Integrated Proteomic and Transcriptomic Investigation of the Acetaminophen Toxicity in Liver Microfluidic Biochip

Microfluidic bioartificial organs allow the reproduction of in vivo-like properties such as cell culture in a 3D dynamical micro environment. In this work, we established a method and a protocol for performing a toxicogenomic analysis of HepG2/C3A cultivated in a microfluidic biochip. Transcriptomic and proteomic analyses have shown the induction of the NRF2 pathway and the related drug metabolism pathways when the HepG2/C3A cells were cultivated in the biochip. The induction of those pathways in the biochip enhanced the metabolism of the N-acetyl-p-aminophenol drug (acetaminophen-APAP) when compared to Petri cultures. Thus, we observed 50% growth inhibition of cell proliferation at 1 mM in the biochip, which appeared similar to human plasmatic toxic concentrations reported at 2 mM. The metabolic signature of APAP toxicity in the biochip showed similar biomarkers as those reported in vivo, such as the calcium homeostasis, lipid metabolism and reorganization of the cytoskeleton, at the transcriptome and proteome levels (which was not the case in Petri dishes). These results demonstrate a specific molecular signature for acetaminophen at transcriptomic and proteomic levels closed to situations found in vivo. Interestingly, a common component of the signature of the APAP molecule was identified in Petri and biochip cultures via the perturbations of the DNA replication and cell cycle. These findings provide an important insight into the use of microfluidic biochips as new tools in biomarker research in pharmaceutical drug studies and predictive toxicity investigations

Microtechnology-based organ systems and whole-body models for drug screening

After drug administration, the drugs are absorbed, distributed, metabolized, and excreted (ADME). Because ADME processes affect drug efficacy, various in vitro models have been developed based on the ADME processes. Although these models have been widely accepted as a tool for predicting the effects of drugs, the differences between in vivo and in vitro systems result in high attrition rates of drugs during the development process and remain a major limitation. Recent advances in microtechnology enable more accurate mimicking of the in vivo environment, where cellular behavior and physiological responses to drugs are more realistic; this has led to the development of novel in vitro systems, known as organ-on-a-chip systems. The development of organ-on-a-chip systems has progressed to include the reproduction of multiple organ interactions, which is an important step towards body-on-a-chip systems that will ultimately predict whole-body responses to drugs. In this review, we summarize the application of microtechnology for the development of in vitro systems that accurately mimic in vivo environments and reconstruct multiple organ models.OAIID:RECH_ACHV_DSTSH_NO:T201623717RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A002014CITE_RATE:3.781FILENAME:3. (2016.06) Microtechnology-based organ systems and.pdfDEPT_NM:화학생물공학부EMAIL:[email protected]_YN:YFILEURL:https://srnd.snu.ac.kr/eXrepEIR/fws/file/ce1256c8-4084-4576-aa21-3470ab81611a/linkCONFIRM:

Social entrepreneurship for sexual health (SESH): a new approach for enabling delivery of sexual health services among most-at-risk populations.

Joseph Tucker and colleagues argue for social entrepreneurship, a new approach to help improve delivery of sexual health services. published_or_final_versio