Significance and therapeutic implications of endothelial progenitorcells in angiogenic-mediated tumour metastasis

Cancer conveys profound social and economic consequences throughout the world. Metastasis is respon-sible for approximately 90% of cancer-associated mortality and, when it occurs, cancer becomes almostincurable. During metastatic dissemination, cancer cells pass through a series of complex steps includingthe establishment of tumour-associated angiogenesis. The human endothelial progenitor cells (hEPCs)are a cell population derived from the bone marrow which are required for endothelial tubulogenesisand neovascularization. They also express abundant inflammatory cytokines and paracrine angiogenicfactors. Clinically hEPCs are highly correlated with relapse, disease progression, metastasis and treatmentresponse in malignancies such as breast cancer, ovarian cancer and non-small-cell lung carcinoma. It hasbecome evident that the hEPCs are involved in the angiogenesis-required progression and metastasis oftumours. However, it is not clear in what way the signalling pathways, controlling the normal cellularfunction of human BM-derived EPCs, are hijacked by aggressive tumour cells to facilitate tumour metas-tasis. In addition, the actual roles of hEPCs in tumour angiogenesis-mediated metastasis are not wellcharacterised. In this paper we reviewed the clinical relevance of the hEPCs with cancer diagnosis, pro-gression and prognosis. We further summarised the effects of tumour microenvironment on the hEPCsand underlying mechanisms. We also hypothesized the roles of altered hEPCs in tumour angiogenesisand metastasis. We hope this review may enhance our understanding of the interaction between hEPCsand tumour cells thus aiding the development of cellular-targeted anti-tumour therapies

MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells

background: MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate the response sensitivities of metastatic breast cancer cells to miR-7 and the roles of miR-7 in the interaction of endothelial cells and metastatic cancer cells. methods: Expression profile of miRNAs in a breast cancer specimen cohort and breast cancer cells were determined using real-time quantitative miRNA assays. Effect of the altering expression of miR-7 on migration, invasion, proliferation, interaction and underlying molecular mechanism of breast cancer cells and endothelial cells was investigated after treatment with the synthesised mimic of miR-7. Luciferase activity analysis was performed to validate Wave-3 as a novel target of miR-7. results: miR-7 expression was negatively correlated with the stage, grade and survival of the breast cancer patients. There was also differential expression of miRNAs including miR-7 in the breast cancer cells. The synthesised mimic of miR-7 inhibits the motility and wound healing potential of breast cancer cells. The highly metastatic MDA-MB-231 cells are more sensitive to the miR-7 treatment than the poorly invasive MCF-7 cells. Treatment with miR-7 downregulated the expression of EGFR, IGF1R and Wave3 in MDA-MB-231 cells but not in MCF-7 cells. In addition, we further demonstrated that miR-7 inhibited the proliferation, migration and invasion of endothelial cells. And more importantly, miR-7 suppressed the homing and migration of endothelial cells to more aggressive tumour cell conditions. conclusions: Given the dual inhibitory effect of miR-7 on metastatic breast cancer cells alone and the interaction of endothelial cells with the tumour-conditioned microenvironment, we suggest miR-7 may be a new therapeutic candidate for its capacity not only to prevent breast cancer cell spreading but also to inhibit tumour-associated angiogenesis in the metastatic breast cancer

BLIS-Net: Classifying and Analyzing Signals on Graphs

Graph neural networks (GNNs) have emerged as a powerful tool for tasks such as node classification and graph classification. However, much less work has been done on signal classification, where the data consists of many functions (referred to as signals) defined on the vertices of a single graph. These tasks require networks designed differently from those designed for traditional GNN tasks. Indeed, traditional GNNs rely on localized low-pass filters, and signals of interest may have intricate multi-frequency behavior and exhibit long range interactions. This motivates us to introduce the BLIS-Net (Bi-Lipschitz Scattering Net), a novel GNN that builds on the previously introduced geometric scattering transform. Our network is able to capture both local and global signal structure and is able to capture both low-frequency and high-frequency information. We make several crucial changes to the original geometric scattering architecture which we prove increase the ability of our network to capture information about the input signal and show that BLIS-Net achieves superior performance on both synthetic and real-world data sets based on traffic flow and fMRI data

Plasticity plays a dominant role in regulating the phenological variations of sugar maple populations in Canada

Global changes affect the growing conditions of terrestrial ecosystems, causing a mismatch between plant phenology and local climates in Northern regions. Due to their long lifespan and irregular regeneration periods, trees cannot respond quickly enough to climate variability through long-term genetic adaptation. In this study, we explored the phenological plasticity and genetic variation among populations of bud burst in sugar maple (Acer saccharum Marsh.) seedlings from 30 Canadian provenances with contrasting climates planted in two common gardens near and at the northern limit of the species’ range. We tested the hypothesis that phenotypic plasticity and genetic variation among populations affect bud phenology. We expect that phenotypic plasticity is more important in regulating bud phenology due to the high variability in short-term weather events characterizing this part of North America. Bud development and leafing occurred in April–May, with complete bud burst lasting between 21 and 29  days. On average, bud swelling differed by 12  days between common gardens. Both factors site (common gardens) and provenance significantly affected bud burst, demonstrating phenological plasticity and genetic variation of sugar maple, respectively. A significant interaction between site and provenance was also found. Overall, the site (11.8–90.3%) contributed more than provenance (0–3.1%) to the variance in timings of bud burst, indicating a dominant role of plasticity in regulating spring phenology. Our study demonstrated the concurring effects of genetic variation and phenological plasticity of sugar maple and revealed the dominant role of the latter factor. The high plasticity observed in sugar maple has a crucial role in the phenological adaptation of maple and the survival of its local populations in a context of changing climate

