Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508.

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

Deep-Learning-Based Color Doppler Ultrasound Image Feature in the Diagnosis of Elderly Patients with Chronic Heart Failure Complicated with Sarcopenia.

The neural network algorithm of deep learning was applied to optimize and improve color Doppler ultrasound images, which was used for the research on elderly patients with chronic heart failure (CHF) complicated with sarcopenia, so as to analyze the effect of the deep-learning-based color Doppler ultrasound image on the diagnosis of CHF. 259 patients were selected randomly in this study, who were admitted to hospital from October 2017 to March 2020 and were diagnosed with sarcopenia. Then, all of them underwent cardiac ultrasound examination and were divided into two groups according to whether deep learning technology was used for image processing or not. A group of routine unprocessed images was set as the control group, and the images processed by deep learning were set as the experimental group. The results of color Doppler images before and after processing were analyzed and compared; that is, the processed images of the experimental group were clearer and had higher resolution than the unprocessed images of the control group, with the peak signal-to-noise ratio (PSNR) = 20 and structural similarity index measure (SSIM) = 0.09; the similarity between the final diagnosis results and the examination results of the experimental group (93.5%) was higher than that of the control group (87.0%), and the comparison was statistically significant (P < 0.05); among all the patients diagnosed with sarcopenia, 88.9% were also eventually diagnosed with CHF and only a small part of them were diagnosed with other diseases, with statistical significance (P < 0.05). In conclusion, deep learning technology had certain application value in processing color Doppler ultrasound images. Although there was no obvious difference between the color Doppler ultrasound images before and after processing, they could all make a better diagnosis. Moreover, the research results showed the correlation between CHF and sarcopenia.

Resveratrol potentiates the anti-tumor effects of rapamycin in papillary thyroid cancer: PI3K/AKT/mTOR pathway involved.

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of papillary thyroid cancer. While rapamycin has been shown to exhibit anti-tumor effects, it may also activate AKT, resulting in increased cell survival and drug resistance, thereby limiting its anti-tumor effects. Resveratrol can also inhibit tumor growth by regulating the PI3K/AKT/mTOR signaling pathway. The present study investigated the anti-tumor effects of the combined use of rapamycin and resveratrol in papillary thyroid cancer. We first treated two human papillary thyroid cancer cell lines (KTC-1 and TPC-1) with single or combined administration, and examined the effects on proliferation, the cell cycle, apoptosis, and invasion/migration of papillary thyroid cancer cells. A mouse xenograft model was induced with KTC-1 and TPC-1 cells followed by treatment with single or combined administration. Body weight and tumor size were monitored to assess the toxicity of each compound. The phosphorylation of AKT and the mTORC1 target p70S6 kinase (p70S6K) in tumors was also examined. Both rapamycin and resveratrol inhibited proliferation, altered the cell cycle, and induced apoptosis of papillary thyroid cancer cells. Invasion and migration were also reduced, as was the tumor growth rate in the xenograft model. Co-administration significantly enhanced the anti-tumor effects than use of any one drug, and significantly reduced the phosphorylation of AKT and p70S6K compared to treatment with rapamycin alone. Overall, compared to single use of rapamycin or resveratrol, co-administration had a synergistic effect in inhibiting proliferation and invasion/migration of papillary thyroid cancer cells and inducing apoptosis. Resveratrol is sensitizing the anti-tumor effects of rapamycin and the PI3K/AKT/mTOR signaling is involved. Although further animal and clinical studies are needed to clarify the mechanism and assess drug safety, the present study suggests that the combination of rapamycin and resveratrol may be a promising strategy for the treatment of papillary thyroid cancer.

Expression of hepatitis B virus 1.3-fold genome plasmid in an SV40 T-antigen-immortalized mouse hepatic cell line.

