Molecular biomarkers for preeclampsia

Preeclampsia is a sudden pregnancy complication that can interfere with the blood flow to the placenta and possibly to the fetus, it can lead to low birth weight, prematurity and death. It is also a leading cause of maternal mortality. A new Tel Aviv University study identifies novel molecular biomarkers of preeclampsia, signaling the potential for an early diagnostic blood test.

Research for the study was led by Dr. Noam Shomron and Prof. Moshe Hod and conducted by Liron Yoffe and other lab members, all affiliated with TAU's Sackler School of Medicine, and in collaboration with Prof. Kypros Nicolaides of King's College, London. Preeclampsia is a serious disease that endangers the health, sometimes even the lives, of the mother and the fetus.

The causes of  preeclampsia is unknown if caught in time it has a simple and proven remedy: low doses of aspirin administered from the 16th week until the end of pregnancy. Medical practitioners have assessed a woman's risk of preeclampsia by referring to previous pregnancies, blood pressure levels and other general symptoms. Blood test could predict preeclampsia and, in turn, allow doctors to provide treatment that would prevent the  onset of the disease.

Researchers examined the blood samples from thousands of pregnant women in their first trimester, the team then narrowed their focused to 75 specific blood samples: 35 taken from women who eventually contracted preeclampsia, and 40 taken from those who completed their pregnancies in full health. The researchers extracted the RNA molecules (snippets of molecular information present in human cells) from the plasma of the samples and sequenced these using Next Generation Sequencing (NGS).

The scientists discovered the new biomarkers by analyzing the data using computational methods that included statistical analyses and machine learning algorithms. They identified 25 small RNA molecules that were differentially expressed between the preeclampsia and the control groups. Based on those RNA molecules, they developed a model for the classification of preeclampsia samples.

These findings indicate the predictive value of circulating small RNA molecules in the first trimester, and lay the foundation for producing a novel early non-invasive diagnostic tool for preeclampsia, which could reduce the life-threatening risk for the mother and fetus.
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Links between epigenetic aging and bipolar disorder

Bipolar disorder may involve accelerated epigenetic aging, which could explain why persons with the disorder are more likely to die from age-related diseases. Chronological age is measured in the amount of time that a person has been alive, epigenetic age measures molecular markers of chemical modifications to DNA. Bipolar disorder has been previously associated with accelerated aging but the mechanisms are unknown.

The chemical modifications could be precipitated by the disorder itself or by poor lifestyle habits in diet, exercise, tobacco use and illegal substance use. Controlling these factors is just as important as taking medications. Using blood samples, the researchers compared patients with bipolar disorder,  siblings of bipolar patients and healthy controls.

They also found that while older bipolar disorder patients had significantly accelerated epigenetic aging compared to controls, no difference was found in younger patients.A difference wasn't detected in younger patients because they haven't had as much exposure to stressful events. This gave us a hint that cumulative chronic exposure to stress would relate to accelerated aging.

 We would see it more in older people who have experienced a lifetime of stress in dealing with the disease. Along with the epigenetic clock, the study included two other biologic clocks: telomere length and mitochondrial DNA copy numbers. The epigenetic acceleration correlated with the number of copies of mitochondrial DNA, suggesting that the cross-talk between the nucleus and the mitochondria might be underlying the premature aging in bipolar disorder.
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Aging impairs immune response to flu

Aging impairs the immune system's response to the flu virus in multiple ways, weakening resistance in older adults, researchers examined the innate immune response to the flu virus. They collected blood samples from healthy young adults and older adults.

They isolated monocytes, a type of white blood cell, from the samples and stimulated the monocytes with either flu virus or a mimic of the virus. The immune response in cells from older adults was severely impaired in critical ways, the researchers found.

To fight the flu virus, the body needs to activate potent antiviral proteins called interferons. But in older adults, this response is weakened by age-related damage to a molecule, TRAF3, that signals immune cells to make interferon. Without that signal, and another involving antiviral genes, resistance to flu falls short.
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The secrets of Ebola

In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone. Conducting a sweeping analysis of everything from enzymes to lipids to immune-system-associated molecules, the teamfound 11 biomarkers that distinguish fatal infections from nonfatal ones and two that, when screened for early symptom onset, accurately predict which patients are likely to die.

Health workers collected blood samples from patients after they were diagnosed with Ebola and at multiple points thereafter.They obtained 29 blood samples from 11 patients who ultimately survived and nine blood samples from nine patients who died from the virus. For comparison, the research team also obtained blood samples from 10 healthy volunteers with no exposure to Ebola virus.
"Our team studied thousands of molecular clues in each of these samples, sifting through extensive data on the activity of genes, proteins and other molecules to identify those of most interest.

The team found that survivors had higher levels of some immune-related molecules, and lower levels of others compared to those who died. Plasma cytokines, which are involved in immunity and stress response, were higher in the blood of people who perished. Fatal cases had unique metabolic responses compared to survivors, higher levels of virus, changes to plasma lipids involved in
processes like blood coagulation, and more pronounced activation of some types of immune cells.

