New study links ultra-processed foods and colorectal cancer in men

For many Americans, the convenience of pre-cooked and instant meals may make it easy to overlook the less-than-ideal nutritional information, but a team led by researchers at Tufts University and Harvard University hope that will change after recently discovering a link between the high consumption of ultra-processed foods and an increased risk of colorectal cancer.

In a study published Aug. 31 in The BMJ, researchers found that men who consumed high rates of ultra-processed foods were at 29% higher risk for developing colorectal cancer -- the third most diagnosed cancer in the United States -- than men who consumed much smaller amounts. They did not find the same association in women.

"We started out thinking that colorectal cancer could be the cancer most impacted by diet compared to other cancer types," said Lu Wang, the study's lead author and a postdoctoral fellow at the Friedman School of Nutrition Science and Policy at Tufts. "Processed meats, most of which fall into the category of ultra-processed foods, are a strong risk factor for colorectal cancer. Ultra-processed foods are also high in added sugars and low in fiber, which contribute to weight gain and obesity, and obesity is an established risk factor for colorectal cancer."

The study analyzed responses from over 200,000 participants -- 159,907 women and 46,341 men -- across three large prospective studies which assessed dietary intake and were conducted over more than 25 years. Each participant was provided with a food frequency questionnaire every four years and asked about the frequency of consumption of roughly 130 foods.

For the study in BMJ, participants' intake of ultra-processed foods was then classified into quintiles, ranging in value from the lowest consumption to the highest. Those in the highest quintile were identified as being the most at risk for developing colorectal cancer. Although there was a clear link identified for men, particularly in cases of colorectal cancer in the distal colon, the study did not find an overall increased risk for women who consumed higher amounts of ultra-processed foods.

The Impacts of Ultra-Processed Foods

The analyses revealed differences in the ways that men and women consume ultra-processed foods and the prospective associated cancer risk. Out of the 206,000 participants followed for more than 25 years, the research team documented 1,294 cases of colorectal cancer among men, and 1,922 cases among women.

The team found the strongest association between colorectal cancer and ultra-processed foods among men come from the meat, poultry, or fish-based, ready-to-eat products. "These products include some processed meats like sausages, bacon, ham, and fish cakes. This is consistent with our hypothesis," Wang said.

The team also found higher consumption of sugar-sweetened beverages, like soda, fruit-based beverages, and sugary milk-based beverages, is associated with an increased risk of colorectal cancer in men.

However, not all ultra-processed foods are equally harmful with regard to colorectal cancer risk. "We found an inverse association between ultra-processed dairy foods like yogurt and colorectal cancer risk among women," said co-senior author Fang Fang Zhang, a cancer epidemiologist and interim chair of the Division of Nutrition Epidemiology and Data Science at the Friedman School.

Overall, there was not a link between ultra-processed food consumption and colorectal cancer risk among women. It's possible that the composition of the ultra-processed foods consumed by women could be different than that from men.

"Foods like yogurt can potentially counteract the harmful impacts of other types of ultra-processed foods in women," Zhang said.

Mingyang Song, co-senior author on the study and assistant professor of clinical epidemiology and nutrition at the Harvard T.H. Chan School of Public Health, added that, "Further research will need to determine whether there is a true sex difference in the associations, or if null findings in women in this study were merely due to chance or some other uncontrolled confounding factors in women that mitigated the association."

Although ultra-processed foods are often associated with poor diet quality, there could be factors beyond the poor diet quality of ultra-processed foods that impact the risk of developing colorectal cancer.

The potential role of food additives in altering gut microbiota, promoting inflammation, and contaminants formed during food processing or migrated from food packaging may all promote cancer development, Zhang noted.

Analyzing the Data

With more than a 90% follow-up rate from each of the three studies, the research team had ample data to process and review.

"Cancer takes years or even decades to develop, and from our epidemiological studies, we have shown the potential latency effect -- it takes years to see an effect for certain exposure on cancer risk," said Song. "Because of this lengthy process, it's important to have long-term exposure to data to better evaluate cancer risk."

