Covid-19 virus infects, replicates in human intestinal cells

The novel coronavirus can infect and replicate in cells that line the inside of the human intestines, according to a study that could explain why some patients with COVID-19 experience gastrointestinal symptoms.

The finding, published in the journal Science, shows that the intestines are a target organ for the SARS-CoV-2 virus.

Studies have shown that the virus enters epithelial cells in the lungs by exploiting an enzyme called ACE2, allowing it to replicate and spread further, according to the researchers, including those from Erasmus Medical Center in the Netherlands.

The ensuing damage results in some of the respiratory symptoms that COVID-19 is known for, which can range from coughing and shortness of breath to pneumonia in more severe cases, they said.

The researchers noted that preliminary observations suggest that the virus may also infect cells in the gut.

Patients sometimes show gastrointestinal symptoms like diarrhea, and researchers know that gut epithelial cells also harbour ACE2, they said.

The team generated three dimensional (3D) structures that display all cell types of the human small intestinal epithelium and grew them in four different culture conditions.

The human small intestinal organoids grown in different conditions expressed varying amounts of ACE2, and could be infected with SARS-CoV-2, the researchers said.

Using electron microscopy, they discovered that the virus infected both mature and progenitor enterocytes, which are intestinal absorptive epithelial cells that line the inner surface of the intestines.

The researchers also found that the virus provoked the activity of genes involved with antiviral responses.

The rates of infection were similar across the organoid models, indicating that even low quantities of ACE2 may be enough for the virus to infect epithelial cells, they said. 

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Simple blood test to improve ovarian cancer diagnosis

A new study, published in the journal Scientific Reports, found that testing for a specific immune biomarker allows clinicians to identify whether growths on the ovaries are cancerous or not, without the need for tests like the MRI scans or ultrasounds. Ovarian cancer is one of the most common gynaecologic cancers, with the highest mortality rate. About 300,000 new cases are diagnosed globally each year, with an estimated 60 per cent of women dying within five years after diagnosis.

“Our new test is as accurate as the combined results of a standard blood test and ultrasound. This is especially important for women in remote or disadvantaged communities, where under-resourced hospitals may not have access to complex and expensive equipment like ultrasound machines or MRI scanners,” said study senior author Magdalena Plebanski from the RMIT University in Australia. “It also means patients with benign cysts identified through imaging could potentially be spared unnecessary surgeries,” Plebanski added.

According to the researchers, the test could be an important diagnostic tool for assessing suspicious ovarian growths before operations. “This study looked at women with advanced ovarian cancer, but we hope further research could explore the potential for adding this biomarker to routine diagnostic tests at earlier stages of the disease,” Plebanski said.

The study used an immune marker for inflammation (IL-6) together with cancer markers to detect epithelial ovarian cancer in blood. According to the researchers, results were validated across two separate human trial cohorts. “Every day in Australia, four women are diagnosed with ovarian cancer and three will die from the disease,” Plebanski said.

“Developing tests that are simpler and more practical may help get more women to hospital for treatment more effectively, with the hope that survival rates will improve,” Plebanski concluded.

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Thirdhand smoke does affect cells in humans

People often think that third-hand smoke is not harmful, however, it does affect us negatively. Third-hand smoke can damage epithelial cells in the respiratory system by stressing cells and causing them to fight for survival, suggests a study.

“Our data show that cells in humans are affected by third-hand smoke (THS). The health effects of THS, have been studied in cultured cells and animal models, but this is the first study to show a direct effect of third-hand smoke on gene expression in humans,” said Prue Talbot, who led the research.

Third-hand smoke, or THS, results when exhaled smoke and smoke emanating from the tip of burning cigarettes settles on surfaces such as clothing, hair, furniture, and cars. Not strictly smoke, THS refers to the residues left behind by smoking.

“THS can resurface into the atmosphere and can be inhaled unwillingly by non-smokers,” said Giovanna Pozuelos, the first author of the study. The researchers obtained nasal scrapes from four healthy nonsmokers who had been exposed to THS for three hours in a laboratory setting.

They found 382 genes were significantly over-expressed; seven other genes were under-expressed. They then identified pathways affected by these genes. “THS inhalation for only three hours significantly altered gene expression in the nasal epithelium of healthy nonsmokers,” said Pozuelos.

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Third-hand smoke can damage one's respiratory system

The hazards of second-hand smoke are well-known. Now, scientists found even third-hand smoke could do harm to one's respiratory health by changing gene expressions.

The study  showed that the third-hand smoke can damage epithelial cells in the respiratory system, coercing those cells into a fight for survival.

The third-hand smoke, or THS, results when the exhaled smoke and smoke emanating from the burning cigarettes settle on surfaces like clothing, hair and furniture.

