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Study: Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines

  • By Carl Lanore
Int J Mol Sci. 2016 Jan 29;17(2). pii: E176. doi: 10.3390/ijms17020176.

Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines (OVCAR-429 and PA-1) and Potentiates the Effect of G1 Arrest by Targeting CDKs.

Shen CJ1,2Chang CC3Chen YT4,5Lai CS6,7Hsu YC8,9.


Melatonin is found in animals as well as plants. In animals, it is a hormone that anticipates the daily onset of darkness and regulates physiological functions, such as sleep timing, blood pressure, and reproduction. Melatonin has also been found to have anti-tumor properties. Malignant cancers are the most common cause of death, and the mortality rate of ovarian tumor is the highest among gynecological diseases. This study investigated the anti-tumor effects of melatonin on the ovarian cancer lines, OVCAR-429 and PA-1. We observed the accumulation of melatonin-treated cells in the G₁ phase due to the down-regulation of CDK (cyclin-dependant kinase) 2 and 4. Our results suggest that in addition to the known effects on prevention, melatonin may also provide anti-tumor activity in established ovarian cancer.


CDK; cell cycle; melatonin; ovarian cancer


UNC researchers identify how hepatitis A virus causes liver injury

  • By Carl Lanore

Team also discovers viral pathway to infect new species





Chapel Hill, NC - Hepatitis researchers have long thought that immune cells sent by the body to attack virus-infected cells in the liver cause the acute liver injury associated with hepatitis A virus (HAV) and other hepatitis viruses. Yet, investigators at the University of North Carolina at Chapel Hill have discovered that it is an immediate, intrinsic response of the HAV-infected cell that results in liver inflammation. These results were published in the journal Science.

"The virus evokes a response in the infected cell that activates a pre-programmed cell death pathway," said Stanley Lemon, M.D., one of the study's authors and a professor of medicine at UNC's School of Medicine and UNC's Institute for Global Health & Infectious Diseases. "In effect, the cell commits suicide, sacrificing itself along with the virus in an effort to save the host. This results in inflammation within the liver that we recognize as hepatitis."

Hepatitis A virus is a vaccine preventable form of infectious hepatitis. HAV is found worldwide and is transmitted through ingestion of food and water that is contaminated with the feces of an infected person. Frozen strawberries used in drinks at a smoothie chain led to a hepatitis A outbreak this summer in seven states.

Symptoms of hepatitis A include nausea, stomach pain, fever, sore throat, headache and diarrhea. People infected with HAV may not experience any symptoms, but shed the virus for two to four weeks. During this period, an infected person can pass the virus to others. HAV does not cause chronic liver disease like hepatitis B and C viruses. But in rare cases, it can cause acute liver failure, which is often fatal.

In addition to identifying how the virus causes acute liver injury, the UNC team, along with colleagues at North Carolina State University, established a new animal model of infection with the virus. For decades, researchers believed only primates - humans, chimpanzees and a few species of monkeys - could be infected by HAV. However, when the team interrupted the intrinsic cellular antiviral response in mice, they discovered the virus could jump species.

"The ability of the virus to jump into mice is dependent upon knocking out the mouse interferon system, which HAV cannot do on its own," said Lemon. "Host species jumps are incredibly important for viral emergence, and the factors that control the odds of this happening are not well known. We have defined the host interferon system as a very important barrier to a host species jump."

The UNC research team, led by Lemon and Jason Whitmire, Ph.D., Associate Professor in UNC's Department of Genetics, is now poised to investigate the complicated interplay of nonspecific "innate" and specific "adaptive" immune responses that ultimately control the infection and eliminate HAV from the host - processes that are not well understood for any of the five human hepatitis viruses.


Scientists make embryos from non-egg cells

  • By Carl Lanore


Scientists have shown for the first time that embryos can be made from non-egg cells, a discovery that challenges two centuries of received wisdom.

Eggs can be 'tricked' into developing into an embryo without fertilisation, but the resulting embryos, called parthenogenotes, die after a few days because key developmental processes requiring input from sperm don't happen.

However, scientists from the Department of Biology & Biochemistry at the University of Bath have developed a method of injecting mouse parthenogenotes with sperm that allows them to become healthy baby mice with a success rate of up to 24 per cent.

This compares to a rate of zero per cent for parthenogenotes or about two per cent for nuclear transfer cloning.