The studies included:

• The Nurses' Health Study (1986-2014): 121,700 registered female nurses between the ages of 30 and 55
• The Nurses' Health Study II (1991-2015): 116,429 female nurses between the ages of 25 and 42
• The Health Professional Follow-up Study (1986-2014): 51,529 male health professionals between the ages of 40 and 75.

After an exclusionary process for past diagnoses or incomplete surveys, the researchers were left with prospective data from 159,907 women from both NHS studies and 46,341 men.

The team adjusted for potential confounding factors such as race, family history of cancer, history of endoscopy, physical activity hours per week, smoking status, total alcohol intake and total caloric intake, regular aspirin use, and menopausal status.

Zhang is aware that since the participants in these studies all worked in the healthcare field, the findings for this population may not be the same as they would be for the general population, since the participants may be more inclined to eat healthier and lean away from ultra-processed foods. The data may also be skewed because processing has changed over the past two decades.

"But we are comparing within that population those who consume higher amounts versus lower amounts," Zhang reassured. "So those comparisons are valid."

Changing Dietary Patterns

Wang and Zhang previously published a study that identified a trend in increased ultra-processed food consumption in U.S. children and adolescents. Both studies underscore the idea that many different groups of people may be dependent on ultra-processed foods in their daily diets.

"Much of the dependence on these foods can come down to factors like food access and convenience," said Zhang, who is also a member of the Tufts Institute for Global Obesity Research. "Chemically processing foods can aid in extending shelf life, but many processed foods are less healthy than unprocessed alternatives. We need to make consumers aware of the risks associated with consuming unhealthy foods in quantity and make the healthier options easier to choose instead."

Wang knows that change won't happen overnight, and hopes that this study, among others, will contribute to changes in dietary regulations and recommendations.

"Long-term change will require a multi-step approach," Wang added. "Researchers continue to examine how nutrition-related policies, dietary recommendations, and recipe and formula changes, coupled with other healthy lifestyle habits, can improve overall health and reduce cancer burden. It will be important for us to continue to study the link between cancer and diet, as well as the potential interventions to improve outcomes.

Research reported in this article was supported by awards from the National Institutes of Health's National Institute on Minority Health and Health Disparities (R01MD011501), National Cancer Institute (UM1CA186107; P01CA087969; U01CA176726; U01CA167552; and R00CA215314), and a Mentored Research Scholar Grant in Applied and Clinical Research from the American Cancer Society. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institutes of Health.

Journal Reference:

1. Lu Wang, Mengxi Du, Kai Wang, Neha Khandpur, Sinara Laurini Rossato, Jean-Philippe Drouin-Chartier, Euridice Martínez Steele, Edward Giovannucci, Mingyang Song, Fang Fang Zhang. Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies. BMJ, 2022; e068921 DOI: 10.1136/bmj-2021-068921 

Courtesy:

Tufts University, Health Sciences Campus. "New study links ultra-processed foods and colorectal cancer in men: Researchers found that men who consumed high rates of ultra-processed foods were at higher risk for developing colorectal cancer than those who did not." ScienceDaily. ScienceDaily, 31 August 2022. <www.sciencedaily.com/releases/2022/08/220831210024.htm>.

 

Artificial photosynthesis can produce food without sunshine

Scientists have found a way to bypass the need for biological photosynthesis altogether and create food independent of sunlight by using artificial photosynthesis. The technology uses a two-step electrocatalytic process to convert carbon dioxide, electricity, and water into acetate. Food-producing organisms then consume acetate in the dark to grow. The hybrid organic-inorganic system could increase the conversion efficiency of sunlight into food, up to 18 times more efficient for some foods.

Photosynthesis has evolved in plants for millions of years to turn water, carbon dioxide, and the energy from sunlight into plant biomass and the foods we eat. This process, however, is very inefficient, with only about 1% of the energy found in sunlight ending up in the plant. Scientists at UC Riverside and the University of Delaware have found a way to bypass the need for biological photosynthesis altogether and create food independent of sunlight by using artificial photosynthesis.

