Aerobic exercise may help treat drug or alcohol addiction, says study

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.

17-year-old Pratyusha Jha, wakes up scrambling for newspapers these days to look for any news about her pending board exams and is anxious about what the future has in store for her.

Similar concerns are shared by Bipin Kumar, a class 12 student, who says the announcement of board exams from July 1 to 15 brought limited clarity as the larger questions remain unanswered.

The COVID-19 lockdown, came with a different set of concerns for class 12 students, whose board exams were postponed midway following the outbreak of coronavirus, putting on hold their future plans as well.

"Everyday I have been looking for news about the exams and about entrance exam dates. I feel unfortunate that this happened during the year I was supposed to take the big college leap. I don't want my future decisions to be shaped by this very year as what I opt to study now will remain with me lifelong," Pratyusha told PTI.

Ending some uncertainty for students, HRD Minister Ramesh Pokhriyal 'Nishank' on Friday announced that the pending class 10 and 12 board exams will be held from July 1 to 15. While class 12 exams will be conducted across the country, the class 10 exams are only pending in North East Delhi where they were affected due to the law and order situation.

"The anxiety doesn't end here, there is no date sheet yet. What will be the modalities of exams, how will we reach centres, what protocols have to be followed, there is no clarity on that. My friends and I keep calling our school teachers and also the CBSE helpline to seek some clarity," Bipin Kumar said.

Vaibhav Sharma, a class 12 student in Gurgaon said, "There is no clarity yet. I wanted to apply for DU, but now that the exams are taking place in July when will the results be declared, when will cut offs be announced. If I don't get a good college here, will I be able to travel to different cities for admission, nothing is known yet."

Similarly, for the students in northeast Delhi, the wait for the exams has become a "test of patience" as they were postponed first in the area due to law and order situation, and later due to the coronavirus outbreak, resulting in a four-month-long wait for the exams.

"It has become an endless wait and now I don't feel like studying too. Right from childhood, we are taught that board exams are too crucial and have to be focussed at least two years in advance. But now, it is a different picture altogether," Rani Kumari, a resident of Chandbagh said.

Universities and schools across the country have been closed and exams postponed since March 16 when the Centre announced a countrywide classroom shutdown as one of the measures to contain the COVID-19 outbreak.

Later, a nationwide lockdown was announced on March 24, which has now been extended till May 17.

The board was not able to conduct class 10 and 12 exams on eight examination days due to the coronavirus outbreak. Further, due to the law and order situation in North East Delhi, the board was not able to conduct exams on four examination days, while a very small number of students from and around this district were not able to appear in exams on six days.

The board had last month announced that it will only conduct pending exams in 29 subjects which are crucial for promotion and admission to higher educational institutions. The modalities of assessment for the subjects for which exams are not being conducted will be announced soon by the board.

The schedule has been decided in order to ensure that the board exams are completed before competitive examinations such as engineering entrance JEE-Mains, which is scheduled from July 18-23, and medical entrance exam NEET, which is scheduled on July 26.

The University Grants Commission (UGC) has issued guidelines to universities that new academic session for freshers will begin from September while for the existing students from August.

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.