Eating high-cholesterol diet may up colon cancer risk: study

Agencies
January 27, 2018

Los Angeles, Jan 27: People eating a high- cholesterol diet are at an increased risk of developing colon cancer, a study warns.

Scientists discovered that boosting mice's cholesterol levels spurred intestinal stem cells to divide more quickly, enabling tumours to form 100 times faster.

The study, published in the journal Cell Stem Cell, has identified a molecular pathway that could serve as a new drug target for colon cancer treatment.

"We were excited to find that cholesterol influences the growth of stem cells in the intestines, which in turn accelerates the rate of tumour formation by more than 100- fold," said Peter Tontonoz, from the University of California, Los Angeles in the US.

"While the connection between dietary cholesterol and colon cancer is well established, no one has previously explained the mechanism behind it," Tontonoz said.

The scientists increased cholesterol in the intestinal stem cells in some of the mice by introducing more of the substance into their diets.

In others, the researchers altered a gene that regulates phospholipids, the primary type of fat in cell membranes, which spurred the cells into producing more cholesterol on their own.

The stem cells' ability to multiply increased in both groups.

As the animals' cholesterol levels rose, their cells divided more rapidly, causing the tissue lining their guts to expand and their intestines to lengthen. These changes significantly sped up the rate of tumour formation in their colons.

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Agencies
July 4,2020

The Union health ministry on Friday revised the dosage of anti-viral drug remdesivir to be administered to coronavirus patients in the moderate stage of illness from the earlier six days to five days as it issued an updated 'Clinical Management Protocols for COVID-19'.

The drug, administered in the form of injection, should be given at a dose of 200 mg on day one followed by 100 mg daily for four days (total five days), the new treatment protocols stated.

The Health Ministry on June 13 had allowed the use of remdesivir for restricted emergency use in moderate cases under "investigational therapies".

"Under emergency use authorisation, remdesivir may be considered for patients in moderate stage requiring oxygen support," the document stated.

It is not recommended for those with severe renal impairment and high level of liver enzymes, pregnant and lactating women, and those below 12 years, it said.

The ministry also okayed off-label application of tocilizumab, a drug that modifies the immune system or its functioning, and convalescent plasma for treating COVID-19 patients in the moderate stage of illness as "investigational therapies".

It also recommended hydroxychloroquine for patients during the early course of the disease and not for critically-ill patients.

On June 27, the ministry had included an inexpensive, widely used steroid dexamethasone in treatment protocols for COVID-19 patients in the moderate to severe stages of their illness among other therapeutic measures.

The ministry advised use of dexamethasone, which is already used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects, as an alternative choice to methylprednisolone for managing moderate to severe cases of coronavirus infection.

India's COVID-19 cases soared by over 20,000 in a day for the first time taking the country's total tally to 6,25,544 on Friday while the death toll climbed to 18,213 with 379 new fatalities, according to the Union Health Ministry data updated at 8 am.

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Agencies
June 22,2020

A team of scientists has produced first open source all-atom models of full-length COVID-19 Spike protein that facilitates viral entry into host cells – a discovery that can facilitate a faster vaccine and antiviral drug development.

The group from Seoul National University in South Korea, University of Cambridge in the UK and Lehigh University in the US produced the first open-source all-atom models of a full-length S protein.

The researchers say this is of particular importance because the S protein plays a central role in viral entry into cells, making it a main target for vaccine and antiviral drug development.

"Our models are the first full-length SARS-CoV-2 spike (S) protein models that are available to other scientists," said Wonpil Im, a professor in Lehigh University.

"Our team spent days and nights to build these models very carefully from the known cryo-EM structure portions. Modeling was very challenging because there were many regions where simple modeling failed to provide high-quality models," he wrote in a paper published in The Journal of Physical Chemistry B.

Scientists can use the models to conduct innovative and novel simulation research for the prevention and treatment of Covid-19.

Though the coronavirus uses many different proteins to replicate and invade cells, the Spike protein is the major surface protein that it uses to bind to a receptor.

The total number of global COVID-19 cases was nearing 9 million, while the deaths have increased to over 467,000, according to the Johns Hopkins University.

With 2,279,306 cases and 119,967 deaths, the US continues with the world's highest number of COVID-19 infections and fatalities, according to the CSSE.

Brazil comes in the second place with 1,083,341 infections and 50,591 deaths.

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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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