NMT Applications in Physiology and Diseases

Viabilities

Cell Viabilities

Specific Areas:

in vivo detection of the activity of the egg
in vivo detection of activity of the embryo
in vivo detection of cell fusion signal

The cells need to maintain a normal physiological state by means of material exchange with their environments, including ionic/molecular exchanges, such as Ca²⁺, K⁺ and Cl^-, H⁺ etc.

Therefore, the >NMT which can detect these ionic fluxes with living samples, is a straight forward tool to evaluate cell viabilities.

Examples:

Detection of egg viability via Ca²⁺ fluxes

Trimarchi JR, et al. Zygote, 2000:15-24

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Pharm.&Effi.

Pharmacological research and efficacy evaluation

Specific Areas:

Pharmacological mechanisms of specific drugs
Mechanisms of drug resistance
Evaluation of drugs for personalized treatments
Screening drugs

Ionic/molecular (Ca²⁺, H⁺, O₂ etc.) fluxes are real time and quantitative indicators of physiological activities, and thus also become good quantitative indicators for drugs’ pharmacological effects.

So, the intuitive data provided by NMT is an easy way to understand these pharmacological in a more dynamic patten.

Examples:

Doxorubicin induced differences of H⁺ fluxes between drug-resistant tumor cells and normal ones

Song J, et al. Acta Biophysica Sinica, 2008, 24: 191-197

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Apoptosis

Apoptosis and Cell Death

Specific Areas:

Apoptosis mechanisms
Prediction of Cell Death
Study the toxicological mechanism of toxicity of the cell

The ionic / molecular fluxes is one of the fundamental characteristics of life. So, when cells undergo apoptosis, K⁺ , H⁺ or other ions/molecule will change accordingly.

Therefore, NMT is a perfect tool to study the apoptotic process through the direct measurements of ionic/molecular activities.

Examples：

（1） K⁺ effluxes as early indicators of apoptosis in mouse embryonic cells

Trimarchi JR, et al. Biology of Reproduction,2000, 63: 851-857.

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（2）K⁺ Effluxes with STS treatments in the process of cell senescence

Valencia-Cruz G, et al.Am J Physiol Cell Physiol, 2009, 297: C1544-C1553.

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Physiol.

Physiological Regulations

Specific Areas :

Study the mechanisms of regulation of metabolism, neuronal transmission , circulatory and other important physiological processes
Induced tumors, neurodegenerative diseases, cardio-cerebral vascular diseases such as abnormal physiological regulation
Study the new functions of proteins
Functions of NO, dopamine and other signaling molecules

Ca²⁺, H⁺, of K⁺ and Na⁺, O₂ ions/molecules play important roles in the physiological regulation of all organisms. In order to achieve the precise control of the physiological activities, the fluxes of these ions / molecules have to be maintained at certain fashions. Therefore, NMT provides an indispensable tool to study these indicators of the physiological regulations.

Examples:

（1）Found a possible mechanism how the bone plasma Ca²⁺ is regulated

Marenzana M, et al. Bone, 2005, 37: 545-554.

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（2）Maternaldiabetes withlow oxygen metabolism of the embryo can induce embryonic neural tube defects

Li R,et al.Am J Physiol Endocrinol Metab, 2005, 289: E591–E599.

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Neuro.

Neuroscience

Specific Areas:

Signaling in neuron
Glutamate toxicity
Polarity growth of neuron synapse

Neurons are electrically excitable cells which produce relatively large amounts of ATP and consume correspondingly large amounts of O2 to drive the ion pumps that restore intracellular Na+ and Ca2+ levels after synaptic activity and action potentials. NMT can record the O2 consumption, Ca2+ flux in single neurons.

NMT recording of O2 consumption in single neurons.

Gleichmann M, et al. J Neurochem, 2009,109: 644-655

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Diabetes

Specific Areas:

Regulation mechanisms of endocrine processes
Induced diabetes and its complications
Evaluation of treatments of diabetes drugs

Diabetes is a serious threat to human health, but also induced a lot of complications. Pathogenesis of diabetes is a very complex physiological regulation process, which involves Ca²⁺, H⁺, K⁺ and Na⁺, O₂ and many other ions / molecules.

So, Non-invasive Micro-test Technique (NMT) is an ideal tool to study these ions/molecules to reveal the physiological regulation of cells, tissues, organs and other samples.

Examples:

Maternal diabetes resulting in low oxygen metabolism of the embryo can induce embryonic neural tube defects

Li R,et al.Am J Physiol Endocrinol Metab, 2005, 289: E591–E599.

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Cancers

Cancer

Specific Areas:

Using NMT to detect the microenvironment in tumer cells
Research on drug resistence in tumer cells
Direct detect O₂ consumption and H⁺ flux in the conditions of low oxygen and pH

Paclitaxelinduced H⁺ influxin human breast tumor tissue

Song J, et al. Acta Biophysica Sinica, 2008, 24: 191-197

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Other Diseases

Specific Areas:

Research on the roles of drug in Alzheimer’s disease (AD)
Find a new mechanism in disease
Evaluate new drug efficacy for disease therapies

Alzheimer’s disease (AD) is the most common form of dementia within the ageing population. A major pathological hallmark of AD is the deposition of insoluble extracellular b-amyloid (Ab) plaques. Zn7MT-2A is a new drug which is blocked Cu(II)-Ab induced changes in ionic homeostasis and subsequent neurotoxicity of cultured cortical neurons. MT-2A might represent a different therapeutic approach as the metal exchange between MT and Ab leaves the Ab in a Zn-bound, relatively inert form.

Detect Ca²⁺ and K⁺ fluxes of neurons after drug treatment.

Chung RS et al. (2010). PLoS ONE 5(8): e12030. doi:10.1371/journal.pone.0012030

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