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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Genetic mutations start after conception

Hundreds of minor genetic mutations start to form in the cells of an embryo after conception, some of these mutations occur as sex cells are forming in the embryo. That means they can become part of the embryo's genome and be passed on to the next generation.

This opens up a larger perspective on human development,  this shows that some of our genome does not come from our parents.These early genetic mutations are also similar to those found in cancers, cancers can occur as a normal byproduct of cell division, this mat be the causes of neurodevelopmental disorders such as schizophrenia or autism.

These conditions are primarily the result of genetic abnormalities, but no single gene inherited by parents has been found to cause a large number of cases.The study may also help explain why one identical twin might have a genetic disorder while the other is healthy, or why some members of a family who carry a disease-causing mutation do not get sick.
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Women are more fit than men

Women can process oxygen more quickly than men during exercise. Quick oxygen uptake places less strain on the body's cells and is considered an important measure of aerobic fitness.

The study compared oxygen uptake and muscle oxygen extraction between young men and women of similar age and weight during treadmill exercise. Women consistently outperformed men with around 30 per cent faster oxygen handling throughout the body.

Researchers discovered that women's muscles extract oxygen from the blood faster, which, scientifically speaking, indicates a superior aerobic system.
By processing oxygen faster, women are less likely to accumulate molecules linked with muscle fatigue, effort perception and poor athletic performance.
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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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Juluca for treating virologically suppressed HIV-1 Infection

FDA Approves Juluca (dolutegravir and rilpivirine) for the maintenance and treatment of virologically suppressed HIV-1 Infection. This is the first complete treatment regimen containing only two drugs to treat certain adults with human immunodeficiency virus type 1 (HIV-1) instead of three or more drugs included in standard HIV treatment.

Juluca is a fixed-dose tablet containing two previously approved drugs (dolutegravir and rilpivirine) to treat adults with HIV-1 infections whose virus is currently suppressed on a stable regimen for at least six months, with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.

Limiting the number of drugs in any HIV treatment regimen can reduce toxicity for patients, HIV weakens a person’s immune system by destroying important cells that fight disease and infection. Juluca’s safety and efficacy in adults were evaluated in two clinical trials of 1,024 participants whose virus was suppressed on their current anti-HIV drugs.

 Participants were randomly assigned to continue their current anti-HIV drugs or to switch to Juluca. Results showed Juluca was effective in keeping the virus suppressed and comparable to those who continued their current anti-HIV drugs. The most common side effects in patients taking Juluca were diarrhea and headache.

Serious side effects include skin rash and allergic reactions, liver problems and depression or mood changes. Juluca should not be given with other anti-HIV drugs and may have drug interactions with other commonly used medications.
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Vitamin D may prevents Rheumatoid arthritis

Maintaining sufficient vitamin D levels may prevent the onset of inflammatory diseases like rheumatoid arthritis, it is less effective once inflammatory disease is established because diseases such as rheumatoid arthritis leads to vitamin D insensitivity. The impact of vitamin D on inflammatory disease cannot be predicted using cells from healthy individuals or even from the blood of patients with inflammation as cells from the disease tissue are different.

If vitamin D is to be used in patients with rheumatoid arthritis, clinicians may need to prescribe much higher doses than currently provide a treatment that also corrects the vitamin D insensitivity of immune cells within the joint. Vitamin D is a potent modulator of the immune system. In particular, vitamin D can suppress inflammation in autoimmune diseases such as rheumatoid arthritis. Patients with rheumatoid arthritis are frequently vitamin D deficient and may receive vitamin D supplementation.

The study involved using paired peripheral blood and synovial fluid from the inflamed joint of patients with rheumatoid arthritis. The current understanding of vitamin D and rheumatoid arthritis is based on studies of patient blood which may not truly represent the situation at the site of inflammation -the joints. Investigating responses to the active form of vitamin D in immune cells from the inflamed joints of patients with rheumatoid arthritis compared to blood from the same patients, the inflamed joint immune cells were much less sensitive to active vitamin D.

This occurred because immune cells from the joints of rheumatoid arthritis patients are more committed to inflammation, and therefore less likely to change, even when they respond to vitamin D. Maintaining sufficient vitamin D may prevent the onset of inflammatory diseases like rheumatoid arthritis. However, for patients who already have rheumatoid arthritis, providing vitamin D might not be enough. Instead much higher doses of vitamin D may be needed, or possibly a new treatment that corrects the vitamin D insensitivity of immune cells within the joint.
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Folic acid may reduce autism risk from pesticide

Taking folic acid during the window around conception reduced the risk associated with pesticides, researchers examined many children who had been diagnosed with ASD, the researchers interviewed their mothers about their household pesticide exposure during pregnancy, folic acid and B vitamin intake.

