Biomedicine News

Alexey Levin, Voice of America

Reprogrammed lymphocytesAmerican scientists have achieved new success in converting ordinary somatic cells into full-fledged analogues of embryonic stem cells.

This alteration is carried out by introducing additional genes into the cell nuclei, triggering the processes of rewriting genetic information from chromosomal DNA to informational RNA.

Until now, fibroblasts, one of the varieties of skin cells, have been used as the starting material. Studies conducted in different laboratories have shown that to transform a fibroblast into a functioning model of an embryonic stem cell, it is enough to embed only four specially selected genes into it.

As a result of such an operation, skin cells begin to behave like stem cells isolated from embryos. They demonstrate the same ability to transform into cells of any specialized tissues as real embryonic stem cells. Biologists have a special term for this property – pluripotence. For this reason, reprogrammed somatic cells are called induced pluripotent cells. Such cells can now be obtained from both animal fibroblasts and human fibroblasts.

Employees of the Institute of Biomedical Research named after Whitehead decided to use cells of a completely different nature as raw materials. They have not yet conducted experiments with human cells, they have worked with mouse cells. Jacob Hanna and his colleagues rearranged the hereditary structures of mature B-lymphocytes, cells of the immune system responsible for the production of antibodies.

This task turned out to be more difficult and required the introduction of not four, but five genes. However, the researchers overcame all obstacles and managed to create full-fledged induced pluripotent cells.

Nanofiber for spinal cordChicago researchers have created a liquid biopolymer that heals spinal cord injuries.

It consists of organic molecules that, under certain conditions, spontaneously line up into hollow tubes of nanometer diameter, intertwining with each other. It is such transformations that take place when it enters the injured area of the spinal cord. As a result, it is covered with the thinnest mesh, which creates a support for the growth of new nerve fibers.

Materials science professor Samuel Stapp and his collaborators tested the therapeutic possibilities of their invention in experiments on mice. The spinal cord fibers conducting motor and sensory impulses were cut in these animals. As a result, the mice lost the ability to move their hind limbs and feel the lower half of the body.

The next day, scientists injected new material directly into the affected areas. Observations have shown that this procedure not only stimulates the growth of new nerves, but also promotes the healing of scars left after the initial injury. Although it did not lead to a complete cure of the animals, they still partially recovered their lost motor functions. They could no longer run, but after two months they were able to move independently.

Professor Stapp became one of the founders of the young company Nanotope, which intends to improve the new material in order to use it in clinical practice. Scientists have already started testing its effects on human cell cultures and have not yet revealed any negative effects.

Cellular reprogramming against Parkinson's diseaseResearchers at the Massachusetts Institute of Technology and Harvard University have obtained encouraging results when using specially designed nerve cells to fight a severe neurodegenerative disease – Parkinson's disease.

To begin with, it is worth recalling our previous message on this topic. At the end of March, American and Japanese scientists announced that in this way they managed to improve the condition of mice in which brain damage similar to Parkinson's disease was artificially caused. In those experiments, embryonic stem cells obtained using a well-developed therapeutic cloning technique were used.

This term is commonly used to denote the receipt of cloned embryos for the use of their cells or tissues for medical purposes. Scientists extracted stem cells from grown embryos and, with the help of biostimulators, forced them to turn into exactly those neurons that die in Parkinson's disease. Then these neurons were implanted in the very mice from which the genetic material was taken for cloning. In animals that underwent such a transplant, there was a significant reduction in the symptoms of parkinsonism.

The new experiments carried out in the laboratory of the well-known stem cell specialist Rudolf Janisch, on a superficial examination, may seem almost a simple repetition of previous experiments. They also used animals in which exactly those neurons that die in Parkinson's disease were destroyed – only this time they were not mice, but rats.

Experimenters, as before, first created new nerve cells of this type, and then injected them into the brains of sick animals. After 8 weeks, almost all rats that had such a transplant had a significant decrease in the intensity of symptoms of Parkinson's disease.

However, this is by no means the whole story. The principal feature of the new experiments is that they did not use embryonic stem cells at all. Marius Wernig and his group members used a much newer technology for creating stem cells, or rather, their very close analogues, instead of therapeutic cloning.

They extracted skin cells from the animals' tails and subjected them to genetic reprogramming. Four genes were implanted into the cell nuclei with the help of viral carriers, which forced the "operated" cells to acquire almost the same ability for diverse transformations that real embryonic stem cells possess. After that, scientists in a standard way forced these cells to give rise to specialized neurons needed for the treatment of Parkinson's disease.

Such functioning models of embryonic stem cells are called induced pluripotent cells, IPCs.  For the first time, their creation was announced only in 2007, and first animal IPCs were obtained, and then human ones. Soon, American researchers successfully used IPC in animal experiments for gene therapy of a severe disease of the hematopoietic organs, sickle cell anemia. The results of the new experiments allow us to hope that IPCs can also become raw materials for obtaining nerve cells that restore brain function in Parkinson's disease.

