Carbohydrates may be key to better malaria vaccine: study

Agencies
September 17, 2017

Melbourne, Sept 17: Scientists have for the first time found that carbohydrates on the surface of malaria parasites play a critical role in malaria's ability to infect mosquito and human hosts.

The discovery may help improve the only vaccine approved to protect people against Plasmodium falciparum malaria - the most deadly form of the disease, researchers said.

The study found that the malaria parasite 'tags' its proteins with carbohydrates in order to stabilise and transport them, and this process was crucial to completing the parasite's lifecycle.

"We found that the parasite's ability to 'tag' key proteins with carbohydrates is important for two stages of the malaria lifecycle," said Justin Boddey, from Walter and Eliza Hall Institute in Australia.

"It is critical for the the earliest stages of human infection, when the parasite migrates through the body and invades in the liver, and later when it is transmitted back to the mosquito from an infected human, enabling the parasite to be spread between people," said Boddey, who led the study published in the journal Nature Communications.

Interfering with the parasite's ability to attach these carbohydrates to its proteins hinders liver infection and transmission to the mosquito, and weakens the parasite to the point that it cannot survive in the host, researchers said.

Malaria infects over 200 million people worldwide each year and kills around 650,000 people, predominantly pregnant women and children.

Efforts to eradicate malaria require the development of new therapeutics, particularly an effective malaria vaccine.

The first malaria vaccine approved for human use - RTS,S/AS01 - was approved by European regulators in July 2015 but has not been as successful as hoped, with marginal efficacy that wanes over time, researchers said.

"The protein used in the RTS,S vaccine mimics one of the proteins we have been studying on the surface of the malaria parasite that is readily recognised by the immune system," said Ethan Goddard-Borger from Walter and Eliza Hall Institute.

"With this study, we have shown that the parasite protein is tagged with carbohydrates, making it slightly different to the vaccine, so the antibodies produced may not be optimal for recognising target parasites," Goddard-Borger said.

He said there were many documented cases where attaching carbohydrates to a protein improved its efficacy as a vaccine.

"It may be that a version of RTS,S with added carbohydrates will perform better than the current vaccine," Goddard-Borger said.

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Agencies
June 20,2020

The World Health Organisation has warned that the COVID-19 pandemic is entering a "new and dangerous" phase. Thursday saw the most cases in a single day reported to the WHO.

Tedros Adhanom Ghebreyesus said the day had seen 150,000 new cases with half of those coming from the Americas and large numbers also from the Middle East and South Asia, the BBC reported.

He said the virus was still spreading fast and the pandemic accelerating.

He acknowledged people might be fed up with self-isolating and countries were eager to open their economies but he said that now was a time for extreme vigilance.

Maria van Kerkhove, technical lead of the WHO's COVID-19 response, told a press conference the pandemic is "accelerating in many parts of the world".

"While we have seen countries have some success in suppressing transmission and bringing transition down to a low level, every country must remain ready," she said.

Mike Ryan, the head of the WHO's Health Emergencies Programme, said that some countries had managed to flatten the peak of infections without bringing them down to a very low level.

"You can see a situation in some countries where they could get a second peak now, because the disease has not been brought under control," he said.

"The disease will then go away and reduce to a low level, and they could then get a second wave again in the autumn or later in the year."

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Agencies
May 19,2020

New York, May 19: Cigarette smoke spurs the lungs to make more of the receptor protein which the novel coronavirus uses to enter human cells, according to a study which suggests that quitting smoking might reduce the risk of a severe coronavirus infection.

The findings, published in the journal Developmental Cell, may explain why smokers appear to be particularly vulnerable to severe COVID-19 disease.

"Our results provide a clue as to why smokers who develop COVID-19 tend to have poor clinical outcomes," said study senior author Jason Sheltzer, a cancer geneticist at Cold Spring Harbor Laboratory in the US.

"We found that smoking caused a significant increase in the expression of ACE2, the protein that SARS-CoV-2 uses to enter human cells," Sheltzer said.

According to the scientists, quitting smoking might reduce the risk of a severe coronavirus infection.

They said most individuals infected with the virus suffer only mild illness, if they experience any at all.

However, some require intensive care when the sometimes-fatal virus attacks, the researchers said.

In particular, they said three groups have been significantly more likely than others to develop severe illness -- men, the elderly, and smokers.

Turning to previously published data for possible explanations for these disparities, the scientists assessed if vulnerable groups share some key features related to the human proteins that the coronavirus relies on for infection.

First, they said, they focused on comparing gene activity in the lungs across different ages, between the sexes, and between smokers and nonsmokers.

The scientists said both mice that had been exposed to smoke in a laboratory, and humans who were current smokers had significant upregulation of ACE2.

According to Sheltzer, smokers produced 30-55 per cent more ACE2 than their non-smoking counterparts.

While the researchers found no evidence that age or sex impacts ACE2 levels in the lungs, they said the influence of smoke exposure was surprisingly strong.

However, they said, the change seemed to be temporary.

According to the data, the level of the receptors ACE2 in the lungs of people who had quit smoking was similar to that of non-smokers.

The study noted that the most prolific producers of ACE2 in the airways are mucus-producing cells called goblet cells.

Smoking is known to increase the prevalence of such cells, the scientists said.

"Goblet cells produce mucous to protect the respiratory tract from inhaled irritants. Thus, the increased expression of ACE2 in smokers' lungs could be a byproduct of smoking-induced secretory cell hyperplasia," Sheltzer explained.

However, Sheltzer said other studies on the effects of cigarette smoke have shown mixed results.

"Cigarette smoke contains hundreds of different chemicals. It's possible that certain ingredients like nicotine have a different effect than whole smoke does," he said.

The researchers cautioned that the actual ACE2 protein may be regulated in ways not addressed in the current study.

"One could imagine that having more cells that express ACE2 could make it easier for SARS-CoV-2 to spread in someone's lungs, but there is still a lot more we need to explore," Sheltzer said.

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News Network
May 13,2020

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

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