MicroRNA for treating cancer and asthma

A microRNA that regulates inflammation shows promise as a treatment for inflammatory diseases such as asthma and cancer. The microRNA, known as miR-223, is highly expressed in blood cells that cause inflammation (neutrophils). When they're working correctly, those blood cells protect the body against infections, but sometimes they damage host tissue instead of microbes, causing chronic inflammation and disease.

To uncover the link between miR-223 and inflammation, a Purdue University research team created a zebrafish totally deficient of miR-223. Then they cut off a small chunk of its fin. "The inflammation was really robust," said Qing Deng, a professor of biological sciences at Purdue and corresponding author of the paper. "Neutrophils accumulated at the wound and they just kept coming. This is consistent with the literature, but we wanted to understand why."

Extensive gene expression analysis led them to pathway NF-kB, a protein complex found in nearly all animal cell types that regulates inflammation and cell proliferation. Heightened activation of this pathway is the cause of increased inflammation, although it's limited to the deeper, or basal, layer of the epithelium. This means any therapeutics would need to reach the basal layer to work.

The same pathway plays an important role in human bronchial epithelial cells, which are critical in the development of asthma, according to the study. MiR-223 suppresses the pathway, which means supplementing it to epithelial cells could help control inflammatory disease.
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Links between processed foods and cancer

Ultra-processed foods include packaged baked goods and snacks, fizzy drinks, sugary cereals, ready meals and reconstituted meat products often containing high levels of sugar, fat, and salt, but lacking in vitamins and fibre. A few studies have linked ultra-processed foods to higher risks of obesity, high blood pressure and cholesterol levels.

A team of researchers based in France and Brazil, set out to evaluate potential associations between ultra-processed food intake and risk of overall cancer, as well as that of breast, prostate, and bowel (colorectal) cancers. Their findings are based on 104,980 healthy French adults (22% men; 78% women) with an average age of 43 years who completed at least two 24-hour online dietary questionnaires, designed to measure usual intake of 3,300 different food items.

Foods were grouped according to degree of processing and cases of cancer were identified from participants' declarations validated by medical records and national databases over an average of five years. Several well known risk factors for cancer, such as age, sex, educational level, family history of cancer, smoking status and physical activity levels, were taken into account.

The results show that a 10% increase in the proportion of ultra-processed foods in the diet was associated with increases of 12% in the risk of overall cancer and 11% in the risk of breast cancer. No significant association was found for prostate and colorectal cancers. Further testing found no significant association between less processed foods (such as canned vegetables, cheeses and freshly made unpackaged bread) and risk of cancer, while consumption of fresh or minimally processed foods (fruits, vegetables, pulses, rice, pasta, eggs, meat, fish and milk) was associated with lower risks of overall cancer and breast cancer.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers point to some limitations. For example, they cannot rule out some misclassification of foods or guarantee detection of every new cancer case. Nevertheless, the study sample was large and they were able to adjust for a range of potentially influential factors.
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Molecule could prevent prediabetes

Levels of CoQ and the presence of insulin resistance were analysed in a range of experimental laboratory settings, mouse models and samples from humans, as part of an ambitious research collaboration conducted with the University of Sydney, Victor Chang Cardiac Research Institute, Duke University School of Medicine, Garvan Institute of Medical Research, Genentech Inc. and the University of New South Wales.

Concentrations of CoQ were found to be lower in insulin resistant body fat and muscle tissue. When the researchers replenished CoQ, insulin resistance or pre-diabetes was reversed. Co-author Dr Daniel Fazakerley from the University of Sydney's School of Life and Environmental Science and Charles Perkins Centre said CoQ provides a vital role in converting nutrients like fat and sugar into usable energy.

CoQ is found in mitochondria, the power plants in the cells of human body, where it is required for the flow of electricity to the cell's 'motor' which is responsible for energy production. Energy production can also generate reactive chemical species-often referred to as 'reactive oxygen species' or 'oxidants' as by-products, which can be damaging to cells. Previous studies have shown that these oxidants can cause insulin resistance. Our study has found that lower mitochondrial CoQ enhanced oxidant formation by mitochondria.

Replenishing CoQ in mitochondria, either in cells or in animals, we were able to restore 'normal' mitochondrial oxidants and reverse insulin resistance. Eating a high fat, high sugar diet has long been known to be a major risk factor for obesity and pre-diabetes. Replenishing CoQ could prove an invaluable preventive measure for insulin resistance- or pre-diabetes-linked diseases such as type 2 diabetes, cardiovascular disease, cancers and dementia.

