Association of ADP­ribosylation factor family genes with prognosis and immune infiltration of breast cancer.

Breast cancer (BC) is the most common type of cancer found in women. ADP-ribosylation factors (ARFs) are a group of small proteins that bind to GTP and are involved in controlling different cellular functions. The function and evolution of multiple ARFs in BC have remained to be fully elucidated, despite existing studies on this protein family in Homo sapiens and other species. In the present study, a systematic analysis of ARF expression levels in BC tissues compared to normal breast tissues was performed using data from The Cancer Genome Atlas database. The analysis revealed significantly higher expression of ARFs in BC tissues. In addition, the prognostic significance of ARF1 and ARF3-6 expression levels was assessed in patients with BC. Of note, elevated ARF1 expression was associated with reduced rates of distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) in affected individuals. Similarly, patients with high expression levels of ARF3 had lower post-progression survival (PPS) rates. In addition, patients with higher ARF4 expression had worse PPS and patients with high ARF5 expression exhibited lower DMFS. Patients with high ARF6 expression had worse DMFS, OS, RFS and predictive power score values. Furthermore, the expression of ARF was found to be strongly linked to the infiltration of various immune cell types, namely dendritic cells, macrophages, neutrophils, CD8+ T cells and B cells. These significant associations offer a solid foundation for the potential utilization of new therapeutic targets and predictive markers for the treatment of BC.

Bioinformatic analysis reveals an association between Metadherin with breast cancer prognosis and tumor immune infiltration.

Breast cancer metastasis and invasion are both promoted by the oncoprotein Metadherin (MTDH). However, the the role of Metadherin in breast cancer progression and its role in the immune microenvironment. Are not clear. A bioinformatic analysis was performed to demonstrate the prognostic value of Metadherin in BC. In the present study, we found that Metadherin is overexpressed in BC and is significantly correlated with individual cancer stage, age, subclasses, menopause and nodal metastasis status. Metadherin overexpression was associated with a significant decrease in OS and DSS. Cox multivariate analysis indicated that Metadherin was an independent negative prognostic indicator for OS and DSS. Moreover, Metadherin hypomethylation status was associated with poor prognosis. A negative correlation was also noted between Metadherin overexpression and the number of plasmacytoid dendritic cells, cluster of differentiation 8+ T cells, and natural killer cells. Association patterns varied with different subtypes. Various associations between Metadherin levels and immune cell surface markers were revealed. A total of 40 groups of BC and adjacent normal breast tissue samples were collected. Metadherin mRNA was detected by PCR, and its expression levels in BC tissues were significantly increased compared with those noted in normal tissues. The expression levels of Metadherin were also measured in normal and BC cell lines, respectively, and similar conclusions were obtained. The Metadherin mRNA levels were knocked down in SK-BR3 and MDA-MB-231 cell lines and the cell proliferative and migratory activities were determined using Cell Counting Kit-8 and scratch assays, respectively. The results indicated that the cell proliferative and migratory abilities were reduced following knockdown of Metadherin expression. Therefore, Metadherin may be considered as a novel prognostic biomarker in BC.

Comprehensive analysis of ACKR family members in breast cancer using prognostic values.

Breast cancer (BC) is by far the most prevalent malignancy found in the female population. Atypical chemokine receptors (ACKRs) are a subclass of G-protein-coupled receptors, which are characterized by disrupted ligand binding and a breakdown of signaling following ligand binding. The evolution and function of multiple ACKRs in BC have yet to be fully elucidated, although certain findings on this family have been reported in several studies in Homo sapiens and other species. The present study identified that the expression level of ACKRs was significantly lower in breast carcinoma (BRCA) tissues compared with normal breast tissues through searches of the Tumor Immune Estimation Resource, UALCAN and Gene Expression Profiling Interactive Analysis databases. Additionally, when comparing BRCA tissues with normal breast tissues, it was found that there was obvious hypomethylation in the promoters of ACKR1, ACKR3 and ACKR5, as well as a marked hypermethylation in the promoters of ACKR2 and ACKR6. In determining the prognosis of patients with BRCA, the expression levels of ACKR1, ACKR2, ACKR3, ACKR4 and ACKR6 were all found to be important factors. The values for distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) were all found to be lower in patients with BRCA who had a low expression level of ACKR1. In addition, the RFS rates for patients with BRCA were lower when the expression of ACKR2 was low, and worse values for DMFS, OS and RFS were found to be highly correlated with higher expression levels of ACKR3. Moreover, the DMFS, OS, RFS and predictive power score values were worse in those patients with low ACKR4 expression, and the RFS values for patients with BRCA were also found to be lower when the expression level of ACKR6 was low. Additionally, dendritic cells, macrophages, neutrophils, T cells with CD4+ status, T cells with CD8+ status and B cells were all substantially linked with ACKR expression, as well as immune cell infiltration. Taken together, the findings of the present study may offer a theoretical foundation for the creation of novel targets and prognostic indicators for BRCA therapy.

​Efficacy and safety of pyrotinib in combination with albumin­bound paclitaxel for the treatment of HER2­positive advanced breast cancer: A real­world study.