Of course, these experiments are still very, very far from creating effective therapies for Parkinson's disease and other neurodegenerative diseases. Scientists still do not know how artificial neurons behave after transplantation and what connections they enter into with other brain cells. Researchers will also have to check how safe such a transplant is and, in particular, prove that it does not threaten the occurrence of brain tumors. So there is a lot of work ahead.

Bacteria on bacteriaResearchers from the Massachusetts Institute of Technology have successfully tested an experimental method of bacterial production of a previously unknown antibiotic.

Unicellular organisms often synthesize chemical compounds that help them survive in competition with other inhabitants of the microcosm. These substances have been used for many decades in medicine under the name of antibiotics to fight various infections. The first of the antibiotics that entered clinical practice, the famous penicillin, was discovered by the Scottish bacteriologist Alexander Fleming back in 1929.

Although nowadays many antibiotics are produced using synthetic chemistry methods, the main source of new drugs of this type are microorganisms - bacteria and fungi. Therefore, scientists are constantly testing the ability of a wide variety of microbes to produce compounds with antibacterial properties. Recently, genetic information has been widely used in such searches.

This is the path taken by MIT researchers working in the laboratory of Professor of microbiology Anthony Sinsky. In the course of their experiments, they decoded the genome of the soil bacterium Rhodococcus fascians. It turned out that her hereditary information includes several genes that encode the synthesis of substances structurally similar to already known antibiotics. If the bacterium was simply grown on nutrient media, these genes were inactive. However, they started working when the experimenters began to cultivate it together with another soil bacterium from the Streptomyces family.

Microbes of this group serve as a source of a number of strong antibiotics, including streptomycin and erythromycin. The researchers expected that the studied bacterium would react to the streptomycete neighborhood by activating its antimicrobial genes.

The idea turned out to be successful. One of the strains of the bacterium Rhodococcus fascians in these conditions began to produce a previously unknown substance, with which he eventually suppressed the reproduction of Streptomyces bacteria. Scientists have named the new compound rodostreptomycin. Chemical analysis has shown that this compound belongs to the group of aminoglycosides, a well-known family of broad-spectrum antibiotics, which also contains such well-known drugs as neomycin, gentamicin and amikacin.

Its properties have yet to be determined, but the first tests showed that it kills pathogenic strains of E. coli and microbes of the species Helicobacter pilory, which are the main cause of ulcerative lesions of the stomach and duodenum. 

The rhodostreptomycin molecule contains a previously unknown ring atomic structure that can become the foundation for the chemical synthesis of new drugs. So there is reason to believe that even if rodostreptomycin itself does not enter clinical practice, it may turn out to be the ancestor of a whole generation of promising antibiotics.

Antimalarial drug cures toxoplasmosisThe experimental drug JPC-2056, which will soon enter clinical trials as a cure for malaria, may become a new highly effective means of combating toxoplasmosis.

Both of these diseases are caused by parasitic protozoa, only of a different nature. Malaria occurs when infected with protozoa of the genus plasmodium, which are carried by anopheles mosquitoes. Toxoplasmosis develops when the protozoa Toxoplasma gondii enter the body, which penetrate through the digestive tract. This disease affects the lymphatic system and is especially dangerous for people with weakened immune systems.

The drug JPC-2056 has already fully passed preclinical testing on animals. She showed that this drug affects all varieties of the malaria parasite without exception, including those that, due to mutations, have acquired resistance to standard antimalarial drugs. It blocks the action of the enzyme dihydrofolate reductase, which plays a key role in the vital activity of plasmodium. The same enzyme is produced by the pathogens of toxoplasmosis. Therefore, researchers from the University of Chicago, led by Professor Rima McLeod, decided to check whether it is possible to fight this disease with the help of JPC-2056.

Their hypothesis was fully confirmed. Experiments on mice infected with toxoplasmosis allowed us to establish that JPC-2056 completely eliminates all the symptoms of the disease in just a few days. Experiments on cell cults have shown that this drug completely destroys toxoplasmosis parasites. This allows us to hope that after completing the course of treatment, the disease will not relapse.  Chicago scientists believe that JPC-2056 will prove to be excellent in clinical trials.

Healing HormonesIt is hoped that osteoporosis will be managed with the help of a thyroid-stimulating hormone that stimulates the thyroid gland.

This is stated in an article by researchers at the New York medical Center "Mount Sinai". They experimented on rats with artificially induced osteoporosis. Sick animals were injected with recombinant human thyroid-stimulating hormone, the production of which was mastered by the American biotechnology company Genzyme. It turned out that just one injection per week leads to a gradual normalization of bone density, which falls with osteoporosis. Since thyroid-stimulating hormone was administered in low doses, there were no malfunctions in the thyroid gland.

The researchers emphasize that hormone therapy effectively strengthens the spongy bone tissue of the hips and spine. This tissue wears out greatly with age, which increases the risk of life-threatening fractures of the femoral neck and contributes to the curvature of the spinal column.

Thyroid-stimulating hormone is synthesized in the pituitary gland, one of the main endocrine glands of the brain.  Acting on the thyroid gland, it causes it to produce biologically active substances triiodothyronine and thyroxine, which are involved in regulating metabolism. In recent years, a recombinant version of this hormone has been used to treat thyroid cancer.