However, oral CoQ supplements may not effectively restore mitochondrial CoQ due to its low absorption. The research has provided an impetus to find alternate means of increasing CoQ in mitochondria to treat insulin resistance and pre-diabetes. If not an external supplement, perhaps we can stimulate the body to form more of the coenzyme itself.
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Cell phone radiation linked to cancer

Cell phone radiation could pose a risk of certain cancers, the preliminary findings of two new major studies from the National Institutes Health suggest. Six percent of male rats exposed to the same kind of radiation our cell phones emit - though in much larger quantities - developed a type of cancer called a schwannoma in their hearts.

Smartphones and other wireless devices put out small amounts of low frequency microwave radiation when they connect networks and transmit information. This energy is not nearly as strong as ultraviolet radiation or X-ray energy, but the new studies add to the mounting evidence that even microwave radiation, in high doses, can pose some health risks.

The NTP researchers exposed rats and mice to high levels of radiation over the course of 18 hours each day, alternating 10-minute exposures with 10-minute periods without exposures. Radiation surges when cell phones are trying to connect to faint network signals or transmit large amounts of information.

Stop sleeping with your cell phone: Anything closer than arm's length could cause cancer and infertility, health officials warn. Experts warn that it is these inconsistent exposures that make the devices risky. There were 'statistically significant' differences in the incidence of heart schwannoma tumors in rats.

Schwannomas develop from peripheral nervous cells, called Schwann cells. They develop inside the sheath that covers nerves, wrapping and interfering with nerves themselves. In humans, these tumors are usually benign. These noncancerous schwannomas are most common in the vestibular nerve that connects the brain and the ear.

Malignant schwannomas can start anywhere, but seem to be most common in the leg, arm or lower back, sometimes causing a bump, pain, muscle weakness or tingling. Though they are not common in human hearts, cardiac tissue is a good target for cell phone radiation. Microwave radiation works by heating water. Muscle tissue - like the heart - is 75 percent water, while fat, for example, is only about 10 percent water.

That means that muscular tissues are especially affected by cell phone radiation, which may explain why the nerve tumors were most likely to form in a highly muscular organ. Counter-intuitively, bigger animals are more sensitive to radiation. The higher rate of tumors in males 'was probably due to the fact that male rats simply absorb more radiation than females as a function of the size of the animal.

Cancer risks for mice were negligible, and female rats that were pregnant - and therefore larger - were also more sensitive to radiation. The levels of microwave radiation the animals were exposed to were much higher than we encounter from human cell phones, humans are, larger than rats. It is also worth note that radiation exposures in the study would still comply with federal regulations on heat microwave heat generated by cell phones, and still there were increased risks of at least one cancer for rats.
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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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Nicotine in E-cigarettes may cause cancer

The nicotine in e-cigarettes seems to damage DNA in ways that may increase cancer risk, the damage was seen both to DNA and its ability to repair itself, making cells more likely to mutate and develop into cancer, said lead researcher Moon-shong Tang, a professor of environmental medicine at New York University School of Medicine.

Reseachers exposed laboratory mice to e-cigarette vapor, which contains both nicotine and liquid solvents. They also exposed mice to the nicotine and the solvents separately. The vapors were produced using 4.2 volts of electricity, at or below the level at which most commercial e-cigarettes function.

Prior studies have shown that e-liquid heated using higher levels of electricity could produce harmful chemicals. This research team wanted to investigate the risk posed to people using a typical e-cigarette. They found the solvent alone does not cause DNA damage, nicotine with e-cigarette solvent caused the same damage as nicotine alone. The researchers also exposed cultured human lung and bladder cells to nicotine, and found the same effects-DNA damage and suppressed DNA repair.
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Smoking linked to heart disease and stroke

Smoking just one cigarette a day has a higher risk of developing coronary heart disease and stroke than expected. The researchers say their findings have important consequences for many smokers and health professionals who believe that smoking only a few cigarettes carries little or no harm. They argue that smokers should stop completely instead of cutting down to significantly reduce their risk of heart disease and stroke.

