Vitamin D-3 could 'reverse' damage to heart

By probing the effect that vitamin D-3 has on the cells that make up the lining of blood vessels, scientists at Ohio State University in Columbus have identified for the first time the role that the "sunshine vitamin" plays in preserving cardiovascular health.

The 'sunshine vitamin' has been shown to preserve heart health.

In a paper published in the International Journal of Nanomedicine, they describe how they used nanosensors and a cell model to identify the molecular mechanisms that vitamin D-3 can trigger in the endothelium, which is the thin layer of tissue that lines blood vessels.

It was previously believed that the endothelium served no other purpose than to act as an inert "wrapper" of the vascular system, allowing both water and electrolytes to pass in and out of the bloodstream.

However, advances over the past 30 years have revealed that the endothelium acts more like an organ that lines the whole of the circulatory system from the "heart to the smallest capillaries," and whose cells carry out many unique biological functions.

Changes to the endothelium have been linked to several serious health problems, including high blood pressure, insulin resistance, diabetes, tumor growth, virus infections, and atherosclerosis, which is a condition wherein fatty deposits can build up inside arteries and increase the risk of heart attack and stroke.

Vitamin D-3 has role beyond bone health

The new study suggests that vitamin D-3 — a version of vitamin D that our bodies produce naturally when we expose our skin to the sun — plays a key role in preserving and restoring the damage to the endothelium that occurs in these diseases.

Some other natural sources of vitamin D-3 include egg yolks and oily fish. It is also obtainable in the form of supplements. Vitamin D-3 is already well-known for its role in bone health.

"However," explains senior author Tadeusz Malinski, a professor in the department of chemistry and biochemistry, "in recent years, in clinical settings people recognize that many patients who have a heart attack will have a deficiency of D-3."

"It doesn't mean that the deficiency caused the heart attack," he adds, "but it increased the risk of heart attack."

Nanosensors probed effect of D-3 on cells

For their study, Prof. Malinski and colleagues developed a measuring system using nanosensors, or tiny probes that are 1,000 times smaller than the thickness of human hair and can operate at the level of atoms and molecules.

They used the nanosensors to track the impact of vitamin D-3 on molecular mechanisms in human endothelial cells that had been treated to show the same type of damage that occurs from high blood pressure.

The findings suggest that vitamin D-3 is a powerful trigger of nitric oxide, which is a molecule that plays an important signaling role in the control of blood flow and the formation of blood clots in blood vessels.

The researchers also found that vitamin D-3 significantly reduces oxidative stress in the vascular system.

They note that their study "provides direct molecular insight to previously published observations that have suggested that vitamin D-3 deficiency-induced hypertension is associated with vascular oxidative stress." The effects of vitamin D-3 were similar in both Caucasian and African American endothelial cells.

Could D-3 reverse cardiovascular damage?

The study authors note that while their findings came from tests performed on a cellular model of high blood pressure, "[T]he implications of the influence of vitamin D-3 on dysfunctional endothelium is much broader."

They suggest that vitamin D-3 has the potential to significantly reverse the damage that high blood pressure, diabetes, atherosclerosis, and other diseases inflict on the cardiovascular system.

"There are not many," Prof. Malinski adds, "if any, known systems which can be used to restore cardiovascular endothelial cells which are already damaged, and vitamin D-3 can do it."

"

This is a very inexpensive solution to repair the cardiovascular system. We don't have to develop a new drug. We already have it."

Prof. Tadeusz Malinski

The end of toxic chemo? Blocking vitamin B-2 may stop cancer

New research published in the journal Aging finds a compound that stops cancer cells from spreading by starving them of vitamin B-2. 

The findings may revolutionize traditional chemotherapy.

Current chemotherapy has a wide range of serious side effects, but that may be about to change, suggests new research.

" A new era of chemotherapy?

A team of British-based researchers set out to find a non-toxic therapeutic agent that targets the mitochondria of cancer cells.

Mitochondria are energy-producing organelles found inside each cell. The compound recently found by the scientists can stop cancer stem-like cells from proliferating by interfering with their energy-creating process inside the mitochondria.

The team was led by Prof. Michael Lisanti, the chair of translational medicine at the University of Salford in the United Kingdom, and the new study can be accessed here.

