Researchers develop better way to make painkiller from trees

Steven Karlen, left, and Vitaliy Tymokhin, scientists with the Great Lakes Bioenergy Research Center, examine a reactor used to convert chemicals in poplar trees into paracetamol, the active ingredient in Tylenol.
Photo Credit: Chelsea Mamott

Scientists at the University of Wisconsin–Madison have developed a cost-effective and environmentally sustainable way to make a popular pain reliever and other valuable products from plants instead of petroleum.

Building on a previously patented method for producing paracetamol – the active ingredient in Tylenol – the discovery promises a greener path to one of the world’s most widely used medicines and other chemicals. More importantly, it could provide new revenue streams to make cellulosic biofuels — derived from non-food plant fibers — cost competitive with fossil fuels, the primary driver of climate change.

“We did the R&D to scale it and make it realizable,” says Steven Karlen, a staff scientist at the Great Lakes Bioenergy Research Center who led the research published recently in the journal ChemSusChem.

Paracetamol, also known as acetaminophen, is one of the most widely used pharmaceuticals, with a global market value of about $130 million a year. Since it was introduced in the early 1900s, the drug has traditionally been made from derivatives of coal tar or petroleum.

Drug shows promise for slowing progression of rare, painful genetic disease

A CT angiography scan of a person with ACDC disease showing abnormal calcification of the blood vessels in the legs and feet.
Image Credit: Courtesy of National Institutes of Health

A drug used to treat certain bone diseases shows promise for slowing the progression of a rare, painful genetic condition that causes excessive calcium buildup in the arteries, known as arterial calcification due to deficiency of CD73 (ACDC). These results are from a first-in-human clinical trial supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study, published in the journal Vascular Medicine, could lead to the first effective treatment for the rare disease.

ACDC, which has no known cure, often targets the arteries of the legs and can make walking painful and difficult. It can also affect the joints of the hands, causing pain and deformities. In severe cases, the condition can lead to potential limb loss. Symptoms of the disease often begin in the late teens and 20s. An extremely rare disease, it is believed to affect only about 20 people worldwide and has an estimated prevalence of less than 1 in 1 million. Previous studies have identified the gene for ACDC disease and the biochemical mechanism behind it. More recent studies by the NHLBI research team identified an existing drug, called etidronate, as a potential treatment for ACDC based on disease models in animals and human cells.

Pollen is a promising sustainable tool in the bone regeneration process

Scientists have used pollen to grow hydroxyapatite capsules, so the mineral can better support bone regeneration
Photo Credit: Alex Jones

A study has shown pollen grains can be used as green templates for producing biomaterials, showcasing their potential to support drug delivery and bone regeneration.

With an increasingly ageing population, bone fractures are becoming more common. Bone is generally able to self-repair but if the fracture is too big or the person affected too fragile, as for example people with osteoporosis, the use of bone fillers can help.

Hydroxyapatite (HAp) is an inorganic mineral present in human bone and teeth, which can be used to support bone regeneration. It makes up somewhere between 65 per cent and 70 per cent of the weight of human bone. Healthcare professionals often use synthetic and natural HAp when carrying out bone repair treatments.

A team at the University of Portsmouth has worked with international colleagues to explore sustainable ways to improve the process. 

They examined the feasibility of using pollen grains as bio-templates for growing calcium phosphate minerals in the lab - particularly hydroxyapatite (HAp) and β-tricalcium phosphate (TCP), which are types of calcium phosphate used for bone repair.

Repurposed Cancer Drugs May Improve Tuberculosis Treatment

Mycobacterium tuberculosis bacteria.
Image Credit: NIAID, NIH

Researchers have identified a combination of existing cancer drugs that may improve treatment for tuberculosis.

In a study conducted in rabbits and led by Harvard Medical School researchers at Massachusetts General Hospital, the repurposed drugs enhanced delivery of antibacterial medications that target tuberculosis-causing bacteria.

Although it is often overlooked in industrialized countries such as the United States, tuberculosis remains one of the deadliest diseases globally, causing millions of deaths every year.

Sometimes, patients die even after being treated, either because tuberculosis bacteria develop resistance to antibacterial drugs or because the ability to deliver medications to infected lung tissue is poor.

To address the latter challenge, researchers repurposed a pair of cancer drugs already approved by the U.S. Food and Drug Administration. The drugs were originally designed to enhance drug delivery to cancer cells by improving the structure and function of blood vessels around tumors, which can be compromised in cancer.

