International Journal of Translational Science

Introduction

Pranela Rameshwar — 2024-02-03

This first issue of the relaunched journal includes five articles. The subject of these inter- and multi-disciplinary articles represents the journal’s goal to reach a wide audience. Sinha and colleagues showed how their molecular research is closely linked to a preclinical stage to prevent breast cancer cells entering dormancy, as well as to target established dormant breast cancer cells. The group previously showed that CDH2 is significant for gap junctional intercellular communication, which allowed the cancer cells to communicate with endogenous bone marrow cells resulting in cycling quiescence (1). The group reported on CDH2 as a therapeutic target for breast cancer (1). The paper in this issue cloned and analyzed the 5′ regulatory region of CDH2, and addressed how small non-coding microRNA could regulate CDH2 expression. This adds to additional method to target CDH2 to reverse and prevent breast cancer dormancy. The paper by Barboza and colleagues focused on lung carcinoma. Specifically, the group showed PDCD2 blunting the cycling of lung carcinoma by inhibiting the G0/G1 transition. The latter occurred by suppressed expression of cyclin D1.

CDH2-microRNA Axis Provides Insights into Sustained Breast Cancer Dormancy in the Bone Marrow Niche

Garima Sinha — 2024-02-05

Despite long-term remission of breast cancer (BC), cancer resurgence remains a clinical issue. This issue is mostly due to BC cells (BCCs) being able to survive in dormancy for decades. This is particularly relevant to the bone marrow (BM) where the dormant BCCs survive as cancer stem cells (CSCs). The BM niche maintains BCCs in dormancy, and also mediates dedifferentiation of BCCs to CSCs. Since dormancy can occur at any time during the disease, including decades before clinical diagnosis, it is important to understand how these cells survive to allow for the development of safe treatments. Dormant BCCs establish gap junctional intercellular communication (GJIC) with BM niche such as fibroblasts and mesenchymal stem cells (MSCs). GJIC requires connexin 43 (Cx43) but cannot be a safe target since this connexin is also important for hematopoietic function. This study focused on N-cadherin (CDH2) because it facilitates Cx43-mediated GJIC between BCCs and BM niche cells. We found Cx43 and CDH2 mutually regulated their gene expression. Cloning of the 5 $^{'}$ regulatory regions of CDH2 unraveled DNA sequences as possible elements of repressor and activator transcription. We identified potential transcription factors (TFs) that could regulate CDH2 and showed how miRNAs that could cross GJIC might be responsible for regulating the TFs. The axis developed by CDH2 and miRNAs provide insights into how CDH2 is maintained at low level to sustain BC dormancy. The findings, together with previous findings, provide avenues for therapeutic intervention to safely reverse and target dormant BCCs in the BM niche.

Cryopreservation of Large Number of Human Hematopoietic Cells – A Model for Research Space with Limited Resources

Seda Ayer — 2024-02-05

Unlike cell lines, cells from primary human tissues are valuable, requiring storage for long-term use. Large number of primary cells require the most efficient method of shipment, when relevant, and cryopreservation to preserve the viability and function. Shipping of cells could be determined by the specific experimental question. These issues are particularly important for primary cells such as hematopoietic stem cells, which cannot expand in vitro. There is minimum issues when cryopreserving relatively small number of cells from tissues such as umbilical cord blood and bone marrow aspirates. However, cryopreservation of >200 × 10⁹ primary cells comes with challenges to identify the most efficient method for long-term storage. Here we report on processes to achieve efficient cell health and recovery of hematopoietic cells from mobilized peripheral blood cells (MPBs). We also determined overnight shipment of MPBs led to overall outcomes when shipped in the cold, as compared to room temperature. We found that cryopreservation of 50 × 10⁶ cells in 2 mL led to maximum recovery of hematopoietic cell subsets. The implication for these conditions to achieve efficient long-term storage is discussed. These methods will benefit small research laboratories such as those at academic settings and start-up companies with limited resources.

A Model of Translational Science Using the National Science Foundation Model of Innovative International Collaboration*

Thomas O’Neal — 2024-02-05

This paper reviews how an innovative and creative program, when delivered as tool to assist technology commercialization and to provide entrepreneurship training and support in the wake of disasters. It leverages the innovative Corp methodology developed and deployed under the National Science Foundation to include international innovation (I-Corp). This methodology uses scientific methodology to reduce risks for startups by teaching employing customer discovery and market validation techniques. The review discusses the relevance of incorporating Caribbean innovation.

Targeted Disruption of PDCD2 Delays G1/S Transition in Lung Carcinoma by Inhibiting Cyclin D1 Transcription

Nora Barboza — 2024-02-05

We previously reported on high expression of define PDCD2 in human malignancies. Knockdown of PDCD2 reduced the proliferation of leukemia and lung carcinoma cells. However, the mechanism by which PDCD2 reduces tumor proliferation remains unclear. This study tested the hypothesis that lowered PDCD2 would delay the proliferation of A549 lung carcinoma cells. Entry of A549 cells into S-phase was significantly (p-value 0.05) delayed when PDCD2 was knockdown. This correlated with a significant downregulation of cyclin D1, and AKT phosphorylation. Inhibition of the PI3K/AKT signaling pathway by Ly294002 decreased levels of PDCD2. These findings are consistent with a role for PDCD2 to mediate the entry of A549 cells into the cell cycle. Resting A549 cells showed PDCD2 localizing in the nucleus and plasma membrane and became diffuse with cell division, suggesting that PDCD2 is mitogen-dependent and may be involved in the proper timing of cell cycle. These findings may represent a promising venue to develop PDCD2 in clinical applications.

A Theory of Gravitational Generation to Mitigate Space-Induced Low Gravity – Relevance to Premature Aging in Space

Anish Rangdal — 2024-02-05

Artificial gravity is among the key goals for successful long-term space exploration. Over the last century, several possible theoretical models have been proposed. As far as we are aware, use of centrifugal rotation is the only major form of artificial gravity that has been significantly tested. There are disadvantages to this system including the high degree of speed needed to produce a force to recapitulate earth’s gravitational field. We tested the potential efficacy of diamagnetic levitation as a form of artificial gravity. This study capitalized on its unique capacity to uphold desired aesthetic attributes while adjusting gravitational forces per specific conditional requirements. The model emphasized on methods by which diamagnetic levitation negate the detrimental consequences of prolonged weightlessness on human physiology, leading to premature age. By offering a detailed exploration of the potential of diamagnetic levitation and its implications, this research contributes to a deeper understanding of the critical role of the potential for artificial gravity on long-term visit to space. The findings and insights presented herein serve as a valuable resource for future space missions and the development of space habitation technologies, guiding interdisciplinary scientists towards the realization of safer, healthier, and more sustainable human ventures beyond earth’s confines. We discussed the positive impact on premature aging for long-term habitation in space.