Starving cancer cells of energy

Prof. Lisanti and his colleagues used drug-screening to identify the compound, which is called diphenyleneiodonium chloride (DPI).

As the researchers explain, various cell assays and other cell culture experiments revealed that DPI reduced over 90 percent of the energy produced in the cells' mitochondria.

DPI achieved this by blocking vitamin B-2 — also known as riboflavin — which depleted the cells of energy.

Our observation is that DPI is selectively attacking the cancer stem cells, by effectively creating a vitamin deficiency [...]. In other words, by turning off energy production in cancer stem cells, we are creating a process of hibernation. Prof. Michael Lisanti 

The cancer stem cells are the ones that produce the tumor. "It's extraordinary," continues Prof. Lisanti, "the cells just sit there as if in a state of suspended animation."

Importantly, DPI proved to be non-toxic for so-called "bulk" cancer cells, which are largely thought to be non-tumorigenic.This suggests that the compound might be successful where current chemotherapy fails. The team explains, "DPI treatment can be used to acutely confer a mitochondrial-deficient phenotype, which we show effectively depletes [cancer stem-like cells] from the heterogeneous cancer cell population."

"These findings have significant therapeutic implications for potently targeting [cancer stem-like cells] while minimizing toxic side effects," they add.

"[W]e believe," say the scientists, "that DPI is one of the most potent and highly selective [cancer stem-like cells] inhibitors discovered to date."

The findings are particularly significant given the dire need for non-toxic cancer therapies and the serious side effects of conventional chemotherapy.

"The beauty of [DPI] is that [it] makes the cancer stem cells metabolically inflexible so [that] they will be highly susceptible to many other drugs," explains Prof. Lisanti.

Study co-author Prof. Federica Sotgia also comments on the significance of the recent findings, saying, "In terms of chemotherapies for cancer, we clearly need something better than what we have at present, and this is hopefully the beginning of an alternative approach to halting cancer stem cells."

In fact, the authors specialize in finding alternative, non-toxic therapies, and they hope that their most recent findings will mark the beginning of a new era of chemotherapy — perhaps one that uses non-toxic molecules to target the mitochondrial activity of cancer stem-like cells.

The researchers propose to call these new molecules "mitoflavoscins."

Source: https://www.medicalnewstoday.com/articles/320784.php

Is chemo at the heart of cancer regrowth?

Some cancers are difficult to beat, even with modern drugs. New research sheds light on how one type of chemotherapy provides a safe haven for tumor cells, boosting cancer recurrence and growth in the long-run.

In the midst of 'sleeping' cancer cells, something is stirring.

Finding the right drug to treat a cancer can be just like searching for a needle in a haystack; cancer cells are particularly good at evading everything that modern medicine throws at them.

The hallmark of a good chemotherapy is to stop or slow the growth of a tumor.

Many drugs achieve this by activating a pathway called programmed cell suicide, or apoptosis. However, some cancer types are resistant to apoptosis. Other avenues must therefore be pursued to destroy these tumors.

An alternative is to damage the DNA genetic code within cancer cells to the point where it is beyond repair. The cells then respond by activating a process called cellular senescence.

Discovered more than 50 years ago, senescence is thought to be a state of irreversible growth arrest. This means that the cells stay where they are but do not grow any further.

However, senescence turned out not to be the fool-proof method of eradicating cancer that some had hoped.

Scientists have now found a missing piece of the puzzle that could explain why senescence might provide a breeding ground for cancer stem cells, leaving the way open for tumors to grow back and spread.

Senescence sends cancer cells to 'sleep'

Writing in the journal Frontiers in Oncology last month, Markus Schosserer, Ph.D. — an assistant professor at the University of Natural Resources and Life Sciences in Vienna, Austria — explains that senescence is important in embryogenesis, wound healing, and the natural aging process.

Senescence can also be harnessed to send cancer cells into a state that can be likened to extended sleep — in that the cells are alive but not dividing.

"The basic arguments about the role of senescence in cancer protection are as follows: senescent cells have lost the ability to undergo cell division permanently, although they may be metabolically fully active," writes Prof. Schosserer. "This would certainly protect individuals carrying a primary cancer from further cancerous growth."