The research, published in Nature Food, uses a two-step electrocatalytic process to convert carbon dioxide, electricity, and water into acetate, the form of the main component of vinegar. Food-producing organisms then consume acetate in the dark to grow. Combined with solar panels to generate the electricity to power the electrocatalysis, this hybrid organic-inorganic system could increase the conversion efficiency of sunlight into food, up to 18 times more efficient for some foods.

"With our approach we sought to identify a new way of producing food that could break through the limits normally imposed by biological photosynthesis," said corresponding author Robert Jinkerson, a UC Riverside assistant professor of chemical and environmental engineering.

In order to integrate all the components of the system together, the output of the electrolyzer was optimized to support the growth of food-producing organisms. Electrolyzers are devices that use electricity to convert raw materials like carbon dioxide into useful molecules and products. The amount of acetate produced was increased while the amount of salt used was decreased, resulting in the highest levels of acetate ever produced in an electrolyzer to date.

"Using a state-of-the-art two-step tandem CO₂ electrolysis setup developed in our laboratory, we were able to achieve a high selectivity towards acetate that cannot be accessed through conventional CO₂ electrolysis routes," said corresponding author Feng Jiao at University of Delaware.

Experiments showed that a wide range of food-producing organisms can be grown in the dark directly on the acetate-rich electrolyzer output, including green algae, yeast, and fungal mycelium that produce mushrooms. Producing algae with this technology is approximately fourfold more energy efficient than growing it photosynthetically. Yeast production is about 18-fold more energy efficient than how it is typically cultivated using sugar extracted from corn.

"We were able to grow food-producing organisms without any contributions from biological photosynthesis. Typically, these organisms are cultivated on sugars derived from plants or inputs derived from petroleum -- which is a product of biological photosynthesis that took place millions of years ago. This technology is a more efficient method of turning solar energy into food, as compared to food production that relies on biological photosynthesis," said Elizabeth Hann, a doctoral candidate in the Jinkerson Lab and co-lead author of the study.

The potential for employing this technology to grow crop plants was also investigated. Cowpea, tomato, tobacco, rice, canola, and green pea were all able to utilize carbon from acetate when cultivated in the dark.

"We found that a wide range of crops could take the acetate we provided and build it into the major molecular building blocks an organism needs to grow and thrive. With some breeding and engineering that we are currently working on we might be able to grow crops with acetate as an extra energy source to boost crop yields," said Marcus Harland-Dunaway, a doctoral candidate in the Jinkerson Lab and co-lead author of the study.

By liberating agriculture from complete dependence on the sun, artificial photosynthesis opens the door to countless possibilities for growing food under the increasingly difficult conditions imposed by anthropogenic climate change. Drought, floods, and reduced land availability would be less of a threat to global food security if crops for humans and animals grew in less resource-intensive, controlled environments. Crops could also be grown in cities and other areas currently unsuitable for agriculture, and even provide food for future space explorers.

"Using artificial photosynthesis approaches to produce food could be a paradigm shift for how we feed people. By increasing the efficiency of food production, less land is needed, lessening the impact agriculture has on the environment. And for agriculture in non-traditional environments, like outer space, the increased energy efficiency could help feed more crew members with less inputs," said Jinkerson.

This approach to food production was submitted to NASA's Deep Space Food Challenge where it was a Phase I winner. The Deep Space Food Challenge is an international competition where prizes are awarded to teams to create novel and game-changing food technologies that require minimal inputs and maximize safe, nutritious, and palatable food outputs for long-duration space missions.

"Imagine someday giant vessels growing tomato plants in the dark and on Mars -- how much easier would that be for future Martians?" said co-author Martha Orozco-Cárdenas, director of the UC Riverside Plant Transformation Research Center.

Andres Narvaez, Dang Le, and Sean Overa also contributed to the research.

The research was supported by the Translational Research Institute for Space Health (TRISH) through NASA (NNX16AO69A), Foundation for Food and Agriculture Research (FFAR), the Link Foundation, the U.S. National Science Foundation, and the U.S. Department of Energy. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the Foundation for Food and Agriculture Research.