Individual studies have reported that smoking only one to five cigarettes per day is associated with a higher than expected risk of heart disease. To investigate this further, a team of researchers led by Professor Allan Hackshaw at the UCL Cancer Institute at University College London analysed the results of 141 studies and estimated the relative risks for smoking one, five, or 20 cigarettes per day. They found that men who smoked one cigarette per day had 46% of the excess risk of heart disease and 41% of the excess risk of stroke associated with smoking 20 cigarettes per day (much higher than the expected 5%).

For women, those who smoked one cigarette per day had 31% of the excess risk of heart disease and 34% of the excess risk of stroke associated with smoking 20 cigarettes per day. Women's heart disease risk was more than doubled with one cigarette per day, when only studies that controlled for several factors were included in the analysis. Large proportion of the risk of coronary heart disease and stroke comes from smoking only a couple of cigarettes each day.

Cardiovascular disease, not cancer, is the greatest mortality risk for smoking, causing about 48% of smoking-related premature deaths. Any exposure to smoking is too much, there is no safe level of smoking. Smokers should quit instead of cutting down, using appropriate cessation aids if needed, to significantly reduce their risk of stroke and heart disease.
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Links between gum disease and cancer

Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists Dominique Michaud at Tufts University School of Medicine and Elizabeth Platz of the Johns Hopkins Bloomberg School of Public Health and Kimmel Cancer Center.

Researchers used data from comprehensive dental exams performed on many participants from Maryland, Minnesota, Mississippi, and North Carolina, as part of their participation in the Atherosclerosis Risk in Communities (ARIC) study who were then followed from the late 1990s until 2012.

 During the follow-up period, 1,648 new cancer cases were diagnosed. The research team found a 24 percent increase in the risk of developing cancer among participants with severe periodontitis, compared to those with mild to no periodontitis at baseline.

Among patients who had no teeth-which can be a sign of severe periodontitis, the increase in risk was 28 percent. The highest risk was observed in cases of lung cancer, followed by colorectal cancer. When the researchers did sub-group analyses, they found that participants with severe periodontal disease had more than double the risk of developing lung cancer, compared with no periodontitis.

An 80 percent increase in risk of colon cancer observed for participants who were edentulous at baseline, which is consistent with prior findings, and among never smokers, a two-fold higher risk was noted for participants with severe periodontitis, compared to those who had no periodontitis.

The research team accounted for the impact of smoking among the participants, since people who smoke are more likely to get periodontal disease, and smoking raises the risk of lung and colon cancers. Looking at data for the people who had never smoked, they also found evidence that having severe periodontal disease was related to an increased risk of lung cancer and colorectal cancer.

The researchers found no links between increased risk of breast, prostate or blood/lymphatic cancer and periodontitis. The link between periodontitis and increased cancer risk was weaker or not apparent in African-American participants from the ARIC study, except in cases of lung and colorectal cancer. Advanced gum disease-periodontitis, is caused by bacterial infection that damages the soft tissue and bone that support the teeth.
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Sitting for long hours linked to visceral fat

Sitting for long hours leads to building of fat around the body's organs and increases the risk of type 2 diabetes and heart disease. A study found people who spent a large amount of time sitting down had higher levels of visceral and total abdominal fat. Visceral fat is unseen and wrapped around the liver, pancreas and kidneys. Carrying a high amount is known to be associated with insulin resistance - the driving factor for type 2 diabetes.

There's a difference between subcutaneous fat, the type of fat that lies directly under the skin and visceral fat, which is unseen and around human organs. According to an expert, slim-looking people can have this dangerous fat on the inside, that's wrapped around the liver, pancreas and kidneys.
Visceral abdominal fat is also linked to an increased risk of cancer, stroke and heart disease. Researchers used MRI to scan  participants who were likely to develop type 2 diabetes. They also used ccelerometers that were placed around their waists to measure how much time these people spent sitting over the course of a week.

The researchers found that the link between visceral fat and sitting was strongest for those who did not meet the public health recommendation of 150 weekly minutes of moderate-intensity physical activity. Using MRI techniques and physical activity monitors have shown that the more time spent sedentary, the stronger the association with higher levels of internal and abdominal fat. This was particularly so if the long periods of sedentary behavior were uninterrupted.

When cortisol the stress hormone is too high for too long, it can increase the amount of fat that's stored around the stomach. Dieting alone is not enough combining healthy eating with stress management techniques can help. Cortisol is created in the body’s adrenal gland, it is essential to give get-up-and-go human need to get motivated and focused, which is why it’s usually elevated in the morning. It's also released during exercise and periods of acute stress. It regulates energy by selecting the right amount of carbohydrate, fat, or protein the body needs to meet the physiological demands placed on it.

