. Scientific Frontline: Pharmaceutical
Showing posts with label Pharmaceutical. Show all posts
Showing posts with label Pharmaceutical. Show all posts

Monday, March 18, 2024

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.” 

Monday, March 11, 2024

“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.

Wednesday, March 6, 2024

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.

Monday, March 4, 2024

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.”

Sunday, February 25, 2024

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.”

Thursday, February 22, 2024

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.

Wednesday, February 14, 2024

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.”

Tuesday, February 13, 2024

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.

Sunday, December 24, 2023

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.

Wednesday, December 20, 2023

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.”

Monday, December 18, 2023

New possibilities for a healing toxin

Richard Kammerer and Oneda Leka in one of the PSI laboratories in front of an apparatus that is used, among other things, to purify proteins.
Photo Credit: Paul Scherrer Institute/Mahir Dzambegovic

PSI researchers have discovered a surprising trick that could expand the possibilities for medical use of botulinum toxin A1, better known under the name Botox, as an active agent. They have developed antibody-like proteins that speed up the enzyme’s effect on the transmission of nerve signals. This suggests that Botox might, for example, be able to relief pain more quickly than before. The study has now been published in the journal Nature Communications.

Botulinum neurotoxin A1, better known under the trademark Botox, is actually a nerve toxin produced by bacteria. It gained widespread public awareness through its use as a cosmetic aid. Many people have it injected into wrinkles to make them look younger. The substance blocks signal transmission from nerves to muscles, thus relaxing them so that facial features appear smooth. What is less well known: Botox is also used very often in therapeutic medicine to treat conditions that can be traced back to cramping muscles or faulty nerve signals, including pains, spasms, bladder weakness, grinding of teeth, and misalignments, for example of the eyes. Botox is even used in treating stomach cancer, to block the vagus nerve and thus slow down tumor growth.

In any therapy, it is crucial to use this highly effective medicine in a very targeted manner with careful dosage, since Botox is the most potent natural nerve toxin of all, which can lead to dangerous paralysis in a clinical picture called botulism. Just one hundred nanograms or so administered intravenously can be enough to kill a person, because the toxin paralyses the respiratory muscles, along with others.

Thursday, December 14, 2023

New study eyes nutrition-rich chia seed for potential to improve human health

Chia seeds.
Photo Credit: Pankaj Jaiswal.

Oregon State University scientists have sequenced the chia genome and in doing so provided a blueprint for future research that capitalizes on the nutritional and human health benefits of the plant.

In the just-published paper, the researchers identified chia genes associated with improving nutrition and sought after properties for pharmaceuticals that could be used to treat everything from cancer to high blood pressure. The seeds of the chia plant have received widespread attention in recent years because of the nutritional punch they pack.

Others have sequenced the chia genome, but this paper provides a more detailed look at the molecular level and the potential of genetic data mining with a keen focus on human health applications.

“This research opens up possibilities for scientists to study chia seed through the lens of improving human health while at the same time continuing to further our knowledge of all the nutritional benefits of chia,” said Pankaj Jaiswal, a professor in the Department of Botany and Plant Pathology in the College or Agricultural Sciences at Oregon State.

Wednesday, December 13, 2023

Enzymes Can’t Tell Artificial DNA From the Real Thing

Like adding new letters to an existing language’s alphabet to expand its vocabulary, adding new synthetic nucleotides to the genetic alphabet could expand the possibilities of synthetic biology. This image shows a rendering of RNA polymerase (center) and a synthetic nucleotide (lower right).
Image Credit: UC San Diego Health Sciences

The genetic alphabet contains just four letters, referring to the four nucleotides, the biochemical building blocks that comprise all DNA. Scientists have long wondered whether it’s possible to add more letters to this alphabet by creating brand-new nucleotides in the lab, but the utility of this innovation depends on whether or not cells can actually recognize and use artificial nucleotides to make proteins.

Now, researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have come one step closer to unlocking the potential of artificial DNA. The researchers found that RNA polymerase, one of the most important enzymes involved in protein synthesis, was able to recognize and transcribe an artificial base pair in exactly the same manner as it does with natural base pairs.

The findings, published in Nature Communications, could help scientists create new medicines by designing custom proteins.

New treatment for deadly uterine cancer

left to right, Dr Asmerom Sengal, Professor Pamela Pollock.
Photo Credit: Courtesy of Queensland University of Technology

QUT scientists have discovered a promising new therapy for a deadly type of endometrial cancer that has a poor prognosis if the cancer spreads or returns after initial treatment, a plight that affects 15-20 per cent of endometrial cancer patients.

  • Testing of new drug inhibited uterine tumor cell growth in lab and mice models
  • The drug blocks the receptor of the growth factor in tumors that is associated with a low survival rate
  • The inhibitor also reduced the tumors blood vessel formation

Dr Asmerom Sengal and Associate Professor Pamela Pollock from QUT’s School of Biomedical Sciences, published their research in Nature Precision Oncology with a recommendation that the strength of their findings indicated they should proceed to patient trials.

