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Protein promotes cancer,suppresses anti-tumour immunity

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New York, Researchers have found that a protein involved in immune response to microbes also can fuel cancer development and suppress the response to the disease.

Working in mouse models of lung cancer, the research team found TANK-binding kinase 1 (TBK1) and its adaptor proteiTBK-binding protein 1 (TBKBP1) contribute to tumorigenesis when they are activated by growth factors rather than by innate immune mechanisms.

“Our work also provides the first evidence that TBK1 functions in cancer cells to mediate immunosuppression, suggesting that targeting TBK1 will both inhibit tumour growth and promote antitumor immunity,” said study senior author Shao-Cong Sun from University of Texas in the US.

Recent research indicated that TBK1, which normally mediates induction of type 1 interferon in response to viruses or bacteria, also promotes the survival and reproduction of KRAS-dependent cancer cells.

For the findings published in the journal Nature Cell Biology, the research team set out to identify TBK1’s impact on cancer cells and its role in cancer development in vivo.

In a series of experiments, the researchers showed that TBK1 and TBKBP1 form a growth factor signaling axis that activates mTORC1 to promote tumour development.

The pathway consists of TBKBP1 recruiting TBK1 to protein kinase C-theta (PKC), through a scaffold protein called CARD10, enabling PKC to activate TBK1.

To test the protein’s therapeutic potential, the research team treated mice with KRAS-driven lung cancer with amlexanox, a drug approved by the Food and Drug Administration as a paste to treat certain oral ulcers.

The drug was recently identified as a TBK1 inhibitor. Mice injected with amlexanox had a steep reduction in the number and size of lung tumors.

KRAS-driven cancer is resistant to immune response, but the researchers found amlexanox sensitised tumours to blockade of the CTLA-4 checkpoint on immune T cells.

Knocking down TBK1 in the KRAS-driven mouse model increased the frequency of effector CD4 helper T cells and CD8 cell-killing T cells in the lungs of the mice.

A similar experiment in another mouse model also reduced the frequency of immune-suppressing myeloid-derived suppressor cells.

Additional experiments implicated TBK1 in promotion of glycolysis – a sugar-burning metabolic process that also suppresses the immune system – and the increased presence of PD-L1, a protein on tumour cells that turns off attacking T cells by connecting with the PD-1 protein on their cell surface.

Treatment with amlexanox and anti-CTLA-4 immunotherapy stimulated immune response and reduced tumour size and frequency in the mouse models.

“We’re continuing to examine the signaling function of TBK1 in different types of immune cells using animal models and to assess the therapeutic potential of TBK1 using preclinical cancer models,” Sun said.

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Is China suppressing the corona virus infections!

American cities are on high alert as two coronavirus cases are confirmed in Chicago and Washington while 1,000 Americans have been told to evacuate Ground Zero in Wuhan.

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New Delhi, Jan 27: China is facing accusations from the world community of suppressing and playing down the coronavirus outbreak and the scale of infections which some reports say now I as high as 90,000 while the official Beijing figure is just 1,975.

International media reports have said cited a nurse treating coronavirus sufferers in China who claims 90,000 people have already been infected.

A nurse wearing a protective suit and face mask treating the sick in Wuhan has claimed that 90,000 people have already been infected by the coronavirus. However, the nurse’s report has been viewed almost two million times on YouTube. In the footage, she warns people not to go outside and to refrain from celebrating the Chinese New Year.

The animal virus epidemic originated in China, where it has infected more than 1,970 people and killed 56, and has spread worldwide.

International critics are saying that the China is censoring the numbers and sanitising videos from the internet. China’s President Xi Jinping has already warned of ‘grave situation’ as killer coronavirus accelerates.

American cities are on high alert as two coronavirus cases are confirmed in Chicago and Washington while 1,000 Americans have been told to evacuate Ground Zero in Wuhan.

Canadian authorities on Saturday confirmed the first case of coronavirus – a man in his 50s from Toronto.

The countries which have reported these cases include Singapore, Malaysaia, South Korea, Japan, Vietnam, Australia, Nepal, France, Canada, the US, Thailand, Taiwan, Hong Kong and Macau.

But the Global Times revealed that vital resources, including masks and goggles, were urgently needed. The accusations of a cover-up echo the furore surrounding the SARS (severe acute respiratory syndrome) epidemic in 2002 when the government concealed the existence of the illness not just from the outside world but from its own people.

Hong Kong leader Carrie Lam on Saturday declared a virus emergency in the city of 7.3 million, extending school cancellations until February 17 and cancelling all official visits to mainland China.

China has quarantined three cities in an effort to contain the spread of the coronavirus — encompassing a total population of some 35 million people.

Other reports say several cities are under lockdown with a combined population of 47 million including Wuhan, Huanggang, Ezhou, Chibi, Jingzhou, Zhijiang, Qianjiang, Xiantao, Xianning, Huangshi, Dangyang, Enshi, Xiaogan. Jingmen and Shantou.

Reports say that Wuhan continues to be under complete lockdown. Police have been stationed at the borders of Wuhan to block the roads preventing any sort of movement into the quarantined city. The city’s pharmacies have been swamped by people wanting to stock up on medicines.