Children whose mothers took 800 or more micrograms of folic acid and other prenatal vitamins had a lower risk of developing autism spectrum disorder ASD even when their mothers were exposed to household or agricultural pesticides.

Mothers who took less than 800 micrograms and encountered household pesticides had higher risk of having a child who developed an ASD than their counterparts who took 800 micrograms of folic acid or more and were not exposed to pesticides.

The risk increased for women exposed several times, women with low folic acid intake who were exposed to agricultural pesticides during a window from three months before conception to three months afterward were at higher risk. Folic acid can reduce the risk of developing autism but it can not prevent it completely. Avoiding chronic pesticide before and during pregnancy can prevents ASD.

Folate plays a critical role in DNA methylation- a process by which genes are turned off or on, as well as in DNA repair and synthesis. These are important during periods of rapid growth when there are lots of cells dividing in developing fetus. Taking folic acid can improve genomic functions.
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Microbes compete for nutrients and hinder metabolism

Choline is a water soluble nutrient, it supports energy, brain function and keeps the metabolism active. It contributes to resources that cells used to make modifications to DNA, and with less choline the cell's ability to modify and regulate genes can be impaired.

Tissues from the liver to the brain had altered epigenetic patterns in mice with high levels of choline-eating microbes.
Epigenetic modifications change how genes are expressed. The nutritional demand for the nutrient increases during pregnancy to support epigenetic regulation and cellular health in the developing fetus, and studies have linked choline deficiency during pregnancy in humans with altered behavior in children.

 Choline is found in high amounts in soybeans, eggs, meat, fish, cauliflower, milk and other foods. To test whether microbiomes could compete with their hosts for the nutrient. Researchers used germ-free mice that were colonized with defined populations of microbes to test whether microbiomes could compete with their hosts for the nutrient.

Some mice had choline eaters; others had communities where choline consumption was disrupted by mutating a single gene. When the mice were fed with a high-fat diet, which induces a range of metabolic diseases in mice, the animals with choline-eating microbes added more abdominal fat, and had fattier livers, than their counterparts with microbes that couldn't eat choline.

The offspring of mice with choline-eating bacteria had altered epigenetic patterns in their brains, suggesting problems with normal development. In mice that were genetically susceptible to behavioral problems, those that had choline-eating microbes showed anxious behaviors.

Epigenetic regulation explains the negative effects of choline-eating microbiomes, the byproduct of bacterial choline metabolism, known as Trimethylamine N-oxide TMAO, is also linked to negative outcomes. In another experiments, researchers observed much higher levels of TMAO in the mice that hosted choline-eating bacteria.

The toxic TMAO might work together with disrupted epigenetic patterns to create the long list of metabolic and developmental disruptions seen in these animals. The toxic effects of TMAO accumulation also complicate potential dietary remedies, more choline in the diet might lead to more TMAO rather than fixing nutritional shortages.
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New way of treating HIV

 HIV drugs target the virus, the virus is not stable; it always mutates because the virus can become resistant to effective drugs, directing the immune system to kill the disease is better than targeting the virus with drug.

Some people are okay with HIV suppressing treatment, but more people are experiencing drug resistance. HIV- 1 is the most widespread, HIV can be classified into R5 and X4 viruses.

R5 viruses are linked with primary infection while X4 viruses occur in later stages of HIV diseases in some HIV patients. Detection of X4 is an indication that the patient's HIV infection has progressed to dangerous state.

Immune system protein suppresses damaging HIV strains, X4, by preventing the virus from infecting cells can be improve on, strengthening the immune system to kill the virus will be more effective because viruses cannot escape the body's immune system.
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Breastfeeding reduces cancers risk

Breastfeeding releases the production of prolactin, this prevents regular monthly menstruation. This reduces lifetime exposure to estrogen hormone. High estrogen levels is associated with breast cancer.

It also removes cells with damaged DNA that could lead to tumour development in breast. For every five months a woman breastfeeds, her risk of breast cancer is reduced by two percent.

Breastfeeding burns excess calories, it releases oxytocin hormone which returns uterus to its pre- pregnancy size and may reduce uterine bleeding after birth.