The study is published today (Tuesday, 13 September, 2016) in the journal Nature Communications.

Molecular embryologist Dr Tony Perry, senior author of the study, said: "This is first time that full term development has been achieved by injecting sperm into embryos.

"It had been thought that only an egg cell was capable of reprogramming sperm to allow embryonic development to take place.

"Our work challenges the dogma, held since early embryologists first observed mammalian eggs around 1827 and observed fertilisation 50 years later, that only an egg cell fertilised with a sperm cell can result in a live mammalian birth."

The idea was the brain child of Dr Toru Suzuki in Dr Perry's team in the University of Bath's Laboratory of Mammalian Molecular Embryology, who performed the study together with team member Dr Maki Asami and colleagues from the University of Regensburg and the Fraunhofer Institute for Toxicology and Experimental Medicine in Germany.

The baby mice born as a result of the technique seem completely healthy, but their DNA started out with different epigenetic marks compared with normal fertilisation. This suggests that different epigenetic pathways can lead to the same developmental destination, something not previously shown.

The discovery has ethical implications for recent suggestions that human parthenogenotes could be used as a source of embryonic stem cells because they were considered inviable. It also hints that in the long-term future it could be possible to breed animals using non-egg cells and sperm. Although this is still only an idea, it could have potential future applications in human fertility treatment and for breeding endangered species.

Dr Paul Colville-Nash, from the Medical Research Council (MRC) who funded the work, said: "This is an exciting piece of research which may help us to understand more about how human life begins and what controls the viability of embryos, mechanisms which may be important in fertility. It may one day even have implications for how we treat infertility, though that's probably still a long way off."

Measuring new hormone may reduce teenagers wrongly diagnosed with PCOS

  • By Carl Lanore

Measuring blood levels of the recently discovered hormone irisin may improve diagnosis rates of teenagers with polycystic ovary syndrome, according to research presented today at the 55th Annual European Society for Paediatric Endocrinology Meeting


Measuring blood levels of the recently discovered hormone irisin may improve diagnosis rates of teenagers with polycystic ovary syndrome, according to research presented today at the 55th Annual European Society for Paediatric Endocrinology Meeting. The findings may reduce the number of unnecessary treatments prescribed to otherwise healthy girls.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to 12% of women. Women with PCOS are more likely to suffer from irregular periods, have excessive levels of male hormones and may have difficulty in conceiving due to irregularities in the ovaries. Doctors are cautious when diagnosing PCOS in teenagers because the symptoms can be confused with normal pubertal changes. Having tools that make diagnoses more accurate can reduce unnecessary treatment for otherwise healthy teenagers at a critical stage in their lives.

The cause of PCOS is unknown and there is currently no cure for the condition. Previous studies have associated high levels of irisin, a newly discovered hormone which is released from muscles and regulates energy metabolism, with PCOS in adults.

In this study, Greek researchers from Aghia Sophia Children's Hospital in Athens compared the hormones of 23 teenagers with PCOS with 17 healthy teenagers of the same age and BMI. They found that teenagers with PCOS had significantly higher irisin levels compared to the control group, and that this was associated with higher levels of the male sex hormone testosterone, a key marker of PCOS.

The findings suggest that irisin could be a marker for PCOS allowing the condition to be diagnosed more easily. "Teenagers who get an early diagnosis of PCOS can sooner start to deal with the physical and psychological symptoms caused by this lifelong condition," said lead researcher Dr Flora Bacopoulou. "Whether it's through counselling or medication, girls can manage their symptoms and decrease the risk of further complications such as fertility problems, hirsutism (excessive hair growth) and type-2 diabetes".

The group will next focus on confirming their results and investigate the biological role of irisin in PCOS. "If high irisin levels in teenagers with PCOS is established, this could lead to the development of treatments for PCOS. Lifestyle changes and different exercise-related signals that regulate the secretion of irisin could provide a potential option for the management of PCOS. The potential of irisin as a meaningful drug target in PCOS is very promising," said Dr Bacopoulou.


High variability suggests glycemic index is unreliable indicator of blood sugar response

  • By Carl Lanore

Glycemic index values can vary by 20 percent within an individual and 25 percent among individuals, according to the results of a controlled feeding clinical trial


BOSTON (September 7, 2016)--The glycemic index of a given food, a value that aims to quantify how fast blood sugar rises after eating it, can vary by an average of 20 percent within an individual and 25 percent among individuals, report scientists from the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HRNCA) at Tufts University.

