MicroRNA for treating cancer and asthma

A microRNA that regulates inflammation shows promise as a treatment for inflammatory diseases such as asthma and cancer. The microRNA, known as miR-223, is highly expressed in blood cells that cause inflammation (neutrophils). When they're working correctly, those blood cells protect the body against infections, but sometimes they damage host tissue instead of microbes, causing chronic inflammation and disease.

To uncover the link between miR-223 and inflammation, a Purdue University research team created a zebrafish totally deficient of miR-223. Then they cut off a small chunk of its fin. "The inflammation was really robust," said Qing Deng, a professor of biological sciences at Purdue and corresponding author of the paper. "Neutrophils accumulated at the wound and they just kept coming. This is consistent with the literature, but we wanted to understand why."

Extensive gene expression analysis led them to pathway NF-kB, a protein complex found in nearly all animal cell types that regulates inflammation and cell proliferation. Heightened activation of this pathway is the cause of increased inflammation, although it's limited to the deeper, or basal, layer of the epithelium. This means any therapeutics would need to reach the basal layer to work.

The same pathway plays an important role in human bronchial epithelial cells, which are critical in the development of asthma, according to the study. MiR-223 suppresses the pathway, which means supplementing it to epithelial cells could help control inflammatory disease.
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Onions could fight antibiotics resistance

A type of onion could fight against antibiotic resistance in cases of tuberculosis TB, a UCL and Birkbeck-led study suggests. Researchers believe the antibacterial properties extracted from the Persian shallot could increase the effects of existing antibiotic treatment.

The study was led by Dr. Sanjib Bhakta of Birkbeck, University of London and UCL's Professor Simon Gibbons, who worked with a team of scientists from Birkbeck, UCL, the University of Greenwich, the University of East London and Royal Free Hospital. When a patient has a bacterial infection, they may be prescribed an antibiotic. In the case of TB, they will likely be prescribed a cocktail of four antibiotics including Isoniazid and Rifampicin – but increasingly, the pathogens in bacterial infections are developing resistance to antibiotic drugs.

This means the drug loses its ability to effectively control or kill harmful bacteria, and is free to grow and cause further damage to the patient which, can be passed along to the population at large. Therefore, there is a pressing need to develop new classes of antibacterials to combat antibiotic resistance, which this research may help progress. The team investigated extracts of bulbs from Allium Stipitatum – also known as the Persian shallot and used as a staple part of Iranian cooking- and its antibacterial effects.

They synthesised the chemical compounds present in these plants in order to better understand and optimise their antibacterial potential. They tested four different synthesised compounds, all of which showed a significant reduction in the presence of the bacteria in the multidrug-resistant tuberculosis-the most promising candidate of which, with highest therapeutic index, inhibited growth of the isolated TB cells by more than 99.9%.

The team concluded that the chemical compounds may work as templates for the discovery of new drug treatment to combat strains of tuberculosis, which have previously developed resistance to anti-bacterial drugs.Natural products from plants and microbes have enormous potential as a source of new antibiotics. Nature is an amazingly creative chemist and it is likely that plants such as the Persian shallot produce these chemicals as a defence against microbes in their environment.
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Exercise changes gut microbiota

What we eat affects the microbes that live in our intestine, collectively known as the gut microbiota. According to two new studies, however, exercise has the same effect. Two new studies suggest that exercise independent of diet can alter the composition of gut microbiota. In mouse and human experiments, researchers discovered that physical activity independent of diet alters the composition of gut microbiota in a way that increases the production of short-chain fatty acids (SCFAs) that are beneficial for health.

The diversity of gut bacteria can be modified through exercise alone. The study included three groups of mice: one group of mice was sedentary, the other group had access to a running wheel (the exercise group), while the remaining group was sedentary and germ-free, meaning that they did not possess any gut microbiota due to being bred in a sterile environment.

The researchers took fecal material from both the exercise and sedentary groups and transplanted it into the colons of the germ-free mice. Exercise increased beneficial gut microbes
As a result of fecal transplantation, the previously germ-free mice developed gut microbiota that had comparable composition to their donor groups.

The germ-free mice that received fecal material from the exercise group had higher levels of gut microbes that produce an SCFA called butyrate, which is known to reduce inflammation and promote gut health. Additionally, when these mice were given a chemical that triggers colitis, or inflammation of the colon, the researchers witnessed a surprising response. There was a reduction in inflammation and an increase in the regenerative molecules that promote a faster recovery.

Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.
Researchers included 32 sedentary adults, of whom 18 were lean and 14 were obese. The participants took part in a supervised exercise program, which involved 30–60 minutes of endurance exercise, 3 days per week, for a total of 6 weeks. Once the 6-week exercise program ceased, subjects were asked to revert to sedentary behavior for 6 weeks.

Fecal samples were obtained from each participant before and after the exercise training program, and before and after the 6-week sedentary period.
Throughout the study period, subjects continued with their usual diets.
The researchers found that all participants experienced an increase in SCFA levels especially butyrate, following the 6-week exercise program, but these levels declined when subjects reverted to sedentary behavior.

With the help of genetic testing, the researchers found that the increase in SCFA levels correlated with alterations in the levels of gut microbes that produce SCFAs, including butyrate.
The greatest increases in SCFA-producing gut microbes after exercise, the team reports, noting that their levels were much lower at baseline. Subjects who were obese experienced "modest" increases in gut microbes that produce SCFAs.
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Using mouthwash increases the risk of obesity and diabetes

Using mouthwash twice a day significantly raises the risk of obesity and developing type 2 diabetes, according to a new study. Swilling with the anti-bacterial fluid could be killing beneficial microbes which live in the mouth and protect against the conditions. People who used the product twice a day were around 55 percent more likely to develop diabetes or dangerous blood sugar spikes.

Popular mouthwash solutions include ingredients that kill good and bad bacterial. Most of these antibacterial ingredients in mouthwash are not selective- they do not target specific oral bacteria-instead, these ingredients can act on a broad range of bacteria.
Researchers looked at overweight people who were at risk of developing diabetes. Over the study period, around 17 per cent developed diabetes or pre-diabetes, but that rose to 20 per cent for those using mouthwash once a day, and 30 per cent for those using it in the morning and evening.

Helpful bacteria in the mouth can protect against obesity and diabetes, as it helps the body produce nitric oxide. This important molecule helps trillions of our cells to communicate with each other by transmitting signals throughout the entire body and regulates insulin levels and our metabolism. Commonly-used mouthwashes typically contain powerful bacteria-killing formulas including cetylpyridinium chloride, chlorhexidine, triclosan, alcohol, fluoride, peroxide and essential oils. However, the researchers warn killing off good helpful bacteria also makes room for harmful bacteria to thrive.
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Aging leads to an imbalance in gut bacteria

According to a new study in PLOS Pathogens, different changes to the microbial community of the stomach may be the reason why conditions are associated with different risk levels and types of gastric tumor. Autoimmune disease or infection with Helicobacter pylori bacteria can damage the stomach and reduce gastric acid secretion.

Despite their similar effects, each of these conditions is associated with higher risk of a different type of gastric tumor. Meanwhile, widely used medications known as proton pump inhibitors PPIs also reduce gastric acid secretion, but they do not increase cancer risk. Elderly people tend to have different gut bacteria profiles from younger people.

This new research suggests that this change in balance is linked to inflammaging, which is related to most late-onset diseases and disorders. Inflammaging is a catch-all term for the tendency of elderly people to have generalized inflammation. It is thought to be related to evolved changes that the immune system undergoes as a person gets older.

It isn’t clear whether aging causes inflammation or inflammation causes aging, but the two go hand-in-hand, and susceptibility to many diseases goes along with both of them. Researchers took samples from older mice – whose gut bacteria composition, like humans’, changes with age – and introduced them to the bodies of younger mice. After the procedure, the younger mice developed chronic inflammation, like the inflammaging that would normally have struck them later in life.

They also transplanted gut bacteria from one group of younger mice to another group of mice of around the same ages to see if the immune response was just to the introduction of foreign bacteria. The mice with transplanted gut bacteria from older ones developed inflammaging.

The differences in the responses suggested to the researchers that aging leads to an imbalance in gut bacteria, such that there are more ‘bad’ bacteria than good in the microbiome. The proliferation of the bad bacteria leaves the gut lining more permeable to toxins that can contaminate the bloodstream and lead to disorders like inflammatory bowel disease, obesity, diabetes, anxiety, autism and cancer.
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Inflammation heals skin faster

Wounds and harmful inflammation provoking experiences impart long lasting memories to stem cells in the skin, teaching them to heal subsequent injuries faster. These stem cells, which replenish the skin's outer layer take their cue from the body's response to injury or infection.

