Antibody possible treatment for severe fatty liver disease

Micrograph of non-alcoholic fatty liver disease (NAFLD). Masson's trichrome & Verhoeff stain. The liver has a prominent (centrilobular) macrovesicular steatosis (white/clear round/oval spaces) and mild fibrosis (green). The hepatocytes stain red.  Macrovesicular steatosis is lipid accumulation that is so large it distorts the cell's nucleus.
Image Credit: Nephron CC BY-SA 3.0

There is currently no drug for treating non-alcoholic fatty liver disease, which affects many people with type 2 diabetes and which can result in other serious liver diseases. A study led by researchers from Karolinska Institutet has now identified a drug candidate for the treatment of fatty liver. The preclinical study, published in the Journal of Hepatology, indicates that an antibody that blocks the protein VEGF-B presents a possible therapeutic option for fatty liver disease.

“Fatty liver is associated with several serious and sometimes fatal diseases,” says the study’s first author Annelie Falkevall, researcher at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden. “With the therapeutic principle that we’ve developed, it might be possible to prevent fatty liver and hopefully lower the risk of liver failure and terminal liver cancer.”

For decades, obesity and overweight have been a common global disease that, amongst other problems, has caused a sharp rise in the incidence of type 2 diabetes. According to the Swedish Diabetes Association, there are 500,000 cases of diabetes in Sweden alone, of which 85 to 90 percent are type 2.

Researchers Develop New Method to Improve Burn Assessment

The handheld THz Scanner is shown in operation.
Photo Credit: Terahertz Biophotonics Laboratory, Stony Brook University

Stony Brook Engineers Employ New Device and Neural Networks with Terahertz Spectroscopy

An important component to a more successful treatment course for burns is correctly assessing them, and current methods are not accurate enough. A team of Stony Brook University researchers believe they created a new method to significantly improve burn assessment. They are employing a physics-based neural network model that uses terahertz time-domain spectroscopy (THz-TDS) data for non-invasive burn assessment. The team combines the approach with a handheld imaging device that they developed specifically for fast THz-TDS imaging of burn injuries. Details of their method are published in a paper in Biomedical Optics Express.

Studies have shown that the accuracy of burn diagnosis is only about 60 to 75 percent when trying to decide which one of the burns needs surgical intervention (skin grafting) or which burns can heal spontaneously. The Stony Brook team has found with their method using THz-TDS — broadly defined as detecting and measuring properties of matter with picosecond short pulses of electromagnetic fields — that THz spectroscopic imaging can increase the accuracy rate of burn diagnosis and classification to approximately 93 percent.

Reading out RNA structures in real time

The fluorescent blinking of cyanine dye (Alexa Fluor 647, pink star) bound to RNA changes depending on the structure of the RNA. When the RNA is folded like a hairpin, the fluorescent blinking is fast, and when the RNA switches to a G-quadruplex, the blinking is slow
Illustration Credit: Akira Kitamura

A new microscopic technique allows for the real-time study of RNA G-quadruplexes in living cells, with implications for the fight against amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease and Stephen Hawking’s disease, is a neurodegenerative disease that results in the gradual loss of control over the muscles in the body. It is currently incurable and the cause of the disease is unknown in over 90% of all cases — although both genetic and environmental factors are believed to be involved.

The research groups of Dr. Akira Kitamura at the Faculty of Advanced Life Science, Hokkaido University, and Prof. Jerker Widengren at the KTH Royal Institute of Technology, Sweden, have developed a novel technique that is able to detect a characteristic structure of RNA in real time in live cells. The technique, which is based on fluorescence-microscopic spectroscopy, was published in the journal Nucleic Acids Research.

Combined steroid and statin treatment could reduce ‘accelerated ageing’ in preterm babies, study in rats suggests

Potentially life-saving steroids commonly given to preterm babies also increase the risk of long-term cardiovascular problems, but a new study in rats has found that if given in conjunction with statins, their positive effects remain while the potential negative side-effects are ‘weeded out’.
Photo Credit: Hush Naidoo Jade Photography

Cambridge scientists gave new-born rats, which are naturally born prematurely, combined glucocorticoid steroids and statin therapy. The results, published today in Hypertension, show that the combined treatment led to the elimination of negative effects of steroids on the cardiovascular system while retaining their positive effects on the developing respiratory system.