Liquid crystal nanoparticles supercharge antibiotics for cystic fibrosis

Image Credit: Copilot Dall E-3 AI generated

Cystic fibrosis is the most common, life-limiting genetic condition in Australia. It affects the lungs, digestive system, and reproductive system, producing excess mucus, infections, and blockages.

Now, thanks to a $500,000 grant from Brandon BioCatalyst's CUREator incubator, through their CSIRO-funded Minimizing Antimicrobial Resistance Stream, University of South Australia researchers are advancing the development of liquid crystal nanoparticle-formulated antibiotics to more accurately target and eliminate difficult-to-cure lung infections in people with cystic fibrosis.

Funded by the Medical Research Future Fund CUREator provides grant funding to support the development of Australian biomedical research and innovations.

The study will use a patent-protected platform technology, invented by UniSA’s Centre for Pharmaceutical Innovation to establish new therapies for cystic fibrosis sufferers. UniSA will also work with the Cystic Fibrosis Airways Research Group at the Women’s and Children’s Hospital to advance the platform.

Researchers a step closer to a cure for HIV

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

A new study involving University of Bristol researchers has shown a virus-like particle (HLP) can effectively 'shock and kill' the latent HIV reservoir.

By 2030, the World Health Organization (WHO), the Global Fund and UNAIDS are hoping to end the human immunodeficiency virus (HIV) and AIDS epidemic. An international team of researchers led by Professor Eric Arts from the Schulich School of Medicine & Dentistry, Canada, and Dr Jamie Mann, Senior Lecturer at the University of Bristol, has brought us another step closer to meeting this goal, by finding an effective and affordable targeted treatment strategy for an HIV cure. 

In a first, the study published in Emerging Microbes and Infections demonstrated the team's patented therapeutic candidate. The HIV-virus-like-particle (HLP), is 100 times more effective than other candidate HIV cure therapeutics for people living with chronic HIV on combined antiretroviral therapy (cART). If successful in clinical trials, HLP could be used by millions of people living around the world to free them of HIV. This study was done using blood samples from people living with chronic HIV. 

HLPs are dead HIV particles hosting a comprehensive set of HIV proteins that increase immune responses without infecting a person. When compared with other potential cure approaches, HLP is an affordable biotherapeutic and can be administered by intramuscular injection – similar to the seasonal flu vaccine. 

New vaccine against a highly fatal tropical disease – and potential bioterror weapon – demonstrates efficacy in animal studies

Burkholderia pseudomallei infecting a human cell. The bacteria (red) are polymerizing actin (green).
 Photo Credit: Courtesy of Christopher T. French.

In a mouse study, UCLA researchers tested a vaccine against the bacterium that causes melioidosis and found it was highly protective against the disease, which is endemic in many tropical areas, causing approximately 165,000 cases with 89,000 fatalities around the world each year. 

The bacterium, called Burkholderia pseudomallei, is spread through contact with contaminated soil and water through inhalation, ingestion or broken skin. It is so dangerous that it is categorized as a Tier 1 Select Agent of bioterrorism, and it can cause rapidly fatal pneumonia when inhaled in low doses. If aerosolized and unleashed in a terror attack, it could lead to widespread death.

To date there are no licensed vaccines against the bacterium, said senior author Dr. Marcus Horwitz, Distinguished Professor of Medicine, in the division of infectious diseases, and of Microbiology, Immunology and Molecular Genetics at the David Geffen School of Medicine at UCLA.

“A safe and effective vaccine is needed to prevent this disease as melioidosis is often difficult to diagnose, requires very lengthy treatment lasting three to six months, and has a high fatality rate even in high resource settings,” Horwitz said. “Such a vaccine would be of great benefit to people living in endemic regions, travelers, and military personnel stationed in these areas, and it would also reduce the risk from an intentional release of B. pseudomallei in a bioterrorist attack.” 

Adding ribociclib to hormone therapy reduces the risk of breast cancer recurrence

Photo Credit: National Cancer Institute

A new treatment approach that combines a targeted therapy drug with hormone therapy significantly increased the amount of time a person with stage 2 or 3 HR-positive, HER2-negative early breast cancer lives without the cancer returning, according to a new study co-led by UCLA Health Jonsson Comprehensive Cancer Center investigators.

The team found adding ribociclib, a drug that belongs to a class of CDK4/6 inhibitors, to standard hormone therapy not only improved invasive-free survival in women with this type of early-stage breast cancer, but also improves distant disease-free survival and recurrence-free survival.

The results were published today in the New England Journal of Medicine and findings were presented last year at the American Society of Clinical Oncology Annual Meeting in Chicago.