In randomized, controlled, repeated tests involving 63 healthy adults, researchers found that individual blood sugar responses after consuming a fixed amount of white bread could range across all three glycemic index categories (low, medium, or high). Part of this variability could be attributed to insulin index and baseline HbA1c levels, which reflect long-term glucose control--evidence that glycemic index values are influenced by an individual's metabolic responses to food.

The study, published in the American Journal of Clinical Nutrition on Sept. 7, suggests glycemic index has limited utility as a tool to predict how a food affects blood sugar levels.

"Glycemic index values appear to be an unreliable indicator even under highly standardized conditions, and are unlikely to be useful in guiding food choices," said lead study author Nirupa Matthan, Ph.D., scientist in the Cardiovascular Nutrition Laboratory at the USDA HNRCA. "If someone eats the same amount of the same food three times, their blood glucose response should be similar each time, but that was not observed in our study. A food that is low glycemic index for you one time you eat it could be high the next time, and it may have no impact on blood sugar for me."

Developed as a way to help diabetic individuals control their blood sugar, glycemic index is intended to represent the inherent effect a food has on blood sugar levels. However, glycemic index is becoming used for broader purposes such as food labeling, and has served as the basis for several popular diets.

To study whether glycemic index values are accurate and reproducible, Matthan and her colleagues recruited 63 volunteers, who underwent six testing sessions over 12 weeks. Volunteers fasted and abstained from exercise and alcohol before each session. They then consumed either white bread, a simple carbohydrate that served as the test food, or a glucose drink, which served as a reference control, in random order. Each contained 50 grams of available carbohydrate. Blood glucose levels were measured at multiple time points for five hours after eating, and glycemic index was calculated by standard formulas.

An unreliable guide

The team found that the average glycemic index value of white bread for the study population was 62, placing it in the category of a "medium" glycemic index food.

However, deviations averaged 15 points in either direction, effectively placing white bread in all three glycemic index categories. It would be considered a low glycemic index food (average values of 35 to 55) for 22 of the volunteers, intermediate glycemic index (57 to 67) for 23 volunteers , and high glycemic index (70 to 103) for 18 volunteers . Even within the same individual, glycemic index values could differ by more than 60 points between trials.

"Reports frequently tout the benefits of choosing foods with low glycemic index and glycemic load values. Our data suggest those values may not be reliable in terms of a daily intake. A better approach to choosing foods is to consume a diet primarily composed of vegetables, fruits, whole grains, nonfat and low-fat dairy products, fish, legumes (beans), lean meats with preference to preparing food with liquid vegetable oils, and equally as important, to choose healthy foods and beverages you really enjoy," said senior study author Alice H. Lichtenstein, D.Sc., senior scientist and director of the Cardiovascular Nutrition Laboratory at the USDA HNRCA. Lichtenstein is also the Gershoff Professor at the Friedman School of Nutrition Science and Policy at Tufts.

The variability in glycemic index values occurred despite sample sizes larger than required by standard calculations. The study cohort of 63 individuals far exceeded the 10 individuals used by typical glycemic index methodology, as did the six feeding challenges and five-hour blood glucose measuring window.

The team also tested for the influence of biological characteristics: sex, body-mass index, blood pressure, physical activity, and several others. Most factors had only a minor statistical effect on glycemic index variability. Blood insulin response as measured by insulin index and HbA1c, a measure of longer term glucose control, had the largest effect, accounting for 15 and 16 percent of the variability, respectively.

The authors note their findings do not suggest that a high glycemic index food may be healthy, or that a low glycemic index food unhealthy. Both glycemic index and glycemic load--a value that adjusts glycemic index to serving size--reflect only food containing carbohydrates, and no one eats food in isolation. The high variability of glycemic index and glycemic load reveal limitations in their clinical and public health applicability, and glycemic index estimates and subsequent associations with chronic disease risk needs to be reconsidered, say the authors.

"Based on our results, we feel strongly that glycemic index is impractical for use in food labeling or in dietary guidelines at the individual level," Matthan said. "If your doctor told you your LDL cholesterol value could vary by 20 percent, it would be the difference between being normal or at high risk for heart disease. I don't think many people would find that acceptable."

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