It prevents children from developing different types of cancers, babies who are breastfed may not become obese in future. Breastfeeding prevents all childhood diseases and reduces the risk of sudden infant death syndrome SIDS.
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Cancer cells suppress the immune system

Human immune systems prevents different diseases including cancer, for cancer to spread and multiply, they must find a way to avoid the body's immune system.

Degenerated cells in the body cause an inflammatory reaction and influence other blood cells to the extent that the immune system is suppressed.

Tumor cells influence their environment in order to avoid an immune response and to facilitate their growth. Solid tumors manipulate macrophages of the immune system.

The relationship between leukemia cells and monocytes becomes a catalyst for cancer development. Programmed death-ligand 1PD-L1 also known as cluster receptor occurs more frequently on the surface of these nourishing cells, and suppresses the immune response for cancer to grow.

The immune response is suppressed so much that the cancer cells can multiply without any hindrance. The monocytes send out semiochemicals, which belong to the inflammation response of the immune system and support the growth and multiplication of the cancer cells.

Scientists treated monocytes and macrophages of humans and mice with suspect exosomes, as well as purified Y RNA from those exosomes, in a culture dish. In both cases, the cells changed similarly to how they would in chronic lymphatic leukemia CLL patients.

They carry more PD-L1 receptors to their surface and emit semiochemicals that accelerate the immune response and create favorable growth conditions for leukemia cells.

Adding Toll-like receptors TLR inhibitors such as Chloroquin, a medication used for malaria and rheumatic inflammation can inhibit YRNA.

CLL cells was able to suppress the reproduction of cancer cells markedly.
This makes Chloroquin a good substance for a combination therapy along with other agents for cancer treatment.
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Causes of type 2 diabetes

Type 2 diabetes is a disorder of metabolism, the condition occurs when the body does not produce enough insulin or the insulin produced does not work properly.

Insulin resistance means that the cells of the body do not fully respond to insulin that is released. This makes glucose to remains in the blood instead of being moved into the cells.

Common symptoms of Type 2 diabetes are: extreme thirst, frequent urination fatigue, blurred vision, sudden weight loss and increased appetite.

It can reduce life expectancy if it is not managed properly and cause different health complications. These factors increase the risk of developing type 2 diabetes.

Age increases the risk of diabetes, diabetes is common among adults, aging and insulin resistance are closely connected because old people gain weight and become inactive.

Another risk factor is being overweight
especially if you are large around the middle because it increases pressure on body’s ability to use insulin properly to control blood sugar levels.

The pressure of blood flowing through the arteries varies at different times in the heartbeat cycle and the systolic pressure measures the pressure when heart contracts and blood is forced through the arteries. High blood pressure can increase the risk of type 2 diabetes.

Genetics can contribute to the risk of developing type 2 diabetes. Parents can transfer it to their children. Mutations in any gene involved in controlling glucose levels can increase risk of type 2 diabetes. These include genes that control: production of glucose, production and regulation of insulin and how glucose levels are measured in the body

High blood glucose levels during pregnancy may leads to the development of type 2 diabetes in future.

Healthy eating, an active lifestyle and regular medical examination can reduce the risk of type 2 diabetes.
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Nerlynx drug for early breast cancer treatment

Breast cancer starts when cells in the breast begin to grow out of control. The cancers can start from different parts of the breast. It can start from the ducts that carry milk to the nipple or in the glands that make breast milk.

The U.S. Food and Drug Administration FDA has approved Nerlynx a once-daily oral tyrosine kinase inhibitor for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer.

Nerlynx is a prescription medicine used to treat adults who have early-stage breast cancer, which is HER2-positive and has previously been treated with the medicine trastuzumab.

Nerlynx may cause serious side effects like diarrhea, liver problems, fatigue,
vomiting, fever, rash, right upper abdominal pain, weight loss and urinary tract infection UTI.

Pregnant women, nursing mother and women planning to get pregnant can not use Nerlynx.
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How sugar spreads cancer

Researchers have discovered how sugar modification in cells enhances the spread of skin cancer.

The study reveals that FUT8, an enzyme that transfers the sugar fucose onto proteins, is the major cause of melanoma metastasis.

Scientists thought that the process in which carbohydrates attach to cell called glycosylation plays an important role in melanoma progression.

Researchers examined more than 30 samples of cancer tissue in patients, focusing on a particular type of glycosylation fucosylation, or the addition of sugars to a molecule by FUT8 and other enzymes.

