Anti-addiction medication

Drug addiction continues to plague vast numbers of people across the world, destroying and ending lives, while attempts to develop more effective pharmaceutical addiction treatments continue.
Vigabatrin is an anti-epilepsy medication approved by the Food and Drug Administration that has also been shown to be effective against addiction to cocaine, nicotine, methamphetamine, heroin and alcohol in animal models.

In humans, vigabatrin eliminates cocaine addiction in 28 percent of patients. It works by blocking an enzyme-aminobutyric acid (GABA) aminotransferase, which breaks down GABA. The result is higher levels of this neurotransmitter in the brain and diminished narcotic-activated release of dopamine. Long-term vigabatrin therapy can have serious side effects however, causing eye damage in up to 40 percent of those treated.

In previous work, the researchers designed a compound, CPP-115, that is 186 times more efficient in inactivating GABA aminotransferase than vigabatrin. In this study, they used computational molecular dynamics simulations of CPP-115 in complex with the enzyme to develop a new and improved agent with 10 times greater efficiency.

The drug should also be less likely to cause side effects, as it has fewer off-target activities in in vitro tests. In initial rat experiments, the new compound was far better at blocking dopamine release after a cocaine or nicotine stimulus than CPP-115.
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Symdeko for treating cystic fibrosis

The U.S. Food and Drug Administration (FDA) has approved Symdeko (ivacaftor/tezacaftor tablets and ivacaftor tablets) for treating the underlying cause of cystic fibrosis (CF) in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor.

Do not take Symdeko if you take certain medicines or herbal supplements such as: antibiotics such as rifampin (Rifamate, Rifater) or rifabutin (Mycobutin) seizure medicines such as phenobarbital, carbamazepine (Tegretol, Carbatrol, Equetro), or phenytoin (Dilantin, Phenytek)

Symdeko consists of 2 different tablets. The yellow tablet is marked with ‘V100’ and contains the medicines tezacaftor and ivacaftor. Take one yellow tablet in the morning. The light blue tablet is marked with ‘V150’ and contains the medicine ivacaftor. Take one light blue tablet in the evening. Take the yellow tablet and the light blue tablet about 12 hours apart.

Always take Symdeko with food that contains fat. Foods like egg, butter, peanut butter, cheese, pizza, and whole-milk dairy products such as whole milk, cheese, and yogurt. If you miss a dose and it is six hours or less from the time you usually take the yellow tablet in the morning or the light blue tablet in the evening, take the missed dose with food that contains fat as soon as you can. Then take your next dose at your usual time and it is more than six hours from the time you usually take the yellow tablet in the morning or the light blue tablet in the evening, do not take the missed dose. Take your next dose at the usual time with food that contains fat. Do not take more than usual dose to make up for a missed dose.

Symdeko can cause dizziness in some people who take it. Do not drive a car, use machinery, or do anything that needs you to be alert until you know how Symdeko affects you. Avoid food or drink that contains grapefruit or Seville oranges while you are taking Symdeko. It can cause serious side effects, including: high liver enzymes in the blood.

Call your doctor right away if you have any of the following symptoms of liver problems:pain or discomfort in the upper right stomach (abdominal) area, yellowing of your skin or the white part of your eyes, loss of appetite, nausea or vomiting, dark amber-colored urine. Abnormality of the eye lens (cataract) in some children and adolescents treated with Symdeko or treated with ivacaftor alone. If you are a child or adolescent, your doctor should perform eye examinations before and during treatment to look for cataracts. The most common side effects include: headache, nausea, sinus congestion and dizziness.
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Small molecule reduce the spread of cancer

One small molecule that regulate gene expression plays a big role in keeping human safe from the machinations of cancer. In human lung cancer cells, low levels of the microRNA, miR-125a-5p, which enables the death of aberrant cells like cancer cells, correlates with high levels of the protein TIMP-1, which is already associated with a poor prognosis in patients with cancer.

Conversely, when they decrease TIMP-1 levels in these highly lethal cancer cells, tumor spread goes down while rates of cell death go up along with expression of miR-125a-5p, says Dr. Mumtaz V. Rojiani, cancer biologist in the Department of Medicine at the Medical College of Georgia and a member of the Molecular Oncology and Biomarkers Program at the Georgia Cancer Center at Augusta University.