“We found that adding ribociclib to the standard hormone therapy resulted in a relative reduction in the recurrence rate by as much as 25%,” said first author of the study Dr. Dennis Slamon, chair of hematology-oncology at the David Geffen School of Medicine at UCLA and director of clinical and translational research at the UCLA Health Jonsson Comprehensive Cancer Center. “And that’s huge for this the group of patients, who make up 70% to 75% of breast cancer cases.”

Many patients with this type of breast cancer are treated with surgery, and in some cases with radiation and chemotherapy, followed by endocrine therapy for up to 10 years to help reduce their risk of recurrence.

Alzheimer’s Drug Fermented with Help from AI and Bacteria Moves Closer to Reality

Photo-Illustration Credit: Martha Morales/The University of Texas at Austin

Galantamine is a common medication used by people with Alzheimer’s disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn’t commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug. 

Now, researchers at The University of Texas at Austin have developed tools — including an artificial intelligence system and glowing biosensors — to harness microbes one day to do all the work instead. 

In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe’s normal cellular metabolism.  Essentially, the bacteria are programmed to convert food into medicinal compounds.

“The goal is to eventually ferment medicines like this in large quantities,” said Andrew Ellington, a professor of molecular biosciences and author of the study. “This method creates a reliable supply that is much less expensive to produce. It doesn’t have a growing season, and it can’t be impacted by drought or floods.” 

“Molecular Rosetta Stone” Reveals How our Microbiome Talks to Us

Bacteria in the gut convert bile acids produced by the liver into a wide array of new compounds. These molecules are akin to the language of the gut microbiome, allowing them to influence distant organ systems.
Photo Credit: Lakshmiraman Oza

Researchers from Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have uncovered thousands of previously unknown bile acids, a type of molecule used by our gut microbiome to communicate with the rest of the body.

“Bile acids are a key component of the language of the gut microbiome, and finding this many new types radically expands our vocabulary for understanding what our gut microbes do and how they do it,” said senior author Pieter Dorrestein, Ph.D., professor at Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of pharmacology and pediatrics at UC San Diego School of Medicine. “It’s like going from ‘See Spot Run’ to Shakespeare.”

The results, as described by study co-author and bile acids expert Lee Hagey, Ph.D, are akin to a molecular Rosetta stone, providing previously unknown insight into the biochemical language microbes use to influence distant organ systems.

Unveiling Inaoside A: An Antioxidant Derived from Mushrooms

Discovering a new antioxidant compound, Inaoside A from Laetiporus cremeiporus
Image credit: Atsushi Kawamura from Shinshu University, Japan

Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers from Shinshu University discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds.

The search for novel bioactive compounds from natural sources has gained considerable momentum in recent years due to the need for new therapeutic agents to combat various health challenges. Among a diverse array of natural products, mushrooms have emerged as a rich reservoir of bioactive molecules with potential pharmaceutical and nutraceutical applications. The genus Laetiporus has attracted attention for its extracts exhibiting antimicrobial, antioxidant, and antithrombin bioactivities. The species Laetiporus cremeiporus, spread across East Asia, has also been reported to show antioxidant properties. However, the identification and characterization of specific antioxidant compounds from this species have not been conducted.

In a groundbreakng study, researchers led by Assistant Professor Atsushi Kawamura from the Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, along with Hidefumi Makabe from the Department of Agriculture, Graduate School of Science and Technology, Shinshu University, and Akiyoshi Yamada from the Department of Mountain Ecosystem, Institute for Mountain Science, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, recently discovered the antioxidant compound derived from L. cremeiporus.

DNA Aptamer Drug Sensors Can Instantly Detect Cocaine, Heroin and Fentanyl – Even When Combined with Other Drugs

Photo Credit: Nastya Dulhiier

Researchers from North Carolina State University have developed a new generation of high-performance DNA aptamers and highly accurate drug sensors for cocaine and other opioids. The sensors are drug specific and can detect trace amounts of fentanyl, heroin, and cocaine – even when these drugs are mixed with other drugs or with cutting agents and adulterants such as caffeine, sugar, or procaine. The sensors could have far-reaching benefits for health care workers and law enforcement agencies.

“This work can provide needed updates to currently used tests, both in health care and law enforcement settings,” says Yi Xiao, associate professor of chemistry at NC State and corresponding author of two studies describing the work.

“For example, drug field testing currently used by law enforcement still relies on chemical tests developed a century ago that are poorly specific, which means they react to compounds that may not be the drug they’re looking for,” Xiao says.

“And the existing aptamer test for cocaine isn’t sensitive and specific enough to detect clinically relevant amounts of the drug in biological samples, like blood. The sensors we developed can detect cocaine in blood at nanomolar, rather than micromolar, levels, which represents a 1,000-fold improvement in sensitivity.”