Journal Reference:

1. Elizabeth C. Hann, Sean Overa, Marcus Harland-Dunaway, Andrés F. Narvaez, Dang N. Le, Martha L. Orozco-Cárdenas, Feng Jiao, Robert E. Jinkerson. A hybrid inorganic–biological artificial photosynthesis system for energy-efficient food production. Nature Food, 2022; 3 (6): 461 DOI: 10.1038/s43016-022-00530-x 

Courtesy:

University of California - Riverside. "Artificial photosynthesis can produce food without sunshine." ScienceDaily. ScienceDaily, 23 June 2022. <www.sciencedaily.com/releases/2022/06/220623122624.htm>.

 

Scientists develop a new non-opioid pain killer with fewer side effects

A promising new non-opioid painkiller (analgesic) with potentially fewer side effects compared to other potent painkillers, has been discovered.

A team of scientists, co-led by researchers from the School of Life Sciences, University of Warwick, has investigated a compound called BnOCPA (benzyloxy-cyclopentyladenosine), found to be a potent and selective analgesic which is non-addictive in test model systems. BnOCPA also has a unique mode of action and potentially opens a new pipeline for the development of new analgesic drugs.

The research by the team at Warwick, together with colleagues at the University of Cambridge, University of Bern, Monash University, Coventry University and industrial collaborators, is published in Nature Communications in a paper entitled "Selective activation of G?ob by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression."

In the UK between one third and one half of the population report moderately to severely disabling chronic pain. Such pain has a negative impact on quality of life and many of the commonly used pain killers produce side effects. Opioid drugs, such as morphine and oxycodone, can lead to addiction and are dangerous in overdose. There is therefore an unmet need for new and potent pain killing drugs.

Many drugs act via proteins on the surface of cell surfaces that activate adapter molecules called G proteins. The activation of G proteins can lead to many cellular effects. BnOCPA is unique in that it only activates one type of G protein, leading to very selective effects and thus reducing potential side effects.

Dr Mark Wall, from the School of Life Sciences at the University of Warwick, who led the research said: "The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to generate potent painkillers to help patients cope with chronic pain."

Professor Bruno Frenguelli, principal investigator on the project, from the University of Warwick's School of Life Sciences, said: "This is a fantastic example of serendipity in science. We had no expectations that BnOCPA would behave any differently from other molecules in its class, but the more we looked into BnOCPA we discovered properties that had never been seen before, and which may open up new areas of medicinal chemistry."

Professor Graham Ladds, co-principal investigator on the project, from the University of Cambridge, said: "This is an amazing story looking at agonist bias for a GPCR. Not only does BnOCPA have the potential to be a new type of painkiller, but it has shown us a new method for targeting other GPCRs in drug discovery."

Journal Reference:

1. Mark J. Wall, Emily Hill, Robert Huckstepp, Kerry Barkan, Giuseppe Deganutti, Michele Leuenberger, Barbara Preti, Ian Winfield, Sabrina Carvalho, Anna Suchankova, Haifeng Wei, Dewi Safitri, Xianglin Huang, Wendy Imlach, Circe La Mache, Eve Dean, Cherise Hume, Stephanie Hayward, Jess Oliver, Fei-Yue Zhao, David Spanswick, Christopher A. Reynolds, Martin Lochner, Graham Ladds, Bruno G. Frenguelli. Selective activation of Gαob by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-31652-2 

Courtesy:

University of Warwick. "Scientists develop a new non-opioid pain killer with fewer side effects." ScienceDaily. ScienceDaily, 20 July 2022. <www.sciencedaily.com/releases/2022/07/220720102521.htm>.

 

 

People generate their own oxidation field and change the indoor air chemistry around them

People typically spend 90 percent of their lives inside, at home, at work, or in transport. Within these enclosed spaces, occupants are exposed to a multitude of chemicals from various sources, including outdoor pollutants penetrating indoors, gaseous emissions from building materials and furnishings, and products of our own activities such as cooking and cleaning. In addition, we are ourselves potent mobile emission sources of chemicals that enter the indoor air from our breath and skin.

