Hawthorn Berries Stop Roleaux Formations – University of Ontario Institute of Technology, Faculty of Science, 2000 Simcoe Street North, Oshawa, Ontario L1H 7K4, Canada Email: [email protected]
B Center for Research in Physics and Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, USA
Hawthorn Berries Stop Roleaux Formations
Red blood cells suspended in quiescent plasma tend to aggregate into multicellular clusters, including linearly stacked columnar spindles that can reversibly form more complex clusters or branched networks. Although these aggregates play an important role in establishing hemorheological and pathological properties, the biophysics behind their self-assembly into dynamic mesoscopic structures remains poorly understood. We use coarse-grained molecular modeling to simulate low-hematocrit erythrocytes subjected to short-term implicit depletion forces and demonstrate not only that depletion interactions are sufficient to explain the sudden dispersion–aggregate transition, but also that the volume fraction of depleted macromolecules controls morphology of small aggregates. We observe a sudden transition from dispersion to linear columnar rolls, followed by the slow appearance of disordered amorphous clusters of many short rolls at higher volume fractions. This work demonstrates how discocyte topology and short-lived nonspecific physical interactions are sufficient to self-assemble erythrocytes into distinct aggregate structures with markedly different morphologies and biomedical implications.
Recent Advances On The Role Of Cytokines In Atherosclerosis
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Endothelial Cell Dysfunction And The Pathobiology Of Atherosclerosis
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Andrea Angius 1, *, † , Paolo Cossu-Rocca 2, 3, † , Caterina Arru 4 , Maria Rosaria Muroni 2 , Vincenzo Rallo 1, 4 , Kyriako Carru 4 , Paolo Uva 5 , Giovanna Pira 4 , Sandra Orru 6 and Maria Rosaria De Miglio 1, *
Stockley`s Herbal Medicine`s Interactions
Received: September 28, 2020 / Revised: November 5, 2020 / Accepted: November 5, 2020 / Published: November 7, 2020
Triple-negative breast cancer (TNBC) is an aggressive tumor with high histologic differentiation, high recurrence rates, and frequent metastases, accounting for approximately 25% of breast cancer-related deaths. This review analyzes the emerging roles and molecular mechanisms by which miRNAs influence the pathogenesis and prognosis of basal phenotype TNBC and their potential clinical utility. Progress made in the molecular taxonomy of TNBC has had minimal clinical impact, while miRNAs may serve as prognostic/predictive biomarkers for TNBC subtypes. As there are currently no other therapeutic options for the treatment of TNBC other than chemotherapy, various studies have been reviewed to conclude that ncRNAs may be candidates for drug development and drug resistance. Targeted approaches to epigenetic mechanisms and clarification of the molecular mechanisms of specific miRNAs in TNBC subtypes are fully warranted. This review may provide a collection of biomarkers potentially useful in the clinical setting and suggests that combining miRNA-based therapeutic strategies with conventional treatments can synergize antitumor effects, improving patient outcome.
The development of new studies, classification and therapeutic options are urgently needed due to the fact that TNBC is a heterogeneous malignancy. Expression of high-molecular-weight cytokeratins identifies a biologically and clinically distinct subset of TNBCs with a basal phenotype, accounting for about 75% of TNBCs, while the remaining 25% comprise all other intrinsic subtypes. The triple-negative phenotype in basal-like breast cancer (BLBC) renders it insensitive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapy; for this reason, chemotherapy alone may be considered an affordable systemic treatment approach, even if it has a poor prognosis. Therefore, the treatment of these subgroups of patients is a serious challenge for oncologists due to the heterogeneity of the disease and the lack of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been associated with massive deregulation of cellular processes underlying human malignancies. Thus, epigenetics is a promising area of cancer research. Increasing evidence suggests that specific miRNA clusters/signatures may be clinically useful for TNBCs with a basal-like phenotype. Epigenetic mechanisms of tumorigenesis ensure progress in the treatment, diagnosis and prevention of cancer. This review aims to summarize epigenetic findings related to the miRNAome in TNBC with a basal phenotype.
Triple negative breast cancer; basal-like breast cancer; miRNA; epigenetic modulation; molecular classification of TNBC; internal molecular subtypes; breast cancer triple negative breast cancer; basal-like breast cancer; miRNA; epigenetic modulation; molecular classification of TNBC; internal molecular subtypes; breast cancer
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Ten to twenty percent of invasive breast cancer (BC) is the type of breast cancer that predominates in young women under the age of 50; among African, American, and Latin American women; and in women with higher premenopausal BMI, earlier age of menarche, and higher parity. Specifically, the triple negative phenotype (TNP) is defined by ER/PR/HER2-negative immunostaining, typically with higher Ki-67 antigen expression, higher mitotic index, and BRCA1 gene mutations (approximately 75%). TNBC exhibits an aggressive behavior with high histologic grade, high recurrence rate approximately 2 or 3 years after treatment compared to other subtypes of BC, and frequent distant metastases; thus, it accounts for about 25% of deaths related to breast cancer [1, 2, 3, 4, 5]. TNBC exhibits various molecular and clinicopathological features  and is histologically classified as high-grade invasive breast cancer without a specific type. “Special types” are still subtypes of TNBC, but differ in biological behavior and clinical course .
BLBC is characterized by gene expression typically found in the basal or myoepithelial cells of the breast, as evidenced by high molecular weight cytokeratin, predominantly CK5/6, and EGFR expression, with about 75% termed TNP, as well as ER/PR/HER2 . negative immunohistochemical (IGH). The remaining 25% includes all other “characteristic” molecular subtypes of breast cancer. BLBC shows a short survival after progression to metastatic disease, with a higher prevalence of cerebral and pulmonary metastases relative to the luminal subtypes [8, 9]. Notably, 80% of TNBCs show basal features: TNBC and BLBC phenotypes are virtually synonymous [ 10 ], although immunohistochemical expression, transcriptomic and clinical data suggest that they are not equivalent [ 11 , 12 ].
Lack of hormone and HER2 receptors renders TNBC insensitive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapy, so surgery, radiation therapy, and mostly nonspecific chemotherapy (eg, anthracycline and taxane regimens) remain the mainstays. basis for the treatment of these patients, often with serious side effects affecting the quality of life [5, 13]. The treatment of TNBC is a major challenge for oncologists both because of the heterogeneity of the disease and the lack of unambiguous molecular targets.
MicroRNAs (miRNAs) are a family of endogenous short single-stranded non-coding RNAs that regulate gene expression by interacting with complementary mRNA target sequences, causing either mRNA degradation or translational repression . MiRNAs regulate numerous processes [14, 15], and their dysregulation is closely related to cancer, which involves alteration of biological functions . Variations in miRNA levels have been analyzed comparing normal and neoplastic tissues [17, 18] in several subtypes of breast cancer  with different responses to endocrine therapy . Several miRNAs have been associated with the pathogenesis of TNBC [ 21 , 22 ] and could be potential predictors of anticancer drug efficacy and prognosis [ 23 , 24 , 25 ]. The recognition of gene expression regulator-classified miRNAs as epigenetic elements involved in cancer development means that they can potentially be used as therapeutic targets and diagnostic/prognostic biomarkers to achieve high-accuracy tumor classification .
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This review summarizes the emerging roles of miRNAs in the pathogenesis and prognosis of TNBC with a basal-like phenotype (BLP) and discusses their potential clinical utility.
The morphologic and molecular heterogeneity of TNBC, the poor prognosis, and the lack of specific targeted therapy require a detailed understanding of the biology and classification of this type of cancer. The foundation was laid by the gene expression profile based on high-performance technologies