Dr Asmerom said endometrial cancer confined within the uterus could be cured with surgery however, if it had spread to the abdomen and other organs patients had limited treatment options.

“Previously, we found women with endometrial cancer who have an incorrect growth factor receptor called fibroblast growth factor receptor 2c (FGFR2c) on the tumor cell surface have a poor survival rate,” Dr Asmerom said.

Sunday, November 12, 2023

Researchers identify previously unknown step in cholesterol absorption in the gut

Illustration Credit: Scientific Frontline

UCLA researchers have described a previously unknown step in the complex process by which dietary cholesterol is processed in the intestines before being released into the bloodstream – potentially revealing a new pathway to target in cholesterol treatment.

Although an existing drug and statins impact part of the process, an experimental drug being studied in UCLA research labs appears to specifically target the newfound pathway, possibly adding a new approach to the cholesterol management toolbox.

“Our results show that certain proteins in the Aster family play a critical role in moving cholesterol through the absorption and uptake process,” said Dr. Peter Tontonoz, a UCLA professor and researcher in Pathology and Laboratory Medicine and Biological Chemistry, senior author of an article in Science. “The Aster pathway appears to be a potentially attractive target for limiting intestinal cholesterol absorption and reducing levels of plasma cholesterol.”

Cholesterol from food is absorbed by cells that line the inner surface of the intestines – enterocytes – where it is processed into droplets that eventually reach the bloodstream. But this journey involves a multistep process.

Wednesday, November 8, 2023

New antifungal molecule kills fungi without toxicity in human cells, mice

The mechanism for a critical but highly toxic antifungal is revealed in high resolution. Self-assembled Amphotericin B sponges (depicted in light blue) rapidly extract sterols (depicted in orange and white) from cells. This atomic level understanding yielded a novel kidney-sparing antifungal agent. 
Illustration Credit: Jose Vazquez

A new antifungal molecule, devised by tweaking the structure of prominent antifungal drug Amphotericin B, has the potential to harness the drug’s power against fungal infections while doing away with its toxicity, researchers at the University of Illinois Urbana-Champaign and collaborators at the University of Wisconsin-Madison report in the journal Nature.

Amphotericin B, a naturally occurring small molecule produced by bacteria, is a drug used as a last resort to treat fungal infections. While AmB excels at killing fungi, it is reserved as a last line of defense because it also is toxic to the human patient – particularly the kidneys. 

Ural Scientists Have Synthesized a New Substance for the Treatment of Alzheimer’s Disease


Scientists from the Ural Federal University, the Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences, together with colleagues from India have developed a method for creating safe and non-toxic substances that could become the basis for drugs for Alzheimer's disease. Using the new technology, they synthesized and tested several compounds of tacrine analogues, which toxicity is estimated to be from two to five times lower than that of the known drug. The description of the new method and the compounds obtained was published in the Journal of Heterocyclic Chemistry

"We believe that our technology will help to create safe substances that will become the basis for future drugs for Alzheimer's disease. Our studies have shown that the toxicity of the resulting substances is two to five times lower than that of tacrine. At the same time, they are effective as they help to increase the level of acetylcholine in the cerebral cortex, which slows down the destruction of neuronal connections. This allows patients to maintain their cognitive functions and lead an active and fulfilling life for as long as possible," explains Nibin Joy Muthipeedika, Senior Researcher at the UrFU Organic Synthesis Laboratory.

Monday, October 30, 2023

Bowel cancer: aspirin activates protective genes

Photo Credit: günter

Colorectal cancer (bowel cancer) is the third most common form of cancer worldwide, with around 1.9 million newly diagnosed cases and 900,000 deaths every year. Therefore, preventive substances represent an urgent clinical need. Aspirin/acetylsalicylic acid has proven to be one of the most promising candidates for the prevention of colorectal cancer. Among other findings, studies have shown that when patients with cardiovascular diseases took low doses of aspirin over several years, it reduced their risk of colorectal cancer. Furthermore, aspirin can inhibit the progression of colorectal cancer. Now a team led by Heiko Hermeking, Professor of Experimental and Molecular Pathology at LMU, has investigated which molecular mechanisms mediate these effects.

As the researchers report in the journal Cell Death and Disease, aspirin induces the production of two tumor-suppressive microRNA molecules (miRNAs) called miR-34a and miR-34b/c. To do this, aspirin binds to and activates the enzyme AMPK, which in turn alters the transcription factor NRF2 such that it migrates into the cell nucleus and activates the expression of the miR-34 genes. For this activation to succeed, aspirin additionally suppresses the oncogene product c-MYC, which otherwise inhibits NRF2.

Featured Article

Two artificial intelligences talk to each other

A UNIGE team has developed an AI capable of learning a task solely on the basis of verbal instructions. And to do the same with a «sister» A...

Top Viewed Articles