Treating fibrosis with a chemical derived from Lawsonia inermis

Treatment with Lawsone converts a liver with fibrosis into a healthy liver.
Image Credit: Osaka Metropolitan University

Lawsonia inermis is best known for making henna, a versatile dye that is used to change the color of skin and clothes. Now, researchers from Osaka Metropolitan University have found another use for the pigments extracted from the dye: treating liver disease.

Specifically, they could treat liver fibrosis, a disease that causes excess fibrous scar tissue to build up in the liver as a result of chronic liver injury caused by lifestyle choices such as excessive drinking. Patients with liver fibrosis have increased risks of cirrhosis, liver failure, and cancer. Despite 3–4% of the population having the advanced form of the disease, treatment options remain limited.

New AI Model for Drug Design Brings More Physics to Bear in Predictions

This illustration shows the mesh of anchoring points the team obtained by discretizing the manifold, an estimation of the distribution of atoms and the probable locations of electrons in the molecule. This is important because, as the authors note in the new paper, treating atoms as solid points "does not fully reflect the spatial extent that real atoms occupy in three-dimensional space."
Image Credit: Liu et al./PNAS

When machine learning is used to suggest new potential scientific insights or directions, algorithms sometimes offer solutions that are not physically sound. Take for example AlphaFold, the AI system that predicts the complex ways in which amino acid chains will fold into 3D protein structures. The system sometimes suggests "unphysical" folds—configurations that are implausible based on the laws of physics—especially when asked to predict the folds for chains that are significantly different from its training data. To limit this type of unphysical result in the realm of drug design, Anima Anandkumar, Bren Professor of Computing and Mathematical Sciences at Caltech, and her colleagues have introduced a new machine learning model called NucleusDiff, which incorporates a simple physical idea into its training, greatly improving the algorithm's performance.

Broad-Bayer collaboration leads to drug candidate for a hard-to-treat type of lung cancer

Broad Communications Scientists in the Broad-Bayer oncology alliance have developed a drug candidate, sevabertinib, that could be a new lung cancer treatment.
Illustration Credit: Agnieszka Grosso

An alliance of scientists at the Broad Institute and Bayer Pharmaceuticals have developed a drug candidate, sevabertinib, that could be a new treatment for a group of lung cancer patients who have few options today.

In a new study published in Cancer Discovery, the team described their efforts to develop sevabertinib. They tested the compound in various lung cancer models and showed its potential to treat non-small cell lung cancers that harbor certain mutations in the ERBB2 gene, which encodes the HER2 protein. These mutations occur in 2 to 4 percent of patients with non-small cell lung cancer, or roughly 40,000 to 50,000 people diagnosed globally each year. These patients tend to be women, including those who are younger, have never smoked, and have a poor prognosis. 

The study also reported data from two participants in Bayer’s phase 1/2 clinical trial of the compound. Based on these findings and other data from this ongoing clinical trial, the drug candidate is currently under Priority Review at the FDA, an expedited review of therapies that treat serious conditions. If approved, it would be the first FDA-approved cancer drug based on Broad discoveries, and the first new medicine from the Broad-Bayer oncology research alliance. 

Muscle wasting reversed in patients with rheumatoid arthritis

Photo Credit: Roger Vaughan

Patients with rheumatoid arthritis increased their leg muscle volume when treated with an anti-rheumatic drug, offering new hope for improved muscle health.

Publishing in the prestigious journal, The Lancet Rheumatology, the team from Newcastle University and The Newcastle upon Tyne Hospitals NHS Foundation Trust describe how 15 patients were given Tofacitinib, a Janus kinase (JAK) inhibitor used to treat RA, as part of an experimental medicine study. After 6 months their leg muscles increased in size, particularly in the thigh.  

Sarcopenia is a progressive, age-related musculoskeletal disease characterized by the loss of muscle mass, strength, and physical performance, increasing the risk of falls, fractures, physical disability, and mortality. Currently there are no medicines approved to reverse this muscle-wasting disease. It is commonly seen in patients with rheumatoid arthritis where chronic inflammation contributes to the loss of muscle mass and strength.

Clinical trial marks key milestone in fight against antibiotic resistance

Infections with antibiotic-resistant bacteria cause a significant burden of disease worldwide.
Photo Credit: Scientific Frontline / AI Generated

An international clinical trial, led by The University of Queensland, has been hailed as a significant step forward in the global challenge of antibiotic resistance.

UQ researchers have led the first randomized trial across 6 countries to examine a new antibiotic, cefiderocol, in the treatment of life-threatening, drug-resistant infections.

