Two Protein Receptors Play Key Roles in Allergic Asthma and COPD

Two receptors of the inflammatory molecule leukotriene B4 play opposing roles in turning inflammation ‘on’ and ‘off’ for allergic asthma and COPD, according to researchers from Japan.

The first receptor, “BLT1,” promotes inflammation; the second, “BLT2,” can weaken inflammation during an allergic reaction. Previously, BLT2 was believed to increase inflammatory reaction, according to researchers.

“Leukotriene B4 levels are elevated in the airways of the patients with asthma and COPD, and the opposite role of BLT1 and BLT2 in allergic inflammation implies that drug development should target BLT1 and BLT2 differently,” said Hiromasa Inoue, MD, study author from the Department of Pulmonary Medicine at the Graduate School of Medical and Dental Sciences at Kagoshima University in Kagoshima, Japan.

“We hope that better anti-asthma drugs or anti-COPD drugs will be produced in the future to treat millions of patients who suffer from severe asthma and COPD.”

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Health Benefits of Kava

Kava is a root that has been used traditionally for hundreds of years to relieve a whole range of symptoms, such as anxiety and insomnia, and it may be able to sort out your health problems. Just be sure to consult your doctor before trying kava to avoid any negative side effects, such as dermopathy or liver damage. Here are 8 health issues that kava can fix:

1. It reduces anxiety
Multiple studies have shown that that kava is effective at treating anxiety, regardless of the symptoms and type of disorder. This is because it activates GABA-A receptors, which calm the body and mind down. Kava prevents a decrease in serotonin, norepinephrine, and dopamine via the inhibition of monoamine oxidase. Additionally, it also relaxes the muscles by decreasing beta adrenaline receptor activity.
2. It relieves depression
Kava is able to induce a pleasant mental state, which is why it is often used as an alternative to antidepressants (benzodiazepines). The kavalactones found in kava increase levels of dopamine, serotonin, and even GABA, while simultaneously decreasing glutamate levels in cell models.

3. It helps you sleep better
Kava can help in the treatment of sleep disorders such as insomnia by reducing stress levels that are associated with it. Kava’s sedative effects come from the blocking of calcium and sodium ion channels, increasing of neurotransmitter binding to GABA-A receptors, and the inhibition of monoamine oxidase B.
4. It protects against brain damage
Kavalactones that can be extracted from kava greatly lower the chances of brain damage caused by oxidative stress in disorders such as Alzheimer’s and Parkinson’s disease. These extracts activate the Nrf2 antioxidant response pathway and increase the concentration of antioxidant enzymes (heme oxygenase-1), thereby combating oxidative stress.

5. It relieves symptoms of menopause
If you are currently going through menopause, then you may need to start consuming more kava. This is because by increasing dopamine levels in the brain, inhibiting monoamine oxidase-B and activating GABA-A receptors, kava is able to treat many of menopause's worst symptoms, such as irritability, insomnia, depression, and anxiety.
6. It decreases the severity of epilepsy and seizures
Kava has been found to help treat seizures and epilepsy, either by itself or in combination with diazepam. This is because kava is able to reduce motor activity, increase seizure thresholds, and improve the anticonvulsant effect of diazepam.

7. It improves brain functioning
Just 300mg of kava is enough to improve performance in working memory tasks, visual processing, and even attention levels. This is because kavapyrones are actually active in certain parts of your brain, such as the hippocampus, caudate nucleus, and amygdala.
8. It fights cancer
When it comes to cancer, there are many ways that kava can be useful. For starters, kava is known to reduce the size of breast cancer cells, and may even prevent breast cancer metastasis. Kava has also been found to reduce the growth of prostate cancer tumors, inhibit colon cancer, and even stop the progression of bladder cancer.

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New cancer drug for children safe, effective

A first-of-its-kind drug targeting a fused gene found in many types of cancer has been found to be effective in 93 per cent of paediatric patients tested, scientists say.
Most cancer drugs are targeted to specific organs or locations in the body.
 
Larotrectinib is the first cancer drug to receive government approval,breakthrough therapy designation for patients with a specific fusion of two genes in the cancer cell, no matter what cancer type.
"In some cancers, a part of the TRK gene has become attached to another gene, which is called a fusion," said an assistant professor.

"When this occurs, it leads to the TRK gene being turned on when it's not supposed to be and that causes the cells to grow uncontrollably.
"What is unique about the drug is it is very selective; it only blocks TRK receptors," said the lead author of the research.
Larotrectinib, targets TRK fusions, which can occur in many types of cancer.
While the TRK fusions occur in only a small percentage of common adult cancers, they occur frequently in some rare paediatric cancers, such as infantile fibrosarcoma, cellular congenital mesoblastic nephroma, and papillary thyroid cancer.
"Every patient with a TRK fusion-positive solid tumour treated on this study had their tumour shrink. The nearly universal response rate seen with larotrectinib is unprecedented," the author said.

TRK, short for tropomyosin receptor kinase, is a gene that plays a key role in brain and nervous system development and has a limited role in nervous system functions such as regulating pain in later life.

Larotrectinib belongs to a class of molecules known as kinase inhibitors, which work by cutting back on the enzymatic activity of a key cellular reaction, researchers said.

The selectivity of the drug means it does not cause the severe side effects associated with many traditional cancer treatments, and none of the patients with TRK fusions had to quit the study because of a drug-induced side effect, they said. 

