Project description:Dermal fibrosis is a significant barrier to effective wound healing, with excessive myofibroblast activation and extracellular matrix deposition leading to scar formation and compromised tissue function. Current in vitro models for studying dermal fibrosis, such as monolayer cultures and human skin equivalents (HSEs), have limited physiological relevance or scalability for drug screening. Here, we present a dermis-on-a-chip platform to enable screening of anti-fibrotic compounds in physiologically-relevant 3D dermal microtissues. Upon treatment with transforming growth factor beta (TGFβ), the tissues exhibited hallmarks of fibrosis, including impaired integrity, increased tensile forces, altered cellular morphology, and a pro-fibrotic cytokine profile. Conversely, incorporation of QHREDGS (Q-peptide), an angiopoietin-1 derived peptide with known regenerative properties, selectively modulated these fibrotic changes. Q-peptide was found to reduce TGFβ-induced tensile forces, suppress smooth muscle actin (SMA) expression, and upregulate certain cytokines associated with wound repair. Overall, these findings demonstrate the utility of dermis-on-a-chip model in compound screening.
Project description:The individualized treatment of tumors has always been an urgent problem in clinical practice. Organoids-on-a-chip can reflect the heterogeneity of tumors and is a good model for in vitro anticancer drug screening. In this study, surgical specimens of patients with advanced colorectal cancer will be collected for organoid culture and organoids-on-a- chip. Use organoids-on-a-chip to screen tumor chemotherapy drugs, compare the results of patients’ actual medication regimens, and study the guiding role of organoids in the formulation of precise tumor treatment plans. The investigators will compare the response of organoids to drugs in vitro with the patient’s response to actual chemotherapy and targeted drugs and explore the feasibility and accuracy of organoids-on-a-chip based drug screening for advanced colorectal cancer. The project will establish a screening platform for chemotherapeutic drugs and targeted drugs based on colorectal cancer organoids to quickly and accurately formulate personalized treatment plans for clinical patients.
Project description:Transcriptional expression data for bioactive small molecules for mechanism identification. Keywords: Expression profiling by array MCF7 cells were treated with either NSC76022 (thaspine) or DMSO control for six hours, to identify compound specific gene regulation.
Project description:HCC is the sixth most common cancer and the third leading cause of cancer-related death worldwide. It has a high mortality rate, yet lacks effective treatment options. We used our Gene expression profile Predictor on chemical Structures (GPS) platform to discover novel and selective anti-HCC drug candidates. GPS is a deep learning-based drug discovery system for the screening of a large compound library and de novo designing of novel compounds that can reverse transcriptional phenotype. To achieve this, a previously defined HCC signature was queried against the GPS-generated transcriptomic profiles for compounds in the ZINC library with almost seven million drug-like compounds. Top-ranked compounds were nominated for testing their cytotoxicities in HCC cell lines in vitro, and their efficacy in vivo.
Project description:Skin has distinct characteristics depending on the anatomical site; however, the cell and molecular differences, and their functional implications, have been little described. RNA-sequencing of healthy adult mouse skin from the abdomen, back, and face/cheek has revealed that dermis from different sites is distinct, and that this aligns with their diverse embryonic origins (abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm, and cheek dermis from neural crest). The functional implications for wound repair are evident from the differences in extracellular matrix and cell migration observed in tissue and dermal fibroblasts from these sites, and the histological and transcriptional variations during a wound response.
Project description:The dermis is divided into two distinct layers. The upper, papillary dermis is characterized by thin and sparse fibers. The lower, reticular dermis is composed of solid tissue made up of thicker highly dense fibers. It has been reported that cultured fibroblasts isolated from the papillary and the reticular dermis exhibit different properties. In this study, we analyzed gene expression profiles of human papillary dermis and reticular dermis obtained using laser capture microdissection.
Project description:Transcriptional profiling of adult zebrafish cornea against dermis as a reference. Three biological repeats with dye swap (6 chips of 1x22k for 6 data sets).
Project description:Preservation of the denatured dermis can facilitate wound repair as well as restore hand function.Denatured dermis can be reversibly recovered after deep partial thermal injury. In this dataset, we include the m6A methylated RNA data obtained from normal skin tissues (C group) and denatured dermis (T group).