Associate Professor Patrick Harris, of UQ’s Centre for Clinical Research, said the drug was found to be effective and safe in treating bloodstream infections.

"The study is the first randomized controlled trial to specifically examine the use of cefiderocol in bloodstream infections and sepsis," he said.

“With increasing global antimicrobial resistance, there is a need for the development of new antibiotics.’’

Antibody discovered that blocks almost all known HIV variants in neutralization assays

Image Credit; Scientific Frontline / AI Generated

 A Cologne-led research team has discovered the antibody 04_A06, which neutralizes the human immunodeficiency virus (HIV) in almost all tested variants in vitro and even overcomes typical resistance mechanisms. The discovery potentially opens up new perspectives for the prevention and treatment of HIV infections.

An international research team led by the University of Cologne has discovered an antibody that could advance the fight against HIV. The newly identified antibody 04_A06 proved to be particularly effective in laboratory tests. It was able to neutralize 98.5 percent of more than 300 different HIV strains, making it one of the broadest antibodies against HIV identified. In experiments with humanized mice – animals whose immune system has been modified to resemble that of humans – 04_A06 permanently reduced the HIV viral load to undetectable levels. Most other HIV antibodies, in contrast, only achieve short-term effects in this animal model, as resistance develops quickly. The study ‘Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bNAb for HIV-1 prevention and therapy’ was published in Nature Immunology.

New mechanism revealed: How leukemia cells trick the immune system

Thoas Fioretos, Niklas Landberg, and Carl Sandén are the research team behind the study now being published in Nature Cancer.
Photo Credit: Tove Smeds

A research team at Lund University in Sweden has discovered a mechanism that helps acute myeloid leukemia cells to evade the body’s immune system. By developing an antibody that blocks the mechanism, the researchers could restore the immune system’s ability to kill the cancer cells in laboratory trials and in mice. The discovery is published in Nature Cancer.

Immunotherapy has improved the treatment for many cancers, but progress has been limited in leukemia. Acute myeloid leukemia (AML) is particularly intractable, with a five-year survival rate of just over 30 per cent. The existing treatments are often aggressive and may include both strong chemotherapy and stem cell transplantations.

“We wanted to see if we could find surface proteins unique to leukemia stem cells, and which would therefore act as interesting targets for a targeted treatment. If such proteins were not present on healthy blood stem cells it might be possible to attack the tumor – without harming the healthy blood system,” says Thoas Fioretos, research group leader and professor of clinical genetics at Lund University, and senior consultant at Skåne University Hospital.

Scientists Have Created New Lanthanum Complex Promising for Anti-cancer Therapy

Lanthanum complexes demonstrate antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia.
Photo Credit: Louis Reed

As a result of the joint work of an international group of scientists from Russia (Ural Federal University), Bulgaria (Medical University, Sofia), and Spain (Complutense University of Madrid, Rey Juan Carlos University), a new lanthanum (III) complex with a luminescent triazole ligand has been obtained that is able to selectively regulate the level of reactive oxygen species (ROS) in cells. The result opens up prospects for the development of new anti-cancer and anti-infective drugs. The interim results of the study were published in the journal Molecules.

“New lanthanum complexes demonstrate a wide range of biological effects such as antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia. In a study that we conducted together with biologists from the Medical University of Sofia, we found out that both lanthanum complexes of La(III) and free organic ligands can affect the level of reactive oxygen species. At the same time, we found that they have a dual effect: in some tests, they act as antioxidants, protecting healthy cells, in others, as pro-oxidants, contributing to the death of tumor cells. This specific focus of action makes them promising candidates for the development of new drugs for cancer,” said Natalia Belskaya, Professor at UrFU Department of Technology pf Organic Synthesis.

Potential new therapeutic target for asthma discovered

Photo Credit: Cnordic Nordic

A new way to treat asthma symptoms and even repair previously irreversible lung damage could be on the horizon following the discovery of a potential new therapeutic target by scientists at the Universities of Aberdeen and Manchester.

Current treatments for asthma largely involve controlling the inflammation of lung tissue using steroid inhalers. However, 4 people die every day in the UK from asthma related complications. With funding from the Medical Research Foundation and Asthma UK, a team of researchers from the University of Aberdeen and the University of Manchester have investigated the scarring that occurs in lung tissue as a result of asthma and have been able to reverse these changes in animal models.

Although still in the early stages of development, this discovery paves the way for a new way to treat not only asthma, but many different diseases in which similar structural changes in tissues occur. Such diseases include conditions like chronic obstructive pulmonary disease (COPD), chronic heart disease and cirrhosis of the liver and account for approximately 40% of deaths worldwide.