Preterm birth (before 37 weeks) is one of the greatest killers in perinatal medicine today. One in ten babies are born preterm in high-income countries; this can increase to almost 40% in low- and middle-income countries.

Preterm babies are extremely vulnerable because they miss out on a crucial final developmental stage in which the hormone cortisol is produced and released exponentially into the unborn baby’s blood. Cortisol is vital to the maturation of organs and systems that are needed to keep the baby alive once born.

For example, in the lungs, cortisol ensures that they become more elastic. This allows the lungs to expand so the baby can take its first breath. Without cortisol the new-born lungs would be too stiff, which leads to respiratory distress syndrome (RDS) and could be fatal.

More multi-resistant germs since the beginning of the Ukraine war

Martina Cremadus, Hans-Jörg Berthold and Niels Pfennigwerth (from left) monitor the occurrence of multi-resistant bacteria in the National Reference Center for Gram-negative Hospital Pathogens.
Photo Credit: RUB, Marquard

The pathogens reach German hospitals with refugees and war injuries. Researchers recommend clinics to screen as a precaution.

Since the outbreak of the war in Ukraine, certain hospital pathogens that are resistant to many antibiotics have been detected much more frequently in German hospitals. The pathogen Klebsiella pneumoniae is also resistant to the reserve antibiotics of carbapenems due to a combination of two enzymes. Together with the Robert Koch Institute (RKI), the National Reference Center (NRZ) for gram-negative hospital pathogens located at the Ruhr University Bochum has been able to demonstrate that many of the reported cases are related to patients from Ukraine. The researchers therefore recommend that this group be examined for the germ before being admitted to the hospital. They report in the journal Eurosurveillance.

Avoiding burnout of white blood cells

The immune system (T cell) attacks a human tumor cell.
Image Credit: M. Oeggerli (Micronaut 2019), Marcel Philipp Trefny, and Prof. Alfred Zippelius, Translational Oncology, University Hospital Basel, supported by Pathology University Hospital Basel, and C-CINA, Biozentrum, University of Basel

A research group at the University of Basel has identified a gene that drives T lymphocytes to exhaustion. This finding opens up new approaches for more effective immunotherapies.

A tough battle requires endurance. This is also true for white blood cells as they tackle cancer – or more specifically for T lymphocytes or T cells, a group of white blood cells involved in the immune system’s fight against cancer cells. However, T cells can become exhausted during this fight.

Researchers from the Department of Biomedicine at the University of Basel and University Hospital Basel recently identified a gene that seems to contribute to this exhaustion. The findings of their research project, which was funded by the Swiss National Science Foundation, were published in the journal Nature Communications.

Smart Contact Lens that Diagnoses and Treats Glaucoma

Schematic illustration of a theranostic smart contact lens for glaucoma treatment.
Illustration Credit: Pohang University of Science and Technology

POSTECH research team led by Professor Sei Kwang Hahn proposes a new paradigm for monitoring and control of intraocular pressure in glaucoma patients.

Glaucoma is a common ocular disease in which the optic nerve malfunctions due to the increased intraocular pressure (IOP) caused by drainage canal blocking in the eye. This condition narrows the peripheral vision and can lead to vision loss in severe cases. Glaucoma patients have to manage IOP levels for their lifetime. Automatic monitoring and control of the IOP in these patients would significantly improve their quality of life.

Recently, a research team at POSTECH has developed a smart contact lens by combining an IOP sensor and a flexible drug delivery system to manage IOP measurement and medication administration.

A new tool for examining processes in the cerebellum

The Bochum research team: Bianca Preissing, Lennard Rohr, Ida Siveke and Tatjana Surdin (from left)
Photo Credit: © RUB, Marquard

Light can start a signal cascade in the cerebellum. This also illuminates processes that play an important role in cerebellar diseases.

Processes in the cerebellum are involved in various diseases that affect motor learning. A new tool developed by a Bochum working group helps to investigate this better: a light-activated protein that is coupled with part of an exciting receptor. Thanks to this optogenetic tool, light can activate a signaling pathway in the nerve cells of the cerebellum and observe its effects. So, the group around Dr. Ida Siveke from the working group of Prof. Dr. Stefan Herlitze at the Ruhr University Bochum show that the signal path is involved in cerebellar-controlled motor learning. The researchers report in the iSience journal.