But how do the chemicals disappear again? In the atmosphere outdoors, this happens to a certain extent naturally by itself, when it rains and through chemical oxidation. Hydroxyl (OH) radicals are largely responsible for this chemical cleaning. These very reactive molecules are also called the detergents of the atmosphere and they are primarily formed when UV light from the sun interacts with ozone and water vapor.

Indoors, on the other hand, the air is of course far less affected by direct sunlight and rain. Since UV rays are largely filtered out by glass windows it has been generally assumed that the concentration of OH radicals is substantially lower indoors than outdoors and that ozone, leaking in from outdoors, is the major oxidant of indoor airborne chemical pollutants.

OH radicals are formed from ozone and skin oils

However, now it has been discovered that high levels of OH radicals can be generated indoors, simply due to the presence of people and ozone. This has been shown by a team led by the Max Planck Institute for Chemistry in cooperation with researchers from the USA and Denmark.

"The discovery that we humans are not only a source of reactive chemicals, but we are also able to transform these chemicals ourselves was very surprising to us," says Nora Zannoni, first author of the study published in the research magazine Science, and now at the Institute of Atmospheric Sciences and Climate in Bologna, Italy. "The strength and shape of the oxidation field are determined by how much ozone is present, where it infiltrates, and how the ventilation of the indoor space is configured," adds the scientist from Jonathan Williams' team. The levels the scientists found were even comparable to outside daytime OH concentrations levels.

The oxidation field is generated by the reaction of ozone with oils and fats on our skin, especially the unsaturated triterpene squalene, which constitutes about 10 percent of the skin lipids that protect our skin and keep it supple. The reaction releases a host of gas phase chemicals containing double bonds that react further in the air with ozone to generate substantial levels of OH radicals. These squalene degradation products were characterized and quantified individually using Proton Transfer reaction Mass Spectrometry and fast gas chromatograph-mass spectrometry systems. In addition, the total OH reactivity was determined in parallel enabling the OH levels to be quantified empirically.

The experiments were conducted at the Technical University of Denmark (DTU) in Copenhagen. Four test subjects stayed in a special climate-controlled chamber under standardized conditions. Ozone was added to the chamber air inflow in a quantity that was not harmful to humans but representative of higher indoor levels. The team determined the OH values before and during the volunteers' stay both with and without ozone present.

In order to understand how the human-generated OH field looked like in space and time during the experiments, results from a detailed multiphase chemical kinetic model from the University of California, Irvine were combined with a computational fluid dynamics model from Pennsylvania State University, both based in the USA. After validating the models against the experimental results, the modeling team examined how the human-generated OH field varied under different conditions of ventilation and ozone, beyond those tested in the laboratory. From the results, it was clear that the OH radicals were present, abundant, and forming strong spatial gradients.

"Our modeling team is the first and currently the only group that can integrate chemical processes between the skin and indoor air, from molecular scales to room scales," said Manabu Shiraiwa, a professor at UC Irvine who led the modeling part of the new work. "The model makes sense of the measurements -- why OH is generated from the reaction with the skin."

Shiraiwa added that there remain unanswered questions, like the way humidity levels impact the reactions the team traced. "I think this study opens up a new avenue for indoor air research," he said.

Adapt test methods for furniture and building materials

"We need to rethink indoor chemistry in occupied spaces because the oxidation field we create will transform many of the chemicals in our immediate vicinity. OH can oxidize many more species than ozone, creating a multitude of products directly in our breathing zone with as yet unknown health impacts." This oxidation field will also impact the chemical signals we emit and receive," says project leader Jonathan Williams, "and possibly help explain the recent finding that our sense of smell is generally more sensitive to molecules that react faster with OH."

The new finding also has implications for our health: Currently, chemical emissions of many materials and furnishings are being tested in isolation before they are approved for sale. However, it would be advisable to also conduct tests in the presence of people and ozone, says atmospheric chemist Williams. This is because oxidation processes can lead to the generation of respiratory irritants such as 4-oxopentanal (4-OPA) and other OH radical-generated oxygenated species, and small particles in the immediate vicinity of the respiratory tract. These can have adverse effects, especially in children and the infirm.

