Researchers discover antibiotics with unique approach to attacking bacteria

A new group of antibiotics with a unique approach to attacking bacteria has been discovered, making it a promising clinical candidate in the fight against antimicrobial resistance.

The newly-found corbomycin and the lesser-known complestatin have a never-before-seen way to kill bacteria, which is achieved by blocking the function of the bacterial cell wall. The discovery comes from a family of antibiotics called glycopeptides that are producedM by soil bacteria.

The researchers also demonstrated in mice that these new antibiotics can block infections caused by the drug resistant Staphylococcus aureus which is a group of bacteria that can cause many serious infections.

The findings were published in Nature today.

Bacteria have a wall around the outside of their cells that gives them shape and is a source of strength.

Antibiotics like penicillin kill bacteria by preventing building of the wall, but the antibiotics that we found actually work by doing the opposite – they prevent the wall from being broken down. This is critical for cell to divide.

 In order for a cell to grow, it has to divide and expand. If you completely block the breakdown of the wall, it is like it is trapped in a prison, and can't expand or grow."    Beth Culp, study's first author, PhD candidate in biochemistry and biomedical sciences at McMaster

Looking at the family tree of known members of the glycopeptides, researchers studied the genes of those lacking known resistance mechanisms, with the idea they might be an antibiotic demonstrating a different way to attack bacteria.

"We hypothesized that if the genes that made these antibiotics were different, maybe the way they killed the bacteria was also different," said Culp.

The group confirmed that the bacterial wall was the site of action of these new antibiotics using cell imaging techniques in collaboration with Yves Brun and his team from the Université de Montréal.

Culp said: "This approach can be applied to other antibiotics and help us discover new ones with different mechanisms of action. We found one completely new antibiotic in this study, but since then, we've found a few others in the same family that have this same new mechanism."

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
https://gscrochetdesigns.blogspot.com. one can see my crochet creations  
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
https://kneereplacement-stickclub.blogspot.com. for info on knee replacement 

Common foods alter gut bacteria by influencing viruses

In science today, food and gut bacteria are two topics that are guaranteed to fuel interest and debate. Both, of course, are interrelated, and a new study focuses on some subtleties of this relationship.

The lack of a healthy population of gut bacteria compromises our health; the same is true when we do not eat a healthful diet. However, scientists do not entirely understand the exact impact of specific foods on gut bacteria.

This knowledge gap is due, in part, to the unbelievable complexity of the microbiome. One factor that muddies the water is bacteriophages, or phages for short.

The phage

Phages are viruses that only attack bacteria. Within the gut, these viruses outnumber the dizzyingly numerous gut bacteria.

Each phage only attacks a specific type of bacterium, meaning that it can influence levels of gut bacteria. Phages need bacteria to live, so if bacteria are absent, the phages cannot survive.
This means that any foods that influence phages can influence gut bacteria and vice versa. For example, if the population of one type of phage increases, the bacteria that they consume will dwindle, potentially making room for another species of bacteria to multiply.

In this way, viruses can affect the overall microbiome — by pruning one species, they provide space for other species to fill.

Switching from prophage

Most phages in the gut are present in a dormant form — their DNA is integrated into the bacteria's genome. In this form, they are called prophages.

Scientists have identified certain compounds that trigger prophages to return to their active form. When this happens, hundreds of new phages burst out of the bacterial cell, killing the host and attacking other bacteria; these compounds include soy sauce, nicotine, and some antibiotics, such as ciprofloxacin. To date, the list of phage-promoting compounds is relatively short.

It is essential to uncover which chemicals fuel phage activity. Because phages attack and kill bacteria, if we understand how to manipulate them, they could work as powerful, natural antibiotics.

A recent study set out to expand the list of compounds that induce phage activity. The scientists from San Diego State University, CA, published their findings in the journal Gut Microbes. They hope that their results will introduce the "possibility of using diet to intentionally landscape the human gut microbiome via prophage induction."

"We could actually tackle certain conditions by adjusting the foods we consume that will affect microbial diversity, which in turn will influence health and diseases."  Research associate Lance Boling

To investigate, the researchers chose a wide range of compounds that might influence phage activity. They selected a range of bacteria from two phyla that are common in the gut: Bacteroidetes and Firmicutes. They included both beneficial and pathogenic strains of bacteria.