Cortisol is released from the body’s adrenal glands and floods the body with glucose  when the body is stressed, the simplest form of carbohydrate and preferred energy source – to give muscles an immediate supply of energy. Insulin-the hormone that reduces blood sugar – is also released to prevent the glucose being stored as fat and make it freely available to give the immediate energy to deal with an event. Hormone balance will returns to normal when stress is reduce.
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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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Gene therapy may kill HIV

Gene therapy may have the potential to eradicate HIV in people infected with the virus, new animal research suggests. The science centers around the use of "chimeric antigen receptor" (CAR) genes. In laboratory work with monkeys, these engineered cells have destroyed HIV-infected cells for more than two years, scientists reported.

T-cells are the cells that are largely responsible for human ability to fight off pathogens and get rid of infections in the body. Every T-cell has a unique receptor, or molecule, on it. That receptor allows the cell to recognize a specific target-a bacteria, or fungus or virus. And when it recognizes that target, it's called into duty to clear it from the body. Taking artificial receptors- CAR that can go on to these cells and allow them to recognize what we want them to recognize," he noted. "In this case that's HIV."

First, the team genetically engineered CAR to find and bind to simian/human immunodeficiency virus (SHIV), a lab-engineered HIV hybrid composed of human virus and monkey virus. Then the researchers modified the DNA of certain blood-forming stem cells so they would carry SHIV-killing CAR. The resulting cells were introduced into the bloodstream of four male juvenile SHIV-infected macaque monkeys.

The engineered cells successfully took up residence in each monkey's bone marrow. The cells moved widely throughout the body, targeting and killing SHIV-infected cells, without producing any notable adverse side effects. The advantage of the stem cell-based approach is that once these cells are grafted into the body, they continuously produce new T-cells that have this gene in them that can target HIV cells.

Plans are underway for a human trial, this study shows both that these cells will respond to HIV and that it's safe. This strategy is unlikely to fully work on its own, CAR will most likely need to be used with antiretroviral therapy. CAR therapy is already leading to impressive results in cancer and holds promise for HIV eradication.
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Cancer alters the circadian clock to survive

Tumor cells use the unfolded protein response to alter circadian rhythm, which contributes to more tumor growth, Hollings Cancer Center researchers at the Medical University of South Carolina (MUSC) find. A key part of the circadian clock opposes this process. For tumors to grow and spread, cancer cells must make larger than normal amounts of nucleic acids and protein, so they can replicate themselves. Yet in both normal and cancer cells that increase their synthesis of protein, a small percent of those proteins do not fold properly.

When that happens, the cell activates its unfolded protein response (UPR), which slows down the making of new proteins while the misfolded proteins are refolded. Eventually, the buildup of misfolded proteins becomes toxic and leads to cell death. However, cancer cells have learned to use the UPR to slow protein synthesis when needed, in order to handle the backlog of misfolded proteins. This helps them survive in conditions that would kill normal cells.

This pattern of adaptation is often seen in tumor cells. UPR and circadian rhythm are linked together to lead the clockwork of the cell and also that cancer cells use the UPR to manipulate the circadian clock in ways that allow them to survive conditions that are toxic to normal cells. Researchers formulated a new idea based on what was known about protein synthesis in the cell. The UPR is altered in tumors, and second, cells establish a circadian rhythm to regulate metabolism by producing levels of certain proteins that rise and fall in coordination with natural cycles of light and dark.

 Scientists had observed that circadian rhythm is altered in tumor cells. Since protein production is tied to circadian rhythm. Research team used chemicals to activate the UPR in osteosarcoma cells. They found that, when activated, the UPR changes levels of an important protein called Bmal1, which is a transcription factor that rises and falls with cycles of light and dark. As it does, it regulates the expression of major circadian rhythm genes.

When cells were exposed to cycles of light and dark, Bmal1 levels peaked during dark hours. But when the UPR was chemically activated, Bmal1 stayed low during both light and dark phases, which caused a phase shift in the expression of circadian genes. When one of the main parts of the UPR machinery was absent in cells, the phase shift did not happen.

