The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.     

Formation and wear mechanism of nickel titanium intermetallics during heat treatment of nickel coating on Ti-6Al-4V substrate

In the present work, inter-diffusion of nickel and titanium and formation of Ni-Ti intermetallic compounds on Ti-6Al-4V substrate have been studied. Initially, nickel was electrodeposited on the alloy using a modified Watts bath solution at a current density of 2 A dm^?2 for 1?h. The coated specimens were then heat treated for different durations at 750, 800 and 850 °C under argon atmosphere. The effects of temperature and time on the characteristics, hardness and wear resistance of intermetallic phases were investigated. The results showed that a multilayer structure was formed after heat treatment, an outer layer of residual nickel, an area of intermetallic layers with different compositions followed by a solid solution of Ni-Ti. It was also observed that an increase in time or temperature at first led to the formation of thicker intermetallic layers; however, after passing a critical point, the intermetallic layers seem to dissolve into the substrate. Furthermore, the wear rates of the diffusion treated samples were four times lower compared to Ti-6Al-4V alloy when sliding against AISI 52100 hardened steel.     

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.     

Producing fully-lamellar microstructure for wrought beta-gamma TiAl alloys without single α-phase field

Fine-grained fully-lamellar (FL) microstructure is desired for TiAl components to serve as compressor/turbine blades and turbocharger turbine wheels. This study deals with the process and phase transformation to produce FL microstructure for Mo stabilized beta-gamma TiAl alloys without single α-phase field. Unlike the α + γ two-phased TiAl or beta-gamma TiAl with single α-phase field, the wrought multi-phase TiAl–4/6Nb–2Mo–B/Y alloys exhibit special annealing process to obtain FL microstructure. Short-term annealing at temperatures slightly above β-transus is recommended to produce the desired FL microstructure. The related mechanism is to guarantee the sufficient diffusion homogenization of β stabilizers during single β-phase annealing, and further avoid α decomposition by α → γ + β when cooling through α + β + γ phase field. The colony boundary β phase contributes to fine-grained nearly FL microstructure, by retarding the coarsening of the α phase grains.     

胸腺五肽辅助治疗肺癌对免疫功能影响及其疗效的系统评价

为了系统地评价胸腺五肽作为辅助药物治疗各种肺癌的疗效及其对机体免疫功能的影响，利用电子检索收集有关胸腺五肽联合放疗或化疗方案治疗肺癌的临床随机对照试验文献，对符合纳入标准的文献，采用RevMan5.3 软件进行系统评价。最终共纳入文献 9 篇，总样本量 784 例。Meta 分析结果表明，胸腺五肽作为辅助药物治疗各种肺癌提高总有效率的差异无统计学意义[OR ＝ 1.44, 95%CI(0.99, 2.10), P ＝0.06 ＞ 0.05]。在对免疫功能的影响方面，胸腺五肽的使用显著增高外周血中的 CD3+ 细胞水平[OR ＝ 5.88, 95% CI(2.34, 9.42), P ＝0.001]，CD4+ 细胞水平也显著上升[OR ＝8.32, 95%CI(5.22, 11.42), P ＜ 0.00001] , CD4＋ /CD8＋比值也有明显的提高[OR ＝ 0.38, 95% CI(0.18, 0.59), P＝0.0002]，但 CD8+ 细胞水平的差异无统计学意义[OR ＝－3.12, 95% CI ( －9.02, 2.79), P ＞0.05]。总的来说，本研究在一定程度上反映了在辅助治疗肺癌方面，胸腺五肽能显著提高外周血中的 CD3+ 细胞水平、CD4+ 细胞水平、CD4+/CD8+ 比值。而对于治疗的有效率、CD8+ 细胞水平，差异无统计学意义。     

Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

高强WSTi544221合金组织与性能研究

研究了轧制变形量对WSTi544221合金棒材显微组织和力学性能的影响,并对Φ10 mm规格的棒材进行不同制度的固溶+时效处理,对比了不同热处理状态下棒材的组织和力学性能。结果表明,随着轧制变形量的增大,WSTi544221合金棒材的晶粒细化程度增大,强度逐渐提高,但塑性变化不大。经870℃×1 h/WC+520℃×6 h/AC固溶+时效处理后,强度与塑性可以获得良好匹配,当抗拉强度达到1 610 MPa、屈服强度达到1 531 MPa时,延伸率和断面收缩率可分别保持在12%和43%。     

Role of Extracellular Vesicles in Epithelial Ovarian Cancer: A Systematic Review

Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.