From 117 food compounds, they narrowed down their search to just 28. The researchers observed the growth of bacteria in the presence of each specific compound; they also observed its growth without the compound as a control. Next, they used flow cytometry, a process that is sensitive enough to detect unimaginably small virus particles.

Which foods influence phages?

Of the 28 candidates, 11 compounds produced levels of virus particles at a rate higher than the controls, which signifies that they influenced phage activity.

Some of the most significant phage boosts occurred in the presence of clove, propolis (a compound produced by bees), uva ursi (also known as kinnikinnick or bearberry), and aspartame.

Conversely, some foods reduced the number of virus particles; most notably, these included rhubarb, fernet (a type of Italian liquor), coffee, and oregano.

To complicate matters, some compounds boosted phage activity associated with some bacteria, but reduced phage activity related to others; these compounds include toothpaste, grapefruit seed extract, and pomegranate.

According to the authors, one of the most potent antibacterial foods was hot tabasco sauce, which "reduced the growth of all three [gastrointestinal] species, except the opportunistic pathogen P. aeruginosa, by an average of 92%."

Tabasco contains vinegar, but when they tested vinegar alone, it only reduced bacterial growth by 71%. They believe that capsaicin — the spicy compound in chilis — may explain the additional antibacterial capabilities. However, in the experiments with tabasco, no virus particles were found, so phages are unlikely to be involved.

The future

These findings are important. Scientists now know that the microbiome can influence our physical and mental health; it can also cause inflammation and increase cancer risk. If scientists can work out how to alter the microbiome in specific ways, they can, in theory, remove or reduce these risks.

As one of the authors, Forest Rohwer, explains, "The ability to kill specific bacteria, without affecting others, makes these compounds very interesting."

The new list of compounds is by no means exhaustive, of course, as Rohwer says, "There are probably thousands of compounds that would be useful for eliminating unwanted bacteria."

The authors hope that scientists will continue along these lines. They also explain that scientists will need to try to figure out the molecular mechanisms that switch the phage from inactivity to activity.

This is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
https://gscrochetdesigns.blogspot.com. one can see my crochet creations  
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
https://kneereplacement-stickclub.blogspot.com. for info on knee replacement 

Vancomycin may boost effectiveness of radiation therapy to fight cancer

In a study, researchers have found that giving a dose of the common antibiotic Vancomycin not only helped immune cells kill tumours that were directly treated with radiation, but also kill cancer cells that were further away in the body. The antibiotic vancomycin alters the gut microbiome in a way that can help prime the immune system to more effectively attack tumour cells after radiation therapy.

More than half of all patients with solid tumours undergo  radiation therapy at some point during their treatment. In recent years, multiple studies have shown that giving patients higher doses of radiation over the course of fewer treatments- called hypo-fractionated radiotherapy- can induce a stronger immune response in patients. In addition, hypo-fractionated doses have the ability to impact other tumours cells in the body that weren't directly treated with radiation. This is known as the abscopal effect.

Our study shows that vancomycin seems to boost the effectiveness of the hypo-fractionated radiation itself on the targeted tumour site while also aiding the abscopal effect, helping the immune system fight tumours away from the treatment site, said the  senior author. 

Researchers chose vancomycin for a few specific reasons. First, it mostly targets gram-positive bacteria, making it disruptive to the gut microbiome. Second, it's a large molecule, which means it stays in the gut and does not circulate to the rest of the body the way other antibiotics do. The fact that it is not systemic limits the impact it has on the rest of the body's microbiome.

In this study, researchers found vancomycin specifically improved the function of dendrite cells, which are the messenger cells that T cells rely on to know what to attack. While researchers used melanoma, lung and cervical cancer models for this work, they note the approach could have implications for a wide variety of cancer types. This study also builds off the team's previous research, which showed a similar effect in T cell therapies, meaning it adds to a growing body of evidence.

Still, the researchers note this study only scratches the surface when it comes to understanding the connection between the makeup of the gut microbiome and its impact on radiotherapy-induced immune responses to cancer. They say further research is needed to understand the implications of specific strains or clusters of bacteria.

