OBJECTIVES: The objective of this review is to assess the effectiveness of TCM as a treatment option for musculoskeletal symptoms in patients with breast cancer who were treated with aromatase inhibitors (AIs).
METHODS: A comprehensive literature search was conducted using PubMed, the Cochrane Library, SAGE journals, Scopus, EMBASE, Web of Science, Medline, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), Wanfang, and Chinese Medical Journal Database (CMJ) from May 2020 to November 2020. The literature review included randomized controlled trials (RCTs) of TCM for AI-related musculoskeletal symptoms.
RESULTS: Four RCTs incorporating TCM were assessed by meta-analysis and reported favorable effects in reducing worst pain score (n = 284, mean difference [MD]: 2.31; 95% CI, 1.74 to 2.88; P
AIM: This study aimed to investigate the role of epigenetics via transcription repressor, repressor element silencing transcription factor (REST) and histone deacetylases (HDACs) in enhancing Nav1.5 and nNav1.5 expression in human breast cancer by assessing the effect of HDAC inhibitor, trichostatin A (TSA).
METHODS: The less aggressive human breast cancer cell line, MCF-7 cells which lack Nav1.5 and nNav1.5 expression was treated with TSA at a concentration range 10-10,000 ng/ml for 24 h whilst the aggressive MDA-MB-231 cells was used as control. The effect of TSA on Nav1.5, nNav1.5, REST, HDAC1, HDAC2, HDAC3, MMP2 and N-cadherin gene expression level was analysed by real-time PCR. Cell growth (MTT assay) and metastatic behaviors (lateral motility and migration assays) were also measured.
RESULTS: mRNA expression level of Nav1.5 and nNav1.5 were initially very low in MCF-7 compared to MDA-MB-231 cells. Inversely, mRNA expression level of REST, HDAC1, HDAC2, and HDAC3 were all greater in MCF-7 compared to MDA-MB-231 cells. Treatment with TSA significantly increased the mRNA expression level of Nav1.5 and nNav1.5 in MCF-7 cells. On the contrary, TSA significantly reduced the mRNA expression level of REST and HDAC2 in this cell line. Remarkably, despite cell growth inhibition by TSA, motility and migration of MCF-7 cells were enhanced after TSA treatment, confirmed with the up-regulation of metastatic markers, MMP2 and N-cadherin.
CONCLUSIONS: This study identified epigenetics as another factor that regulate the expression level of Nav1.5 and nNav1.5 in breast cancer where REST and HDAC2 play important role as epigenetic regulators that when lacking enhances the expression of Nav1.5 and nNav1.5 thus promotes motility and migration of breast cancer. Elucidation of the regulatory mechanisms for gain of Nav1.5 and nNav1.5 expression may be helpful for seeking effective strategies for the management of metastatic diseases.
MATERIALS AND METHODS: One hundred twenty mL of full blood was obtained from four healthy human volunteers. The human immune system was simulated using an in vitro model, called MIMIC. Under EBNE treatment, monocyte transendothelial migration through reversed endothelial layers was observed. Using PTE and LTE modules, monocytes were differentiated into dendritic cells with lipopolysaccharide, then co-cultured with T- and B-cells for cytokine and immunoglobulin (Ig) production. The human cytokine array G2000 and quantitative human Ig isotyping array were used to identify the cytokine profile and Ig isotypes, respectively.
RESULTS: IgE, IgA, and IgG3 levels were significantly raised by EBNE. These cytokines, including brain-derived neurotrophic factor, ciliary neurotrophic factor, glial cell line-derivative neurotrophic factor, insulin-like growth factor 1, and insulin-like growth factor binding protein 4, were generated.
CONCLUSION: For the first time, this work uses a MIMIC model to illustrate the impact of EBNE on human immune response. This new understanding of EBN's immunoregulatory effect allows for further exploration of how EBN interacts with the human immune system.