Transcriptomic Analysis of Cytokine-Treated Tissue-Engineered Cartilage as An In Vitro Model of Osteoarthritis

Osteoarthritis (OA), as the most common form of arthritis and a leading cause of disability worldwide, currently has no disease-modifying drugs. Inflammation plays an important role in cartilage degeneration in OA, and pro-inflammatory cytokines, IL-1β and TNF-α, have been shown to induce degradative changes along with aberrant gene expression in chondrocytes, the only resident cells in cartilage. The goal of this study was to further understand the transcriptomic regulation of tissue-engineered cartilage in response to inflammatory cytokines using an in vitro miPSC model system. We performed RNA sequencing for the IL-1β or TNF-α treated tissue-engineered cartilage derived from murine iPSCs, and analyzed transcriptomic profiles by comparing with those of two different osteoarthritis models and human OA cartilage samples. We investigated differentially expressed genes (DEGs) as well as gene set enrichment and protein-protein interaction network, showing a significant similarity between model systems and human OA cartilage. Our analysis revealed a significant number of overlapping DEGs, together with consistent pathway enrichment in inflammatory response, cytokine-mediated response and extracellular matrix organization, which support that the murine iPSC model system can replicate many of the characteristics of OA cartilage at the transcriptomic level, specifically in the catabolic aspect of inflammation induce OA. The murine iPSC model system provides a method for studying the pro-inflammatory response and pathogenesis in OA cartilage and will be a valuable dataset for identifying therapeutic targets of inflammation-induced OA

The Endocrine Disruptor Mono-(2-Ethylhexyl) Phthalate Affects the Differentiation of Human Liposarcoma Cells (SW 872)

Esters of phthalic acid (phthalates) are largely used in industrial plastics, medical devices, and pharmaceutical formulations. They are easily released from plastics into the environment and can be found in measurable levels in human fluids. Phthalates are agonists for peroxisome proliferator-activated receptors (PPARs), through which they regulate translocator protein (TSPO; 18 kDa) transcription in a tissue-specific manner. TSPO is a drug- and cholesterol-binding protein involved in mitochondrial respiration, steroid formation, and cell proliferation. TSPO has been shown to increase during differentiation and decrease during maturation in mouse adipocytes. The purpose of this study was to establish the effect of mono-(2-ethylhexyl) phthalate (MEHP) on the differentiation of human SW 872 preadipocyte cells, and examine the role of TSPO in the process. After 4 days of treatment with 10 µM MEHP, we observed changes in the transcription of acetyl-CoA carboxylase alpha, adenosine triphosphate citrate lyase, glucose transporters 1 and 4, and the S100 calcium binding protein B, all of which are markers of preadipocyte differentiation. These observed gene expression changes coincided with a decrease in cellular proliferation without affecting cellular triglyceride content. Taken together, these data suggest that MEHP exerts a differentiating effect on human preadipocytes. Interestingly, MEHP was able to temporarily increase TSPO mRNA levels through the PPAR-α and β/δ pathways. These results suggest that TSPO can be considered an important player in the differentiation process itself, or alternatively a factor whose presence is essential for adipocyte development

The Pausing Strategies in Chinese Preschool Children's Narratives

Purpose: Language production, a dynamic process involving real-time language processing, is crucial for children's language and communication development. To explore the early development of children's real-time language production, this study investigated Chinese preschool children's pausing strategies in narratives and their associations with verbal working memory and vocabulary abilities. Method: A picture-elicited narrative task was employed. Sixty Mandarin-speaking children aged 4-5 years were asked to tell a story according to the book Frog, Where Are You? The pausing types and positions in narratives were coded and analyzed. Additionally, children's verbal working memory and vocabulary were measured. Results: The results showed that 4- to 5-year-old children prefer to use silent pauses and tend to produce pauses within clauses. The total frequency of pausing decreases with age and shows a significant gender difference. Girls prefer to use within-clause pauses, whereas boys prefer to use between-clause pauses. More importantly, children's pausing frequency is closely associated with their verbal working memory and vocabulary, in which working memory plays a more important role.Conclusions: This study is a first-step exploration of pausing strategies in 4- to 5-year-old Chinese children's narratives. The developmental characteristics of pausing strategies shown in typically developing children serve as a crucial reference for interventions for children with language deficits

