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Structural neuroplasticity such as neurite extension and dendritic spine dynamics is enhanced by brain-derived neurotrophic factor (BDNF) and impaired by types of inhibitory molecules that induce growth cone collapse and actin depolymerization, for example, myelin-associated inhibitors, chondroitin sulfate proteoglycans, and negative guidance molecules. These inhibitory molecules can activate RhoA/rho-associated coiled-coil containing protein kinase (ROCK) signaling (known to restrict structural plasticity). Intermittent hypoxia (IH) and high-intensity interval training (HIIT) are known to upregulate BDNF that is associated with improvements in learning and memory and greater functional recovery following neural insults. We investigated whether the RhoA/ROCK signaling pathway is also modulated by IH and HIIT in the hippocampus, cortex, and lumbar spinal cord of male Wistar rats. The gene expression of 25 RhoA/ROCK signaling pathway components was determined following IH, HIIT, or IH combined with HIIT (30 min/day, 5 days/wk, 6 wk). IH included 10 3-min bouts that alternated between hypoxia (15% O2) and normoxia. HIIT included 10 3-min bouts alternating between treadmill speeds of 50 cm·s−1 and 15 cm·s−1. In the hippocampus, IH and HIIT significantly downregulated Acan and NgR2 mRNA that are involved in the inhibition of neuroplasticity. However, IH and IH + HIIT significantly upregulated Lingo-1 and NgR3 in the cortex. This is the first time IH and HIIT have been linked to the modulation of plasticity-inhibiting pathways. These results provide a fundamental step toward elucidating the interplay between the neurotrophic and inhibitory mechanisms involved in experience-driven neural plasticity that will aid in optimizing physiological interventions for the treatment of cognitive decline or neurorehabilitation. NEW & NOTEWORTHY: Intermittent hypoxia (IH) and high-intensity interval training (HIIT) enhance neuroplasticity and upregulate neurotrophic factors in the central nervous system (CNS). We provide evidence that IH and IH + HIIT also have the capacity to regulate genes involved in the RhoA/ROCK signaling pathway that is known to restrict structural plasticity in the CNS. This provides a new mechanistic insight into how these interventions may enhance hippocampal-related plasticity and facilitate learning, memory, and neuroregeneration. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells have been widely implicated in tumour development and metastases. Moving from the use of two-dimensional (2D) models to three-dimensional (3D) to investigate this relationship is critical to facilitate more applicable and relevant research on the tumour microenvironment. We investigated the effects of altering glucose concentration and the source of foetal bovine serum (FBS) on the growth of two breast cancer cell lines (T47D and MDA-MB-231) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to determine successful conditions to enable their co-culture in 3D tumour spheroid models. Subsequently, these 3D multi-cellular tumour spheroids were used to investigate the effect of hBM-MSCs on breast cancer cell invasiveness. Findings presented herein show that serum source had a statistically significant effect on two thirds of the growth parameters measured across all three cell lines, whereas glucose only had a statistically significant effect on 6%. It was determined that the optimum growth media composition for the co-culture of 3D hBM-MSCs and breast cancer cell line spheroids was 1 g/L glucose DMEM supplemented with 10% FBS from source A. Subsequent results demonstrated that co-culture of hBM-MSCs and MDA-MB-231 cells dramatically reduced invasiveness of both cell lines (F(1,4) = 71.465, p = 0.001) when embedded into a matrix comprising of growth-factor reduced base membrane extract (BME) and collagen. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer is the most diagnosed cancer and the leading cause of cancer death in women globally, and mesenchymal stem cells have been widely implicated in tumour progression. This systematic review and meta-analysis seeks to identify and summarise existing literature on the effects of human mesenchymal stem cells (hMSCs) on the migration of breast cancer cells (BCCs) in vitro, to determine the direction of this relationship according to existing research and to identify the directions for future research., Methods: A systematic literature search was conducting using a collection of databases, using the following search terms: in vitro AND mesenchymal stem cells AND breast cancer. Only studies that investigated the effects of human, unmodified MSCs on the migration of human, unmodified BCCs in vitro were included. Standardised mean differences (SMDs) were calculated to determine pooled effect sizes., Results: This meta-analysis demonstrates that hMSCs (different sources combined) increase the migration of both MDA-MB-231 and MCF-7 cell lines in vitro (SMD = 1.84, P  = .03 and SMD = 2.69, P  < .00001, respectively). Importantly, the individual effects of hMSCs from different sources were also analysed and demonstrated that MSCs derived from human adipose tissue increase BCC migration (SMD = 1.34, P  = .0002) and those derived from umbilical cord increased both MDA-MB-231 and MCF-7 migration (SMD = 3.93, P  < .00001 and SMD = 3.01, P  < .00001, respectively)., Conclusions: To our knowledge, this is the first systematic review and meta-analysis investigating and summarising the effects of hMSCs from different sources on the migration of BCCs, in vitro., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Breast cancer is the most prevalent cancer in women worldwide. In the United Kingdom, approximately 5% of all breast cancers are already metastatic at the time of diagnosis. An abundance of literature shows that exercise can have beneficial effects on the outcome and prognosis of breast cancer patients, yet the molecular mechanisms remain poorly understood. There are several in vitro models that aim to recapitulate the response of breast cancer to exercise in vivo; this systematic review and meta-analysis summarizes the existing literature. The following search terms were used to conduct a systematic literature search using a collection of databases (last search performed May 2020): "in vitro," "exercise," and "breast cancer." Only studies that investigated the effects of exercise on breast cancer in vitro were included. Standardized mean differences (SMD) were calculated to determine pooled effect sizes. This meta-analysis has successfully demonstrated that various identified exercise interventions on breast cancer cells in vitro significantly reduced breast cancer cell viability, proliferation, and tumorigenic potential (SMD = -1.76, P = 0.004, SMD = -2.85, P = 0.003, and SMD = -3.15, P = 0.0008, respectively). A clear direction of effect was found with exercise on breast cancer cell migration in vitro, however this effect was not significant (SMD = -0.62, P = 0.317). To our knowledge, this is the first meta-analysis and systematic review investigating and summarizing literature on exercise and breast cancer in vitro, highlighting models used and priority areas for future research focus.