FAT4 Gene Mutations Cause Many Abnormalities in the Lymphatic System

A mutation in a gene can disrupt the lymphatic system
Photo Credit: Sangharsh Lohakare

Defects in this gene cause everything in the body to swell - even the brain

Mutations in the FAT4 gene can cause Hennekam syndrome, which is characterized by various abnormalities of the lymphatic system. An international team of scientists from Russia (Ural Federal University), Afghanistan, Pakistan and China used molecular dynamic modeling to demonstrate the pathogenicity of the identified mutations. The data obtained will help to determine the predisposition to diseases associated with FAT4 gene activation. The study was supported by the Ministry of Science and Higher Education of the Russian Federation in the framework of the Priority 2030 program and published in the journal Informatics in Medicine Unlocked.

"Hennekam syndrome is a relatively rare (less than 1,000 cases have been reported worldwide) inherited disorder caused by mutations in three different genes - FAT4, ADAMTS3, CCBE1. Abnormalities in the lymphatic system cause everything in the body - including the brain - to swell. This is due to impaired lymphatic transport and, as a result, a large accumulation of protein-rich fluid in the intercellular space. As a result, any affected organ can increase in volume. Signs of this syndrome can also be developmental disorders, strange body deformities, a flat face with swollen eyelids," says Mikhail Bolkov, Senior Researcher at the Department of Immunochemistry at the Ural Federal University and the Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences.

How sound waves trigger immune responses to cancer in mice

The 700kHz, 260-element histotripsy ultrasound array transducer used in Prof. Xu’s lab.
Photo Credit: Marcin Szczepanski/Lead Multimedia Storyteller, Michigan Engineering

Technique pioneered at the University of Michigan could improve outcomes for cancer and neurological conditions

When noninvasive sound waves break apart tumors, they trigger an immune response in mice. By breaking down the cell wall “cloak,” the treatment exposes cancer cell markers that had previously been hidden from the body’s defenses, researchers at the University of Michigan have shown.

The technique developed at Michigan, known as histotripsy, offers a two-prong approach to attacking cancers: the physical destruction of tumors via sound waves and the kickstarting of the body’s immune response. It could potentially offer medical professionals a treatment option for patients without the harmful side effects of radiation and chemotherapy.

Until now, researchers didn’t understand how histotripsy was activating the immune system. A study from last spring showed that histotripsy breaks down liver tumors in rats, leading to the complete disappearance of the tumor even when sound waves are applied to only 50% to 75% of the mass. The immune response also prevented further spread, with no evidence of recurrence or metastases in more than 80% of the animals.

How to make hydrogels more injectable

MIT and Harvard researchers have developed computational models that can predict the properties of materials made from squishy hydrogel blocks.
Image Credit: Courtesy of the researchers

Gel-like materials that can be injected into the body hold great potential to heal injured tissues or manufacture entirely new tissues. Many researchers are working to develop these hydrogels for biomedical uses, but so far very few have made it into the clinic.

To help guide in the development of such materials, which are made from microscale building blocks akin to squishy LEGOs, MIT and Harvard University researchers have created a set of computational models to predict the material’s structure, mechanical properties, and functional performance outcomes. The researchers hope that their new framework could make it easier to design materials that can be injected for different types of applications, which until now has been mainly a trial-and-error process.

“It’s really exciting from a material standpoint and from a clinical application standpoint,” says Ellen Roche, an associate professor of mechanical engineering and a member of the Institute for Medical Engineering and Science at MIT. “More broadly, it’s a nice example of taking lab-based data and synthesizing it into something usable that can give you predictive guidelines that could be applied to things beyond these hydrogels.”

Groundbreaking Biomaterial Heals Tissues From the Inside Out

The biomaterial is based on a hydrogel that Christman's lab developed.
Photo Credit: University of California, San Diego

A new biomaterial that can be injected intravenously, reduces inflammation in tissue and promotes cell and tissue repair. The biomaterial was tested and proven effective in treating tissue damage caused by heart attacks in both rodent and large animal models. Researchers also provided proof of concept in a rodent model that the biomaterial could be beneficial to patients with traumatic brain injury and pulmonary arterial hypertension.

“This biomaterial allows for treating damaged tissue from the inside out,” said Karen Christman, a professor of bioengineering at the University of California San Diego, and the lead researcher on the team that developed the material. “It’s a new approach to regenerative engineering.”