However, what's clear is that antibiotics play a role and can potentially impact treatments and outcomes for cancer patients, the author said. The researchers are planning a phase 1 study to translate this approach into the clinic.

this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
https://gscrochetdesigns.blogspot.com. one can see my crochet creations  
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
https://kneereplacement-stickclub.blogspot.com. for info on knee replacement     

We hope Indian ingenuity will help make cellular therapy for cancer affordable, says Dr Siddhartha Mukherjee

Cancer physician, scientist and author of Pulitzer-winning, The Emperor of All Maladies, Dr. Mukerjee,, is setting up a cellular therapy facility in Bengaluru in the hope of developing drugs. On the sidelines of an event, he tells why personalised medicine and diet are the next frontier for cancer treatment.

At your lab in Columbia University , you and your team of scientists are researching ' living rugs' made from our own cells for cancer treatment. How does this cellular therapy work and what is its potential?
In some forms of leukemia, we could not achieve good results because drugs couldn't distinguish between cancerous and healthy cells. When we attacked the cancer cell, we also attacked the normal one. The idea we patented in my lab is to use gene editing to change the normal cells. For much of the history of cancer, we've focused on cancer cells. Here, we're inverting the logic and saying let's make the normal cells resistant to the therapy with help of gene editing, thereby making the cancer uniquely sensitive to therapy. This uses the human body, the host of cancer, as the element of change. We couldn't change the normal cells earlier because we didn't have the tools, Gene editing provides us with those tools. And all of a sudden, cancer becomes exposed.

How did you think of approaching the problems like this?
The idea occured to me while I was onvacation to Mexico city. I was making drawing with my daughter. One way to make a drawing is to make a black silhouette on white paper. And you can also make a white silhouette in black paper. And I was doing these drawings and began to realise that in cancer we've been using the cancer silhouette against the normal host as the paradign for all treatments. But what if we used the  host as the background and then attack cancer cells? We patented the idea and showed that it can eradicate this untreatable form of leukemia--- acute myeloid leukemia--- in animals and we're rapidly progressing to human studies.

What more can cells tell us about cancer?
A 2nd approach to cancer, we've taken is to ask the question whether other kinds of cells in the body, apart from T-cells, can be used for immunotherapy. One particular type of cell which has never been harnessed before is myeloid, which is a white blood cell and our body's first line of defence against infection. These can penetrate solid tumours, such as ovarian cancer and breast cancer, where Y-cells have not been very successful. A final and 3rd area that we've worked on extensively is personalising cancer medicine. The great irony of cancer is that while it grows so rapidly inside the body, it is difficult to cultivate outside in a lab. But work done by Dutch molecular geneticist, Hans Clevers in the past 10 years whose how to grow cancer cells in a dish. The cells multiply to make a 3-dimensional cluster called an organoid. So, now we take an individual's cancer cells, grow then in a dish and find out what cancer it is and what drugs does it respond to. This allows us to individuate cancer therapy. We're just about to publish a paper to show how you can find completely new cancer drugs and therapies. We're slowly moving away from the protocol-driven therapies which are sort of one-size-fits-all.

The food-is-medicine approach is a grey area in modern science. But your lab is researching the impact of diet on cancers. What have you found so far?
 
We. as a community, have neglected diet for long. Diet is part of the micro-environment of cancer cells, which sustains them. We- and many more labs- have started studying the role of diet in a highly systematic and scientific manner. Certain chemotherapies lead to a rise in blood sugar and hence insulin, which controls sugar. It's a side-effect. And insulin allows cancer cells to become resistant to a particular form of chemotherapy. By reducing the amount of insulin, for instance, through manipulation of the diet ( consuming lots of protein, little fat and no carbs) you can make cancers sensitive to chemotherapy. It's important to note that it's a combination of diet and drugs. The diet on its own won\t help. Human trials for this study are about to start. We\re testing it for lymphoma and endometrial cancers.

You've set up a cellular therapy facility in Bengaluru. Why did you choose India?
 
This is a collaboration with Kiran Majumdar Shaw. We hopefully will be able to deliver T-cell therapy and other cell therapies which have previously been unavailable in India. While the facility has already started we're not producing cells yet because you require incredible infrastructure to make these living drugs. Why India? Because we hope it will bring down the cost of these therapies. In India, the combination of engineering and scientific ingenuity has been able to bring the costs down in IT and tech industries. We are hoping to use the same innovative capacity of local scientists and doctors to be able to reduce the cost five to ten fold and make cellular therapies accessible to more people.


this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.   
https://gscrochetdesigns.blogspot.com. one can see my crochet creations 
https://gseasyrecipes.blogspot.com. feel free to view for easy, simple and healthy recipes    
https://kneereplacement-stickclub.blogspot.com. for info on knee replacement  

New skin patch could deliver cancer medication without pain in one minute

Researchers have developed a new skin patch that could efficiently deliver medication to attack melanoma cancer cells.

