Our findings indicate a significant role of Sema7A in atherosclerosis by mediating endothelial dysfunction in a β1 integrin-dependent manner.

No abstract

Multidrug resistance and tumor migration and invasion are the major obstacles to effective breast cancer chemotherapy, but the underlying molecular mechanisms remain unclear. This study investigated the potential of transgelin 2 and salvianolic acid A to modulate the resistance and the migration and invasion abilities of paclitaxel-resistant human breast cancer cells (MCF-7/PTX). MCF-7/PTX cells were found to exhibit not only a high degree of resistance to paclitaxel, but also strong migration and invasion abilities. Small interfering RNA-mediated knockdown of TAGLN2 sensitized the MCF-7/PTX cells to paclitaxel, and inhibited their migration and invasion abilities. In addition, we also observed that combined salvianolic acid A and paclitaxel treatment could reverse paclitaxel resistance, markedly inhibit tumor migration and invasion, and suppress the expression of transgelin 2 in MCF-7/PTX cells. These findings indicate that salvianolic acid A can reverse the paclitaxel resistance and inhibit the migration and invasion abilities of human breast cancer cells by down-regulating the expression of transgelin 2, and hence could be useful in breast cancer treatments.

These results suggest that linezolid is not superior to vancomycin with respect to both clinical and microbiological cure rates in patients with MRSA NP.

No abstract

Background and Purpose: The clinical use of tirofiban for patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of tirofiban combined with MT in AIS patients.Methods: Patients with AIS who underwent MT from January 2014 to December 2018 were enrolled in three stroke units in China. Subgroup analyses were performed based on stroke etiology which was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Safety outcomes were in-hospital intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) and mortality at 3-month. Efficacy outcomes were favorable functional outcome and functional independence at 3-month and neurological improvement at 24 h, 3 d and discharge.Results: In patients with large artery atherosclerosis (LAA) stroke, multivariate analyses revealed that tirofiban significantly decreased the odds of in-hospital ICH (adjusted OR = 0.382, 95% CI 0.180–0.809) and tended to increase the odds of favorable functional outcome at 3-month (adjusted OR = 3.050, 95% CI 0.969–9.598). By contrast, in patients with cardioembolism (CE) stroke, tirofiban was not associated with higher odds of favorable functional outcome at 3-month (adjusted OR = 0.719, 95% CI 0.107–4.807), but significantly decreased the odds of neurological improvement at 24 h and 3d (adjusted OR = 0.185, 95% CI 0.047–0.726; adjusted OR = 0.268, 95% CI 0.087–0.825).Conclusions: Tirofiban combined with MT appears to be safe and effective in LAA patients, but has no beneficial effect on CE patients.

Maternal separation (MS), a stressful event in early life, has been linked to neuropsychiatric disorders later in life, especially depression. In this study we investigated whether treatment with electroacupuncture (EA) could ameliorate depression-related manifestations in adult animals that had adverse early life experiences. We demonstrated depression-like behavior deficiencies in a sucrose preference test and a forced swimming test in a rat model with neonatal MS. Repeated EA treatment at the acupoints Baihui (GV20) and Yintang (GV29) during adulthood was shown to be remarkably attenuated above behavioral deficits. Using unbiased genome-wide RNA sequencing to investigate alterations in the transcriptome of the prefrontal cortex (PFC), we explored the altered gene sets involved in circadian rhythm and neurotransmitter transporter activity in MS rats, and their expression tended to be reversed after EA treatment. In addition, we analyzed the interaction network of differentiated lncRNA– or circRNA–miRNA–mRNA by using the principle of competitive endogenous RNA (ceRNA). These results suggest that EA at GV20 and GV29 ameliorates depression-related manifestations by regulating the expression of multiple genes.

Breast cancer is one of the most prevalent types of malignant tumor. Paclitaxel is widely used in the treatment of breast cancer; however, the major problem contributing to the failure of chemotherapy in breast cancer is the development of drug resistance. Therefore, it is necessary to identify novel therapeutic targets and reversal agents for breast cancer. In the present study, the protein expression levels of SET, protein phosphatase 2A (PP2A) and phosphatidylinositol 3-kinase (PI3K)/Akt pathway were determined in MCF-7/PTX human breast carcinoma paclitaxel-resistant cells using western blot analysis. Small interference RNAs (siRNAs) were used to knock down the gene expression of SET in MCF-7/PTX cells and the cell viability was assessed following treatment with paclitaxel, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays and flow cytometry. In addition, western blot analysis was used to determined PI3K/Akt pathway activity following SET knockdown. Furthermore, the reversal effects of paeonol on paclitaxel, and its underlying mechanisms of action, were investigated using western blot analysis and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that increased levels of SET and PI3K/Akt pathway proteins were present in the MCF-7/PTX cells, compared with normal MCF-7 cells. Knockdown of SET significantly sensitized MCF-7/PTX cells to paclitaxel and induced cell apoptosis. In addition, the expression levels of the adenosine triphosphate binding cassette (ABC) transporter proteins were significantly reduced in the MCF-7/PTX cells compared with the normal MCF-7 cells. SET-induced paclitaxel resistance was found to be associated with the activation of the PI3K/Akt pathway. Paeonol significantly reduced the mRNA and protein expression levels of SET in the MCF-7/PTX cells. Furthermore, paeonol significantly sensitized the MCF-7/PTX to paclitaxel via regulation of ABC transporters, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein. In addition, paeonol inhibited SET-mediated paclitaxel resistance by attenuating PI3K/Akt pathway activity in the MCF-7/PTX cells. In conclusion, the results of the present study demonstrated that SET was associated with paclitaxel resistance in MCF-7/PTX cells, and that paeonol reversed paclitaxel resistance in MCF-7/PTX cells by downregulating the activity of the SET/PP2A/Akt pathway.