Levels of the circadian protein Bmal1 continued to decrease, as the UPR was increasingly activated. In rodents that had their light-dark cycles suddenly reversed, Bmal1 stopped rising and falling - a clear sign that their circadian rhythms were disrupted. Shifts in light exposure activated the UPR in those rodents' cells.

 The team found that patients with breast, gastric or lung cancers survived longer when they had higher levels of Bmal1 protein. In myc-driven cancers, the UPR was causing the loss of Bmal1 protein, which caused the tumors to grow. Myc-driven tumors lost circadian rhythm, whereas normal cells maintained it. Conversely, high levels of Bmal1 overtook the UPR, thereby allowing protein synthesis to continue, which was toxic to tumor cells . In this way, Bmal1 directly encourages protein synthesis.

Human cancer suppresses circadian rhythm by controlling protein synthesis through Bmal1. Cancer cells survived longer by using the UPR to suppress Bmal1 and short-circuit their circadian rhythms. These results are important for human biology. Every single normal cell in human body has circadian oscillation, resetting the circadian rhythms in cancer cells slows down their proliferation.
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Habits that increase the risk of cancer

Forty per cent of cancer deaths could be prevented with simple lifestyle changes. Quitting smoking, eating healthier and boozing less would stop the disease. Scientists suggest habits responsible for cancer with tobacco proving the biggest burden. Other habits, includes excessive UV radiation, obesity and not exercising enough can be blamed.

Researchers at the QIMR Berghofer Medical Research Institute, Brisbane, said the total amount is greater than 38 per cent because many deaths involved two factors. Even 'small improvements' would reduce the risk of dying prematurely from cancer, the Australian researchers claimed. Their findings, which also highlighted irresponsible sun tanning as a cause, were derived from an analysis of cancer deaths.

Obesity and infections were responsible for five per cent of the deaths while not exercising enough was blamed for 0.8 per cent.Dr David Whiteman, lead researcher of the study published in the International Journal of Cancer, found that the bad habits fueled 41 per cent of cancer deaths in men and 34 per cent in women because men smoke and drink more, spend more time in the sun and don't eat healthy foods.

The researchers concluded that the following eight habits are responsible for 38 per cent of cancer deaths. Researchers at the QIMR Berghofer Medical Research Institute, Brisbane, said the total amount is greater than 38 per cent because many deaths involved two factors. The habits are-Smoking, Poor diet, Boozing, UV radiation, Obesity, Infections, Inactivity and Hormones.
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New pathway for hyperaldosteronism

People with high blood pressure have secondary hypertension, meaning that the root cause of the disease is known. In such cases, when the root cause is treated, blood pressure usually returns to normal or is significantly lowered. Hyperaldosteronism, a condition in which the adrenal glands produce too much aldosterone, is the most common cause of secondary hypertension.
Research, based on a genetic model identifies an unexpected layer in the regulation of adrenal gland development and in hyperaldosteronism.

The body's adrenal glands produce a number of essential hormones, including aldosterone, which balances sodium and potassium in the blood. In hyperaldosteronism, the adrenal glands produce too much aldosterone, leading to low levels of potassium and increased sodium. Excess sodium leads to water retention, increasing the blood volume and blood pressure. The structure of the adrenal glands in mice lacking the Siah1 ubiquitin ligase gene was markedly different and they had increased levels of aldosterone.

Elevated levels of PIAS1, a Siah1 controlled protein is a key regulator of cholesterol biosynthesis,
Siah1 is a ubiquitin ligase that plays an important role in a number of cellular pathways, implicated in neurodegeneration and cancer. Patients that suffer from hyperaldosteronism exhibit mutations or epigenetic deregulation of the key pathway components, pointing to the relevance of our findings to humans and the justification for further exploration of this pathway for therapeutic purposes.
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How weather increases the risk of cancer

Living in a cold climate could make people more likely to get cancer, people are at greater risk in colder countries because of their genes. The same genes which stop human cells from dying in freezing temperatures are also linked to breast and bowel cancer and leukaemia. A researcher says the genes contributing to cooler climates are the same which increase the risk of malignant tumours forming in the body.

Genetic variants found to be beneficial in extreme environments, can also predispose for cancer. Cell resistance at low temperatures and at high altitude probably increases the probability for malignancy.’Previous research from 2010 found grim weather in northern parts of the world may make men more vulnerable to prostate cancer, perhaps due to a lack of vitamin D from the sun.