The study is an advance toward developing a vaccine to treat melanoma.

Our patch has a unique chemical coating and mode of action that allows it to be aplied and removed from the skin in just a minute while still delivering a therapeutic dose of durgs, said one of the researcher.

Researchers have designed a new pH-responsive polymer with 2 parts.

The first part containes amine groups that are positively charged at the pH at which they make the microneedles, but that becomes neutral at the pH of the skin, the researcher explained.

The second part contains carboxylic acid groups with no charge when the microneedles are made, but which become negatively charged when the patch is applied to the skin. 

So, there is an overall change in charge from positive to negative, he said.

While sticky negative-positive -negative layers are still required for layer-by-layer (LbL) film construction, the team's patch quickly switches to repelling negative-negative-negative layers when placed on the skin. After the microneedles pierce the skin and implant the LBL drug film beneath the skin, the drug leaves the patch quickly.

Using chicken ovalbumin as a model antigen, the team vaccinated mice with their patches and compared the results with intramuscular and subcutaneous injections.

The microneedle treatment produced nine times the antibody level as compared to intramuscular injections ( e.g. used for flu shots) and 160 times the antibody level compared to subcutaneous injections ( e.g., used for measles vaccines). They also saw efficient immune activation in surgical samples of human skin.

Our patch technology could be used to deliver vaccines to combat different infectious diseases, he said. But, we're excited by the possibility that the patch is another tool in the oncologists' arsenal against cancer, specifically melanoma, he continued.

To make melanoma vaccine, the researchers developed an antigen that includes a marker frequently over-expressed by melanoma cells, as well as an adjuvant, which creates ageneralised danger signal for the immune system and boosts its response. Then, they tested different LbL microneedle film arrangements of antigen and adjuvant in immune cells derived from mice.

From these experiments, the researchers identified the optimal LbL microneedle structure that appears to activate immune cells directly accessible in the skin. In living mice, these cells could, in turn, migrate to the lymphatic system and recruit other immune cells to attack the melanoma tumour. The researchers now plan to test patches on melanoma tumours in mice.

We're using low-cost chemistry and a simple fabrication scheme to transform vaccination, he said. Ultimately, we want to get a device approved and on the market, he added.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                    PS- THOSE INTERESTED IN RECIPES ARE FREE TO  VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/                                                                                                                                                FOR INFO ABOUT KNEE REPLACEMENT, YOU CAN VIEW MY BLOG-                                                                       https:// kneereplacement-stickclub.blogspot.com/                                                                                                                     FOR CROCHET DESIGNS                                                                                                   

                                https://gscrochetdesigns.blogspot.com

Scientists identify unique pathway for treating deadly brain cancer in kids

Researchers have discovered a new pathway that can attack and improve survival rate in an incurable type of brain cancer among children.

The study suggested that the pathway disrupts the cellular process that contributes to Diffuse Intrinsic Pontine Gliomas (DIPG).

DIPG is a highly aggressive and inoperable type of tumour that grows in the brain stem and usually strikes children less than 10 years old. Most patients do not survive more than a year after diagnosis.

Earlier studies identified a genetic mutation called PPM1D- which is critical for cell growth and cell stress response-- as a contributor to DIPG. Previous efforts to directly attack the PPM1D mutation, however, proved futile in controlling DIPG.

This study has discovered a vulnerability in the metabolic process for creating NAD,, a metabolite that is necessary for all cell life.

This is really an amazing new way to attack this cancer. We found that the mutated gene PPM1D essentially sets the stage for its own demise, said one the study authors.

Researchers found that mutated PPM1D silences a gene called NAPRT, which is key to the production of the NAD metabolite. With NAPRT unavailable, the cell switches to another protein needed to create NAD called NAMPT. By using a drug that inhibits the production of NAMPT, researchers found they could essentially starve to death those cancer cells with the PPM1D mutation.

