Differential Cytotoxicity of Curcumin-Loaded Micelles on Human Tumor and Stromal Cells

peer reviewedAlthough curcumin in the form of nanoparticles has been demonstrated as a potential anti-tumor compound, the impact of curcumin and nanocurcumin in vitro on normal cells and in vivo in animal models is largely unknown. This study evaluated the toxicity of curcumin-loaded micelles in vitro and in vivo on several tumor cell lines, primary stromal cells, and zebrafish embryos. Breast tumor cell line (MCF7) and stromal cells (human umbilical cord vein endothelial cells, human fibroblasts, and human umbilical cord-derived mesenchymal stem cells) were used in this study. A zebrafish embryotoxicity (FET) assay was conducted following the Organisation for Economic Co-operation and Development (OECD) Test 236. Compared to free curcumin, curcumin PM showed higher cytotoxicity to MCF7 cells in both monolayer culture and multicellular tumor spheroids. The curcumin-loaded micelles efficiently penetrated the MCF7 spheroids and induced apoptosis. The nanocurcumin reduced the viability and disturbed the function of stromal cells by suppressing cell migration and tube formation. The micelles demonstrated toxicity to the development of zebrafish embryos. Curcumin-loaded micelles demonstrated toxicity to both tumor and normal primary stromal cells and zebrafish embryos, indicating that the use of nanocurcumin in cancer treatment should be carefully investigated and controlled.3. Good health and well-bein

Extracellular membrane vesicles from keratinocytes

This project was the first to simultaneously study the three different types of extracellular membrane vesicles (EVs) released by skin cells in order to reveal the differences in their bioactive molecular cargo. The results of this project have significantly contributed to the body of knowledge surrounding EV biology especially with regard to keratinocyte-derived EVs and EV mediated keratinocyte – fibroblast interaction. This information will have utility for future research directions in wound and skin biology

Association of extracellular membrane vesicles with cutaneous wound healing

Extracellular vesicles (EVs) are membrane-enclosed vesicles that are released into the extracellular environment by various cell types, which can be classified as apoptotic bodies, microvesicles and exosomes. EVs have been shown to carry DNA, small RNAs, proteins and membrane lipids which are derived from the parental cells. Recently, several studies have demonstrated that EVs can regulatemany biological processes, such as cancer progression, the immune response, cell proliferation, cell migration and blood vessel tube formation. This regulation is achieved through the release and transport of EVs and the transfer of their parental cell-derived molecular cargo to recipient cells. This thereby influences various physiological and sometimes pathological functions within the target cells. While intensive investigation of EVs has focused on pathological processes, the involvement of EVs in normal wound healing is less clear; however, recent preliminarily investigations have produced some initial insights. This review will provide an overview of EVs and discuss the current literature regarding the role of EVs in wound healing, especially, their influence on coagulation, cell proliferation, migration, angiogenesis, collagen production and extracellular matrix remodelling

An analysis of exosomes from keratinocytes and fibroblasts

In recent years, many studies have provided evidence that exosomes secreted by cells contain various components, including microRNAs [1]. It is thought that exosomes have important roles in many biological processes. However, the role of exosomes and their components, especially miRNAs, in wound healing is poorly understood. In order to understand whether or not primary human epidermal keratinocytes and dermal fibroblasts, two important cell types contributing to wound healing process, release exosomes and what species of wound healing-associated miRNAs accumulate in these vesicles, this project will use a combination of methods to isolate and characterize exosomes, to profile exosomal cargo’s, especially miRNAs in exosomes. The results showed that keratinocytes and fibroblasts released exosomes into conditioned media and these exosomes contain some target miRNAs

Deep Sequencing MicroRNAs from Extracellular Membrane Vesicles Revealed the Association of the Vesicle Cargo with Cellular Origin

Extracellular membrane vesicles (EVs) have emerged as potential candidates for diagnostics and therapeutics. We have previously reported that keratinocytes release three types of EVs into the extracellular environment. Importantly, those EVs contain a large number of microRNAs (miRNAs) as cargo. In this study, we examined the expression level of keratinocyte-derived EV miRNAs, their target genes and potential functions. Next generation sequencing results showed that over one hundred miRNAs in each EV subtype exhibited greater than 100 reads per million (RPM), indicating a relatively high abundance. Analysis of the miRNAs with the highest abundance revealed associations with different keratinocyte cell sources. For instance, hsa-miR-205 was associated with the HaCaT cells whereas hsa-miR-21, hsa-miR-203, hsa-miR-22 and hsa-miR-143 were associated with human primary dermal keratinocytes (PKCs). Additionally, functional annotation analysis of genes regulated by those miRNAs, especially with regard to biological processes, also revealed cell-type-specific associations with either HaCaTs or PKCs. Indeed, EV functional effects were related to their parental cellular origin; specifically, PKC-derived EVs influenced fibroblast migration whereas HaCaT-derived EVs did not. In addition, the data in this current study indicates that keratinocyte-derived EVs and/or their cargoes have potential applications for wound healing

Inflammatory mediators drive neuroinflammation in autism spectrum disorder and cerebral palsy

Abstract Inflammation conditions are associated with autism spectrum disorder (ASD) and cerebral palsy (CP), primarily observed in the peripheral immune system. However, the extent of neuro-inflammation and neuro-immune dysregulation remains poorly studied. In this study, we analyzed the composition of cerebrospinal fluid (CSF) to uncover the inflammatory mediators driving the neuro-immune system in ASD and CP patients. Our findings revealed that ASD patients had elevated levels of four inflammatory cytokines (TNF-α, IL-4, IL-21, and BAFF) compared to controls, while CP patients exhibited increased levels of eight inflammatory cytokines (IFN-γ, GM-CSF, TNF-α, IL-2, IL-4, IL-6, IL-17A and IL-12), one anti-inflammatory cytokine (IL-10), and five growth factors (GFs) (NGF-β, EGF, GDF-15, G-CSF and BMP-9) compared to both controls and ASD patients. Additionally, intrathecal infusion of autologous bone marrow mononuclear cells (BMMNCs) led to a slight decrease in TGF-β and GDF-15 levels in the CSF of ASD and CP patients, respectively. Our study provides new insights into the molecular composition of CSF in ASD and CP patients, with the potential to develop more effective diagnosis methods and improved treatment for these diseases. Clinical trial registration CSF samples used in this study are from clinical trials NCT03225651, NCT05307536, NCT02569775, NCT03123562, NCT02574923, NCT05472428 and previous reports [7, 9, 17–19]