Using laboratory mice, the researchers were able to reveal the role of FUT8 in metastasis, they subsequently focused on the factors behind the spread of melanoma.

Addiction of fucose to a particular molecule, L1CAM, by FUT8 spurred melanoma metastasis. When the
enzyme was removed, the onset of the cancer were hindered from spreading.

High sugar intake and your facial beauty

High sugar intake can cause obesity, chronic disease, tooth decay, cause wrinkles on your face and change your complexion.

Glycation is when sugar in your bloodstream bonds onto proteins in the body. The more sugar we eat, the more glycation end products we produce.

Since collagen that keeps our skin plump and firm is the body’s most prevalent protein, it will be affected most and can result in saggy, loose and red facial skin.

Glycation can cause other skin problems, like redness, rosacea and acne. Foods with higher glycemic index
can trigger breakouts.

Sugar triggers the pancreas to produce more insulin, which increases the hormones that stimulate sebum production. Sugar changes complexion by depleting water in the cells causing dark under-eye circles.

Nivolumab drug can kill abestos cancer

Asbestos was once a popular building material, but it was discovered that exposure to it causes mesothelioma cancer.

Mesothelioma affects the lungs, and the lining surrounding the lower digestive tract. Symptoms are chest or lower back pain shortness of breath  and excessive sweating.

Nivolumab is effective for treating melanoma and kidney cancer it blocks PD-1 on the surface of T-cells, then activate immune system cells to hunt down and kill cancer cells.

It’s an example of immunotherapy, a type of cancer treatment which boosts the body’s natural defences in order to fight cancer.

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Symptoms of prostate cancer

The uncontrollable growth of cells in the prostate gland is prostate cancer, it is easy to treat if it is discovered early.

Common symptoms are: frequent urination at night, straining while urinating and back ache.

The most common way to diagnose abnormalities with the prostate gland is through a Prostate Specific Antigen, or PSA test.

PSA is a protein produced by the prostate and released into the blood stream in very small quantities.

More PSA is released when there is a problem with the prostate, and elevated levels can indicate prostatitis, enlarged prostate or prostate cancer.

How the body fight viruses

Viruses are  very small infectious agents that reproduce and grow inside the living cells of other organisms.

Researchers from the University of Rochester Center for RNA Biology examined the role of piRNA in protecting the genetic information in germ cells.

piRNA is a type of ribonucleic acid that is in testes and ovaries, piRNA prevents genetic sequences of viral intruders from attacking testes and ovaries.

Defects or Mutations in piRNA can cause infertility in humans and others animals, scientists used rooster testes to test effects of piRNA.

They discovered that chicken harbour a lot of viruses and discovered that host of a virus can turn a virus into a source of strength to fight with other viruses in future.

Scientists discovered that chickens turn the old virus in their body to piRNA- producing machine. This shows that human and animal protect themselves by using old virus to protect themselves from new virus attack.

Amino acids that starve cancer

Researchers at the cancer research UK discovered that remoing serine and glycine from the diet of mice reduced the growth of lymphoma and intestinal cancer.

Dr Oliver M, of University of Glasgow said the discovery dictate removing of the two proteins through a controlled diet plan will be part of treatment for some cancer patients.

Professor Karen Vousden, Cancer Research UK's chief scientist said the protein restriction should be for a short period of time and must be controlled by doctors for safety of cancer patients.

Amino acids are very important for making proteins, healthy cells can make serine and glycine. Cancer cells depend on these amino acids from the food we eat.

Science communication manager at cancer research UK, Dr Emma Smith said cutting off the nutrients necessary for cancer growth and division to prevent tumors is interesting.

How to make artificial blood for transfusions

According to U.S. National Heart, Lung and Blood Institute, Red blood cells are common components in blood transfusion.

The cells contain haemoglobin that delivers oxygen to the body tissues, scientists have tried to develop chemically modified haemoglobin.

Blood transmissions can save lives of patients that suffered blood loss in an accident. Hospital may not have the right type of blood, scientists have discovered a new method of producing substitute blood to save lives.

Researchers wrapped haemoglobin in polydopamine and test it in the laboratory, it shows polydopamine haemoglobin carrying oxygen effectively and it also prevents methaemoglobin and hydrogen peroxide.

The blood formed-polidopamine haemoglobin, caused minimum cell damage and served as an effective antioxidant. It removes damaging free radicals and reactive oxygen species.