Release date: 2018-05-21

Cell Death and Disease published a study entitled "Using the 'Digestive System of the Chip' to simulate the effects of radiation-related cell death and protective drugs." The authors interviewed the authors on the results and practical significance of the study. Sasan Jalili-Firoozinezhad of the Weiss Institute at Harvard University accepted our interview as the first author.

Can you briefly introduce your research results?

Exposure to ionizing radiation, whether due to medical treatment needs or accidents, may occur in acute radiation syndrome with gastrointestinal manifestations as the main symptom. We used the "chip organ" technology to establish a model of the human digestive tract, which includes the human small intestine villi epithelium and vascular endothelium, which are interconnected. We irradiated the model with radiation to cause radiation-related digestive tract damage. The dose is 8 Gy, and the literature suggests that this dose of radiation can affect the human digestive tract. We found that the levels of markers of various cell damage in epithelial cells and endothelial cells were significantly elevated. The manifestations of cell damage include increased apoptosis (cell death), increased levels of reactive oxygen species (ROS, also known as oxygen free radicals), double-stranded DNA breaks, membrane lipid degradation, and microvilli structure loss. Intercellular connections are also disrupted, and the integrity of the intestinal epithelium is destroyed, and the function of protecting the intestinal wall from bacteria and toxins is also impaired.

Using the "chip digestive system" radiation model, we demonstrated that the use of dimethyl oxalyl glycine (DMOG) prior to exposure to radiation significantly reduced apoptosis, decreased intestinal epithelial permeability, and reduced intestinal epithelial damage. In addition, reactive oxygen species production and lipid degradation were also significantly reduced in epithelial cells and endothelial cells, which was not observed in previous experimental models.

Radiation can cause the height of the villi to become shorter, the microvilli become shorter, and the shape tends to be irregular; DMOG can counteract the damage of the digestive tract by radiation.

Can you briefly introduce the "chip digestive system"? Why has this model been improved in your research?

The "Chip Digestive System" is a microfluidic culture device with a clear, soft, transparent silicone polymer that is similar in size to a computer chip (see top). The device also includes two parallel channels separated by a single apertured membrane, with intestinal epithelial cells arranged on one side of the membrane and vascular endothelial cells aligned on the other side of the membrane. The two channels are filled with culture fluid, and the side chambers on both sides of the chip are periodically aspirated to simulate intestinal peristalsis. After about one week of culture, the chip has a villus structure and has multiple functions of the living intestine.

Unlike previous radiation models, we have added vascular endothelial cells to the chip because recent zoological studies have found that vascular endothelial cells play an important role in radiation-related digestive tract damage. Our research also confirmed this hypothesis: the response of endothelial cells after radiation treatment is significantly stronger than that of epithelial cells, mainly showing more reactive oxygen species, lipid degradation, DNA fragmentation, and apoptosis. More interestingly, when we repeated the experiment in the “chip digestive system” model without endothelial cells, we found that the radiation-treated intestinal epithelial cells did not undergo typical changes, indicating that endothelial cells are radiation-related intestinal dysfunction. The key medium.

What does your research mean for drug developers, doctors, and patients?

Radiation-induced cell junction disruption, intracellular vacuolization, epithelial cells, and separation of endothelial cells from the basement membrane in DMOG-treated and DMOG-treated models.

Bubble on the right: The "chip digestive system" can be used for the development and screening of anti-radiation drugs. These drugs may save the lives of cancer patients, astronauts or accidental nuclear accident victims.

People may be exposed to ionizing radiation (such as nuclear accidents, cosmic rays in space navigation, etc.) or due to medical treatment (radiation). Unexpected exposure may result in mutations in the carcinogenic gene leading to death, with lower doses of radiation, but long-term treatment can still produce side effects. Because healthy people cannot be used in radiation research, current research on anti-radiation drugs can only be limited to animal experiments and cannot be promoted in the population. In this case, the "chip digestive system" radiation model is a powerful tool for studying the underlying mechanisms of radiation-related damage mechanisms. The "chip digestive system" can be used for the development and screening of anti-radiation drugs. These drugs may save the lives of cancer patients, astronauts or accidental nuclear accident victims.

Based on your current research results, can you talk about future research directions? Or talk more about "chip body" in more detail?

When animals and humans are exposed to systemic radiation sufficient to cause a severely damaging dose, the cause of death is primarily radiation-induced multi-system damage to the intestines, lungs, and bone marrow. To this end, we will use the "chip organs" of these systems to model radiation damage. In addition, there is evidence that radiation damage to the intestine can affect radiation damage to the bone marrow of the same individual, and this image is associated with the intestinal flora. Therefore, we have developed a new method of cultivating a complex microbial population on a culture device to simulate the intestinal flora, so that we can study the role of the intestinal flora in radiation-related damage.

Bubbles on the right: ... We connect different "chip organs" through the "vascular channels" where endothelial cells are located, thus creating a "chip body"...

We created a "chip body" by connecting different "chip organs" through the "vascular channels" where endothelial cells are located. We can use the "chip body" to study the interactions between various organs in the case of radiation damage. To create an individualized "chip human body," we used a cell isolated from a patient's biopsy specimen to create a "chip intestine," and other research teams found that a similar model could be established using the patient's induced pluripotent stem cells. Now we are using these new models, coupled with bioinformatics technology and computer-aided methods, to find new anti-radiation drugs.

Source: Science Network

Virus Specimen Collection Tube

Inspection principle:
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♣.Structural composition: Combination of cotton swab and transport medium (VTM).
♣. Product requirements:
The product should be airtight, avoid high temperature, avoid direct sunlight storage. It should be used in a clean, hygienic, pollution-free, and temperature-friendly environment.
♣, Storage conditions and validity period:
â‘ , the product should be stored in a clean, dry and ventilated environment,
②, the temperature is 5℃-35℃;
â‘¢, relative humidity <85%RH;
â‘£, product shelf life: 12 months.
♣. How to use
â‘  Before sampling, mark relevant information on the label of the sampling tube.
â‘¡. Sampling with the corresponding cotton swabs.
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â‘£. For the specific sampling method, please refer to the following:
a) Nasal swab Gently insert the sampling head into the nasal cavity, stop for a while and then slowly rotate to exit, immerse the collected specimen in the Xiangxiang solution, break the excess part and discard it, and tighten the sampling tube cover.
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c), Mycoplasma Chlamydia, Ureaplasma specimen collection
Male: Insert the sampling head into the urethra about 2cm and rotate, stay for a while and then exit, and immerse the collected specimen in the sampling solution.
Female: Wipe the mucus of the cervical orifice, insert the sampling tip into the cervical canal for 1-2 cm for sampling, immerse the collected specimen in the sampling solution, break off the excess part and discard it, and tighten the cap of the sampling tube.
♣. Precautions
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â‘¡ The collected specimens must be sent for inspection in time.
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This single-use Virus Sampling Tube is used for in vitro diagnosis. It cannot be used for human or animal oral or external use. If swallowed, it may cause serious events; it is irritating to eyes and skin. If it is not splashed into the eyes, rinse with water.

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