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China begins developing vaccine as coronavirus toll reaches 56

The National Health Commission said the disease has infected a total of 1,975 people so far. In its latest report, the Commission said 15 deaths and 688 new cases were reported on Saturday.

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Beijing, Jan 26 : China has started developing a vaccine against the rapidly-spreading deadly novel coronavirus strain that has claimed 56 lives and infected nearly 2,000 people in the country.

Xu Wenbo, a scientist at the Chinese Center for Disease Control and Prevention, said on Sunday that scientists had successfully isolated the first strain of the virus, Efe news agency quoted the official newspaper People’s Daily as saying.

The news comes after Chinese President Xi Jinping, following a meeting on Saturday, warned that the spread of the deadly illness was accelerating amid a fast-rising death toll.

Shanghai, one of the biggest cities in China, reported its first death due to the pandemic that has triggered panic across the country with authorities scrambling to stop its further outbreak.

The National Health Commission said the disease has infected a total of 1,975 people so far. In its latest report, the Commission said 15 deaths and 688 new cases were reported on Saturday.

Some 324 patients were said to be serious, while 49 have been discharged from hospitals after recovery.

Hubei, the province where the disease was first reported in its capital Wuhan, reported 52 deaths. One person each has died in Hebei (around Beijing), Heilongjiang (northeast), Henan (centre-east) and Shanghai (east).

Health authorities have carried out checkups on nearly 23,500 people who have come into close contact with infected persons. Out of these, over 21,500 continue to be monitored for symptoms.

At least 25 of China’s 34 provincial divisions have been put on the highest-level health alert.

The southeastern city of Shantou has been partially closed down and interstate bus services in the cities of Beijing, Tianjin, Xian, and the Shandong province suspended.

Passengers at Beijing’s 55 metro stations, including those linked to railway stations and the international airport, will be subjected to temperature screening to detect potential suspect cases.

Those with abnormal body temperatures would be hospitalized, according to state-run news agency Xinhua.

Cleaning and disinfection efforts have begun in metro and bus terminals in Beijing, where at least 51 cases of the so-called “Wuhan pneumonia” have been reported, official daily Global Times said.

Hubei province and other major cities were locked down earlier.

Shanghai has also announced the suspension of the train service that connects the city center with the Anting suburb, bordering Jiangsu province.

The prevention efforts include a large-scale purchase of face masks, as the respiratory system is believed to be the primary method of the virus’ transmission.

Global Times said that 3.16 million face masks were shipped on Sunday to Wuhan.

Authorities have urged people who have recently visited Wuhan to stay inside their houses for 14 days and immediately contact health centres if they develop symptoms associated with the virus.

The disease has already spread to a dozen other countries with Canada confirming its first case on Saturday after a patient in Ontario tested positive. The man was said to have travelled from China recently.

Besides Canada, the cases reported outside China were six in Hong Kong; five each in Thailand and Macao; four in Australia; three each in South Korea, Taiwan, Singapore, Malaysia, Nepal and France; two each in Japan, the US and Vietnam.

Four Chinese nationals have been hospitalised in Pakistan for showing symptoms of the disease, but the country’s health authorities have clarified that there were no confirmed cases of coronavirus as yet.

The World Health Organization has decided not to declare an international health emergency due to strict measures carried out in China that include complete suspension of transport and cancelation of Chinese New Year celebrations.

The symptoms of the new coronavirus, provisionally designated by the WHO as 2019-nCoV, are similar to those of cold but may be accompanied by fever and fatigue, dry cough and dyspnea (shortness of breath).

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Cannabis use disorder more common in adults with pain

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New York, Jan 26 : Researchers have found that non-medical use of cannabis including frequent or problematic use is much more common in adults who have pain than in others.

Since 1996, 34 US states have passed medical marijuana laws and 11 states have legalised recreational cannabis use.

Studies indicate that heavy cannabis use increases the risk of vehicle accidents, respiratory and psychiatric symptoms, and cannabis use disorder.

“Despite this evidence, many people view cannabis use as harmless, and non-medical use of cannabis on a daily or near-daily basis has increased,” said study lead author Deborah Hasin from Columbia University Vagelos College of Physicians and Surgeons in the US.

“In our study, we hoped to identify factors–such as pain–that may increase the risk of cannabis use disorder,” Hasin added.

For the findings, published in the American Journal of Psychiatry, research team analysed data on marijuana use from the National Epidemiologic Surveys on Alcohol and Related Conditions in 2001-2002 and 2012-2013.

The researchers compared non-medical cannabis use patterns in adults with and without pain (approximately 20 per cent of participants in both surveys had moderate to severe pain).

Overall, non-medical marijuana use increased from about four per cent in 2002 to 9.5 per cent in 2013.

In addition, in the most recent survey, those with pain were significantly more likely to engage in frequent non-medical cannabis use than those without pain (5.0 per cent vs. 3.5 per cent).

According to the researchers, the risk of cannabis use disorder was also significantly higher in those with pain (4.2 per cent vs. 2.7 per cent).

Although meta-analyses of cannabis for treating pain show only mixed efficacy, particularly for plant marijuana, 66 per cent of adults now view marijuana as beneficial for pain management, the researchers said.

“Given that about 20 of the adult population experienced moderate to severe pain, this puts a large group of US adults at risk for frequent non-medical use and cannabis use disorder,” Hasin said.

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