Why women develop heart disease later than men decoded

Agencies
October 6, 2017

Toronto, Oct 6: Women have a heart health advantage over men as the interplay between female ovarian hormones and a circadian "clock" molecule protects their cardiac health as they age, a study has found.

The findings, published in the journal Cardiovascular Research, could help prevent heart disease as we grow older.

In earlier studies, researchers from University of Guelph in Canada found that heart attacks were worse for males than for females of similar age.

The study also uncovered a time-of-day effect: heart attacks in males were more severe during sleep.

This led to the idea that the circadian mechanism - tiny clocks in all of our body's cells which regulate our 24-hour day and night processes - might work differently in male and female hearts.

To test that possibility, the researchers studied old mice with a genetic "clock" mutation that desynchronises the circadian mechanism.

"We think of these CLOCK mice as a genetic model of shift work," said Tami Martino, from University of Guelph.

"Surprisingly, ageing male CLOCK mice developed heart disease, but female CLOCK mice did not," said Martino.

Researchers discovered that female heart cells are actually different from those of males.

Cardiolipins in CLOCK male hearts look like those in humans with heart disease, Martino said.

The CLOCK males also had worse cardiac glucose and energy profiles. By contrast, CLOCK female hearts had a healthy cardiolipin profile and better energy, researchers said.

However, the advantage for CLOCK females was lost when the ovaries were removed, a clear sign that hormones such as oestrogen protect the heart even when the circadian mechanism is disturbed, Martino said.

The findings may lead to clinical benefits for women and men, researchers added.

"Maintaining good circadian rhythms is important for achieving healthier and longer lives," Martino said.

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Agencies
February 24,2020

Singapore, Feb 24: Last week Singapore's Ministry of Trade and Industry revised their 2020 GDP growth projections downwards to -0.5 to 1.5 per cent, confirming fears of economic fallout from the coronavirus COVID-19. Just three days earlier, while visiting Changi Airport, the Prime Minister told the media that the country is bracing for a significant hit on the economy and the possibility of a recession.

In the budget announcement on February 18, various measures to help affected companies were announced.

This included a jobs support scheme to help companies retain workers that will see the government offset 8 per cent of wages up to SGD3,600(USD2,600) per worker, per month, for a three-month period. Companies will also get a 25 per cent rebate on their taxes for the year capped at SGD15,000 (USD10,800) per company.

There will be additional support for sectors directly affected by the virus outbreak such as tourism, aviation and retail. Qualifying companies will be given property tax rebates and can apply for temporary bridging loans to ease cash flow. Rebates will be offered on aircraft landing and parking charges as well as rental rebates for shops and cargo agents at Changi Airport.

Overall, the economic package will cost Singapore some USD 4.6 billion, well in excess of the USD 500 million some analysts had predicted. The resulting spending plan including the virus economic package will see a budget deficit of SGD 10.9 billion or 2.1 per cent of GDP, the highest since the Asian financial crisis of 1997.

It is hoped that with financial support, companies in Singapore will not only be able to ride through the current rough patch but be able to position themselves better to take off once the economic crisis brought upon by the contagion is over.

Which then are the Singapore companies that can potentially ride out the current storm and emerge stronger?

Aviation and hospitality firms are among those most impacted by the virus outbreak and Singapore Airlines (SIA) comes to mind. SIA is a well-run company but has seen its share price fall about 5.2 percent since the beginning of the year. In the short term, revenue and profits will no doubt be affected but it will recover in the long run.

Hospitality sector companies like Ascott Residence whose main sponsor is Capitaland, Southeast Asia's largest landlord, and CDL Hospitality, have seen 1.5 and 5.5 percent (respectively) shaved off their share prices since the start of the year.

In reporting financial results for the quarter which ended in December on February 14, Alibaba CEO Daniel Zhang said that due to the virus, they are seeing large changes in buying patterns. With widespread home confinement, there is a growing demand for delivery services including online food and grocery delivery, as well as office apps and streaming entertainment.

Similarly, in Singapore, with more people staying and working from home, the three main food delivery services, Grab Food, Foodpanda and Deliveroo, are doing roaring business. All three are privately held.

In late January, as the scale of the outbreak became more apparent, investors began pouring money into health-product firms in Asia that they think will benefit from the virus outbreak.

Bloomberg reported that when Chinese pharmaceutical companies like Da An Gene Co, Xilong Scientific and Shanghai Kehua Bio-Engineering said they have developed kits for detecting the virus, their stocks soared to hit the 10 per cent daily limit. Firms manufacturing protection gear and air-cleaning equipment climbed more than 10 per cent in Japan, while Malaysian rubber gloves producers climbed at least 5 per cent.

Naturally, many would view that pharmaceutical companies that have the technology and expertise to develop drugs to treat patients with the virus or are able to develop a vaccine, would stand to benefit from the coronavirus outbreak.

Firms like and Johnson & Johnson, Pfizer, MSD, GlaxoSmithKline (GSK) and Sanofi are the pharmaceutical behemoths that dominate the global vaccine market.

However, industry experts speaking to the BBC warned that a pot of gold is not necessarily waiting for any company that successfully develops a vaccine. Although the global vaccine market is expected to grow to USD60 billion this year, it is costly and time-consuming to develop and pass it through for use by the general public.

It is also unclear if Indian pharmaceutical firms will be able to benefit from the demand for medicines that can treat or prevent the virus.

India is the world's largest manufacturer of generic drugs and it supplies 20 percent of the world's drugs by volume. However, it sources 70 percent of its raw material from China. If supplies are disrupted beyond a month to a month and a half, they may see a slow-down in production. According to a CNN report, the companies that are most impacted by material shortages are GSK India, Pfizer (PFE) and Cipla. Other companies like Aurobindo Pharma, Cadila Healthcare and Sun Pharma are said to be carefully monitoring the situation.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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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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