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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Bacteria in milk linked to rheumatoid arthritis

A strain of bacteria found in milk and beef may be a trigger for developing rheumatoid arthritis in people who are at risk, according to a new study from the University of Central Florida. A team of UCF College of Medicine researchers has discovered a link between rheumatoid arthritis and Mycobacterium avium subspecies paratuberculosis, known as MAP, a bacteria found in about half the cows in the United States. The bacteria can be spread to humans through the consumption of infected milk, beef and produce fertilized by cow manure.

For the study, researchers recruited 100 of her patients who volunteered clinical samples for testing. Seventy-eight percent of the patients with rheumatoid arthritis were found to have a mutation in the PTPN2/22 gene, the same genetic mutation found in Crohn's patients, and 40 percent of that number tested positive for MAP. People born with this genetic mutation and who are later exposed to MAP through consuming contaminated milk or meat from infected cattle are at a higher risk of developing rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune and inflammatory disease that causes the immune system to attack a person's joints, muscles, bones and organs. Patients suffer from pain and deformities mostly in the hands and feet. It can occur at any age but the most common onset is between 40 and 60 years old and is three times more prevalent in women. Some RA patients suffer from Crohn's disease and vice versa, the researchers say a national study needs to investigate the incidence of the two diseases in the same patients.
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How alcohol damages DNA and causes cancer

Scientists have shown how alcohol damages DNA in stem cells, helping to explain why drinking increases the risk of cancer, according to latest research. Researchers used mice to show how alcohol exposure leads to permanent genetic damage. Scientists at the MRC Laboratory of Molecular Biology, Cambridge, gave diluted alcohol, chemically known as ethanol, to mice.

They then used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde, a harmful chemical produced when the body processes alcohol. They found that acetaldehyde can break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells.

It is important to understand how the DNA blueprint within stem cells is damaged because when healthy stem cells become faulty, they can give rise to cancer. These new findings therefore help us to understand how drinking alcohol increases the risk of developing 7 types of cancer including common types like breast and bowel.

Some cancers develop due to DNA damage in stem cells while some damage occurs by chance. The study also examined how the body tries to protect itself against damage caused by alcohol. The first line of defence is a family of enzymes called aldehyde dehydrogenases (ALDH). These enzymes break down harmful acetaldehyde into acetate, which our cells can use as a source of energy.

In the study, when mice lacking the critical ALDH enzyme - ALDH2 - were given alcohol, it resulted in four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme. The second line of defence used by cells is a variety of DNA repair systems which, most of the time, allow them to fix and reverse different types of DNA damage. But they don't always work and some people carry mutations which mean their cells aren't able to carry out these repairs effectively.

The study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers. But it's important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defence mechanisms are intact.
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Viruses share gene with some organisms

A new study finds that viruses share some genes exclusively with cells that are not their hosts, viruses swap genes with a variety of cellular organisms and are agents of diversity. The study looked at protein structures in viruses and across all domains of life: from the single-celled microbes known as bacteria and archaea, to eukaryotes, a group that includes animals, plants, fungi and all other living things.

Viruses that infect archaea and bacteria, for example, are not known to infect eukarya. However, they may still interact in non harmful ways with organisms they do not infect. The team used a bioinformatics approach to analyze the genomes of organisms and the viruses that infect them. Rather than focusing on genetic sequences, which can change over the generations, the team examined the functional components of proteins, which they call folds.

 There are more than 1,400 of folds across all domains of life-has a unique 3-D structure that performs a specific operation. Because folds are critical to protein function, they remain stable even as the sequences that code for them change as a result of mutations or other processes.This makes protein folds reliable markers of evolutionary changes over vast time periods, especially for viruses that mutate notoriously fast.

The researchers found hundreds of folds that are present across all domaind of life and in all types of viruses, which suggests that they came from an ancient ancestor of all life forms. Some folds, however, occur only within a single domain and the viruses that infect it, suggesting a transfer of genetic material only between that group of viruses and their hosts. Out of a total of about 2,000 superfamilies of folds, the team found one that was exclusive to archaea and the viruses that infect archaea, 29 shared only by bacteria and the viruses that infect them, and 37 that are exclusive to eukaryotes and their viruses.

The data also point to other, as yet unknown, mechanisms that allow viruses to exchange genetic material with cells, many virus-hallmark genes in cellular organisms those viruses are not known to infect. People tend to think only about viruses that infect and kill their hosts, we have known for decades that a virus will sometimes enter into a cell and incorporate its genetic material into the cell without killing it. In the case of single-celled organisms, those genes are sometimes passed along to future generations. Human DNA, too, contains remnants of viruses.