Researchers had long thought DIPG was a childhood version of adult brain tumours, and so similar treatments for adult gliomas were tested extensively in children and failed. 

The researchers chose to look at the tumour in terms of its potential vulnerabilities, and  thus began a year-ling molecular journey to understand what role the PPM1D mutation played in altering cancer metabolism.

When epigenetic silencing results were analysed, we were gratified to discover that DIPG cells with the PPM1D mutation had created a vulnerability to a key enzyme for which small molecule inhibitors were already available, said one the study's contributing authors.

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                    PS- THOSE INTERESTED IN RECIPES ARE FREE TO  VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/                                                                                                                                                FOR INFO ABOUT KNEE REPLACEMENT, YOU CAN VIEW MY BLOG-                                                                       https:// kneereplacement-stickclub.blogspot.com/                                                                                                                     FOR CROCHET DESIGNS                                                                                                   

                                https://gscrochetdesigns.blogspot.com

Energizing the immune system to eat cancer

Macrophages are immune cells just like T and B cells, but differ in that they can eat cells that are not supposed to be in the body. 

Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. Now researchers  say they've identified how to fuel macrophages with the energy needed to attack and eat cancer cells. It is well established that macrophages can either support cancer cell growth and spread or hinder it. But most tumors also express a signal called CD47, which can lull macrophages into a deep sleep and prevent them from eating. Researchers have found that rewiring macrophage metabolism can overcome this signal and act like an alarm clock to rouse and prepare macrophages to go to work.

Macrophages are immune cells just like T and B cells, but differ in that they can eat cells that are not supposed to be in the body. In fact, they are the most prominent immune cell found in cancer, but unfortunately, most are often convinced to help cancer grow and spread. Cancer cells frequently stop macrophages from attacking them by expressing CD47, a "don't eat me" signal. Researchers now say that merely blocking inhibitory signals like CD47 is not always sufficient to convince macrophages to attack cancer. Instead, two signals are required. First, they need a signal to activate them—such as a toll-like receptor agonist. After that, a second signal—such as a CD47 inhibitor—can lower the threshold needed to wage battle on the cancer.

"It turns out macrophages need to be primed before they can go to work, which explains why solid tumours may resist treatment with CD47 inhibitors alone," said the study's senior author.

The team used this approach by activating macrophages with CpG, a toll-like receptor agonist that sends the first signal, and found that it rapidly induced shrinkage of tumors and prolonged survival of mice even without the requirement of T cells. Unexpectedly, they also found that the activated macrophages were able to eat cancer cells even in the presence of high levels of CD47.

To understand the molecular basis of this phenomenon, the team traced the metabolic activity of macrophages and determined that activated macrophages began to utilize both glutamine and glucose as fuel to support the energy requirements needed for them to eat cancer cells. This rewiring of the macrophages metabolism was necessary for CpG to be effective, and the researchers say these findings point to the importance of macrophage metabolism in determining the outcome of an immune response.

"Cancer does not shrink without the help of macrophages and macrophages need the right fuel to eat cancer cells and shrink tumors," the author said. "To do this, a shift in metabolism is needed to steer the energy in the right direction. It is the metabolism that ultimately allows macrophages to override signals telling them not to do their job."

The researcher points out that patients with diabetes, cardiovascular disease, and other conditions are routinely treated with drugs that could affect macrophage metabolism, but virtually nothing is known about how these drugs might impact immunotherapy responses in cancer, meaning the team's discovery has implications even for existing treatments. 

Provided by: Perelman School of Medicine at the University of Pennsylvania

THIS IS ONLY FOR INFORMATION, ALWAYS CONSULT YOU PHYSICIAN BEFORE HAVING ANY PARTICULAR FOOD/ MEDICATION/EXERCISE/OTHER REMEDIES.                                    PS- THOSE INTERESTED IN RECIPES ARE FREE TO  VIEW MY BLOG-                                                                                           https://gseasyrecipes.blogspot.com/       
                                                                                                                                                                      FOR INFO ABOUT KNEE REPLACEMENT, YOU CAN VIEW MY BLOG-                                                  https:// kneereplacement-stickclub.blogspot.com/           
                                                                           FOR CROCHET DESIGNS                                                                                                                                                                                                  https://gscrochetdesigns.blogspot.com