Antibody reduces allergic reactions to multiple foods in NIH clinical trial

Drug can help protect kids with multiple food allergies during accidental exposure.
Image Credit: Copilot AI

A 16-week course of a monoclonal antibody, omalizumab, increased the amount of peanut, tree nuts, egg, milk and wheat that multi-food allergic children as young as 1 year could consume without an allergic reaction in a late-stage clinical trial. Nearly 67% of participants who completed the antibody treatment could consume a single dose of 600 milligrams (mg) or more of peanut protein, equivalent to 2.5 peanuts, without a moderate or severe allergic reaction, in contrast with less than 7% of participants who received placebo. The treatment yielded similar outcomes for egg, milk, wheat, cashew, walnut and hazelnut at a threshold dose of 1,000 mg protein or more. This suggests the antibody therapy has the potential to protect children and adolescents if they accidentally eat a food to which they are allergic despite efforts to avoid it, according to the investigators. The findings were presented today at the American Academy of Allergy, Asthma & Immunology Annual Meeting in Washington, D.C., and published in The New England Journal of Medicine.

“People with food allergies and their caregivers need to maintain constant vigilance to avoid foods that could cause a potentially life-threatening allergic reaction. This is extremely stressful, especially for parents of young children,” said Jeanne Marrazzo, M.D., M.P.H., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health and the trial’s regulatory sponsor. “Although food avoidance remains critical, the findings reported today show that a medicine can help reduce the risk of allergic reactions to common foods and may provide protection from accidental exposure emergencies.”

Anti-diabetic drugs could lower risk of primary and secondary brain cancer

Photo Credit: Tesa Robbins

Diabetic patients who take anti-diabetic drugs - known as glitazones – long term had a lower risk of primary and secondary brain cancer compared with diabetic patients on other medications, new research led by the University of Bristol has found.

The study, published in BMJ Open, suggests these drugs could be repurposed to prevent brain metastasis in cancer patients who are at high risk of secondary cancers, if the current research is supported by future studies.

PPAR- α agonists (fibrates) and PPAR γ agonists (glitazones) drugs are clinically important due to their widespread safe use to treat high cholesterol (hyperlipidemia) and diabetes.  Previous studies have suggested that fibrates and glitazones may have a role in brain tumor prevention. Given the drug's safety and cost, they have the potential to be repurposed to prevent brain cancers and reduce the risk of secondary tumors by stopping tumor growth.

Using primary care records from the UK GP database Clinical Practice Research Datalink (CPRD), which contains data from a network of over 2,000 GPs from more than 670 practices across the UK, the researchers examined if this theory could be supported.

Scientists help discover new treatment for many cancers

UniSA/CCB Professor Greg Goodall, part of the team that made the landmark discovery.
Photo Credit: Courtesy of University of South Australia 

Australian scientists have made a major discovery that could underpin the next generation of RNA-based therapeutics, and lead to more potent and longer-lasting RNA-based drugs with an even wider array of potential uses.

In a paper published in the journal Nature, Peter MacCallum Cancer Centre scientists Vi Wickramasinghe and Linh Ngo and collaborator Greg Goodall at the University of South Australia and SA Pathology’s Centre for Cancer Biology, have described a new pathway that could help to overcome a major drawback of RNA-based therapeutics to date.

Currently these breakthrough therapeutics utilize mRNA – injectable genetic material that produces a desired therapeutic or vaccine effect, but they can also break down quickly once absorbed into the human body.

“It’s the linear shape of mRNA that makes it relatively unstable and lack durability inside the body and this has been a limiting factor in the potential application of RNA-based therapeutics for diseases such as cancer,” explains Dr Wickramasinghe, senior author on the paper.

Discovery of new plant protein fold may be seed for anti-cancer drugs

The new protein fold from AhyBURP is found in the roots of the peanut plant. The protein uses copper and oxygen to form cyclic peptides. We can investigate how this chemistry occurs more thoroughly now that we know what the protein structure looks like.
Image Credit: Lisa Mydy / University of Michigan

University of Michigan researchers are celebrating their discovery of a new plant biochemistry and its unusual ability to form cyclic peptides—molecules that hold promise in pharmaceuticals as they can bind to challenging drug targets.

Cyclic peptides are an emerging and promising area of drug research.

A new study, led by U-M College of Pharmacy researchers Lisa Mydy and Roland Kersten, revealed a mechanism by which plants generate cyclic peptides.