Some retroelements and transposons are believed to have originated in ancient viruses. Retroelements are sequences copied from RNA viruses into DNA and inserted into the genomes of nonviral organisms. Transposons, also known as "jumping genes," can move from one part of the genome to another.The team also discovered a large subset of virus-specific protein folds that were not present in any cellular genomes. This suggests that viruses can create new genes and, potentially, transfer those genes to cellular organisms.
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Aspiring improves effectiveness of cancer treatment

Adding aspirin to some existing cancer drugs could increase their effectiveness against a group of tumours resistant to treatment, scientists are hoping clinical trials could soon be underway for people with lung, pancreatic and colorectal cancers that have not responded to other therapies.

Cancers driven by mutations in a group of genes, known as RAS, had a low response to treatments with currently no drug directly targeting them. The group of tumours includes some pancreatic, lung and colorectal cancers with very low survival rates, as well as a small percentage of melanomas.
Addition of aspirin to a cancer inhibitor drug, Sorafenib, strongly enhanced its effectiveness against mouse models of lung cancer and melanoma with RAS mutations.

In a multicentre phase three trial for non-small cell lung cancer, Sorafenib alone showed a marginal improvement for patients. Latest research suggests its combination with aspirin could benefit patients with RAS mutations who don't otherwise respond to other treatments.
The drug combination could potentially reduce the dose of Sorafenib required, improving quality of life for patients by reducing adverse impacts that can lead some patients to stop treatment.

Combining it with a relatively high dose of aspirin, two molecular processes are activated and together they work to kill RAS mutant cancer cells. This dual activation also might prevent the tumours acquiring resistance to the treatment, which can happen when the inhibitor drug is given alone.
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Papillomaviruses cause non-melanoma skin cancer

UV radiation has been known for a long time to be a risk factor for the development of skin cancer. Simultaneous infection with human papillomaviruses (HPV) has also been suspected to promote skin cancer, particularly in organ transplant recipients.

Papillomaviruses associated with UV light promote the development of non-melanoma skin cancer. The investigators provide an explanation why the viruses can be detected in benign human cancer precursors but not in advanced carcinoma.
Everyone is infected with skin-typical ("cutaneous") human papillomaviruses (HPV) at some point in their lives, usually in early childhood.

In healthy people, the immune system can fight off the viruses, but this often changes in older age. Recipients of organ transplants whose immune system is suppressed by long-term drug therapy to prevent transplant rejection are particularly at risk. Ultraviolet radiation exposure is generally known to be a major risk factor for skin cancer. Non-melanoma skin cancer occurs primarily on sun-exposed sites of the body.

Researchers used a specific species of mice that usually contracts infection with papillomaviruses shortly after birth, like humans. They compared the virus-infected animals with control animals that were raised in a completely virus-free environment. They exposed the animals to UV radiation at a dose that could be expected during a vacation in Mediterranean regions.

Subsequently, only virus-infected animals developed non-melanoma skin cancer (squamous cell carcinoma ) while the virus-free control animals did not. They noticed a glance that a group of tumors was keratinizing while the other one was not. The keratinizing tumors contained large amounts of viruses - a situation that is also found in precursors of cancer (so-called "actinic keratosis") in humans.

This is a condition where cells of the upper skin layers have started to grow excessively while still resembling the original structure of the skin. The researchers demonstrated that the viruses affect the stability of the host cell's DNA, thus promoting the accumulation of UV-related damage.
By contrast, the second group of tumors did not contain any viruses. This is also the case in patients with advanced carcinoma.

However, tests for antibodies in the animals' blood revealed prior infection with the virus. These tumors exhibited a striking rate of mutations in a gene called p53, which is crucially important for the cell and is regarded the "guardian of the genome". This gene is also defective in many cases of human squamous cell carcinoma, leading to uncontrolled cellular growth.

When the cells grow out of control, the tumor turns more cancerous. The viruses, which are now no longer needed for the tumor to grow, are thus prevented from replicating further. Up until now, the loss of viruses in advanced cases of carcinoma has been a major argument against a role of cutaneous papillomaviruses in the development of cancer.
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Managing antibiotics can not reverse the resistance

Researchers have discovered that reducing the use of antibiotics will not be enough to reverse the growing prevalence of antibiotic resistance for some types of bacteria. Besides passing along the genes bestowing antibiotic resistance to their offspring, many bacteria can also swap genes among themselves through a process called conjugation.