A study on the safety and efficacy of the biomaterial in human subjects could start within one to two years, Christman added. The team, which brings together bioengineers and physicians, presented their findings in Nature Biomedical Engineering.

Focused ultrasound mediated liquid biopsy in a tauopathy mouse model

Hong Chen and her collaborators found that using focused-ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker for neurodegenerative disorders into the blood than without the intervention. This noninvasive method could facilitate diagnosis of neurodegenerative disorders.
Illustration Credit: Chen lab

Several progressive neurodegenerative disorders, including Alzheimer’s disease, are defined by having tau proteins in the brain. Researchers are seeking to identify the mechanisms behind these tau proteins to develop treatments, however, their efforts to detect biomarkers in blood has been hampered by the protective blood-brain barrier.

At Washington University in St. Louis, new research from the lab of Hong Chen, associate professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology in the School of Medicine, and collaborators found that using focused-ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker into the blood than without the intervention. This noninvasive method could facilitate diagnosis of neurodegenerative disorders, the researchers said.

The method, known as sonobiopsy, uses focused ultrasound to target a precise location in the brain. Once located, the researchers inject microbubbles into the blood that travel to the ultrasound-targeted tissue and pulsate, which safely opens the blood-brain barrier. The temporary openings allow biomarkers, such as tau proteins and neurofilament light chain protein (NfL), both indicative of neurodegenerative disorders, to pass through the blood-brain barrier and release into the blood.

New blood test could save lives of heart attack victims

NPY receptors (in green) on human iPS cardiomycytes
Image Credit: Ms Carla Handford, Dr Kun Liu, Dr Dan Li | Herring Group

Researchers from the Herring group in Oxford's Department of Physiology, Anatomy and Genetics have developed a blood test that measures stress hormone levels after heart attacks. The test – costing just £10 – could ensure patients receive timely life-saving treatment.

Cardiovascular disease is the main cause of death in the UK. One of the most common ways in which that manifests is through heart attacks. Clinicians treat around 100,000 patients with very large heart attacks using an emergency procedure called primary percutaneous coronary intervention (PCI). While some of these patients do very well, around a third do not, and some 25,000 people die from heart attacks each year.

New research from Herring lab researchers shows that routine testing for the stress hormone Neuropeptide Y (NPY) in the hours after a heart attack has the potential to save thousands of lives.

Researchers revisit potent drug as promising treatment for acute leukemia

Photo Credit: Louis Reed

The two-pronged attack of a “forgotten drug” simultaneously targets two cancer-causing pathways of leukemia to stop the disease in its tracks

A team of researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore, led by Associate Professor Takaomi Sanda and Dr Lim Fang Qi, has breathed new life into an existing drug — combatting a type of blood cancer called T-cell acute lymphoblastic leukemia, or T-ALL.

The drug, called PIK-75, was initially discovered over a decade ago but was dismissed in favor of newer ones. Now, it has made a comeback that deems it unmissable — the researchers established that the drug could block not just one but two crucial cancer-causing pathways of T-ALL, enabling them to develop new treatments that could effectively stem the disease.

Patients with brain cancer may benefit from treatment to boost white blood cells

A new study led by Washington University School of Medicine reveals at least one cause of low white blood cell counts in patients treated for glioblastoma and demonstrates a potential treatment strategy that improves survival in mice.
Photo Credit: Tima Miroshnichenko

Patients with glioblastoma, a devastating brain cancer, receive treatment that frequently leads to the unfortunate side effect of low white blood cell counts that lasts six months to a year. The low numbers of white blood cells are associated with shorter survival — but the specific reason for the prolonged drop in white blood cells and the link with shorter survival has vexed scientists.

A new study led by Washington University School of Medicine in St. Louis reveals at least one cause of low white blood cell counts in patients treated for glioblastoma and demonstrates a potential treatment strategy that improves survival in mice.

The study is published in the journal Science Translational Medicine.

Patients with this cancer typically do not survive longer than 18 months. The standard treatment is radiation and chemotherapy, after which many patients develop severely low numbers of lymphocytes — a type of white blood cell — in the bloodstream. The cause of these low lymphocyte counts has been something of a mystery because the therapy does not target the bone marrow, where these cells originate, and not all patients experience the problem.