While increasing microRNA levels is technically difficult, further delineating how cancer hijacks these normal body systems may help identify new treatment targets. TIMP-1 has a positive role in a healthy body to balance levels of enzymes the body makes to ease cell movement for things like wound healing or reproduction.

The healthy body and cancer make these enzymes, matrix metalloproteinases, or MMPs, to break down the surrounding matrix that helps keep cells stable. While it's critical to positives like wound healing, when the matrix breakdown is usurped by cancer, it also gives cancer cells this freedom to move.

In cancer, TIMP-1 levels rise dramatically and it has a distinctive role enabling both growth of new blood vessels and inhibition of apoptosis, a cell's natural inclination to die if something unfixable is wrong. In cancer, what the tumor cells do is start secreting a lot more of these enzymes so they can break down the matrix and start migrating and metastasizing.

Classically, TIMP-1 should be inhibiting MMPs but over the years it has been found to have other functions that actually increase tumor aggressiveness. In their studies of TIMP-1 expression in human lung cancer cells, they saw this aggressive response. It turned out that TIMP-1 is like a two-faced individual smiling at cancer sometimes and other times cutting it off.

Increased levels of two-faced TIMP-1 have been found in increased tumor spread and poor prognosis in breast, gastric and colorectal cancers as well as the non-small cell lung cancer the MCG scientists studied, which accounts for about 85 percent of all lung cancers and has a five-year survival rate of under 20 percent.

TIMP-1 overexpression also is associated with increased upregulation of Bcl-2, a protein which can prevent apoptosis, or cell death. To make bad matters worse, a key way chemotherapy works is by inducing apoptosis and TIMP-1 has been associated with potentially deadly drug resistance.
However, with high expression of miR-125a-5p, TIMP-1 becomes the target. One result is increased expression of the gene p53, a known tumor suppressor, which enables cell death.

When ressearchers knocked down TIMP-1 expression, it significantly increased expression of miR-125a-5p. Conversely, when they restored higher levels of TIMP-1, miR-125a-5p expression went down. The look of the cancer cells changed with the level of TIMP-1. At high levels they looked more like cells unshackled from their current location and able to migrate and invade. When they decreased TIMP-1 levels, the cells pretty much stayed put.

 Adding more synthetic miR-125a-5p to the cancer cells, and the lung cancer cells moved more toward a stationary normal look and cell death increased. When they inhibited miR-125a-5p, the cells were ready to roam. Looking at the biopsies of lung cancer patients, they found as expected TIMP-1 expression much higher in the lung cancer tissue than nearby healthy tissue. But they also saw an inverse relationship between high levels of TIMP-1 and miR-125a-5p levels. In fact, tumor cells had almost no miR-125a-5p.
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Are you tired of being tired? Eat these

Are you tired all the time? if yes your level of iron may be low, you can eat the following foods to regain your strength. Egg yolk is a great source of iron. It is needed for production of haemoglobin, the protein in the red blood cells that transports oxygen around the body to produce energy in the muscles, tissues and cells.

A deficiency in iron can lead to a type of anaemia that will leave you feeling drained and weak. This tends to be more common in women, especially if they experience heavy blood loss during menstruation. Eat more of venison than beef, as it contains twice as much iron. Eating Vitamin C-rich foods with plant sources of iron, such as red peppers with tofu or green salad with lentil bake can enhance absorption.

 Brown rice is a good source of fibre-rich complex carbohydrate, eat it regularly with five different fruits and vegetables. Leafy greens such as spinach are packed with magnesium, which makes this a glass of pure energy. If you're low in this mineral, as many people are, you'll feel absolutely drained. Magnesium activates the enzymes that starts energy-production process in the body.