The researchers  obtained nasal scrapes from four healthy nonsmoking women aged 27 to 49 years, who were randomized to receive the clean air exposure first and then THS exposure for three hours. The researchers extracted RNA from them to examine their gene expression changes.

A total of 382 genes among approximately 10,000 genes in the data set were significantly over-expressed and seven other genes were under-expressed, according to the study.

"THS inhalation for only three hours significantly altered gene expression in the nasal epithelium of healthy nonsmokers," said the paper's first author Giovanna Pozuelos, a graduate student at UCR.

Also, the researchers found that the inhalation altered pathways associated with oxidative stress that may cause cancer in the long term.

The nasal membrane tissue is similar to those in the bronchus, so the researchers suggested that the damage could go deeper in the respiratory system.

"Many smoking adults think, 'I smoke outside, so my family inside the house will not get exposed.' But smokers carry chemicals like nicotine indoors with their clothes," said  a professor  who led the research.

"It's important that people understand that THS is real and potentially harmful," said the Prof.

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Aspirin may help counteract impact of obesity on cancer

Aspirin can counter the ill effects of obesity on cancer development, according to a study that may pave the way for new therapies to prevent the deadly disease in those at risk.

Obesity is a known risk factor for certain types of cancer, including colon, pancreatic and breast cancer. Studies have shown its role in promoting tumour growth and malignant progression. However, its role in cancer initiation has been uncertain.

"Epithelial" cells lining the surfaces of organs have the intrinsic ability to remove potentially malignant cells from their midst. This is called the "epithelial defense against cancer" mechanism. Normally, the cells sense harmful cells and push them out by the process called cell competition.

To study how obesity affects this defense mechanism, researchers bred mice that were designed to express a known cancer-inducing mutant protein called Ras Epithelial cells usually remove the potentially malignant Ras-transformed cells.

Feeding the Ras mice high-fat diets, which resulted in severe obesity, suppressed the defense mechanism and therefore increased the number of Ras-transformed cells remaining in the tissue.

This suppression was seen in the intestine and pancreas, but not in the lungs. Furthermore, a month later the Ras-transformed cells developed a tumor in the pancreas of mice with the high-fat diet.

The result supports previous correlations made between intestinal and pancreatic cancer and obesity, but not lung cancer.

Following experiments using the mice model and cultured cells revealed that fatty acids and chronic inflammation cause the suppression of the defense mechanism.

When mice fed a high-fat diet were treated with aspirin, known for its anti-inflammatory properties, the defense mechanism was substantially enhanced. This implies that reinforcing the epithelial defense mechanism with anti-inflammatory drugs could be utilised for cancer prevention.

"This is the first report to show that obesity and chronic inflammation can influence competitive interaction between normal cells and transformed cells. It implies other factors such as infection, smoking, sleeping patterns and aging may also affect cell competition," said the author.

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Natural compound in onions may help fight ovarian cancer

A natural compound isolated from onions may help treat the most common type of ovarian cancer, a new study has claimed

Researchers from Kumamoto University in Japan studied the effects of a natural onion compound, onionin A (ONA), on a preclinical model of epithelial ovarian cancer (EOC) both in vivo and in vitro.

Previously, researchers found that ONA suppressed pro-tumour activation of host myeloid cells.

According to a 2014 review of cancer medicines from the World Health Organisation, EOC is the most common type of ovarian cancer and has a five-year survival rate of about 40 per cent, researchers said.

It has a relatively low lifetime risk that is less than one per cent, but that can increase up to 40 per cent if there is a family history of the disease.

A majority of patients (80 per cent) experience a relapse after their initial treatment with chemotherapy; therefore, a more effective line of treatment is needed.

The group's in vitro experiments showed that EOCs, which usually proliferate in the presence of pro-tumour M2 macrophages, showed inhibited growth after introduction of ONA.

This was thought to be due to ONA influence on STAT3, a transcription factor known to be involved in both M2 polarisation and cancer cell proliferation.

The team also found that ONA inhibited the pro-tumour functions of myeloid-derived suppressor cells (MDSC), which are associated with the suppression of the anti-tumour immune response of host lymphocytes, by using preclinical sarcoma model.

ONA was also found to enhance the effects of anti-cancer drugs by strengthening their anti-proliferation capabilities.

Moreover, experiments on an ovarian cancer murine model that investigated the effects of orally administered ONA resulted in longer lifespans and inhibited ovarian cancer tumour development.

This was considered to be a result of ONA's suppression of M2 polarised macrophages, researchers said.

The study shows that ONA reduces the progression of malignant ovarian cancer tumours by interfering with the pro-tumour function of myeloid cells.