AIM: To investigate the expression of the hepatitis B virus (HBV) 1.3-fold genome plasmid (pHBV1.3) in an immortalized mouse hepatic cell line induced by SV40 T-antigen (SV40T) expression. METHODS: Mouse hepatic cells were isolated from mouse liver tissue fragments from 3-5 d old Kunming mice by the direct collagenase digestion method and cultured in vitro. The pRSV-T plasmid was transfected into mouse hepatic cells to establish an SV40LT-immortalized mouse hepatic cell line. The SV40LT-immortalized mouse hepatic cells were identified and transfected with the pHBV1.3 plasmid. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in the supernatant were determined by an electrochemiluminescence immunoassay at 24, 48, 72 and 96 h after transfection. The expressions of HBsAg and hepatitis B c antigen (HBcAg) in the cells were investigated by indirect immunofluorescence analysis. The presence of HBV DNA replication intermediates in the transfected cells and viral particles in the supernatant of the transfected cell cultures was monitored using the Southern hybridization assay and transmission electronic microscopy, respectively. RESULTS: The pRSV-T plasmid was used to immortalize mouse hepatocytes and an SV40LT-immortalized mouse hepatic cell line was successfully established. SV40LT-immortalized mouse hepatic cells have the same morphology and growth characteristics as primary mouse hepatic cells can be subcultured and produce albumin and cytokeratin-18 in vitro. Immortalized mouse hepatic cells did not show the characteristics of tumor cells, as alpha-fetoprotein levels were comparable (0.58 ± 0.37 vs 0.61 ± 0.31, P = 0.37). SV40LT-immortalized mouse hepatic cells were then transfected with the pHBV1.3 plasmid, and it was found that the HBV genome replicated in SV40LT-immortalized mouse hepatic cells. The levels of HBsAg and HBeAg continuously increased in the supernatant after the transfection of pHBV1.3, and began to decrease 72 h after transfection. The expressions of HBsAg and HBcAg were observed in the pHBV1.3-transfected cells. HBV DNA replication intermediates were also observed at 72 h after transfection, including relaxed circular DNA, double-stranded DNA and single-stranded DNA. Furthermore, a few 42 nm Dane particles, as well as many 22 nm subviral particles with a spherical or filamentous shape, were detected in the supernatant. CONCLUSION: SV40T expression can immortalize mouse hepatic cells, and the pHBV1.3-transfected SV40T-immortalized mouse hepatic cell line can be a new in vitro cell model.

Synthesis, fine structure of 19F NMR and fluorescence of novel amorphous TPA derivatives having perfluorinated cyclopentenyl and benzo[b]thiophene unit.

Three novel triphenylamine (TPA) derivatives having perfluorinated cyclopentenyl and benzo[b]thiophene unit are obtained from 4-bromo-N,N-diphenyl-2-methylbenzo[b]thiophen-5-amine. The new compounds are expected to find their use in thin film devices as charge transport materials and host organic light-emitting materials. It is found that the new compounds show relatively strong fluorescence either in solution or in solid state, and are amorphous due to a special conformation which is elucidated by the fine structure of (19)F NMR. Molecular structure and properties of these compounds is characterized by (1)H NMR, (13)C NMR (broadband decoupled), ESI-HRMS, elemental analysis and thermal analysis (DSC). Fluorescent quantum yield in solution is measured using 9,10-diphenylanthrancene (DPA) as standard fluorescent substance.

Knockdown of Coronin-1C disrupts Rac1 activation and impairs tumorigenic potential in hepatocellular carcinoma cells.

Coronin-1C is an important F-actin binding protein which is critical for cell motility. Furthermore, the expression of this protein was found to be increased in diffuse tumors and was correlated with the degree of tumor malignancy. However, the mechanism(s) through which this protein enhances malignancy in hepatocellular carcinoma (HCC) is poorly understood. In this study, we found that Coronin-1C was overexpressed in human HCC tissues compared with the adjacent non-tumor tissues. Overexpression of Coronin-1C enhanced the cell migration in the human HCC cell line BEL-7402, whereas suppressed cell migration and proliferation were observed in Coronin-1C-knockdown BEL-7402 cells together with impaired cell polarity, disrupted cytoskeleton and decreased Rac-1 activation. Moreover, the Coronin-1C knockdown cells displayed a lower degree of malignancy by inducing smaller tumors in nude mice. Thus, we demonstrated a relationship between Coronin-1C overexpression and human HCC growth through enhancement of tumor cell proliferation and migration, which are correlated with Rac-1 activation.

Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death in SFTS patients remain unclear. METHODS: Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death. RESULTS: Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived. CONCLUSIONS: We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.

Visual saliency: a biologically plausible contourlet-like frequency domain approach.

In this paper we propose a fast frequency domain saliency detection method that is also biologically plausible, referred to as frequency domain divisive normalization (FDN). We show that the initial feature extraction stage, common to all spatial domain approaches, can be simplified to a Fourier transform with a contourlet-like grouping of coefficients, and saliency detection can be achieved in frequency domain. Specifically, we show that divisive normalization, a model of cortical surround inhibition, can be conducted in frequency domain. Since Fourier coefficients are global in space, we extend to this model by conducting piecewise FDN (PFDN) using overlapping local patches to provide better biological plausibility. Not only do FDN and PFDN outperform current state-of-the-art methods in eye fixation prediction, they are also faster. Speed and simplicity are advantages of our frequency domain approach, and its biological plausibility is the main contribution of our paper.