Investigation of the effects of temperature and ions on the interaction between ECG and BSA by the fluorescence quenching method

The effects of temperature and common ions on binding (-)-epicatechin gallate (ECG) to bovine serum albumin (BSA) are investigated. The binding constants (Ka) between ECG and BSA are 1.20 Ч 106 (17°C), 1.38 Ч 106 (27°C), and 5.69 x 106 L mol-1 (37°C), and the number of binding sites (n) were 1.14, 1.15, and 1.26, respectively. These results showed that the increasing temperature improves the stability of the ECG-BSA system, which results in a higher binding constant and the number of binding sites of the ECG-BSA system. The presence of Co2+ and Zn2+ ions decreased the binding constants (Ka) and the number of binding sites (n) of ECG-BSA complex. However, the presence of Cu2+ and Ni2+ increased the affinity of ECG for BSA largely. The positive ΔH and positive ΔS indicated that hydrophobic forces might play a major role in the binding between ECG and BSA

A splicing isoform of TEAD4 attenuates the Hippo–YAP signalling to inhibit tumour proliferation

Aberrant splicing is frequently found in cancer, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo–YAP signalling, a key pathway that regulates cell proliferation and organ size, is under control of a splicing switch. We show that TEAD4, the transcription factor that mediates Hippo–YAP signalling, undergoes alternative splicing facilitated by the tumour suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks an N-terminal DNA-binding domain, but maintains YAP interaction domain. TEAD4-S is located in both the nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumour growth in xenograft mouse models. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether, these data reveal a splicing switch that serves to fine tune the Hippo–YAP pathway

MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2

In this study, we examined the role of the miRNA miR-770-5p in cisplatin chemotherapy resistance in ovarian cancer (OVC) patients. miR-770-5p expression was reduced in platinum-resistant patients. Using a 6.128-fold in expression as the cutoff value, miR-770-5p expression served as a prognostic biomarker and predicted the response to cisplatin treatment and survival among OVC patients. Overexpression of miR-770-5p in vitro reduced survival in chemoresistant cell lines after cisplatin treatment. ERCC2, a target gene of miR-770-5p that participates in the NER system, was negatively regulated by miR-770-5p. siRNA-mediated silencing of ERCC2 reversed the inhibition of apoptosis resulting from miR-770-5p downreglation in A2780S cells. A comet assay confirmed that this restoration of cisplatin chemosensitivity was due to the inhibition of DNA repair. These findings suggest that endogenous miR-770-5p may function as an anti-oncogene and promote chemosensitivity in OVC, at least in part by downregulating ERCC2. miR-770-5p may therefore be a useful biomarker for predicting chemosensitivity to cisplatin in OVC patients and improve the selection of effective, more personalized, treatment strategies

Chemical composition, antioxidant and antitumor activities of sub-fractions of wild and cultivated Pleurotus ferulae ethanol extracts

Pleurotus ferulae is an edible and medicinal mushroom with various bioactivities. Here, the ethanol extracts of wild and cultivated P. ferulae (PFEE-W and PFEE-C) and their subfractions including petroleum ether (Pe-W/Pe-C), ethyl acetate (Ea-W/Ea-C) and n-butanol (Ba-W/Ba-C) were prepared to evaluate their antioxidant and antitumor activities. Both PFEE-W and PFEE-C show the antioxidant activity and PFEE-W is stronger than PFEE-C. The antioxidant activities of their subfractions are in the following order: Ea > Ba > Pe. Moreover, PFEE-W and PFEE-C significantly inhibit the proliferation of murine melanoma B16 cells, human esophageal cancer Eca-109 cells, human gastric cancer BGC823 cells and human cervical cancer HeLa cells through induction of apoptosis, which partially mediated by reactive oxygen species. The antitumor activities of their subfractions are in the following order: Ea ≥ Pe > Ba. Pe-W shows higher antitumor activity compared with Pe-C, which might be correlated with the difference of their components identified by gas chromatography-mass spectrometry. These results suggest that both wild and cultivated P. ferulae have antioxidant and antitumor activities, and cultivated P. ferulae could be used to replace wild one in some functions

