Comprehensive integrated single-cell RNA sequencing analysis of brain metastasis and glioma microenvironment: Contrasting heterogeneity landscapes.

Understanding the specific type of brain malignancy, source of brain metastasis, and underlying transformation mechanisms can help provide better treatment and less harm to patients. The tumor microenvironment plays a fundamental role in cancer progression and affects both primary and metastatic cancers. The use of single-cell RNA sequencing to gain insights into the heterogeneity profiles in the microenvironment of brain malignancies is useful for guiding treatment decisions. To comprehensively investigate the heterogeneity in gliomas and brain metastasis originating from different sources (lung and breast), we integrated data from three groups of single-cell RNA-sequencing datasets obtained from GEO. We gathered and processed single-cell RNA sequencing data from 90,168 cells obtained from 17 patients. We then employed the R package Seurat for dataset integration. Next, we clustered the data within the UMAP space and acquired differentially expressed genes for cell categorization. Our results underscore the significance of macrophages as abundant and pivotal constituents of gliomas. In contrast, lung-to-brain metastases exhibit elevated numbers of AT2, cytotoxic CD4+ T, and exhausted CD8+ T cells. Conversely, breast-to-brain metastases are characterized by an abundance of epithelial and myCAF cells. Our study not only illuminates the variation in the TME between brain metastasis with different origins but also opens the door to utilizing established markers for these cell types to differentiate primary brain metastatic cancers.

Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery.

Conventional chemotherapy, one of the most widely used cancer treatment methods, has serious side effects, and usually results in cancer treatment failure. Drug resistance is one of the primary reasons for this failure. The most significant drawbacks of systemic chemotherapy are rapid clearance from the circulation, the drug's low concentration in the tumor site, and considerable adverse effects outside the tumor. Several ways have been developed to boost neoplasm treatment efficacy and overcome medication resistance. In recent years, targeted drug delivery has become an essential therapeutic application. As more mechanisms of tumor treatment resistance are discovered, nanoparticles (NPs) are designed to target these pathways. Therefore, understanding the limitations and challenges of this technology is critical for nanocarrier evaluation. Nano-drugs have been increasingly employed in medicine, incorporating therapeutic applications for more precise and effective tumor diagnosis, therapy, and targeting. Many benefits of NP-based drug delivery systems in cancer treatment have been proven, including good pharmacokinetics, tumor cell-specific targeting, decreased side effects, and lessened drug resistance. As more mechanisms of tumor treatment resistance are discovered, NPs are designed to target these pathways. At the moment, this innovative technology has the potential to bring fresh insights into cancer therapy. Therefore, understanding the limitations and challenges of this technology is critical for nanocarrier evaluation.

Narrative identity in borderline personality disorder.

Borderline personality disorder (BPD) is a severe psychiatric condition that is associated with functional impairment and pathological traits. It has been argued that identity impairment is one of the core features of BPD, which can be manifested in different ways, including fragmented autobiographical narratives. Here, we considered both the traditional and modern conceptualizations of BPD to examine the relation between identity impairment, as operationalized through autobiographical memory, and features of BPD. We hypothesized that BPD features would be associated with higher levels of fragmentation in narrative identity, narrative intimacy, and narrative coherence in participants' autobiographical memory. To test this hypothesis, we recruited 298 university students who were administered a series of self-report measures of BPD and were asked to describe an autobiographical memory about a turning point in their lives. Narrative identity, but not narrative intimacy nor coherence, was the dominant predictor of BPD features. We discuss our findings in terms of how individuals with features of BPD struggle with many aspects of a distorted sense of self. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ASGR1 but not FOXM1 expression decreases in the peripheral blood mononuclear cells of diabetic atherosclerotic patients.

BACKGROUND: The ASGR1 was recently shown to play a key role in the development of coronary artery disease (CAD), but its exact mechanism of action in the CAD pathogenesis is not yet known. This study evaluates the possible association between the expression level of ASGR1 and its downstream transcription factor FOXM1 in the inflammatory cells of peripheral blood (PBMC) and the pathogenesis of CAD in the Diabetic condition. METHODS: Blood samples were taken from the candidates who had visited the Tehran Heart Center and had underwent diagnostic tests with respect to diabetes and CAD. The peripheral blood cells were harvested, RNA was extracted, and cDNA was synthesized. The qRT-PCR was performed on 79 cDNA samples taken from 49 CAD+ patients and 30 CAD- patients. RESULTS: In this study, we observed a significant decrease of ASGR1 expression in the PBMC of CAD+ patients compared to the CAD- patients. We did not identify any considerable differences in the expression of FOXM1 in patients' subgroups with respect to the diabetes and CAD. CONCLUSION: The results of our study determine the association of ASGR1 expression and CAD pathogenesis. However, we do not know whether this result is the cause or the effect of CAD.

Effect of exercise and morphine on psychological and physical dependencies, BDNF and TrkB gene expression in rat's hippocampus.

OBJECTIVES: To compare the effect of exercise and morphine on abstinence syndrome and hippocampal gene expression in rat model. METHODS: Thirty adult male rats were exposed to voluntary wheel exercise (low, medium, high) for 28 days. The subjects entered Conditioned Place Preference (CPP) apparatus and experienced morphine (low, medium, high) CPP and followed by naloxone test. Correlation between exercise level, morphine injection, concurrent morphine administration and exercise with morphine CPP, BDNF and TrkB genes was determined. Rats were euthanized, decapitated and the hippocampus was removed. The expression of BDNF and TrkB genes were evaluated by real time PCR. RESULTS: Active rats ran an average of 839.18 m/d. A significant (P<0.001) correlation between exercise level, morphine injection, concurrent morphine administration and exercise with morphine CPP and BDNFand TrKB gene expressions was found. CONCLUSION: Voluntary exercise in different levels potentiates the brain rewarding system, CPP scale, and hippocampal BDNF and TrKB expressions. High range of voluntary exercise demonstrated an increase in the likelihood of developing addictive and drug-seeking behavior.

Voluntary Wheel Running Induces Exercise-Seeking Behavior in Male Rats: A Behavioral Study.

BACKGROUND: Research evidence shows that exercise is associated with positive physical and mental health. Moreover, exercise and wheel running in rats activate overlapping neural systems and reward system. The most commonly used models for the study of rewarding and aversive effects of exercise involve using treadmill and wheel running paradigms in mice or rats. The purpose of our experiment was to study the influence of continuous voluntary exercise on exercise-seeking behavior. METHODS: In this experimental study, we used 24 adult male Sprague-Dawley rats weighing 275-300 g on average. Rats were divided into 3 experimental groups for 4 weeks of voluntary wheel running. Each rat ran in the cage equipped with a wheel during 24 hours. A within-subject repeated measure design was employed to evaluate the trend of running and running rates. RESULTS: We found that time and higher levels of exercise will increase exercise tendency. Our results also show that the interaction of exercise within 4 weeks and different levels of exercise can significantly promote rats' exercise-seeking behavior (F = 5.440; df = 2.08; P < 0.001). CONCLUSION: Our data suggest that voluntary wheel running can increase the likelihood of extreme and obsessive exercising which is a form of non-drug addiction.