These findings are part of the project ICHEAR (Indoor Chemical Human Emissions and Reactivity Project) which brought together a group of collaborating international scientists from Denmark (DTU), the USA (Rutgers University), and Germany (MPI). The modeling was part of the MOCCIE project based at the University of California Irvine and the Pennsylvania State University. Both projects were funded by grants from the A. P. Sloan foundation.

Journal Reference:

1. Nora Zannoni, Pascale S. J. Lakey, Youngbo Won, Manabu Shiraiwa, Donghyun Rim, Charles J. Weschler, Nijing Wang, Lisa Ernle, Mengze Li, Gabriel Bekö, Pawel Wargocki, Jonathan Williams. The human oxidation field. Science, 2022; 377 (6610): 1071 DOI: 10.1126/science.abn0340 

Courtesy:

Max Planck Institute for Chemistry. "People generate their own oxidation field and change the indoor air chemistry around them." ScienceDaily. ScienceDaily, 1 September 2022. <www.sciencedaily.com/releases/2022/09/220901151703.htm>.

 

 

Brains cells born together wire and fire together for life

Brain cells with the same "birthdate" are more likely to wire together into cooperative signaling circuits that carry out many functions, including the storage of memories, a new study finds.

Led by researchers from NYU Grossman School of Medicine, the new study on the brains of mice developing in the womb found that brain cells (neurons) with the same birthdate showed distinct connectivity and activity throughout the animals' adult lives, whether they were asleep or awake.

Published online August 22 in Nature Neuroscience, the findings suggest that evolution took advantage of the orderly birth of neurons -- by gestational day -- to form localized microcircuits in the hippocampus, the brain region that forms memories. Rather than attempting to create each new memory from scratch, the researchers suggest, the brain may exploit the stepwise formation of neuronal layers to establish neural templates, like "Lego pieces," that match each new experience to an existing template as it is remembered.

These rules of circuit assembly would suggest that cells born together are more likely to encode memories together, and to fail together, potentially implicating neuronal birthdate in diseases like autism and Alzheimer's, say the authors. With changes to the number of cells born at different days, the developing brain may be more vulnerable on some gestational days to viral infections, toxins, or alcohol.

"Our study's results suggest that which day a hippocampal neuron is born strongly influences both how that single cell performs, and how populations of such cells signal together throughout life," says senior study author György Buzsáki, MD, PhD, the Biggs Professor in the Department of Neuroscience and Physiology at NYU Langone Health. "This work may reshape how we study neurodevelopmental disorders, which have traditionally been looked at through a molecular or genetic, rather than a developmental, lens," says Buzsáki, also a faculty member in the Neuroscience Institute at NYU Langone."

New Understanding

The current study's innovation rests on tracking the activity of neurons of a given birthdate into adulthood. To accomplish this, the researchers relied on a technique that allowed them to transfer DNA into cells that were undergoing division into neurons in the womb. The DNA expressed markers that tagged brain cells that were born on same day, akin to a barcode. This labeling method then enabled the researchers to study these neurons in the adult animal.

Using a combination of techniques, the new study found that neurons of the same birthdate tend to "co-fire" together, characterized by synchronized swings in their positive and negative charges, allowing them to transmit electrical signals collectively. A likely reason for the co-firing, say the authors, is that neurons with the same birthdate are connected via shared neurons.

Past work had shown that activity in the hippocampus can be described in terms patterns of collective neuronal activity during waking and sleep. During sleep, for instance, when each day's memories are consolidated for long-term memory storage, hippocampal neurons engage in a cyclical burst of activity called the "sharp wave-ripple," named for the shape it takes when captured graphically by EEG, a technology that records brain activity with electrodes.

"Our results show that neurons born on the same day become part of the same cooperating assemblies, and participate in the same sharp wave-ripples and represent the same memories," says first author Roman Huszár, a graduate student in Buzsáki's lab. "These relationships, and the pre-set templates they encode, have a key implication for hippocampal function: the storage of a memory about a place or event."