However, he adds, it's not as simple as that. There is plenty of evidence that senescent cancer cells can secrete molecules that cause inflammation and promote a rich environment for cancer to grow back.

Researchers from Germany have now made a surprising discovery: senescence not only helps cancer cells avoid death, but it actually turns them into cancer stem cells.

From 'sleeping beauties' to cancer stem cells

Dr. Clemens A. Schmitt — a professor in the Department of Hematology, Oncology, and Tumor Immunology at Charité-University Medical Center and the Max-Delbrück-Center for Molecular Medicine, both in Berlin, Germany — presented the group's breakthrough findings in Natureyesterday.

For their recent research, the scientists used lymphoma tumor cells from mice. Lymphoma is a type of cancer that affects white blood cells called lymphocytes. When lymphoma cells were treated with drugs to induce senescence, they stopped dividing, as expected.

But they also did something else: the senescent cancer cells started to resemble stem cells. Specifically, the cells started to express genes — such as p21 and p53 — that are vital for maintaining stem cell functions, the collective name for which is "stemness."

The reason why stemness is such a problem in cancer is that cancer stem cells are thought to drive the recurrence and spread, or metastasis, of tumors.

But, if senescent cells do not divide, does it matter that they develop stemness? It seems so.

Stemness speeds up cancer growth

The scientists did not just find evidence of this senescence-associated stemness in their lymphoma model. They also found it in other cell models of cancer, and, crucially, they detected these cells in tumor samples from patients with primary B-cell chronic leukemia, as well.

Next, Prof. Schmitt's team released the cancer cells from senescence, using genetic manipulation. Would the cells re-enter the normal process of cell division? Yes: they started to multiply within a few days.

And multiply they did — much faster, in fact, than cells that had not undergone senescence.

When the team transplanted these previously senescent cancer cells into mice, very few cells were needed to kick-start the development of new lymphoma tumors.These results show that when cells that have acquired stemness escape senescence, they become highly cancerous. But what is the likelihood that cancer cells can outfox the supposedly irreversible state of senescence?

The team found evidence that cancer cells can, in fact, escape senescence, identifying significantly more previously senescent stem cells in tumor samples of patients after lymphoma recurrence than were present in the same individuals when they received their initial treatment.

So, does this spell bad news for senescence-inducing chemotherapy drugs?

Source: https://www.medicalnewstoday.com/articles/320449.php

LXM Humanitarian Foundation Event

E-cigarette flavors found to be toxic

Recent research published in the journal Frontiers in Physiology examines the effect of electronic cigarette vapors on two types of white blood cell. The findings suggest that the compounds that give e-cigarettes their flavor are toxic, with some flavors being worse than others.

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Despite the fact that electronic cigarettes (e-cigarettes) help some people to quit smoking conventional ones, the devices contain many other non-nicotine chemicals, the health effects of which are still being investigated.

Here at Medical News Today, we've been trying to keep you updated on all the latest scientific discoveries when it comes to unraveling the complex effects of using e-cigarettes, or "vaping."

For example, a couple of studies that we reported on suggested that e-cigarettes may have adverse cardiovascular effects, and that they may slow down heart rate.

That said, some of these studies are either observational — and thus unable to explain causality — or performed in mice.

New research, however, takes things to the laboratory. Scientists at the University of Rochester Medical Center in New York set out to test the hypothesis that vaping e-cigarettes that do not contain nicotine would be less harmful than conventional cigarettes.

To this end, the researchers — who were led by senior author Dr. Irfan Rahman — focused on "the immuno-toxicological and the oxidative stress effects by these e-cigarette flavoring chemicals on two types of human monocytic cell lines."

Oxidative stress is a process in which oxygen radicals are produced in excess, resulting in a series of damaging effects, including increased toxicity, damage to our DNA, or even cancer.

Monocytes are a type of white blood cell that play a critical role in our immune response to inflammation. Therefore, the results of the new study are key for our understanding of the relationship between e-cigarettes and our immune system.

Cinnamon, vanilla, buttery flavors the worst

To assess the flavorings' potential for causing oxidative stress, the team measured the production of so-called reactive oxygen species (ROS).