The bacteria tested by researchers have fast conjugation rate, even if you don't use antibiotics the resistance can be maintained. Most resistance to antibiotics arises and spreads through natural selection. Some bacteria have genes that help them survive around of antibiotics, they quickly parent the next generation and pass on those genes.

Many of these genes, however, come at a cost. For example, a mutation may allow a bacterium to build a thicker membrane to survive a particular antibiotic, but that mutation might also make it more difficult for the cell to reproduce. Without the selective pressure of antibiotics killing off the competition, bacteria with this mutation should disappear over time.

The results indicate that for bacteria that swap resistance genes simply managing the amount of antibiotics being used will not turn the tide on the growing problem of resistance. To make any headway, drugs will also be needed that stop the sharing of genes and decrease the rate at which they are passed on through reproduction. One of the drugs is a benign natural product and FDA-approved antipsychotic.
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DNA and RNA editing could heal many diseases

Scientists have discovered two gene editing techniques to fix mutations that cause diseases like cystic fibrosis and Duchenne muscular dystrophy. Both diseases, and about half all human genetic disorders, are caused by mutations in single letters in the human genome, in which an 'A' appears where there should be a 'B.'

The newly-developed gene editing systems can target the smallest units of human DNA or RNA to undo the mutation that causes cystic fibrosis. One system edits DNA in the genome itself, while the other targets RNA, which transports genetic messages for making proteins. The editing systems work in living cells, and if researchers can find ways to deliver them to human patients safely and effectively, they could be used to reverse the mutations that cause genetic diseases.

DNA and RNA contain four base components: adenine, thymine, guanine and cytosine. Cystic fibrosis is caused by an inherited genetic mutation that leads to abnormal mucus production in the lungs and digestive system. The thicker-than-normal mucus builds up in and blocks airways. It can be managed with breathing machines, inhalers and medications, but some affected by it will eventually need lung transplants. There is no cure for cystic fibrosis and it can be fatal.

Cystic fibrosis could be prevented or corrected if only there were a 'G' in the genome where the disease's victims have an 'A.' The new gene editing technologies could rewrite the part of the genome or its messenger that spells cystic fibrosis. The gene editing system is technically called the Adenine Base Editor, or ABE.

The ‘A’ in ABE is for ‘adenine,’ one of four chemical bases that are the smallest elements of our genomes. Adenine is always paired with thymine, and guanine is always paired with cytosine. ABE targets the ‘A,’ adenine, and rearranges its atoms to turn it into guanine. So, where there is an incorrect AT set of base pairs in the genome, ABE can reset it to a GC.

These genetic editors give scientists the remarkable ability to rewrite any mutated base pair in the genome. The gene editors are developments on the CRISPR technology which allows scientists to efficiently target and edit the genome.

RNA editing avoids interfering with the genome itself. Because RNA plays a communication role in humans, rather than being the fundamental genetic information itself, changes to it might be more flexible, and reversible.
However, RNA degrades over time, so the impermanence of changes to its component parts (called nucleoside bases) could be disadvantageous too.
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The use of metabolism to subtype hepatoblastoma tumors

Hepatoblastoma is a rare pediatric liver cancer, usually diagnosed in the first three years of life. There are many subtypes of hepatoblastoma, the two major ones are fetal and embryonal.
Scientists have identified new biomarkers that could accurately classify the two main subtypes of hepatoblastoma, a children liver cancer.

Different types of hepatoblastoma use different nutrients to grow. Some use glucose or fatty acids. The genetics of hepatoblastoma involves frequent mutations in the gene CTNNB1. This gene produces the protein beta-catenin, which is involved in cell-cell adhesion and gene transcription. Because of its dual function, mutations of the CTNNB1 gene can cause hepatoblastoma cancer.

Beta-catenin is a component of a signaling pathway known as Wnt/beta-catenin, which is responsible for regulating the expression of multiple genes. Many components of the Wnt/beta-catenin pathway are affected and overactive in various tumors.

Researchers examined the relationship between the CTNNB1 gene and the cell's metabolism, they discovered that beta-catenin, as part of the Wnt signaling pathway directly regulates the expression of a gene that produces a glucose transporter protein. GLUT3

They used RNA sequencing to identify molecular and metabolic features that are specific to hepatoblastoma. This approach revealed that several enzymes involved in the metabolism of glucose are overexpressed in embryonal hepatoblastoma cells as compared to fetal hepatoblastoma cells.