Moving forward, the team plans additional experiments to identify the genes active in the same birthdate neurons in different brain regions, and to test their role in memory formation and behavior.

Along with Buzsáki and and Huszár, the other study authors were Yunchang Zhang from the NYU Neuroscience Institute and the Center for Neural Science at New York University; and Heike Blockus of the Department of Neuroscience and Zuckerman Mind Brain Behavior Institute at Columbia University. Funding for the study was provide by National Institutes of Health grants RO1 MH122391 and U19 NS107616.

Journal Reference:

1. Roman Huszár, Yunchang Zhang, Heike Blockus, György Buzsáki. Preconfigured dynamics in the hippocampus are guided by embryonic birthdate and rate of neurogenesis. Nature Neuroscience, 2022; DOI: 10.1038/s41593-022-01138-x 

Courtesy:

NYU Langone Health / NYU Grossman School of Medicine. "Brains cells born together wire and fire together for life." ScienceDaily. ScienceDaily, 22 August 2022. <www.sciencedaily.com/releases/2022/08/220822130226.htm>.

Team developing oral insulin tablet sees breakthrough results

A team of University of British Columbia researchers working on developing oral insulin tablets as a replacement for daily insulin injections have made a game-changing discovery.

Researchers have discovered that insulin from the latest version of their oral tablets is absorbed by rats in the same way that injected insulin is.

"These exciting results show that we are on the right track in developing an insulin formulation that will no longer need to be injected before every meal, improving the quality of life, as well as mental health, of more than nine million Type 1 diabetics around the world." says professor Dr. Anubhav Pratap-Singh (he/him), the principal investigator from the faculty of land and food systems.

He explains the inspiration behind the search for a non-injectable insulin comes from his diabetic father who has been injecting insulin 3-4 times a day for the past 15 years.

According to Dr. Alberto Baldelli (he/him), a senior fellow in Dr. Pratap-Singh's lab, they are now seeing nearly 100 per cent of the insulin from their tablets go straight into the liver. In previous attempts to develop a drinkable insulin, most of the insulin would accumulate in the stomach.

"Even after two hours of delivery, we did not find any insulin in the stomachs of the rats we tested. It was all in the liver and this is the ideal target for insulin -- it's really what we wanted to see," says Yigong Guo (he/him), first author of the study and a PhD candidate working closely on the project.

Changing the mode of delivery

When it comes to insulin delivery, injections are not the most comfortable or convenient for diabetes patients. But with several other oral insulin alternatives also being tested and developed, the UBC team worked to solve where and how to facilitate a higher absorption rate.

Dr. Pratap-Singh's team developed a different kind of tablet that isn't made for swallowing, but instead dissolves when placed between the gum and cheek.

This method makes use of the thin membrane found within the lining of the inner cheek and back of the lips (also known as the buccal mucosa). It delivered all the insulin to the liver without wasting or decomposing any insulin along the way.

"For injected insulin we usually need 100iu per shot. Other swallowed tablets being developed that go to the stomach might need 500iu of insulin, which is mostly wasted, and that's a major problem we have been trying to work around," Yigong says.

Most swallowed insulin tablets in development tend to release insulin slowly over two to four hours, while fast-release injected insulin can be fully released in 30-120 minutes.

"Similar to the rapid-acting insulin injection, our oral delivery tablet absorbs after half an hour and can last for about two to four hours long," says Dr. Baldelli.

Potential broad benefits

The study is yet to go into human trials, and for this to happen Dr. Pratap-Singh says they will require more time, funding and collaborators. But beyond the clear potential benefits to diabetics, he says the tablet they are developing could also be more sustainable, cost-effective and accessible.

"More than 300,000 Canadians have to inject insulin multiple times per day," Dr. Pratap-Singh says. "That is a lot of environmental waste from the needles and plastic from the syringe that might not be recycled and go to landfill, which wouldn't be a problem with an oral tablet."

He explains that their hope is to reduce the cost of insulin per dose since their oral alternative could be cheaper and easier to make. Transporting the tablets would be easier for diabetics, who currently have to think about keeping their doses cool.