Sardines, salmon, tuna,meat and egg are excellent sources of Vitamin B12. All B vitamins play a crucial part in the supporting our energy levels. B12 works in partnership with folate (Vitamin B9) to form red blood cells and to enhance the absorption of iron in the body. Avoid refined sugar, alcohol, and processed foods. Stay hydrated- water transport nutrients and oxygen around the body in order to support energy production. Dehydration can reduce your energy  and cause fatigue.
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Selenium protects interneurons in the brain

A team led by Dr. Marcus Conrad, research group leader at the Institute of Developmental Genetics (IDG) at Helmholtz Zentrum München, showed for the first time why selenium is a limiting factor for mammals. The scientists have been investigating for years the processes of a novel type of cell death, known as ferroptosis. The enzyme GPX4, which normally contains selenium in the form of the amino acid selenocysteine, plays an important role.

In order to better understand the role of GPX4 in this death process, they established and studied mouse models in which the enzyme was modified.In one of these models, they observed that mice with a replacement of selenium to sulfur in GPX4 did not survive for longer than three weeks due to neurological complications.

In their search for the underlying reasons, the researchers identified a distinct subpopulation of specialized neurons in the brain, which were absent when selenium-containing GPX4 was lacking.
Furthermore, the scientists were able to show that ferroptosis is triggered by oxidative stress, which is known to occur for instance during high metabolic activity of cells and high neuronal activity.

 Selenium-containing GPX4 protects these specialized neurons from oxidative stress and from ferroptotic cell death. Selenoenzymes are essential in some organisms, including mammals, whereas they are dispensable in other organisms, such as fungi and higher plants.
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Ebola virus inhibited in cell cultures

When the Ebola virus enters the human cell, its only purpose is to copy itself, fast. First it must copy all its proteins, then its genetic material. But by inhibiting a specific enzyme we rob the Ebola virus of its ability to copy itself. And that may potentially prevent an Ebola infection from spreading.

When Ebola virus ravaged West Africa, where thousands of people died from the extremely infectious Ebola infection. Once you are infected, all you can do is hope that your own immune system is able to kill the infection, because there is no treatment for Ebola presently.

However, the researchers behind the new study have found what is called a new host factor for Ebola virus. It can be described as a small part of the host's-for example the human body's-own cells, which the Ebola virus uses to copy itself and produce more infection. The virus uses the host factor enzyme PP2A-B56 to start producing proteins. So if the researchers switch off PP2A-B56, the virus' ability to copy itself and produce more infection is never 'switched on.

When we inhibit the PP2A-B56 enzyme, we remove the first link in a long process, which ends with Ebola spreading. The Ebola infection in cell cultures where we have inhibited the PP2A-B56 enzyme is 10 times smaller after 24 hours compared to infections where we have not inhibited this enzyme. But because the researchers have so far focused on cell cultures, there is still work to be done before their results can be used to treat people infected with Ebola.

 Initially the researchers hope to be able to test it on animals and, in the long term, develop a drug that inhibits the relevant enzyme.The potential of the new discovery may turn out to work on other viruses too, because the structure of Ebola virus is very similar to the other filoviruses.
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Link between obesity and diabetes

Researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight. In obesity, insulin released into the blood by the pancreas is unable to pass through the cells that form the inner lining of blood vessels.

As a result, insulin is not delivered to the muscles, where it usually stimulates most of the body's glucose to be metabolized. Blood glucose levels rise, leading to diabetes and its related cardiovascular, kidney and vision problems.

 A major problem in obesity is the delivery of circulating insulin to the muscle, this problem involves immunoglobulins, which are the proteins that make up circulating antibodies. The researchers found that obese mice have an unexpected chemical change in their immunoglobulins.

The abnormal immunoglobulins then act on cells lining blood vessels to inhibit an enzyme needed to transfer insulin from the bloodstream into the muscle. Type 2 diabetes patients have the same chemical change, and if immunoglobulins from a type 2 diabetic individual is given to a mouse, the mouse will becomes diabetic.
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Natural immune suppressor responsible for early death in leukemia patients

Patients diagnosed with the most common form of leukemia who also have high levels of an enzyme known to suppress the immune system are most likely to die early. High levels of this enzyme, indoleamine 2,3 dioxygenase, or IDO, at diagnosis also identify those who might benefit most by taking an IDO inhibitor along with their standard therapy.