Embryonal hepatoblastoma cells show high levels of glucose uptake, they also discovered that these cells are very sensitive to the perturbation of an enzyme involved in the cell's use of glucose. They immunohistochemistry of the three metabolic biomarkers to distinguish embryonal from fetal components out of a large panel of human hepatoblastoma biopsies.

The study shows that the Wnt/beta-catenin pathway is important for reprograming the energy management of tumor cells. It also provides a new
metabolic classification of human hepatoblastoma that can help oncologists develop novel diagnostic methods and treatments.
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Genetic blood tests can expose cancer

Genetic blood test might expose different types of cancer at early stage,
the blood test discovered blood from DNA fragments released by cancerous tumours.

Examining DNA fragments for mutations found in cancer- causing genes leads to the discovery of blood of many early stage cancers. It exposed colon, breast, lung and ovarian cancers.

Early detection of cancers can leads to effective treatment from onset and save many lives, the test can screen out people without cancer. Genetic blood test for cancer must expose DNA mutations linked to cancer and ignore harmless mutations that is always present in healthy humans.

Exposing cancer and early treatment is the most important aspect of the discovery, differentiating deadly cancers that will hurt people from cancers that may not is very important for the success of the blood test.
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Some moles become melanoma

Moles are growths on the skin that are usually brown or black. They can appear in groups or alone in any parts of the body. As we get older, some moles can change in colour or disappear while others may remain the same.

Moles occur when cells in the skin grow in a cluster instead of being spread throughout the skin. Melanoma is a type of skin cancer, it developed when unrepaired DNA damage skin cells.

Melanomas often resemble moles; some develop from moles. Melanomas can develop from a naevus, but most moles will never become a melanoma.

Dermatologists examined some moles and discovered some had a mutation on the gene known as BRAF, and the remaining samples had a mutation on the NRAS gene.

When either of these genes are mutated it activates the signalling pathway known as MAPK, which is commonly active in melanomas.

Additional genomic events need to occur before a mole becomes malignant. People with a high number of moles, and other risk like fair skin or light coloured hair or eyes, should continue to keep appointment with their dermatologist for regular skin examination.
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Genes are expressed differently in men and women

Men and women differ in obvious ways for example, in the prevalence of certain diseases or reactions to drugs.

Weizmann Institute of Science researchers recently uncovered thousands of human genes that are expressed out to make proteins differently in the two sexes.

Pietrokovski and Gershoni showed that mutations in genes specific to sperm formation persist precisely because the genes are expressed only in men.

 A mutation that is problematic for only half of the population, no matter how detrimental, is freely passed on to the next generation by the other half.

In this study, the researchers expanded their analyses to include genes that, though not necessary for fertility, are still expressed differently in the two sexes.

 To identify these genes, the scientists used a very large study of human gene expression recorded for numerous organs and tissues in the bodies of close to 550 adult donors.

Pietrokovski and Gershoni looked closely at around 20,000 protein-coding genes, sorting them by sex and searching for differences in expression in each tissue. They eventually identified around 6,500 genes with activity that was biased toward one sex or the other in at least one tissue.

For example, they found genes that were highly expressed in the skin of men relative to that in women's skin, and they realized that these were related to the growth of body hair. Gene expression for muscle building was higher in men; storage were higher in women.
Apart from the sexual organs, the researchers discovered quite a few sex-linked genes in the mammary glands -- not so surprising, except that about half of these genes were expressed in men.

The researchers also identified gene expression in the liver in women that regulates drug metabolism, providing molecular evidence for the known difference in drug processing between women and men.

Random DNA mistakes causes cancers

Cancer center scientists reported that unpredictable DNA copying errors is responsible for two - thirds of the mutation that cause cancer. This is confirmed by DNA sequencing and epidemiologic data across the globe.

According to professor John Hopkins Kimmel, anytime a normal cell divides to form two new cells, it makes multiple mistakes, these mistakes are source of cancer mutation that have been ignored in the past. This revealed the reasons why people that embraced healthy lifestyle are having cancer.

Researchers studies 32 types of cancers and estimate that 66 percent of cancer mutations occur from coping mistakes, 29 percent from environmental factors and 5 inherited.

Living healthy lifestyle can reduce rates of cancer mutations because mutation can not be stopped from taking place in the body.