However the new study - which compared international rates of cancer with 240 genetic studies of cancer and seven others in cold and high-altitude countries - suggests where people live affects their genes.Extreme cold weather can cause human cells to die, so that people in freezing countries have genetic mutations to prevent cell death and repair DNA.
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Ozempic for treating type 2 diabetes

Ozempic is an injectable prescription medicine for adults with type 2 diabetes mellitus. It is not recommended as the first choice of medicine for treating diabetes. Ozempic is not a substitute for insulin and is not for use in people with type 1 diabetes or people with diabetic ketoacidosis.Active Ingredient: semaglutide. Inactive Ingredients: disodium phosphate dihydrate, propylene glycol, phenol and water for injection.

Ozempic (semaglutide) injection 0.5 mg or 1 mg, a once-weekly glucagon-like peptide (GLP-1) receptor agonist for the treatment of adults with type 2 diabetes. Do not share your Ozempic pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them. Ozempic may cause serious side effects, including: Possible thyroid tumors, including cancer.

Ozempic and other similar medicines caused thyroid tumors, including thyroid cancer. It is not known if Ozempic will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people. Do not use this medicine if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Ozempic is injected under the skin (subcutaneously) of  stomach (abdomen), thigh, or upper arm. Do not inject Ozempic into a muscle or vein. Use Ozempic one time each week, on the same day each week, at any time of the day. You may change the day of the week you use Ozempic as long as your last dose was given two or more days before. If you miss a dose, take the missed dose as soon as possible within five days after the missed dose. If more than five days have passed, skip the missed dose and take your next dose on the regularly scheduled day.

Ozempic may be taken with or without food. Do not mix insulin and Ozempic together in the same injection. You may give an injection of Ozempic and insulin in the same body area (such as your stomach area), but not right next to each other. Change (rotate) your injection site with each injection. Do not use the same site for each injection.
Common side effects of Ozempic include nausea, vomiting, diarrhea, stomach (abdominal) pain and constipation.
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Overweight women need frequent mammograms

Women with higher body mass index (BMI) face an increased risk of not detecting their breast tumor until it has become large, they need shorter intervals between mammography screening exams. BMI is a measure of body fat based on height and weight, with overweight defined as a BMI of 25 or more. High BMI is associated with a number of health risks, including diabetes and heart disease. However, BMI is not considered as part of breast cancer screening guidelines.

Researchers set out to identify risk factors associated with tumors not being detected until larger than 2 centimeters (cm), or about the size of a peanut, and to examine the implications for long-term prognosis. The 2-cm size is important because it is one of the parameters used to separate stage I and stage II cancers. In addition, tumor size is known to be strongly associated with prognosis.The researchers followed the patients until history and looked for how disease progression was related to BMI and breast density.

For cancers detected at screening, both BMI and breast density were associated with having a large tumor at diagnosis. However, for interval cancers, or cancers detected within two years of a normal mammogram, only BMI was linked with having a large tumor. Women with higher BMI had worse prognosis than women with lower BMI among interval cancers.

Breast density showed no significant association with disease progression. Besides the larger interval cancers, women with high BMI may have other factors that put them at risk for a worse prognosis, including the molecular composition of the tumors and hormone receptor expression levels that make them harder to treat.
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Traumatic event increase a woman's risk of obesity

According to a new study, women who have experienced traumatic events are more likely to become obese. Researchers discovered that the more traumatic events women reported experiencing in the last five years, the more likely they were to become obese. Obesity can leads to elevated risk for cardiovascular disease, diabetes, stroke, and other serious health problems.

As much as 20 percent of people who experience trauma develop post traumatic stress disorder PTSD, but women are twice likely to suffer from the disorder as are their male counter parts. Stress from sources like bullying and economic strain has well-documented links to eating disorders, including over-eating and obesity. Since women are more prone to both extreme stress or PTSD and obesity, the study authors suggest that more attention needs to be paid to these relationships.

The researchers analysed data on both the women’s body mass indexes BMI and self-reported stress. The divided stressors into two categories: Significant traumatic events like physical violence or the death of a child that could have occurred any time in their lives and still be affecting them, and ‘negative life events’ that had occurred in the last five years.