ONA appears to activate anti-tumour immune responses by nullifying the immunosuppressive function of myeloid cells. It has the potential to enhance existing anti-cancer drugs while also having little to no cytotoxic effects  on normal cells, researchers said.

No side effects in animals have been observed. With a little more testing, an oral ONA supplement could greatly benefit cancer patients, they said.
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A natural compound isolated from onions may help treat the most common type of ovarian cancer, a new study has claimed

Researchers from Kumamoto University in Japan studied the effects of a natural onion compound, onionin A (ONA), on a preclinical model of epithelial ovarian cancer (EOC) both in vivo and in vitro.

Previously, researchers found that ONA suppressed pro-tumour activation of host myeloid cells.

Read more at:
http://economictimes.indiatimes.com/articleshow/55013265.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst

A natural compound isolated from onions may help treat the most common type of ovarian cancer, a new study has claimed

Researchers from Kumamoto University in Japan studied the effects of a natural onion compound, onionin A (ONA), on a preclinical model of epithelial ovarian cancer (EOC) both in vivo and in vitro.

Previously, researchers found that ONA suppressed pro-tumour activation of host myeloid cells.

According to a 2014 review of cancer medicines fro ..

Read more at:
http://economictimes.indiatimes.com/articleshow/55013265.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst

Lung protein key in allergies

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People who grow up on farms - especially dairy farms - have way fewer allergy and asthma problems than the rest of us. 

 Now one research team thinks they've brought science closer to understanding why. 

In a study published in Science, researchers report that they were able to pinpoint one possible mechanism for the allergy protection in mice they studied. Surprisingly, the protein that they fingered as the likely allergy-preventer doesn't actually affect the immune system - it affects the structural cells that make up the lining of the lung. 

The research is related to something called the hygiene hypothesis, where a lack of exposure to microbes as a tyke leads to more allergy and asthma. It's what leads microbiologists to say that the best thing you can do for your kid is roll them around on the floor of the subway . That may indeed be true (as long as you roll very, very carefully!) but there's increasing evidence that farms have the best germs for preventing respiratory problems and allergic reactions later in life. 

One study found that just 25 percent of children living on Swiss farms reacted to common allergens like dust mites, pollen, animals and mould, while 45 percent of children in the general population reacted. 

And among Amish children - who obviously have some of the farmiest of farm lives, though other factors may also be at play - reactions fall to a shocking eight percent or less. 

It's still not totally clear what's behind this amazing allergy protection, but many scientists believe that the bacteria native to farms, especially ones that house livestock, may trigger something in children who live nearby. 

The researchers behind the latest study had previously found that the epithelial cells of the lungs are important in the development of allergy responses. 

“How does your body react the first time you inhale an allergen? The first cells that recognise the allergen are not so much the cells of the immune system, but the structural cells that make up the inside of the lungs,” Bart Lambrecht of Ghent University, who co-led the study with Hamida Hammad, said. 

So they wanted to see how this farm effect might be visible in the lungs themselves. 

In their experiment, Lambrecht and Hammad induced dust mite allergies in mice, then showed that exposure to dust from a dairy farm made early in life made them immune. 

Then, they studied the mechanism that was protecting the mice, making their mucous membranes less likely to react to the allergens. They found a protein called A20, which the mice were producing when exposed to the farm dust. When the researchers knocked out the A20 in their subjects' lungs, the farm dust stopped protecting them from allergic reactions. 

A test in mice can't definitively provide answers on human health. But the research team did go one step further - they tested 2 000 children who lived on farms, and they found that those who suffered from allergies in spite of their upbringing had a mutation on the gene related to A20, causing the protein to malfunction.
“A20 was not a coincidence, it was really necessary,” Lambrecht said. “This is linking, showing a cause and effect link, between exposure to farm dust and fewer allergies. I think our study is a big step forward.” 

While there are almost certainly other factors at play in allergy development and prevention, Lambrecht and his colleagues hope that the cells of the lung itself will get more attention in research. This could be a sign, he said, that allergy and asthma vaccines need to be administered by aerosol instead of injection in order to truly be effective. And it may mean that epidemiologists need to think twice before focusing on blood samples alone in their allergy studies. 

“The study opens an new area of investigation in our long quest to understand the hygiene hypothesis, which is the complex interaction of farm exposures and their impact on the function of structural cells of the airway,” said Mark Holbreich, a physician who studies the hygiene hypothesis but was not involved in the new research. 

But while A20 is a fascinating new piece of the puzzle, it's unlikely to put an end to allergies as we know them. 

“We know from many studies that there appear to be multiple factors that contribute to protection,” Holbreich said. “This article adds to our expanding knowledge yet we are still far from developing a means for the primary prevention of allergies and asthma.” 
 Washington Post