Asthma affects more than 7 million people in the UK and severe asthma can have a hugely detrimental impact on an individual’s quality of life. Even when treated, asthma can be fatal and the most recent data shows it contributed to 1,465 deaths in the UK in 20221 – this is despite the availability of new treatments which aim to dampen down inflammation in the lungs.

Opening for a new type of drug for Alzheimer’s Disease

Kaj Blennow and Tohidul Islam.
Photo Credit: Johan Wingborg

A complementary drug to combat Alzheimer’s disease could target a specific part of the nerve cell protein tau. This is the finding of research from the University of Gothenburg, which also offers a better way to measure the effect of treatment among patients.

Researchers from the University of Gothenburg, together with colleagues from the University of Pittsburgh in the US, published their findings in the journal Nature Medicine.

The study provides insights into what happens during the earliest phase when the protein tau is transformed into thread-like strands (fibrils) in the nerve cells. This is one of the processes in Alzheimer’s disease and occurs alongside the formation of amyloid plaques. In healthy individuals, the protein tau stabilizes the tubular building blocks (microtubules) that make up the long projections of the nerve cells.

During the development of Alzheimer’s disease, tau undergoes pathological changes. First, tau forms small, soluble aggregates that are secreted from the nerve cells and are thought to be able to spread these changes to other nerve cells. The protein is then converted into larger, harmful, thread-like strands in the nerve cells.

Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
Image Credit: Scientific Frontline stock image

Throughout history, women have made groundbreaking contributions to science, despite facing significant societal barriers and a lack of recognition. Their relentless pursuit of knowledge and innovation has shaped our understanding of the world and paved the way for future generations of scientists. This article celebrates the achievements of some of these remarkable women, highlighting their struggles and the impact of their work.

The women featured in this article, along with countless others throughout history, have made invaluable contributions to the advancement of science. Their achievements, often accomplished in the face of adversity and societal barriers, have shaped our understanding of the world and paved the way for future generations of scientists. These women demonstrate the power of perseverance, the importance of challenging established norms, and the profound impact that individual dedication can have on scientific progress. By recognizing and celebrating their legacies, we not only honor their contributions but also inspire future generations to pursue their passions and break down barriers in the pursuit of knowledge.

WSU researcher pioneers new study model with clues to anti-aging

Jiyue Zhu and a student work in the laboratory.
Photo Credit: Courtesy of Washington State University

Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.

Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.

But research studying these telomeres at the cellular level has been challenging in humans.

Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using genetically engineered mice.

Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.

Powerful anticancer compound might also be the key to eradicating HIV

Study co-authors Jennifer Hamad and Owen McAteer prepare for a cellular assay, a lab technique used to study living cells. The assay will yield information about the location of EBC-46 compounds that have been introduced into cells in the lab.
Photo Credit: Paul Wender

A compound with the unpresuming designation of EBC-46 has made a splash in recent years for its cancer-fighting prowess. Now a new study led by Stanford researchers has revealed that EBC-46 also shows immense potential for eradicating human immunodeficiency virus (HIV) infections. 

Compared to similar-acting agents, EBC-46 excels at activating dormant cells where HIV is hiding, the study found. These “kicked” cells can then be targeted (“killed”) by immunotherapies to fully clear the insidious virus from the body. By pursuing this “kick and kill” strategy with EBC-46, researchers think achieving permanent elimination of HIV in patients—in other words, a cure—is possible.

"We’re pleased to report that EBC-46 performed extremely well in preclinical experiments as part of a ‘kick and kill’ therapeutic," said study senior author Paul Wender, the Bergstrom Professor of Chemistry at Stanford’s School of Humanities and Sciences. "While we still have a lot of work to do before treatments based on EBC-46 might reach the clinic, this study marks unprecedented progress toward the as-yet-unrealized goal of eradicating HIV.” 

Study explains why some osteoporosis drugs may protect against Covid-19

Drugs already in-use for other conditions could help in the fight against Covid-19 and its variants
Photo Credit: Courtesy of University of York

Researchers have provided the molecular explanation for why some osteoporosis drugs offer protection against Covid-19.

Drugs already in-use for other conditions could help in the fight against Covid-19 and its variants

The study, by researchers at the University of York, builds on work conducted by Harvard Medical School that compared more than 450,000 users of a class of drugs, called bisphosphonates, with non-users during the months leading up to the pandemic in 2020. 

The Harvard study showed that those who used drugs, such as alendronate and zoledronate, had lower odds of testing for SARS-CoV-2 infection, Covid-19 diagnosis and Covid-19-related hospitalization, but the study didn’t explain why this was the case.

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.