SRSF1 modulates PTPMT1 alternative splicing to regulate lung cancer cell radioresistance

Background Radioresistance is the major cause of cancer treatment failure. Additionally, splicing dysregulation plays critical roles in tumorigenesis. However, the involvement of alternative splicing in resistance of cancer cells to radiotherapy remains elusive. We sought to investigate the key role of the splicing factor SRSF1 in the radioresistance in lung cancer. Methods Lung cancer cell lines, xenograft mice models, and RNA-seq were employed to study the detailed mechanisms of SRSF1 in lung cancer radioresistance. Clinical tumor tissues and TCGA dataset were utilized to determine the expression levels of distinct SRSF1-regulated splicing isoforms. KM-plotter was applied to analyze the survival of cancer patients with various levels of SRSF1-regulated splicing isoforms. Findings Splicing factors were screened to identify their roles in radioresistance, and SRSF1 was found to be involved in radioresistance in cancer cells. The level of SRSF1 is elevated in irradiation treated lung cancer cells, whereas knockdown of SRSF1 sensitizes cancer cells to irradiation. Mechanistically, SRSF1 modulates various cancer-related splicing events, particularly the splicing of PTPMT1, a PTEN-like mitochondrial phosphatase. Reduced SRSF1 favors the production of short isoforms of PTPMT1 upon irradiation, which in turn promotes phosphorylation of AMPK, thereby inducing DNA double-strand break to sensitize cancer cells to irradiation. Additionally, the level of the short isoform of PTPMT1 is decreased in cancer samples, which is correlated to cancer patients' survival. Conclusions Our study provides mechanistic analyses of aberrant splicing in radioresistance in lung cancer cells, and establishes SRSF1 as a potential therapeutic target for sensitization of patients to radiotherapy

Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus

BLP as a bacteria component is an important factor in autophagy activation and induces apoptosis. BLP-induced macrophage apoptosis was suppressed by inhibiting autophagy

Stability Analysis of Buck Converter Based on Passivity-Based Stability Criterion

Recently, the stability of DC microgrids has attracted increasing attention. The traditional stability analysis method cannot not meet the requirements for the complexity and bidirectional energy flow of the system. In this paper, a passivity-based stability criterion (PBSC) is proposed to analyze the stability of the cascade system. In order to realize the passivity of the system, an improved feedback control method based on the traditional double-loop control strategy is proposed, which will improve the stability region and guarantee the passivity of the system. Moreover, a Buck-CPL simulation model is established based on MATLAB/Simulink R2008, and the correctness of the theoretical analysis is verified by experiments

F1012-2 Induced ROS-Mediated DNA Damage Response through Activation of MAPK Pathway in Triple-Negative Breast Cancer

We have previously reported that F1012-2, a sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC., exhibits strong effects against Triple Negative Breast Cancer (TNBC). In this study, we found F1012-2 effectively inhibited cell migration and invasion detected by wound healing and transwell assays. In order to elucidate the potential mechanisms of F1012-2, we further studied its effect on DNA damage in TNBC cell lines. Using single cell gel electrophoresis (comet assay), immunofluorescence, and western blotting assays, we found that F1012-2 treatment induced significant DNA strand breaks and γ-H2AX activation. Moreover, exposure to F1012-2 led to overproduction of reactive oxygen species (ROS). NAC treatment completely eliminated ROS, which may be due to the interaction between NAC and F1012-2. A further study of the molecular mechanisms demonstrated that the MAPK signaling pathway participated in the anti-TNBC effect of F1012-2. Pretreatment with specific inhibitors targeting JNK (SP600125) and ERK (PD98059) could rescue the decrease in cell viability and inhibit expressions of JNK and ERK phosphorylation, but SB203580 had no effects. Finally, in the acute toxicity experiment, there were no obvious symptoms of poisoning in the F1012-2 treatment group. An in vivo study demonstrated that F1012-2 significantly suppressed the tumor growth and induced DNA damage. In conclusion, the activity of F1012-2-induced DNA damage in TNBC was found in vivo and in vitro, which might trigger the MAPK pathway through ROS accumulation. These results indicate that F1012-2 may be an effective anti-TNBC therapeutic agent