Dangerous inheritanceGerontologists at Washington State University have confirmed that hereditary factors play a great role in the development of Alzheimer's disease.

Thomas Byrd and his colleagues have been collecting information about the health status of people whose father and mother were victims of this disease for many years. They found data on 111 such parent pairs. These people had a total of 297 adult children of different ages, of which 68 people also suffered from Alzheimer's disease.

Thus, the proportion of patients in this group was 23%, which is much higher than the average figures. The researchers also found that the survey participants most often began to show symptoms of dementia at the age of 66 - much earlier than the average time. This gives grounds to assert again that the tendency to this neurodegenerative disease is transmitted from parents to children.

Medications for metastasesOncologists of the University named after

Washington in St. Louis has found a new way to drug prevention of cancer metastasis.

Tumors arise in the form of primary foci, which can often be surgically removed or destroyed with the help of penetrating radiation. However, such foci can send their cells to other organs, where they give rise to secondary neoplasms. This process is called metastasis. Metastatic tumors are much more difficult to fight, so they are the main cause of death of cancer patients. According to medical statistics, they account for over 90% of terminal cancer cases.

Cancer cells can migrate in various ways, including through the bloodstream. On this journey, they use the help of one of the components of blood, blood plates. This is the name of small corpuscles, which play a major role in blood clotting. Unlike leukocytes and erythrocytes, blood plates do not have nuclei and therefore are not real cells. However, they are involved in many biological processes.

In particular, the blood plates secrete biologically active substances that contribute to the survival of tumor cells. And these cells, for their part, secrete molecules that cause blood plates to stick together on their surface. As a result, the cancer cell acquires a sticky shell that performs two functions at once. It protects this cell from attack from the immune system and at the same time serves as an anchor anchoring it in a new place.

The researchers suggested that metastasis through the bloodstream can be combated by affecting the blood plates. Their experiments have shown that for this it is necessary to act with two drugs at once. One of them is the most common aspirin, which, as has long been known, prevents blood clotting. It deactivates the enzyme cyclooxygenase, which the blood plates use to produce thromboxane, a substance that promotes the formation of blood clots.

However, experiments have shown that aspirin needs an assistant to slow down the growth of metastases. In this capacity, the experimental drug APT102, created by the pharmaceutical company APT Therapeutics, has proven itself well. This medicine blocks the chemical signals by which tumor cells attract blood plates to themselves.

Catherine Weilbacher and her colleagues tested the combined effect of aspirin and APT102 on mice that had been transplanted with aggressive skin and breast tumors. Although such therapy did not put an end to the formation of metastases in bone tissue, it led to a sharp decrease in the size of secondary tumors. The experimenters consider the results very encouraging and intend to continue working in this direction.

Useful harmful mutationsIncomplete versions of three extremely dangerous gene mutations result in great health benefits.

This information is contained in an article by researchers at Yale University. Professor Richard Lifton and his colleagues studied anomalies of three genes NKCC2, ROMK and NCCT, which are directly related to kidney function.

It has long been known that mutations of the first two genes lead to a serious disease, which was first described by American endocrinologist Frederick Bartter in 1962. Mutations of the third NCCT gene cause a similar in symptoms, but not so severe disease, Gitelman syndrome. Both diseases occur only in people who receive defective variants of these genes from both the father and the mother.

In Bartter and Gitelman syndromes, the kidneys secrete excessive amounts of potassium and sodium together with urine. As a result, the content of these elements in the blood drops sharply, which leads to many pathological consequences. For example, children with Bartter syndrome grow up slowly, suffer from muscle weakness and often show mental retardation. In addition, these diseases can develop severe hypotension, a sharp decrease in blood pressure. Therefore, researchers from the Lifton group suggested that people who inherit from their parents only one defective version of any of the three culprit genes will be less likely to develop hypertension.

This hypothesis was confirmed. The collected data suggest that having only one mutant copy of the NKCC2, ROMK or NCCT gene reduces the likelihood of hypertension in middle and old age by about 60% during the first sixty years of life. Scientists believe that the total number of carriers of mutations of this type in the population of the planet is approaching one hundred million.

Green tea against cancerThe staff of the University of Mississippi in Jackson received new data in support of the hypothesis that green tea prevents the growth of malignant tumors.

Oriental doctors have claimed since time immemorial that this drink has many healing properties. It is now known that it contains strong antioxidants, which in principle can hinder the development of many pathological processes. These include epigallocatechin-3-gallate, which protects cells well from breakdowns caused by free radicals. Therefore, its therapeutic potential is of great interest to physicians.

Scientists from Jackson decided to test how this substance affects the progress of breast tumors. This experiment was performed on female mice that had been implanted with tumor cells. A week before transplantation, some animals were daily mixed with pure epigallocatechin-3-gallate in drinking water. It turned out that in these mice, tumors grew three times slower than in mice from the control group who were given clean water.

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24.04.2008