Universal and Sensitive Drug Assessment Biosensing Platform Using Optimal Mechanical Beating Detection of Single Cardiomyocyte.

The preclinical assessment of efficacy and safety is essential for cardiovascular drug development in order to guarantee effective prevention and treatment of cardiovascular disease and avoid human health endangerment and a huge waste of resources. Rhythmic mechanical beating as one of the crucial cardiomyocyte properties has been exploited to establish a drug assessment biosensing platform. However, the conventional label-free biosensing platforms are difficult to perform high-throughput and high-resolution mechanical beating detection for a single cardiomyocyte, while label-based strategies are limited by pharmacologically adverse effects and phototoxicity. Herein, we propose a biosensing platform involving the multichannel electrode array device and the universal mechanical beating detection system. The platform can determine the optimal characteristic working frequency of different devices and dynamically interrogate the viability of multisite single cardiomyocytes to establish the optimized cell-based model for sensitive drug assessment. The subtle changes of mechanical beating signals induced by cardiovascular drugs can be detected by the platform, thereby demonstrating its high performance in pharmacological assessment. The universal and sensitive drug assessment biosensing platform is believed to be widely applied in cardiology investigating and preclinical drug screening.

Flexible Tongue Electrode Array System for In Vivo Mapping of Electrical Signals of Taste Sensation.

Tongue is a unique organ that senses tastes, and the scientific puzzle about whether electricity can evoke taste sensations and how the sensations have been distributed on the tongue has not been solved. Investigations on tongue stimulation by electricity might benefit the developments of techniques for clinical neuromodulation, tissue activation, and a brain-tongue-machine interface. To solve the scientific puzzle of whether electrical stimulation induces taste-related sensations, a portable flexible tongue electrode array system (FTEAS) was developed, which can synchronously provide electrical stimulation and signal mapping at each zone of the tongue. Utilizing the FTEAS to perform tests on the rat tongue in vivo, specific electrical signals were observed to be evoked by chemical and electrical stimulations. The features and distributions of the electric signals evoked during the rat tongue tests were systematically studied and comprehensively analyzed. The results show that an appropriate electrical stimulation can induce multiple sensations simultaneously, while the distribution of each sensation was not significantly distinguished among different zones of the tongue, and at the same time, this taste-related electrical signal can be recorded by the FTEAS. This work establishes a promising platform to solve the scientific puzzle of how sensations are activated chemically and electrically on the tongue and may provide advanced noninvasive oral-electrotherapy and a brain-tongue-machine interface.

Specific recognition of ion channel blocker by high-content cardiomyocyte electromechanical integrated correlation.

Cardiac arrhythmia and drug-induced cardiotoxicity seriously threaten the human life. To develop antiarrhythmic agents and prevent the drug-induced cardiotoxicity, it is demanded to explore the high-specificity and high-efficiency drug screening platforms for preclinical investigations. Here, a specific electromechanical integrated correlation (EMIC) model was established based on the synchronized signal recording of cardiomyocyte-based biosensing system. The cardiomyocyte-based biosensing system consists of an integrated electromechanical device and a synchronized recording instrument. By extracting the feature points and correlation information of both electrical and mechanical signals, the multi-parameters of EMIC are applied for the drug recognition, showing the good specificity to analyze the typical Na+, K+, Ca2+ channel blockers. Further, visualized analysis of EMIC parameters was performed using the extracted parameters of synchronized recording signals to present the drug specific recognition functions. By heat map, radar map, and principal component analysis (PCA), the specific features and patterns were intuitively displayed to achieve the drug recognition. We believe this high-content and high-specific drug recognition strategy will be a promising and alternative method for the preclinical screening of cardiac safety and drug development in biomedical fields.

[Relevant studies on effect of Fuzheng Sanjie recipe in regulating immune microenvironment remodeling of TAMs in Lewis lung cancer mice].

OBJECTIVE: To study the effect of Fuzheng Sanjie recipe in regulating tumor-associated macrophages (TAMs) in Lewis lung cancer mice. METHOD: Efforts were made to establish the Lewis lung cancer mouse model, weigh tumors and calculate the anti-tumor rate. The immunohistochemical method was used to examine the infiltration degree of CD68 + in tumor tissues in each group. ELISA was used to examine the content of IFN-γ, TGF-ß, IL-4, IL-13, IL-6, IL-10, IL-12, TNF-α in mice serum. RESULT: Compared with the tumor-bearing model group, all of the other groups showed higher tumor inhibition rates, i. e. 50.28% for the DDP group, 34.37% for the TCM-preventing group and 66.76% for the Chinese and western medicine group, with statistical difference (P < 0.05), but without statistical difference in the infiltration degree of CD68+. The expressions of the IFN-γ, IL-6, IL-12 in tumor-bearing groups were lower than that in the blank control group, but with higher contents of IL-4, IL-13, TGF-ß. Intervened with different drugs, there were significant differences in content among some relevant cytokines (P < 0.05), as well as statistical differences among the TCM prevention group, the Chinese and western medicine group and the tumor-bearing control group (P <0. 05) , but without statistical difference in TNF-α and IL-10 content from the tumor-bearing control group (P < 0.05). CONCLUSION: Fuzheng Sanjie recipe could reverse the immune remodeling effect and control the tumor growth by down-regulating the expressions of IL-4, IL-13, TGF-α in lung cancer immune microenvironment and up-regulating the expression of IFN-γ.