The first bout of inflammation sensitizes these cells: the next time they sense it coming, they respond more rapidly. Skin can form memories of an inflammatory response, enhancing responsiveness to inflammation, these memories help the skin maintain its integrity, a feature that is beneficial in healing wounds after an injury.

Whether burned by the sun, attacked by microbes, nicked by a cut, the skin quickly becomes inflamed, swollen, and painful as the body seeks to stop the damage and initiate repair. The immune system maintains a memory of inflammation to mount faster responses to recurrent infections.

 Skin is the body's protective barrier, most of the cells in the skin's outermost layer, the epithelium, don't stick around long enough to form such memories but they migrate up through the epithelium and eventually slough off. Deeper within the epithelium, however, reside the stem cells that are responsible for continually replenishing it. These stem cells remain in place long after the skin has recovered from inflammation; and this experience changes the skin.

In experiments with mice, researchers showed that wounds closed more than twice as fast in skin that had already experienced inflammation than in skin that had never been damaged even if the initial inflammatory experience had occurred as long as six months earlier, inflammation-experienced stem cells were better at moving into the wound to repair the breach.

Inflammation triggers a process that physically opens up distinct sites within the cell's chromosomes, making certain genes accessible for activation. Some of these sites remain open long after the skin has recovered, allowing the genes to be turned on faster during a second round of inflammation.

A gene called Aim2, which encodes damage-and-danger sensing protein, appeared particularly crucial: an initial bout of inflammation prompts a sustained increase in its expression. A second assault quickly activates the protein, resulting in the production of an inflammatory signal that boosts the stem cells' ability to migrate into the wound.
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Ways of detecting preterm birth

There is no reliable way to predict whether a woman with a normal pregnancy will go into labor before 37 weeks. After analyzing the properties of cervical mucus, the researchers found that cervical mucus from women who delivered early was different from that of women who delivered later.

This analysis could predict the risk of early labor, potentially allowing doctors to try to intervene earlier to prevent preterm births. The distinctive chemical and mechanical properties of mucus, and how those properties help it to perform many critical roles as part of the body's first line of defense against infection.

Early births are believed to be caused by infections that occur when microbes reach the uterus through the cervical which is made of mucus and normally blocks access to the uterus. Cervical mucus from pregnant women at high risk of early labor was mechanically weaker and more elastic than that of low-risk pregnant women.

Mucus is formed from polymers known as mucins, and the composition and arrangement of these mucins determine how porous the gel is. Researchers collected samples from two groups of patients; the low-risk group included pregnant women and high-risk group included women who went into labor early, between 24 and 34 weeks.

Doctors were able to prevent labor in high-risk women, and the samples were taken after they were stabilized. Researchers tested the ability of negatively charged spheres about 1 micron in diameter to travel through the mucus, and found a small but statistically insignificant difference in porosity between the high- and low-risk samples.

They then decided to do the same test with charged peptide probes, which are small enough to avoid getting stuck in the mucus network but are sensitive to the biochemical modifications of the mucus. With these peptide probes, the researchers found a significant differences in mucus permeability and adhesiveness: The peptides were able to pass through samples from high-risk women much more easily.

Cervical mucus from women at high risk for early labor may be more susceptible to invasion by potentially harmful bacteria and microbes, making it more likely that those women will experience an infection that leads to preterm birth. The altered mucus may be less able to retain healthy immune system components such as antibodies or antimicrobial peptides, which would normally help to combat infection.

Mucins display immunologically active factors that may also lose when the adhesive properties change, this loss of adhesion might be caused by changes in molecular structure of the mucins, in particular, changes in the number and types of sugar molecules that comprise part of their structure.

Measuring the length of cervix is the common way to predict the risk of preterm birth, a shortened cervix is correlated with higher risk, there are also many cases where a shortened cervix does not lead to preterm birth.
Another test involves measuring levels of fetal fibronectin, a material that essentially "glues" the fetal membranes to the uterine wall, in vaginal secretions.
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Foods determined human gut germs

What you eat regularly or don't eat determined the germs in your digestive tract. Many microbial species exist in the human intestine, digest fiber, make vitamins and other molecules. They also strengthen the immune system and protect against harmful bacteria.

Antibiotics, cesarean sections and other lifestyle changes have also changed the composition of microbes in the human gut. People that are eating meat, berries, fruits and vegetables have gut bacteria different and more diverse than the gut bacteria of those that eat processed foods. What we eat can change the balance of microbes in our digestive tracts

Different gut microbes changes with the seasons and diet. Human microbiota can change significantly from day to day, or within hours, in response to what we have been eating.