Circular RNAs in Breast Cancer: An Update

Breast cancer (BC), characterized by high heterogeneity, is the most commonly reported malignancy among females across the globe. Every year, many BC patients die owing to delayed diagnosis and treatment. Increasing researches have indicated that aberrantly expressed circular RNAs (circRNAs) are implicated in the tumorigenesis and progression of various tumors, including BC. Hence, this article provides a summary of the biogenesis and functions of circRNAs, as well as an examination of how circRNAs regulate the progression of BC. Moreover, circRNAs have aroused incremental attention as potential diagnostic and prognostic biomarkers for BC. Exosomes enriched with circRNAs can be secreted into the tumor microenvironment to mediate intercellular communication, affecting the progression of BC. Detecting the expression levels of exosomal circRNAs may provide reference for BC diagnosis and prognosis prediction. Illuminating insights into the earlier diagnosis and better treatment regimens of BC will be potentially available following elucidation of deeper regulatory mechanisms of circRNAs in this malignancy

MIL-101 (Fe) @Ag Rapid Synergistic Antimicrobial and Biosafety Evaluation of Nanomaterials

Metal-organic frameworks (MOFs), which have become popular in recent years as excellent carriers of drugs and biomimetic materials, have provided new research ideas for fighting pathogenic bacterial infections. Although various antimicrobial metal ions can be added to MOFs with physical methods, such as impregnation, to inhibit bacterial multiplication, this is inefficient and has many problems, such as an uneven distribution of antimicrobial ions in the MOF and the need for the simultaneous addition of large doses of metal ions. Here, we report on the use of MIL-101(Fe)@Ag with efficient metal-ion release and strong antimicrobial efficiency for co-sterilization. Fe-based MIL-101(Fe) was synthesized, and then Ag+ was uniformly introduced into the MOF by the substitution of Ag+ for Fe3+. Scanning electron microscopy, powder X-ray diffraction (PXRD) Fourier transform infrared spectroscopy, and thermogravimetric analysis were used to investigate the synthesized MIL-101(Fe)@Ag. The characteristic peaks of MIL-101(Fe) and silver ions could be clearly seen in the PXRD pattern. Comparing the diffraction peaks of the simulated PXRD patterns clearly showed that MIL-101(Fe) was successfully constructed and silver ions were successfully loaded into MIL-101(Fe) to synthesize an MOF with a bimetallic structure, that is, the target product MIL-101(Fe)@Ag. The antibacterial mechanism of the MOF material was also investigated. MIL-101(Fe)@Ag exhibited low cytotoxicity, so it has potential applications in the biological field. Overall, MIL-101(Fe)@Ag is an easily fabricated structurally engineered nanocomposite with broad-spectrum bactericidal activity

Effects of MEHP on SW 872 human preadipocytes.

<p>MEHP enhances differentiation, inhibits cellular proliferation, and decreases mitochondrial TSPO expression in SW 872 cells.</p

The effect of MEHP on TSPO gene expression is mediated by PPAR-α and PPAR-β/δ , and on PKCε gene expression by PPAR-α.

<p>(A) PPAR-α, PPAR-β/δ, PPAR-γ and PKC mRNA levels are greatly reduced following treatment with gene-specific siRNAs compared to treatment with scrambled siRNA. (B) Effect of gene-specific siRNA treatment on TSPO transcription, with or without (+/−) MEHP, compared to similar treatment with scrambled siRNA (SCR). (C) Effect of gene-specific siRNA treatment on PKCε transcription, with or without (+/−) MEHP compared to similar treatment with scrambled siRNA (SCR). Cells were seeded for 24 h before treatment with MEHP, and then transfected with siRNA specific to PPAR-α, PPAR-β/δ, PPAR-γ, and PKCε knockdown. Cell lysates were collected after 4 days. qRT-PCR results are expressed in terms of mean and S.E.M., calculated from three independent experiments. Student's <i>t</i>-test was used to calculate statistical significance compared to scrambled siRNA control in the absence (*) or presence (#) of MEHP; *p<0.05, **p<0.01, ***p<0.001, ^#p<0.05.</p