Machine learning identifies drugs that could potentially help smokers quit

Penn State College of Medicine researchers helped identify eight medications that may be repurposed to help people quit smoking. A team of more than 70 researchers contributed to the analysis of genetic and smoking behavior data from more than 1.3 million people.
Image Credit: Scientific Frontline

Medications like dextromethorphan, used to treat coughs caused by cold and flu, could potentially be repurposed to help people quit smoking cigarettes, according to a study by Penn State College of Medicine and University of Minnesota researchers. They developed a novel machine learning method, where computer programs analyze data sets for patterns and trends, to identify the drugs and said that some of them are already being tested in clinical trials.

Cigarette smoking is risk factor for cardiovascular disease, cancer and respiratory diseases and accounts for nearly half a million deaths in the United States each year. While smoking behaviors can be learned and unlearned, genetics also plays a role in a person’s risk for engaging in those behaviors. The researchers found in a prior study that people with certain genes are more likely to become addicted to tobacco.

Using genetic data from more than 1.3 million people, Dajiang Liu, Ph.D., professor of public health sciences, and of biochemistry and molecular biology and Bibo Jiang, Ph.D., assistant professor of public health sciences, co-led a large multi-institution study that used machine learning to study these large data sets — which include specific data about a person’s genetics and their self-reported smoking behaviors.

Targeting cancer with a multidrug nanoparticle

MIT chemists designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled.
Illustration Credit: Courtesy of the researchers. Edited by MIT News.

Treating cancer with combinations of drugs can be more effective than using a single drug. However, figuring out the optimal combination of drugs, and making sure that all of the drugs reach the right place, can be challenging.

To help address those challenges, MIT chemists have designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled. Using these particles, the researchers were able to calculate and then deliver the optimal ratio of three cancer drugs used to treat multiple myeloma.

“There’s a lot of interest in finding synergistic combination therapies for cancer, meaning that they leverage some underlying mechanism of the cancer cell that allows them to kill more effectively, but oftentimes we don’t know what that right ratio will be,” says Jeremiah Johnson, an MIT professor of chemistry and one of the senior authors of the study.

Health impact of chemicals in plastics is handed down two generations

UC Riverside mouse study finds paternal exposure to phthalates increases risk of metabolic diseases in progeny
Photo Credit: Meruyert Gonullu

Fathers exposed to chemicals in plastics can affect the metabolic health of their offspring for two generations, a University of California, Riverside, mouse study reports.

Plastics, which are now ubiquitous, contain endocrine disrupting chemicals, or EDCs, that have been linked to increased risk of many chronic diseases; parental exposure to EDCs, for example, has been shown to cause metabolic disorders, including obesity and diabetes, in the offspring.

Most studies have focused on the impact of maternal EDC exposure on the offspring’s health. The current study, published in the journal Environmental International, focused on the effects of paternal EDC exposure.

Led by Changcheng Zhou, a professor of biomedical sciences in the School of Medicine, the researchers investigated the impact of paternal exposure to a phthalate called dicyclohexyl phthalate, or DCHP, on the metabolic health of first generation (F1) and second generation (F2) offspring in mice. Phthalates are chemicals used to make plastics more durable.

Supplementation with amino acid serine eases neuropathy in diabetic mice

From left: Michal Handzlik and Christian Metallo
Photo Credit: Salk Institute

Approximately half of people with type 1 or type 2 diabetes experience peripheral neuropathy—weakness, numbness, and pain, primarily in the hands and feet. The condition occurs when high levels of sugar circulating in the blood damage peripheral nerves. Now, working with mice, Salk Institute researchers, in collaboration with the University of California San Diego, have identified another factor contributing to diabetes-associated peripheral neuropathy: altered amino acid metabolism.

The study, published in Nature, adds to growing evidence that some often-underappreciated, “non-essential” amino acids play important roles in the nervous system. The findings may provide a new way to identify people at high risk for peripheral neuropathy, as well as a potential treatment option. The team included UC San Diego bioengineering professor Prashant Mali, microbiome expert professor Rob Knight and pathologist Nigel A. Calcutt.

“We were surprised that dialing up and down a non-essential amino acid had such a profound effect on metabolism and diabetic complications,” says senior author Christian Metallo, a professor in Salk’s Molecular and Cell Biology Laboratory. “It just goes to show that what we think of as dogma can change under different circumstances, such as in disease conditions.”