A review of patients with acute myeloid leukemia, or AML, found increased IDO expression in the bone marrow biopsy, performed to diagnose their disease, correlated with lower overall survival rates and early mortality. It also indicates that IDO expression should routinely be measured when the diagnostic bone marrow biopsy is performed, Everyone has the IDO gene, it's the cancer cells in this scenario that activate the disabler of the immune response that is also used by the fetus and solid tumors.

 Stem cells in the bone marrow are supposed to mature into a variety of cells that enable human blood and immune system function. Instead in AML, stem cells get stuck in an in-between, undifferentiated state called blasts.In leukemia, stem cells get limboed in the blast state so you don't get any maturation. That means there are low platelets so you get clotting problems, you have low neutrophils so you have infections, you have less red blood cells so you get anemic.

Bleeding is a major cause of death for patients and often, significant gum bleeding is the first indicator. The patients who died at six months had a high expression of IDO while the blasts produced relatively little IDO in the patients who lived five years or more. During pregnancy, cells in the placenta trigger an isolated suppression of the mother's immune system so it won't reject the genetically foreign fetus. They showed that IDO locally disables the mother's immune system by degrading tryptophan, an amino acid essential to survival of T cells , orchestrators of the immune system's response.

Later work would show that tumors - and leukemia - also use IDO to hide from the immune response. Conversely, some organ transplant patients who inexplicably express higher levels of IDO, have lower rejection rates of their new organ. Induction therapy is given to get the patient into remission, and is typically followed by more chemotherapy to ensure it stays dormant.
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How protein breakdown causes leukemias and brain cancer

An enzyme that is responsible for the breakdown of specific amino acids in food plays a key role in the development of leukemias and brain cancer. The researchers have discovered a surprising link between energy metabolism and the epigenetic code. These labels in the DNA of cancer stem cells determine the activity of genes and many cellular functions.

Acute myeloid leukemia AML is an aggressive type of blood cancer that often relapses in the wake of successful initial treatment. Stem cells that are resistant to therapy are believed to be responsible. Reseachers examined patient samples by comparing the composition of proteins of AML stem cells and leukemia cells without stem cells properties.

The investigators found suspiciously high levels of an enzyme called BCAT1 in the stem cells. These levels rose even higher during a cancer recurrence. The researchers considered this to be a clue that BCAT1 might be linked to therapy resistance. Cancer researchers have suspected for some time that the BCAT1 enzyme, which is responsible for the breakdown of specific proteins in food, plays a role in the development of malignant tumors.

 They discovered that an overproduction of BCAT1 increases the aggressiveness of malignant brain tumors and breast cancer. BCAT1 reduces the levels of this key molecule and this leads to increased levels of chemical labels in the DNA. The tiny methyl groups that are attached to DNA determine whether particular genes are active or silent and, thus, have an immense impact on all cellular functions.

They increase cancer-promoting methylation of DNA. AML is known for an extremely heterogeneous pattern of genetic alterations. However, misregulated methylation with its drastic consequences for the whole cell appears to be a common characteristic of this malignant disease.

The finding that BCAT1 drives cancer-promoting methylation in AML stem cells and other cancer stem cells opens up new options for therapy. A blockade of the enzyme using a targeted agent might normalize DNA methylation and thereby reduce cancer spread and therapy resistance.
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Aliqopa for treating follicular lymphoma

Aliqopa drug (copanlisib) is for the treatment of adults with relapsed follicular lymphoma who have received systemic therapies. For patients with relapsed follicular lymphoma, the cancer often comes after multiple treatments.

Follicular lymphoma is a slow-growing type of non-Hodgkin lymphoma, a cancer of the lymph system. The lymph system is part of the body’s immune system and is made up of lymph tissue, lymph nodes, the spleen, thymus, tonsils and bone marrow.

Aliqopa is a kinase inhibitor that works by blocking several enzymes that promote cell growth. Common side effects of Aliqopa include high blood sugar levels, diarrhea, fatigue, high blood pressure, low levels of certain white blood cells, nausea, lower respiratory tract infections, and low levels of blood platelets.