Pancreatic enzymes also leaked into the blood of patients who died, suggesting that damage from these enzymes contributes to the tissue damage characteristic of fatal Ebola virus disease. The study showed that levels of two biomarkers, known as L-threonine (an amino acid) and vitamin D binding protein, may accurately predict which patients live and which die. Both were present at lower levels at the time of admission in the patients who ultimately perished.

When Ebola virus leads to death, experts believe it is because of overwhelming viral replication. Symptoms of infection include severe hemorrhaging, vomiting and diarrhea, fever and more. In the current Ebola study, the team found that many of the molecular signals present in the
blood of sick, infected patients overlap with sepsis, a condition in which the body in response to infection by bacteria or other pathogens mounts a damaging inflammatory reaction.
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Parabens can reduce sperm quality

According to the latest research, chemicals found in soap and plastic can reduce sperm quality. Hormone-disrupting chemicals, known as parabens, are significantly associated with an increased number of abnormally sized and shaped sperm, which has previously been linked to infertility.

Parabens, which are also found in certain foods, drugs and cosmetics can also cause DNA damage in sperm, which may hinder a woman's ability to conceive. Exposure to such chemicals also reduces sperms' mobility, making it more difficult for ejaculate to reach an egg. Parabens cause slow-moving sperm of an abnormal size

The researchers analysed the urine samples of men who attended a fertility clinic. The samples' paraben concentrations were assessed. The participants were also interviewed and provided semen, saliva and blood samples.

Results reveal the presence of parabens in urine are significantly associated with an increase number of sperm of an abnormal size and shape, which has previously been linked to infertility.
Parabens are also linked to DNA damage in sperm.

A particular type of the chemical, known as butyl paraben, was found to be particularly associated with reducing sperm quality. Parabens are widely-used preservatives in cosmetic products, including soaps, moisturisers and make-up. They are also found in certain drugs, pesticides, plastics, detergents, foods, toys and flame retardants.

The most common forms of the chemical are methylparaben, propylparaben and butylparaben. Parabens are sometimes combined to increase their effectiveness. Parabens may have developmental, reproductive, neurological and immune-system side effects.
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Previous exposure to West Nile may prevents Zika or make it worse

West Nile virus is a mosquito-borne virus that affect many people, previous exposure to this virus can determine the reaction of affected person to Zika virus. Zika virus is a mosquito-borne virus and relative of West Nile.

 Previous exposure to West Nile Virus could either prevents Zika infection or make it worse. The National Institute of Allergy and Infectious Diseases NIAID will collect blood samples from people that had West Nile virus for presence of West Nile antibodies.

 These antibodies would indicate if the individual once had the virus but fought it off. The blood samples of those that had West Nile virus that fought it off in the past will be used to explore antibody-dependent enhancement ADE, where the presence of certain antibodies can either strengthen or fight a subsequent infection.

Researchers will use blood samples that are positive for West Nile antibodies to carry out tests that will determine whether West Nile antibodies enhance or inhibit Zika virus infection.

If the results show that West Nile enhances Zika, people must prevent mosquito bites. If  West Nile inhibits Zika, a vaccine for West Nile could potentially protect against Zika.
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Diagnosing Zika virus with nanotechnology

Testing for Zika requires that a blood sample be refrigerated and moved to a laboratory, this delay diagnosis and treatment. The researchers tested blood samples taken from people infected with Zika virus and compared it to blood from people that do not have the virus.

 Blood from Zika-infected patients tested positive while blood from Zika-negative controls did not. The assay produced no false-positive results.

Zika infection is either asymptomatic or mildly symptomatic; people infected with Zika don't know they're infected, many people don't become sick after being bitten by an infected mosquito.

 Testing is particularly important for pregnant women because Zika infection can cause congenital Zika syndrome, which contributes to several neurologic problems in the fetus or newborn infant.

Population screening is the effective way of diagnosing the diseases. Using of gold nanorods mounted on paper to detect Zika infection within a few minutes is faster and better than the current method.

The test relies on a protein made by Zika virus that causes an immune response in infected individuals. The protein is attached to tiny gold nanorods mounted on a piece of paper.

The paper then is completely covered with tiny, protective nanocrystals. The nanocrystals allow the diagnostic nanorods to be shipped and stored without refrigeration prior to use.

To use the test, a technician rinses the paper with slightly acidic water, removing the protective crystals and exposing the protein mounted on the nanorods. Then, a drop of the patient's blood is applied. If the patient has come into contact with the virus, the blood will contain immunoglobulins that react with the protein.

Immunoglobulins persist in the blood for a few months, and when they come into contact with the gold nanorods, the nanorods undergo a slight color change that can be detected with a hand-held spectrophotometer. With this test, results and treatments will be immediate.
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