Mydy identified the new plant protein fold and its novel chemistry, which she said had never been seen before. The protein can generate cyclic peptides, one of which holds potential as an anti-cancer drug.

“It’s extremely exciting,” said Mydy, a postdoctoral research fellow in the Department of Medicinal Chemistry. “This type of discovery doesn’t happen too often.”

Sandalwood oil by-product prevents prostate cancer development in mice

Ajay Bommareddy, Ph.D., senior author and an associate professor of pharmacology in the Department of Biomedical Science, FAU Schmidt College of Medicine.
Photo Credit: Courtesy of Florida Atlantic University

Extracted from the core of sandalwood trees (santalum album tree), sandalwood oil has been used for many centuries by several cultures throughout the world for perfume, soaps, incense and candles. With its earthy sweet scent, this essential oil is also used in the food industry and topically in various cosmetic preparations.

Importantly, this natural oil is known for its health benefits and medicinal applications from antibacterial to anticancer because of its phytochemical constituents. In addition to containing esters, free acids, aldehydes, ketones and santenone, sandalwood oil primarily (90 percent or more) constitutes santalol – equal amounts of two compounds, alpha and beta-santalol.

Now, researchers from Florida Atlantic University’s Schmidt College of Medicine and collaborators are the first to demonstrate in vivo the chemo-preventive properties of alpha-santalol against prostate cancer development using a transgenic mouse model.

New COVID vaccine induces good antibody response to mutated viral variants

Photo Credit: CDC

Researchers at Karolinska Institutet and Danderyd Hospital have followed recipients of the new updated COVID-19 vaccine and analyzed the antibody response to different SARS-CoV-2 variants. The results show a surprisingly strong response to the now dominant and highly mutated Omicron variants.

The ongoing COMMUNITY study, which was launched in the spring of 2020 with the regular testing of 2,149 members of the Danderyd Hospital staff, has recently published the results of this autumn’s leg of the study. Twenty-four participants were recorded in this study, the majority of whom were over 64 and had received four or five previous vaccine doses. The article has been peer-reviewed and accepted for publication in the scientific journal The Lancet Infectious Diseases, and is accessible prior to publication on the preprint server, bioRxiv.

Researchers uncover on/off switch for breast cancer metastasis

Songnan Wang (left) and Lingyin Li (right) found that a protein called ENPP1 acts as an on/off switch for breast cancer metastases. High protein levels lead to a high chance of metastasis (as seen by cells growing in the dish on the left), while low levels lead to no metastasis (as seen by no cells growing in the dish on the right).
Photo Credit: Lingyin Li and Songnan Wang

New research from Stanford and the Arc Institute could lead to a new and more effective immunotherapy and help clinicians better predict patient response to existing medicines.

Despite their promise, immunotherapies fail to treat many cancers, including over 80% of some of the most advanced breast cancers. And many of those patients who do respond still experience metastases eventually. New research from Stanford University and the Arc Institute has revealed a better way to predict and improve patient responses.

A team led by Lingyin Li, associate professor of biochemistry at Stanford and Arc Core Investigator, found that a protein called ENPP1 acts as an on/off switch that controls breast cancer’s ability to both resist immunotherapy and metastasize. The study, published on Dec. 20 in the Proceedings of the National Academy of Sciences, showed that ENPP1 is produced by cancer cells and by healthy cells in and around the tumor, and that high patient ENPP1 levels are linked to immunotherapy resistance and subsequent metastases. The research could lead to new, more effective immunotherapies and help clinicians better predict patient response to existing medicines.

“Our study should offer hope for everyone,” said Li, who is also an institute scholar at Sarafan ChEM-H.

Inhaled statins show promise as effective asthma treatment

This diagram shows how the inhaled medication pitavastatin may play a beneficial role in reducing obstructive airway diseases such as asthma.
Illustration Credit: Courtesy of University of California at Davis

Statins are a class of drugs commonly used to lower bad cholesterol, but can they also treat obstructive airway diseases, such as asthma?

UC Davis Health pulmonologists taking part in an NIH-funded study are exploring an innovative approach to determine whether statins may help treat obstructive airway diseases by delivering the medication via inhalation.

“Delivering statins by inhalation is a creative way to deploy a drug that has potent biological effects in pre-clinical cell-based and animal model studies,” said Amir A. Zeki, the principal investigator of the study and professor of internal medicine who specializes in pulmonary, critical care and sleep medicine. “Because oral statins do not penetrate the airway compartment at high enough levels to be effective, delivering statins directly to the lung via inhalation might achieve better local tissue drug levels, and therefore, better clinical results. This allows the use of lower drug doses to achieve efficacy while also minimizing systemic side effects.”