"We hypothesized," the authors write, "that the flavoring chemicals used in e-juices/e-liquids induce an inflammatory response, cellular toxicity, and ROS production."

As expected, the cytotoxicity tests performed by first author Dr. Thivanka Muthumalage and colleagues revealed that treatment with these chemicals increased inflammation and tissue damage. All of this was done by increasing the levels of oxidative stress.

Also, "Mixing a variety of flavors resulted in greater cytotoxicity and cell-free ROS levels compared to the treatments with individual flavors, suggesting that mixing of multiple flavors of e-liquids are more harmful to the users," the researchers add.

Source: https://www.medicalnewstoday.com/articles/320818.php

These brain cells could explain your anxiety

Anxiety is common, but how it affects the brain is, as yet, poorly understood. New research has revealed "anxiety cells," which provides a fresh direction for research into new treatments.

In humans, anxiety is often triggered unnecessarily.

In the wild, an animal that never feels anxiety would quickly become a dead animal.

This is due to the fact that anxiety produces a raised sense of awareness and physiological readiness to fight or fly, which is essential for survival.

For many people, however, anxiety is triggered in situations where it is unnecessary or even unhelpful, such as a crowded mall or when talking to a group of friends.

For these people, anxiety becomes a problem. Rather than a sensible reaction to a life-threatening situation, anxiety becomes triggered inappropriately.

Anxiety disorders are "the most common mental illness" in the United States, affecting an estimated 40 million adults.

Because of this high prevalence, researchers are forging ahead in an effort to uncover what goes on in the brain. It is important to understand which brain circuits are controlling the anxiety response, and what goes wrong with those circuits in people with anxiety disorders.

Digging for 'anxiety cells'

The most recent study was carried out by Mazen Kheirbek, Ph.D., who works at the University of California, San Francisco, and a team from Columbia University Irving Medical Center (CUIMC) in New York.

Kheirbek explains their aims, saying, "We wanted to understand where the emotional information that goes into the feeling of anxiety is encoded within the brain." Their findings are published this week in the journal Neuron.

The team was particularly interested in the hippocampus. This region of the brain plays a role in autobiographical memory and navigation but also appears to play a role in mood and anxiety. In particular, earlier studies have demonstrated that altering activity in the ventral region of the hippocampus reduces anxiety.

To investigate this region in more detail, the scientists measured the output of hundreds of cells in mice's hippocampi while they went about their daily business. It was found that when the animals encountered a situation that made them feel anxious, the neurons in the ventral region of the hippocampus became active.

"We call these anxiety cells because they only fire when the animals are in places that are innately frightening to them. For a mouse, that's an open area where they're more exposed to predators, or an elevated platform."

Rene Hen, Ph.D., a professor of psychiatry at CUIMC

Tracing the 'anxiety cells'

The scientists then traced these cells as they traveled from the hippocampus to the hypothalamus. The hypothalamus controls anxiety behaviors — in humans, this includes the secretion of stress hormones, avoidance behavior, and increased heart rate.

Next, they artificially turned these anxiety cells off. They used a technique called optogenetics, which allows scientists to control individual neurons using pulses of light.

The scientists found that when these cells were switched off, the mice stopped producing fear-related behaviors. Conversely, when these cells were switched on, mice behaved anxiously, despite being in a safe area.

Although other parts of the brain are known to be involved in anxiety, this is the very first time that a group of cells has been found that represent anxiety regardless of the environmental stimulus that brings about the emotion.

Kheirbek explains, "This is exciting because it represents a direct, rapid pathway in the brain that lets animals respond to anxiety-provoking places without needing to go through higher-order brain regions."

Now that these cells have been described, they could provide a new direction for treating anxiety disorders.

Dr. Jeffrey Lieberman, who is the Lawrence C. Kolb Professor and chair of psychiatry at CUIMC, explains, "This study shows how translational research using basic science techniques in animal models can elucidate the underlying basis of human emotions and reasons for mental disorders, thereby pointing the way for treatment development."

Although more work will need to be done, finding a novel target for potential treatments is an exciting step forward.

 Source: https://www.medicalnewstoday.com/articles/320801.php