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Just One Psychedelic Drug Trip Can Cause Changes In Personality That Could Last Years

Psychedelics, such as magic mushrooms, LSD and ayahuasca, are known to have powerful effects on the brain, which can significantly alter consciousness. But how do these substances affect our minds in the long-term?

A new review of studies, has found that even a single psychedelic trip can lead to changes in personality that can potentially last for years.

A team of researchers from Brazil and Spain analyzed 18 studies conducted between 1985 and 2016, all of which examined the relationship between the use of psychedelics and changes in personality.

Most of these studies primarily focused on three substances: LSD (lysergic acid diethylamide), psilocybin (the psychoactive compound in magic mushrooms) and ayahuasca (a powerful hallucinogenic brew, used ritually by the indigenous people of the Amazon).

These drugs produce their effects by binding to receptors of serotonin—a brain chemical which has an influence on our moods and appetites—resulting in hallucinations, euphoria and a host of other sensations.

After reviewing the studies, the researchers found that people who took these substances experienced long-term, perhaps even permanent, personality changes compared to people who had never taken them.

For example, the review found that participants in clinical trials who were given a small dose of psychedelics were rated as having more openness than non-users following their trip. In psychological terms, openness—one of the five main personality traits—is made up of different facets including appreciation of new experiences, attentiveness to inner feelings and intellectual curiosity.

“Psychedelic drug users and non-users appear to differ in some personality traits,” the authors wrote in their review. “Psychedelics administered in controlled settings may induce personality changes, such as increased Openness and Self-Transcendence.”

Furthermore, these changes in personality were beneficial, having a therapeutic and antidepressant effect on the individuals in question, according to findings from a number of the studies analyzed. These effects were felt, in some cases, for a year or longer.

While the link between psychedelics and personality changes has been investigated by scientists since the 1950s at least, for the latest review, the researchers chose to focus on studies published after 1985 as this period witnessed a significant rise in both the number, and quality, of reports looking into this question.

It is important to note, however, that it is difficult to draw concrete conclusions regarding the link between psychedelics and long-term personality changes, as many of the studies involved small numbers of participants.

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Venom from deadly Asian snake may help develop improved painkillers

Venom derived from the long-glanded blue coral snake - one of Southeast Asia's rarest and deadliest snakes - may help develop better painkiller that could help manage pain without the side effect of addiction.

The snake with electric blue stripes and neon-red head and tail grows up to two metres long. Its venom glands extend to 60 centimetres about a quarter of its body length.

Described as "the killer of killers" due to its taste for young king cobras, this snake is unique among snakes because, like scorpions, its venom causes its prey to spasm.

"This venom hits a particular type of sodium channel that is important for the treatment of pain in humans," said Bryan Fry, from the University of Queensland in Australia.

Researchers identified six unusual peptides in the venom of the blue coral snake that can switch on all of its prey's nerves at once. This  immediately immobilises its victim.

The found that the venom used receptors which were critical to pain in humans. Learning how these work may enable improved pain treatment and management, the 'Sydney Morning Herald' reported.

"It's a great example of why studying the really weird animals is a great path for bio-discovery and you can't get any weirder than this snake with the longest venom glands in the world," Fry said.

The findings were published in the journal Toxins.

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Venom derived from the long-glanded blue coral snake - one of Southeast Asia's rarest and deadliest snakes - may help develop better painkiller that could help manage pain without the side effect of addiction.

The snake with electric blue stripes and neon-red head and tail grows up to two metres long. Its venom glands extend to 60 centimetres about a quarter of its body length.

Described as "the killer of ki ..

Read more at:
http://economictimes.indiatimes.com/articleshow/55153320.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst

Key protein behind breast cancer’s spread to brain

In a major breakthrough, a cancer-research team has identified a protein that may be the crucial reason behind breast cancer spreading to the brain.

Using cell models, the researchers at the University of Wisconsin-Madison found that breast cancer cells harness a protein called alphaB-crystallin to help them stick to endothelial cells that line the small blood vessels in the brain.

In addition, this protein enhances the penetration of breast cancer cells through the blood-brain barrier, which normally prevents cells and many molecules from entering the brain.

Once in the brain, breast cancer cells are able to form metastases i.e. spread of a cancer from one organ to another, said a new study published in the journal Clinical Cancer Research.

“We found that reducing the expression of alphaB-crystallin in breast cancer cells hindered the cells’ ability to form brain metastases in mice,” said Vincent Cryns, professor of medicine at University of Wisconsin School of Medicine and Public Health in the US.

“alphaB-crystallin may be a promising drug target that should be explored further,” he added.

The researchers discovered that women with breast tumours that expressed alphaB-crystallin had a shorter survival than women with breast tumours that did not express this protein.

The also found breast tumours that expressed alphaB-crystallin were more likely to be triple-negative breast cancers, an aggressive type of cancer that lacks three receptors – estrogen receptor, progesterone receptor and HER-2.

Triple-negative breast cancers are known to have a high incidence of brain metastasis.

“Our findings suggest that alphaB-crystallin may contribute to the tendency of triple-negative breast cancers to metastasize to the brain and to their poor prognosis,” said Cryns. Yet, he cautioned these findings need to be validated in additional studies.

Brain metastasis is a terrifying complication of advanced breast cancer, with a grim prognosis and few treatment options.

The cancer’s spread to the brain is often undetected until patients start to develop symptoms such as seizures, headaches, and trouble thinking.

These studies were conducted in collaboration with researchers at the University of North Carolina at Chapel Hill, Duke University and other institutions.

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