The present study aimed to determine the efficacy and safety of pyrotinib in combination with albumin-bound paclitaxel in patients with HER2-positive advanced breast cancer (ABC). A total of 48 patients diagnosed with HER2-positive ABC were included in the present study, and these patients were prescribed a combination of pyrotinib and albumin-bound paclitaxel in routine clinical practice. During a 21-day cycle, the standard dosage of pyrotinib was 400 mg single dose/day, which was administered orally, and 130 mg/m2/day albumin-bound paclitaxel on days 1, 8 and 15, which was administered by intravenous drip. The primary efficacy endpoint was progression-free survival (PFS) and the secondary efficacy endpoint was overall response rate (ORR), which was defined as the percentage of patients with complete remission or partial remission. Safety indicators were also observed in the present study. The results of the present study demonstrated that the median PFS (mPFS) was 8.1 months for all patients, ranging from 3.3-10.6 months. Patients receiving pyrotinib as second-line therapy exhibited a longer mPFS of 8.5 months compared with those receiving it as third- or higher-line therapy (mPFS, 5.9 months). In 17 patients with brain metastases, mPFS was 7.3 months, ranging from 4.8-10.1 months. The results of the present study also demonstrated that the ORR for the 48 patients was 33.3%. Notably, diarrhea was the most common grade 3-4 adverse event, occurring in 22.9% of patients, followed by neutropenia (6.3%), leukopenia (4.2%) and anemia (4.2%). Collectively, the results of the present study indicated that pyrotinib-based treatment is effective for patients with HER2+ ABC, including those who have previously been treated with trastuzumab. Thus, the combination of pyrotinib with albumin-bound paclitaxel is recommended due to high levels of efficacy, convenience and tolerability.

Obesity and its impact on female reproductive health: unraveling the connections.

In the modern era, the escalating global prevalence of obesity has profound implications on female reproductive health. Obesity, transcending mere lifestyle choices, has evolved into a complex disorder affecting physiological and metabolic functions. Concurrently, female infertility is rising as a significant global health issue. Obesity, with its extensive systemic effects, is pinpointed as a major disruptor. The convergence of these health challenges reveals a multifaceted scenario: on one hand, obesity directly impacts female reproductive health, particularly in the context of conditions like polycystic ovary syndrome (PCOS) and menstrual disturbances; on the other, the psychosocial consequences of infertility might intensify weight-gain patterns, forming a challenging cycle. Additionally, the economic implications of treating obesity-related infertility are considerable. This review delves into the myriad ways obesity affects female reproductive health, drawing insights from epidemiological, clinical, and molecular studies. It explores the epidemiological relationship between obesity and PCOS, the influence of obesity on menstrual disturbances, and the broader impact of obesity on female infertility. Weight loss, through pharmacological interventions, surgical methods, or lifestyle adjustments, emerges as a promising strategy. Lastly, the efficacy of assisted reproductive technologies, such as IVF, is influenced by obesity, underscoring the importance of an optimal body mass index. The review also highlights the molecular and physiological mechanisms underlying the impact of obesity on female reproductive health, including the disruption of the hypothalamic-pituitary-ovary axis, altered adipokine secretion, and the role of chronic inflammation and oxidative stress.

Nanostructured Metals with an Excellent Synergy of Strength and Ductility: A Review.

Nanocrystalline metals developed based on fine grain strengthening always have an excellent strength, but are accompanied by a drop in ductility. In the past 20 years, substantial efforts have been dedicated to design new microstructures and develop the corresponding processing technologies in order to solve this problem. In this article, the novel nanostructures designed for simultaneously achieving high strength and high ductility developed in recent years, including bimodal grain size distribution nanostructure, nanotwinned structure, hierarchical nanotwinned structure, gradient nanostructure, and supra-nano-dual-phase nanostructure, are reviewed. Based on a comprehensive understanding of the simultaneously strengthening and toughening mechanisms, the microstructures and corresponding processing techniques are mainly discussed, and the related prospects that may be emphasized in the future are proposed.

Monoubiquitination of p120-catenin is essential for TGFß-induced epithelial-mesenchymal transition and tumor metastasis.

Disassembly of intercellular junctions is a hallmark of epithelial-mesenchymal transition (EMT). However, how the junctions disassemble remains largely unknown. Here, we report that E3 ubiquitin ligase Smurf1 targets p120-catenin, a core component of adherens junction (AJ) complex, for monoubiquitination during transforming growth factor ß (TGFß)-induced EMT, thereby leading to AJ dissociation. Upon TGFß treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. Inhibition of T900 phosphorylation or ubiquitination of p120-catenin abrogates TGFß-induced AJ dissociation and consequent tight junction (TJ) dissociation and cytoskeleton rearrangement, hence markedly blocking lung metastasis of murine breast cancer. Moreover, the T900 phosphorylation level of p120-catenin is positively correlated with malignancy of human breast cancer. Hence, our study reveals the underlying mechanism by which TGFß induces dissociation of AJs during EMT and provides a potential strategy to block tumor metastasis.