Bladder-sparing Treatment in Patients with Bacillus Calmette-Guerin-unresponsive Non-muscle-invasive Bladder Cancer: An Analysis of Long-term Survival Outcomes

BACKGROUND: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1-2 yr. OBJECTIVE: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST. DESIGN SETTING AND PARTICIPANTS: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated. INTERVENTION: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). RESULTS AND LIMITATIONS: In total, 114 patients with a median follow-up of 71.2 mo (interquartile range: 32.6-132.2) were analyzed. There were no significant differences in OS (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 0.68-2.89, CONCLUSIONS: An analysis of long-term survival of BCG-unresponsive NMIBC patients receiving BST suggests that it may be safe in patients without LVI and/or variant histology and nonsmokers. Survival outcomes for patients treated with BST may not be inferior to those receiving early RC. PATIENT SUMMARY: Bladder-sparing treatment can be offered to appropriately selected patients who have bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer. Long-term outcomes may not be inferior to those for patients who opt for early radical cystectomy

Synchronization in a Random Length Ring Network for SDN-Controlled Optical TDM Switching

In this paper we focus on optical time division multiplexed (TDM) switching and its main distinguishing characteristics compared with other optical subwavelength switching technologies.We review and discuss in detail the synchronization requirements that allow for proper switching operation. In addition, we propose a novel synchronization algorithm that enables automatic synchronization of software defined networking controlled all-optical TDM switching nodes connected in a ring network. Besides providing synchronization, the algorithmalso can facilitate dynamic slot size change and failure detection. We experimentally validate the algorithm behavior and achieve correct operation for three different ring lengths. Moreover, we experimentally demonstrate data plane connectivity in a ring network composed of three nodes and show successful wavelength division multiplexing space division multiplexing transmission and switching of data bursts when using the proposed algorithm to provide synchronization.</p

Calibrating phenoCam data with phenological observations of a black spruce stand

Bud and leaf development are important phenological events and help in defining the growing period of trees. Canopy greenness derived from PhenoCam has been used to investigate leaf phenology. Questions remain on how much the continuous records of canopy greenness represent bud developmental phases, and how growing period boundaries are related to canopy greenness and bud phenology. In this study, we compared bud phenology of black spruce [Picea mariana (Mill.) B.S.P] during 2015, 2017 and 2018 with the canopy greenness, represented by Green Chromatic Coordinate (GCC), derived from PhenoCam images of a boreal stand in Quebec, Canada. Logit models were applied to estimate the probability of observing sequential phenological phases of bud burst and bud set along with GCC. GCC showed a bell-shaped pattern, with a slow increase in spring, a peak in summer and a gradual decrease in autumn. The start and end of budburst, and bud set, occurred when GCC reached 72% and 92% (spring), and 94% (autumn) of its maximum amplitude, respectively. These GCC values are reliable thresholds indicating the growing period boundaries. Our study builds a bridge between phenological observations and automatic near-surface remote sensing, providing a statistically sound protocol for calibrating PhenoCam with field observations

Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development

Non-proteolytic ubiquitin signaling mediated by Lys63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNF signaling and lipid metabolism in the adipose tissue through modulation of Lys63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells

The Relationships Between Biological Activities and Structure of Flavan-3-Ols

Flavan-3-ols are involved in multiple metabolic pathways that induce inhibition of cell proliferation. We studied the structure-activity relationship of gallic acid (GA) and four flavan-3-ols: epigallocatechin gallate (EGCG), epigallocatechin (EGC), catechin (C), and epicatechin (EC). We measured the cell viability by the MTT assay and we determined the concentration of testing compound required to reduce cell viability by 50% (IC50). All tested compounds showed a dose-dependent and time-dependent inhibitory antiproliferative effect on Hs578T cells; IC50 values varying from the 15.81 to 326.8 μM. Intracellular ROS (reactive oxygen species) were quantified using a fluorescent probe 2′,7′-dichlorofluorescin diacetate (DCFH-DA). Only the treatment with 10 μM EGC and EGCG was able to induce a significant decrease of ROS concentration and increased levels of ROS were registered for 100 μM EGCG, EGC and GA. Flavans-3-ols and GA induced apoptosis in a dose- and time-dependent manner, which indicated that the induction of apoptosis mediated their cytotoxic activity at least partially. The galloylated catechins have shown a stronger antiproliferative activity and apoptotic effect than the one produced by non galloylated catechins. The galloylated flavan-3-ols are potential therapeutic agents for patients with triple negative breast cancer via induction of apoptosis