Serious side effects include infections, high blood sugar levels, hypertension, inflammation of the lung tissues, low neutropenia and severe skin reactions. Women who are pregnant or breastfeeding should not take Aliqopa because it may cause harm to a developing fetus or newborn baby.
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Lockdown gene to increase IVF success rate

In Vitro Fertilization IVF is an assisted reproductive technology, it is the process of fertilization by extracting eggs, retrieving sperm and manually combining an egg and sperm in a laboratory dish. The embryo is then transferred to the uterus.

Human egg and sperm cells have their genes trained to fertilize. After fertilization, the developing embryo begins the genetic program that turns a single cell into a healthy fetus.

Epigenetic changes to the DNA, like the removal of methyl group locks by enzymes, which allows many more genes to be read. Some genes need to be locked down during development, as their genetic messages cause problems for the embryo.

Everything that goes wrong in embryos has the potential to cause infertility or early pregnancy abortions. The scientists sequenced the RNA of more than 30 embryos lacking Trim28 and discovered that Rbmy1a1 gene was unusually active.

The enzyme encoded by Rbmy1a1 produces mRNA transcripts which are harmful to the developing embryo. Detecting the activity of detrimental genes like Rbmy1a1 before an embryo is implanted could improve rates of IVF success.
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New method of fighting malaria

Malaria parasites attack red blood cells and form an internal section where they multiply many times before infecting more cells. The parasites have to break through the internal section and the cell membrane by using different protein and enzymes to prevent coming in contact with red blood cells.

Interrupting the protein lowers the capacity of the parasite, prevents escape and reduces the rate of infection. The parasite in its internal section inside the cell are surrounded by proteins - SERA5 protein.

Researchers knock out the protein using genetic tools, the gene is responsible for production of  SERA5 protein in malaria parasites. They found that the parasites broke through the membranes faster than normal but many got stuck on their way when tested under microscope. It shows that they may not attack other red blood cells.

Malaria parasites can not survive for long outside red blood cells, so if they are prevented from getting to red blood cells  while trying to escape, they might die before they have a chance to infect another cell.

Malaria parasites without SERA5 protein were not as strong as normal parasites with the protein while escaping and infecting new cells.
Researchers are planning to use SERA5 or one of the enzymes to produce an antimalarials drug.
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How enzyme lowers weight gain

Obesity can be prevented with healthy diet and regular exercise. People tend to gain weight as they age, particularly around the stomach.

The researchers were led by Dr. Jay H. Chung, Ph.D., head of the Laboratory of Obesity and Aging Research at the National Heart, Lung, and Blood Institute, which is a part of the NIH.

Specific enzyme inhibitor lowers weight gain by 40 percent
Chung and team investigated the biochemical transformations that take place in animals in their middle age.

Looking at animals that were the equivalent of 45 human years old, Chung and team found that an enzyme - called DNA-dependent protein kinase (DNA-PK) - becomes more active with age.

Furthermore, the researchers found that DNA-PK turns nutrients into fat and lowers the number of mitochondria.

The younger we are, the more mitochondria we have in our bodies. From midlife onward, however, the number of mitochondria starts to decrease.

 It is known that a lower number of mitochondria can lead to obesity, and mitochondrial dysfunction has been associated with a decrease in one's ability to exercise.

To further understand the role of the DNA-PK enzyme, Chung and team tested its effect on two groups of mice. Both groups were fed a high-fat diet, but one group received an inhibitor that blocked the DNA-PK enzyme, while the other group did not.

The group that received the DNA-PK-inhibiting drug gained 40 percent less weight than those that did not receive the drug. Additionally, the drug increased aerobic fitness and decreased the rate of obesity and type 2 diabetes in obese, middle-aged mice.
Finally, the inhibitor also increased the number of mitochondria in the mice's skeletal muscle.

Swimming condition in the uterus and fertility

Before conception can take place in mammals, the semen and the egg must be in good condition. Male and female mammals have to contribute to conception before it can take place.

Researcher in Washington State University has found that uterus in female mice has enzymes that can break semen into watery form and make it easier to swim for conception to take place.

Female mice produce the enzyme using estrogen to cause the process of breaking down the semen. Lack of gene to induce the process will leads to failure of the semen in the uterus.