Publisher Health

A finding by UC Riverside bioengineers could hasten development of lab-grown blood vessels and other tissues to replace and regenerate damaged tissues in human patients. The results are published in ACS Applied Materials and Interfaces.
Curcumin, a compound found in turmeric, has anti-inflammatory and antioxidant properties and is known to suppress angiogenesis in malignant tumors. Bioengineers at UC Riverside have now discovered that when delivered through magnetic hydrogels into stem cell cultures this versatile compound paradoxically also promotes the secretion of vascular endothelial growth factor, or VEGF, that helps vascular tissues grow.
Curcumin’s possible use for vascular regeneration has been suspected for some time but has not been well studied. Huinan Liu, a bioengineering professor in UCR’s Marlan and Rosemary Bourns College of Engineering, led a project to investigate curcumin’s regenerative properties by coating magnetic iron oxide nanoparticles with the compound and mixing them into a biocompatible hydrogel.
When cultured with stem cells derived from bone marrow, the magnetic hydrogel gradually released the curcumin without injuring the cells. Compared to hydrogels embedded with bare nanoparticles, the group of hydrogels loaded with curcumin-coated nanoparticles showed a higher amount of VEGF secretion.
“Our study shows that curcumin released from magnetic hydrogels promotes the cells to secrete VEGF, which is one of the most critical growth factors to enhance the formation of new blood vessels,” said co-author Changlu Xu, a doctoral candidate in Liu’s group who focused on hydrogel research.
The researchers also took advantage of the nanoparticles’ magnetism to see if they could direct the nanoparticles to desired locations in the body. They placed some of the curcumin-coated nanoparticles in a tube behind pieces of fresh pig tissue and used a magnet to successfully direct movement of the nanoparticles.
The achievement suggests the method could eventually be used to deliver curcumin to help heal or regenerate injured tissue.
Liu was joined in the research by her graduate students Radha Daya, Changlu Xu, and Nhu-Y. Thi Nguyen at UC Riverside. The paper, “Angiogenic hyaluronic acid hydrogels with curcumin-coated magnetic nanoparticles for tissue repair,” is available here.
Story Source:
Materials provided by University of California – Riverside. Original written by Holly Ober. Note: Content may be edited for style and length.

Premature births from cesarian (C-sections) and induced deliveries fell by 6.5% during the first month of the Covid-19 pandemic and remained consistently lower throughout — a likely result of fewer prenatal visits due to efforts to slow the spread of the virus, according to new research from Georgia Tech’s School of Economics.
Published April 6 in the journal Pediatrics, the study is the first to examine pandemic-era birth data at scale. The research raises questions about medical interventions in pregnancy and whether some decisions by doctors may result in unnecessary preterm deliveries, according to Assistant Professor Daniel Dench, the paper’s lead author.
“While much more research needs to be done, including understanding how these changes affected fetal deaths and how doctors triaged patient care by risk category during the pandemic, these are significant findings that should spark discussion in the medical community,” Dench said.
Notable Findings
In effect, the study begins to answer a question that never could have been resolved in a traditional experiment: What would happen to the rate of premature C-sections and induced deliveries if women didn’t see doctors as often, especially in person, during pregnancy?
Such an experiment would be unethical, of course. But stay-at-home orders had a side effect of reducing prenatal care visits by more than a third, according to one analysis. That gave Dench and his colleagues — Theodore Joyce at Baruch College and Dr. Howard Minkoff at Maimonides Medical Center — an opportunity to evaluate the impacts, after all.

