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To find immune-related genes with prognostic value in breast cancer, and construct a prognostic risk assessment model to make a more accurate assessment. Moreover, looking for potential immune markers for breast cancer immunotherapy.
The breast cancer (BC) data were retrieved from The Cancer Genome Atlas (TCGA) database as a training set. Through the Weighted gene co-expression network analysis (WGCNA), Kaplan-Meier (KM) analysis, lasso regression analysis and stepwise backward Cox regression analysis, screening for prognosis-related immune genes, a prognostic index was built, and external validation with two data sets of Gene Expression Omnibus (GEO) database was performed. Transcription factor (TF) regulatory network was constructed to identify key transcription factors that regulate prognostic immune genes. Gene set enrichment analysis (GSEA) was used to explore the signal pathways differences between high and low-risk groups, estimate package and TIMER database were used to evaluate the relationship between risk score and tumor immune microenvironment.
We obtained 10 prognosis-related immune genes, and the index showed accurate prognostic value. EN450 chemical structure We also identified 7 prognostic transcription factors. Multiple signaling pathways that inhibit tumor progression were enriched in the low-risk group, and risk score was significantly negatively related to the degree of immune infiltration and the expression level of immune checkpoint genes.
We successfully constructed an independent prognostic index, which not only has a stronger predictive ability than the tumor pathological stage, but also can reflect the immune infiltration of breast cancer patients.
We successfully constructed an independent prognostic index, which not only has a stronger predictive ability than the tumor pathological stage, but also can reflect the immune infiltration of breast cancer patients.Accumulating evidence suggest that apoptosis, autophagy and dysregulation of signaling pathways are common mechanisms involved in Parkinson's disease (PD) pathogenesis, and thus development of therapeutic agents targeting these mechanisms may be useful for the treatment of this disease. Although rutin (a bioflavonoid) is reported to have pharmacological benefits such as antioxidant, anti-inflammatory and antitumor activities, there are very few reports on the activity of this compound in 1-methyl-4-phenylpyridinium (MPP+)-induced PD models. Accordingly, we investigated the effects of rutin on apoptosis, autophagy and cell signaling markers (AKT/AMPK) in SH-SY5Y cells exposed to MPP+. Results show reduced changes in nuclear morphology and mitigation of caspase 3/7 and 9 activities in rutin pre-treated cells exposed to MPP+. Likewise, rutin regulated cell signaling pathways (AKT/AMPK) and significantly decreased protein expression levels of cleaved PARP, cytochrome c, LC3-II and p62. Also, rutin significantly increased protein expression levels of full-length caspase 3 in SH-SY5Y cells treated with MPP+. Transmission electron microscope (TEM) images demonstrated a reduction in autophagosomes in rutin-pretreated SH-SY5Y cells exposed to MPP+. These results provide experimental support for rutin's neuroprotective activity against MPP+-induced toxicity in SH-SY5Y cells, which is as a promising therapeutic agent for clinical trials in humans.Ultrasound, in its new point-of-care conception, has been called the stethoscope of the future. Goal-directed bedside ultrasound examination, performed by a healthcare provider to answer a specific diagnostic question or guide an invasive procedure, is currently revolutionizing medical practice. It is used by various specialties in multiple clinical contexts for procedural, diagnostic, and screening applications. Point-of-care ultrasound is also a strategic technique in clinical radiology; it brings the radiologist closer to the patient (in interaction and understanding) like interventional and angiography procedures and, as an integrative imaging modality, is a vital radiological tool for decision-making in many situations. In this commentary, we present our observations on the use of ultrasound, in a sincere appeal to refrain from omitting ultrasound as a diagnostic technique in this era of deep professional change, in which radiologists must return to being a true clinical semiologist.Obesity increases the risk for breast cancer and is associated with poor outcomes for cancer patients. A variety of rodent models have been used to investigate these relationships; however, key differences in experimental approaches, as well as unique aspects of rodent physiology lead to variability in how these valuable models are implemented. We combine expertise in the development and implementation of preclinical models of obesity and breast cancer to disseminate effective practices for studies that integrate these fields. In this review, we share, based on our experience, key considerations for model selection, highlighting important technical nuances and tips for use of preclinical models in studies that integrate obesity with breast cancer risk and progression. We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women's health.
Few studies have evaluated whether the pharmacokinetics of N-acetyl-cysteine (NAC) are different in Chinese and Caucasian individuals.
This single- and multiple-dose, single-centre, open-label, phase I clinical study was conducted in healthy adult volunteers. All participants received oral NAC 600-mg uncoated tablets, which were administered first as a single dose and, following a 48-h wash-out period, twice daily for 3days. Blood and urine were collected after single- and multiple-dose NAC administration. Adverse event (AE) data were collected throughout the study.
Fifteen Chinese and 15 Caucasian (mostly Italian) individuals (males 66.7%, mean age 36.8years) participated in the study. Pharmacokinetic characteristics of NAC were similar in the two cohorts. Following both single- and multiple-dose administration, plasma concentration of NAC increased rapidly, reaching a peak at approximately 1.0h. Maximum plasma concentration and extent of exposure were higher after multiple doses than after a single dose.