmetry plane and can be characterized by the caustic points at the centers of the caustic lines. These characteristic caustic points originated from inflection/parabolic points with zero in-plane/ex-plane curvature, respectively. By employing the Stroh formalism, the inflection/parabolic points on the slowness surface are studied in terms of the so-called zero-curvature transonic states. Since these transonic states are related to extraordinary degeneracies in the Stroh eigenvalue equation, the conditions for the degeneracies can be regarded as critical conditions for the characteristic caustic points. These conditions provide an overview of global structure of the phonon focusing patterns in tetragonal crystals. A set of caustic lines in vicinity of (001) plane is also investigated and exemplified.

Caustic and anticaustic points in the phonon focusing patterns of cubic crystals.

Phonon focusing patterns are dependent on the existence of concave/saddle regions and acoustic axes in the slowness surface. The main feature of the focusing patterns in cubic crystals can be characterized by the caustic and anticaustic points in the symmetry planes. By applying the Stroh formalism, the caustic and anticaustic points in the symmetry planes are investigated in relation to degeneracies in the Stroh eigenvalue equation. A set of analytical expressions for the locations of the caustic and anticaustic points is derived for cubic crystals.

Existence of extraordinary zero-curvature slowness curve in anisotropic elastic media.

Acoustic wave propagation in elastic media is characterized by the slowness surface. The slowness surface consists of three sheets associated with three modes of wave propagation and the two outer sheets can have zero-curvature locally. It is shown that the outmost sheet can admit extraordinary zero-curvature and the slowness curve can appear as a straight line locally. Using the perturbation method, the conditions for the extraordinary zero-curvature are derived analytically without violating the thermodynamic condition for elastic media. The results can be applied to crystals with higher symmetry and to the study of phonon focusing and surface waves.