Foods can increase the populations of some types of bacteria and reduce others, as their relative numbers change, they secrete different substances, activate different genes and absorb different nutrients.
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Microbes compete for nutrients and hinder metabolism

Choline is a water soluble nutrient, it supports energy, brain function and keeps the metabolism active. It contributes to resources that cells used to make modifications to DNA, and with less choline the cell's ability to modify and regulate genes can be impaired.

Tissues from the liver to the brain had altered epigenetic patterns in mice with high levels of choline-eating microbes.
Epigenetic modifications change how genes are expressed. The nutritional demand for the nutrient increases during pregnancy to support epigenetic regulation and cellular health in the developing fetus, and studies have linked choline deficiency during pregnancy in humans with altered behavior in children.

 Choline is found in high amounts in soybeans, eggs, meat, fish, cauliflower, milk and other foods. To test whether microbiomes could compete with their hosts for the nutrient. Researchers used germ-free mice that were colonized with defined populations of microbes to test whether microbiomes could compete with their hosts for the nutrient.

Some mice had choline eaters; others had communities where choline consumption was disrupted by mutating a single gene. When the mice were fed with a high-fat diet, which induces a range of metabolic diseases in mice, the animals with choline-eating microbes added more abdominal fat, and had fattier livers, than their counterparts with microbes that couldn't eat choline.

The offspring of mice with choline-eating bacteria had altered epigenetic patterns in their brains, suggesting problems with normal development. In mice that were genetically susceptible to behavioral problems, those that had choline-eating microbes showed anxious behaviors.

Epigenetic regulation explains the negative effects of choline-eating microbiomes, the byproduct of bacterial choline metabolism, known as Trimethylamine N-oxide TMAO, is also linked to negative outcomes. In another experiments, researchers observed much higher levels of TMAO in the mice that hosted choline-eating bacteria.

The toxic TMAO might work together with disrupted epigenetic patterns to create the long list of metabolic and developmental disruptions seen in these animals. The toxic effects of TMAO accumulation also complicate potential dietary remedies, more choline in the diet might lead to more TMAO rather than fixing nutritional shortages.
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Sepsis sieve can save your life

Sepsis occurs  when an infection like blood poisoning sparks a violent immune response in which the body attacks its own organs.

Antibiotics can control the infection if it is discovered early to avoid spreading to different parts of the body. A machine that 'sieves' the blood could save people sepsis infections.

The device has been created by a British scientist, it works like a dialysis, the
blood is removed – but in this case it is cleaned of dangerous microbes using magnets.

The machine is to undergo the first human clinical trials next year and is also being tested for use against blood-borne diseases such as malaria and leukaemia.

Designed to be used by intensive care units, blood is removed from veins in the patient's arm and enters the machine, where magnetic particles are added.

These are designed to seek out and bind to the dangerous bacteria that cause sepsis as well as little floating scraps of endotoxins that causes septic cascade.
Once bonded together, they are caught by a powerful magnet and the 'cleaned' blood is then returned to the body.

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How to disorganize bacteria for better infections treatment

Some bacteria are useful, good bacteria in gut - probiotics like GI Jake in gut aid digestion and fight with invading microbes.

Bacteria are everywhere, antibiotics are used to control bacteria that can cause health issues for humans, but some bacteria have developed resistance to common available antibiotics.

Researchers are looking at new method of treating infections that reduce the use of antibiotics.

Bacteria infect people by working in unity, living together in biofilm and communicate using chemical. This leads to severe bacteria attack on the host.

Scientists are trying to break the unity by shaking the bacteria at the right frequency to confuse them and prevent communication to reduce or prevent them from attacking the host.

How bacteria in your mouth may suggest your cancer risk

Bacteria are tiny microorganisms that exist in group, human mouth can have more than 5 billion different bacteria; some are useful while some are harmful to human health.

Jiyoung  Ahn, an associate professor of epidemiology at the New York University school of medicine said people have microbes from the same five main group of bacteria but it may vary from one genus to another.

She said the variability of these bacteria in the month may be linked to people's cancer risk, her team of researchers discovered that people that have higher Porphyromonas  a type of bacteria are at risk of pancreatic cancer.

Earlier research shows that bacteria in the mouth can go throughout the body, interact with receptors on the cells and leads to cancer.