A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.
View Article and Find Full Text PDFDroplet microfluidics are extensively utilized to generate monodisperse cell-laden microgels in biomedical applications. However, maintaining cell viability is still challenging due to overexposure to harsh conditions in subsequent procedures that recover the microgels from the oil phase. Here, a gravity-oriented microfluidic device for end-to-end fabrication of cell-laden microgels is reported, which integrates dispersion, gelation, and extraction into a continuous workflow.
View Article and Find Full Text PDFCellular heterogeneity is crucial for understanding tissue biology and disease pathophysiology. Pharmacological research is being advanced by single-cell metabolic analysis, which offers a technique to identify variations in RNA, proteins, metabolites, and drug molecules in cells. In this review, the recent advancement of single-cell metabolic analysis techniques and their applications in drug metabolism and drug response are summarized.
View Article and Find Full Text PDFTumor-stroma interaction is the core process of tumor metastasis. Therefore, building a model of tumor-stromal cell communication is crucial for understanding the tumor metastasis process and curing cancer completely. In this research, a controllable three-dimensional (3D) tumor-stroma coculture microsphere model based on droplet microfluidic technology was developed to culture human lung cancer cells (A549 cell) and fibroblast cells (NIH-3T3 cell) using core-shell hydrogel microspheres to partition different kinds of cells.
View Article and Find Full Text PDFThis work presented an alternative approach for studying bacteria-cell interactions in three-dimensional (3D) hydrogel microspheres formed by the cross-linking reaction of alginate and calcium-ethylenediaminetetraacetic acid (EDTA-Ca) produced in a microfluidic chip. During the co-culture process of hepatocytes (HepG2) and () 25922, we concluded that the content change of tryptophan metabolites detected via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was related to the cell damage level and the change of interleukin (IL-22) detected by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) was related to the ways of co-cultivation. Compared to the two-dimensional (2D) adherent cell culture process in a Petri dish (2D), the co-culture process of HepG2 and 25922 in hydrogel microspheres indicated more information about metabolism such as the appearance of indole-3-propionic acid (IPA) and possibly IL-22.
View Article and Find Full Text PDFThe pathological studies of cancer tissues and cell molecules could provide an early diagnosis for the treatment of cancer. In this work, we have designed a microfluidic surface extractor (MSE). The MSE has been coupled with electrospray mass spectrometry (extraction reagent, methanol; optimum flow rate, 0.
View Article and Find Full Text PDFAt diagnosis, 10 % of breast cancer patients already have locally advanced or metastatic disease; moreover, metastasis eventually develops in at least 40 % of early breast cancer patients. Osteolytic bone colonization occurs in 80-85 % of metastatic breast cancer patients and is thought to be an early step in metastatic progression. Thus, breast cancer displays a strong preference for metastasis to bone, and most metastatic breast cancer patients will experience its complications.
View Article and Find Full Text PDFPrimary tumors often give rise to disseminated tumor cells (DTC's), which acquire full malignancy after invading distant site(s). Thus, DTC's may be a productive target for preventing prostate cancer metastasis progression. Our prior research showed that PHSCN peptide (Ac-PHSCN-NH2) targets activated α5β1 integrin to prevent invasion and metastasis in preclinical adenocarcinoma models, and disease progression in Phase I clinical trial.
View Article and Find Full Text PDFRADIOTHERAPY IS USED IN THE MANAGEMENT OF PANCREATIC CANCER BECAUSE OF ITS HIGH PROPENSITY FOR LOCOREGIONAL RELAPSE: one third of patients succumb to localized disease. Thus, strategies to improve the efficacy of radiotherapy in pancreatic cancer are important to pursue. We used naturally serum-free, selectively permeable basement membranes and confocal microscopy of fluorescent antibody-stained human Panc-1, MiaPaCa-2, and BxPC-3 pancreatic cancer cell lines to investigate the effects of ionizing radiation on α(5)β(1) integrin fibronectin receptor expression and on α(5)β(1)-mediated invasion.
View Article and Find Full Text PDFActivated alpha5beta1 integrin occurs specifically on tumor cells and on endothelial cells of tumor-associated vasculature, and plays a key role in invasion and metastasis. The PHSCN peptide (Ac-PHSCN-NH(2)) preferentially binds activated alpha5beta1, to block invasion in vitro, and inhibit growth, metastasis and tumor recurrence in preclinical models of prostate cancer. In Phase I clinical trial, systemic Ac-PHSCN-NH(2) monotherapy was well tolerated, and metastatic disease progression was prevented for 4-14 months in one-third of treated patients.
View Article and Find Full Text PDFThe α5β1 integrin fibronectin receptor is an attractive therapeutic target in breast cancer because it plays key roles in invasion and metastasis. While its inactive form is widely expressed, activated α5β1 occurs only on tumor cells and their associated vasculature. The PHSCN peptide has been shown to bind activated α5β1 preferentially, thereby blocking invasion in vitro, and inhibiting growth, metastasis and tumor recurrence in preclinical models.
View Article and Find Full Text PDFAngiogenesis requires endothelial cell invasion and is crucial for wound healing and for tumor growth and metastasis. Invasion of native collagen is mediated by the alpha(5)beta(1) integrin fibronectin receptor. Thus, alpha(5)beta(1) up-regulation on the surfaces of endothelial cells may induce endothelial cell invasion to stimulate angiogenesis.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
May 2008
The dorsal motor nucleus of the vagus (DMV) contains preganglionic neurons that control gastric motility and secretion. Stimulation of different parts of the DMV results in a decrease or an increase in gastric motor activities, suggesting a spatial organization of vagal preganglionic neurons in the DMV. Little is known about how these preganglionic neurons in the DMV synapse with different groups of intragastric motor neurons to mediate contraction or relaxation of the stomach.
View Article and Find Full Text PDFAlthough the complete genomes of a number of organisms have been sequenced, the biological functions of many genes are still not known. Because experimentally studying the functions of those genes one by one requires tremendous time, it is vital to use published resources like microarray gene expression data for computational analysis of gene functions. One example is YJL103C, a yeast gene of unknown function in the Saccharomyces Genome Database (SGD).
View Article and Find Full Text PDFBiochem Biophys Res Commun
October 2003
It is well recognized that a product of obese (ob) locus and body weight control hormone, leptin, acts on both short-term satiety for meal-induced termination of food intake (gastric phase) and long-term satiety for energy expenditure via the hypothalamus. The considerable sources of leptin are chief cells for gastric phase and adipocytes for the long-term satiety. The objective of this study was to demonstrate if CCK enhances leptin synthesis and secretion in isolated canine gastric chief cells.
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