Emission from diesel engines linked to premature death

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.

COVID-19 mostly kills through an overreaction of the immune system, whose function is precisely to fight infections, say scientists who have decoded the mechanisms, symptoms, and diagnosis of the disease caused by the SARS-Cov-2 coronavirus.

In a study published in the journal Frontiers in Public Health, the researchers explained step-by-step how the virus infects the airways, multiplies inside cells, and in severe cases causes the immune defences to overshoot with a "cytokine storm".

This storm is an over-activation of white blood cells, which release too-great amounts of cytokines -- inflammation-stimulating molecules --into the blood, they said.

"Similar to what happens after infection with SARS and MERS, data show that patients with severe COVID-19 may have a cytokine storm syndrome," said study author Daishun Liu, Professor at Zunyi Medical University in China.

"The rapidly increased cytokines attract an excess of immune cells such as lymphocytes and neutrophils, resulting in an infiltration of these cells into lung tissue and thus cause lung injury," Liu said.

The researchers explained that the cytokine storm ultimately causes high fever, excessive leakiness of blood vessels, and blood clotting inside the body.

It also causes extremely low blood pressure, lack of oxygen and excess acidity of the blood, and build-up of fluids in the lungs, they said.

The researchers noted that white blood cells are misdirected to attack and inflame even healthy tissue, leading to failure of the lungs, heart, liver, intestines, kidneys, and genitals.

This multiple organ dysfunction syndrome (MODS) may worsen and shutdown the lungs, a condition called acute respiratory distress syndrome, (ARDS), they said.

This, the researchers explained, happens due to the formation of a so-called hyaline membrane -- composed of debris of proteins and dead cells -- lining the lungs, which makes absorption of oxygen difficult.

Most deaths due to COVID-19 are therefore due to respiratory failure, they said.

The researchers explained that in the absence of a specific antiviral cure for COVID-19, the goal of treatment must be to the fight the symptoms, and lowering the mortality rate through intensive maintenance of organ function.

For example, an artificial liver blood purification system or renal replacement therapy can be used to filter the blood through mechanical means, they said.

The team noted that especially important are methods to supplement or replace lung function, for example with non-invasive mechanical ventilation through a mask, ventilation through a tube into the windpipe, the administration of heated and humidified oxygen via a tube in the nose, or a heart-lung bypass.

The researchers stressed the importance of preventing secondary infections.

They noted that SARS-Cov-2 also invades the intestines, where it causes inflammation and leakiness of the gut lining, allowing the opportunistic entry of other disease-causing microorganisms.

The researchers advocate that this should be prevented with nutritional support, for example with probiotics -- beneficial bacteria that protect against the establishment of harmful ones -- and nutrients and amino acids to improve the immune defences and function of the intestine.

"Because treatment for now relies on aggressive treatment of symptoms, preventative protection against secondary infections, such as bacteria and fungi, is particularly important to support organ function, especially in the heart, kidneys, and liver, to try and avoid further deterioration of their condition," Liu added.

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.