Living through just one traumatic life event increased the risk of obesity by 11 percent, over that of women who reported no traumatic events. Those that had experienced four or more ‘negative life events’ were at a 36 percent greater risk of obesity.Women are living longer and are more at risk for chronic illnesses, such as cardiovascular disease, obesity is related to increased risks of heart attack, stroke, diabetes and cancer, and contributes to spiraling healthcare costs.
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Cinvanti for treating chemotherapy - induced nausea and vomiting

The U.S. Food and Drug Administration has approved Cinvanti (aprepitant) injectable emulsion, for intravenous infusion. Cinvanti is a substance P/neurokinin-1 (NK1) receptor antagonist, indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

Cinvanti is the first and only polysorbate 80-free, intravenous formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed CINV. Cinvanti is the first intravenous formulation to directly deliver aprepitant, the active ingredient in Emend® capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist to significantly reduce CINV in both the acute phase (0 – 24 hours after chemotherapy) and the delayed phase (24 – 120 hours after chemotherapy).

Cinvanti does not contain polysorbate 80 or any other synthetic surfactant. Pharmaceutical formulations containing polysorbate 80 have been linked to hypersensitivity reactions, including anaphylaxis and irritation of blood vessels resulting in infusion-site pain. Cinvanti was approved based on data demonstrating the bioequivalence of Cinvanti to Emend IV® (fosaprepitant), supporting its efficacy for the prevention of acute and delayed CINV following HEC and MEC.
Results from 2 pivotal randomized, cross-over bioequivalence studies of Cinvanti and Emend IV showed subjects receiving Cinvanti reported fewer adverse events than those receiving Emend IV, including substantially fewer infusion-site reactions.

Cinvanti is contraindicated in patients with hypersensitivity to any of the components of Cinvanti. Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with fosaprepitant, a prodrug of aprepitant, and with oral aprepitant. Symptoms including flushing, erythema, dyspnea, hypotension and syncope have been reported. If symptoms occur, discontinue Cinvanti. Do not reinstate if symptoms occur with first-time use. Use of pimozide with Cinvanti is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide.

Use of Cinvanti may result in clinically significant CYP3A4 Drug Interactions. Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use with other drugs that are CYP3A4 substrates may result in increased plasma concentration of the concomitant drug. Use of Cinvanti with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to Cinvanti.

Avoid use of Cinvanti in pregnant women as alcohol is an inactive ingredient for Cinvanti. There is no safe level of alcohol exposure in pregnancy. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9). Additional monitoring for adverse reactions in these patients may be warranted when Cinvanti is administered.

In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy. The most common adverse reactions with the 3-day oral aprepitant regimen in conjunction with MEC were fatigue and eructation. The most common adverse reactions with the single-dose intravenous fosaprepitant regimen in conjunction with HEC were generally similar to that seen in prior HEC studies with oral aprepitant. The most common adverse reactions with a single-dose of Cinvanti were headache and fatigue.

While chemotherapy is one of the most effective and commonly used therapies to help patients fight cancer, it is accompanied by debilitating side effects, including varying degrees of nausea and vomiting, often attributed as a leading cause of premature discontinuation of cancer treatment. The goal of antiemetic therapy is to prevent CINV in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy). The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have categorized chemotherapy regimens based on the degree to which they cause nausea and vomiting: low emetogenic chemotherapy (LEC); moderately emetogenic chemotherapy (MEC); and highly emetogenic chemotherapy (HEC).
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Mental health condition surpreses the immune system

According to new research, depression increases the risk of an early death.
Men's risk of a premature death increases three-fold when suffering from the mental health condition, while women's risk is heightened by up to 50 percent.

Depression causes the release of stress hormones that suppress the immune system, putting sufferers at an increased risk of conditions such as cancer. People with the mental health condition may have unhealthy lifestyle habits, including a poor diet, inactivity and excessive alcohol intake.

Researchers analyzed more than 3000 adults between 1952 and 1967, 1968 and 1990, and 1991 and 2011. The study's participants' had an average age of 50 when the trial started. Results reveal depression increases the risk of an early death by up to three times. Men's risk increases three-fold, while women's peaks at 51 percent.

Depression is linked to the release of stress hormones that suppress the immune system, putting sufferers at increased risk of disorders including multiple sclerosis, arthritis and some. cancers. People with depression may also neglect their physical health through lifestyle habits such as a poor diet, inactivity, smoking and excessive alcohol intake. The mental health condition is more prevalent in women, however, past findings suggest men suffer the effects of it more as they are often less inclined to seek help.

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