Journal Reference:

1. Yigong Guo, Alberto Baldelli, Anika Singh, Farahnaz Fathordoobady, David Kitts, Anubhav Pratap-Singh. Production of high loading insulin nanoparticles suitable for oral delivery by spray drying and freeze drying techniques. Scientific Reports, 2022; 12 (1) DOI: 10.1038/s41598-022-13092-6 

Courtesy:

University of British Columbia. "Team developing oral insulin tablet sees breakthrough results." ScienceDaily. ScienceDaily, 30 August 2022. <www.sciencedaily.com/releases/2022/08/220830093215.htm>.

 

Mosquitoes have neuronal fail-safes to make sure they can always smell humans

When female mosquitoes are looking for a human to bite, they smell a unique cocktail of body odors that we emit into the air. These odors then stimulate receptors in the mosquitoes' antenna. Scientists have tried deleting these receptors in attempts to make humans undetectable to mosquitoes.

However, even after knocking out an entire family of odor-sensing receptors from the mosquito genome, mosquitoes still find a way to bite us. Now, a group of researchers, publishing in the journal Cell on August 18, found that mosquitoes have evolved redundant fail-safes in their olfactory system that make sure they can always smell our scents.

"Mosquitoes are breaking all of our favorite rules of how animals smell things," says Margo Herre, a scientist at Rockefeller University and one of the lead authors of the paper.

In most animals, an olfactory neuron is only responsible for detecting one type of odor. "If you're a human and you lose a single odorant receptor, all of the neurons that express that receptor will lose the ability to smell that smell," says Leslie Vosshall of the Howard Hughes Medical Institute and a professor at Rockefeller University and the senior author of the paper. But she and her colleagues found that this is not the case in mosquitoes.

"You need to work harder to break mosquitoes because getting rid of a single receptor has no effect," says Vosshall. "Any future attempts to control mosquitoes by repellents or anything else has to take into account how unbreakable their attraction is to us."

"This project really started unexpectedly when we were looking at how human odor was encoded in the mosquito brain," says Meg Younger, a professor at Boston University and one of the lead authors of the paper.

They found that neurons stimulated by the human odor 1-octen-3-ol are also stimulated by amines, another type of chemical mosquitoes use to look for humans. This is unusual since according to all existing rules of how animals smell, neurons encode odor with narrow specificity, suggesting that 1-octen-3-ol neurons should not detect amines.

"Surprisingly, the neurons for detecting humans through 1-octen-3-ol and amine receptors were not separate populations," says Younger. This may allow all human-related odors to activate "the human-detecting part" of the mosquito brain even if some of the receptors are lost, acting as a fail-safe.

The team also utilized single-nucleus RNA sequencing to see what other receptors individual mosquito olfactory neurons are expressing. "The result gave us a broad view of just how common co-expression of receptors is in mosquitoes," says Olivia Goldman, another lead author of the paper.

Vosshall thinks that other insects may have a similar mechanism. Christopher Potter's research group at Johns Hopkins University recently reported that fruit flies have similar co-expression of receptors in their neurons. "This may be a general strategy for insects that depend heavily on their sense of smell," says Vosshall.

In the future, Meg Younger's group plans to uncover the functional significance of the co-expression of different types of olfactory receptors.

This work was partially supported by the U.S. National Institute of Health.

Journal Reference:

1. Margaret Herre, Olivia V. Goldman, Tzu-Chiao Lu, Gabriela Caballero-Vidal, Yanyan Qi, Zachary N. Gilbert, Zhongyan Gong, Takeshi Morita, Saher Rahiel, Majid Ghaninia, Rickard Ignell, Benjamin J. Matthews, Hongjie Li, Leslie B. Vosshall, Meg A. Younger. Non-canonical odor coding in the mosquito. Cell, 2022; 185 (17): 3104 DOI: 10.1016/j.cell.2022.07.024 

Courtesy:

Cell Press. "Mosquitoes have neuronal fail-safes to make sure they can always smell humans." ScienceDaily. ScienceDaily, 18 August 2022. <www.sciencedaily.com/releases/2022/08/220818122351.htm>.