Researchers at LSU Health New Orleans Neuroscience Center of Excellence and Karolinska Institutet have discovered a potential biomarker for Alzheimer’s disease diagnosis that may also serve as a therapeutic target. Examining cerebrospinal fluid samples from patients with cognitive impairment ranging from subjective impairment to a diagnosis of Alzheimer’s disease, they found a shift in the profile of specialized lipid mediators from pro-resolving to pro-inflammatory. The results of the exploratory study are published in the Springer journal, Cellular and Molecular Neurobiology.
Specialized lipid mediators are bioactive compounds composed of polyunsaturated fatty acids like DHA and EPA. They are signaling molecules that regulate a wide range of cellular responses including cell growth and death, as well as infection and inflammation. Specialized lipid mediators have unique properties and roles in inflammation. Pro-inflammatory lipid mediators promote inflammation, and pro-resolving lipid mediators resolve inflammation.
It takes several years or more for Alzheimer’s disease (AD) to develop into dementia, and neuroinflammation is a key early contributor. During that time, subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) can be used as intermediary diagnoses of increasing severity. The population of this study consisted of 136 participants — 53 with SCI, 43 with MCI and 40 with an Alzheimer’s disease diagnosis. The researchers assessed 22 lipids in samples of the participants’ cerebrospinal fluid (CSF), including pro-resolving lipid mediators, pro-inflammatory lipid mediators, prostaglandins, their fatty acid precursors and intermediate derivatives. Neuroprotection D1 (NPD1), discovered by the Bazan lab, is one the pro-resolving lipid mediators studied.
The research team found that levels of pro-resolving lipid mediators were correlated with severity of cognition impairment -the greater the severity, the lower the levels of the lipid mediators that resolve inflammation. They also found a relationship between cognition impairment severity and pro-inflammatory lipid mediators — the greater the degree of cognition impairment, the higher the levels of the lipid mediators that promote inflammation.
“Based on these findings, we are expanding our work to brain cell-specific targets, besides neurons, astrocytes and microglia, as well as additional novel protective signals, which would allow us to explore slowing down AD onset,” says Nicolas Bazan, MD, PhD, Boyd Professor and Director of LSU Health New Orleans Neuroscience Center of Excellence. “For this purpose, we have set up 10-x genomics to decipher not only the genes but also epigenomics engaged in early disease states. Since the CSF lipidome changes were closely correlated with detailed clinical and radiological AD patient status, we believe that the studied events are revealing novel essential mechanisms of brain health. A uniqueness of our approach is that we have discovered mechanisms and, more importantly, molecules that target those mechanisms and could became therapeutics.”
Other members of the LSU Health New Orleans research team include Drs. Khanh V. Do, Bokkyoo Jun, and Marie-Audrey I. Kautzmann. Ceren Emre, who recently completed her PhD at the Karolinska Institutet, worked at LSU Health New Orleans Neuroscience Center of Excellence for eight months before the pandemic. Other researchers from the Karolinska Institutet include Drs. Erik Hjorth, Ying Wang, Makiko Ohshima, Maria Eriksdotter, and Senior Professor Marianne Schultzberg, Bazan’s key collaborator.
Funding from the EENT Foundation of New Orleans, the Swedish Research Council, the Swedish Alzheimer’s Foundation, Stockholm County Council and the China Scholarship Council supported the research.

Mutation of a gene called ARID2 plays a role in increasing the chance that melanoma, a deadly skin cancer, will turn dangerously metastatic, Mount Sinai researchers report.
The findings suggest that patients whose melanoma tumors have an ARID2 mutation may have a more aggressive cancer and may need to be treated differently, according to a study published in Cell Reports in April.
“Our study is the first to characterize the tumor-suppressive functions of ARID2 in melanoma,” said the study’s lead author Emily Bernstein, PhD, Professor of Oncological Sciences at The Tisch Cancer Institute at Mount Sinai. “We modeled ARID2 mutations by removing the ARID2 protein completely from melanoma cells and studied the consequences in the petri dish and in animal models. Recreating actual mutations that patients harbor is challenging, but now possible by genome editing, and would further provide a more accurate model; such studies are ongoing in the lab.”
Melanoma is the deadliest form of skin cancer, and develops in the cells that produce melanin, the pigment that gives people’s skin its color. While melanoma can be treated successfully when caught early, it can also be quite aggressive and spread from tumors as small as a couple millimeters to vital organs like the brain. Understanding metastatic melanoma is essential to save lives from this disease, which affects 200,000 people a year worldwide.
ARID2 is part of a chromatin remodeling complex and frequently mutated in melanoma. In this study, scientists used melanoma tumor models to measure the role of the ARID2 gene in cancer progression. They assessed the effects of ARID2 loss on the epigenetic landscape, a dynamic DNA and protein platform that provides molecular instructions on gene expression, which in turn shapes cellular functions and behaviors. They found that without ARID2, melanoma cells exhibit increased metastatic behaviors.
Researchers from New York University and Purdue University contributed greatly to this research. This study was funded by the National Cancer Institute, American Skin Association, and National Cancer Center.
Story Source:
Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine. Note: Content may be edited for style and length.

Imaging at near-atomic resolution of a key immune protein commonly known as STING has revealed a previously unrecognized binding site that appears to be pivotal for launching immune attacks, UT Southwestern scientists report in a new study. The findings, published in Nature, could lead to new ways of manipulating STING to prompt stronger immune responses or stem its action in autoimmune diseases.
“For the first time, this work provides a precise picture of the activated state of STING, critical for understanding its role in both normal immunity as well as autoimmune diseases,” said study author Xuewu Zhang, Ph.D., Professor of Pharmacology and Biophysics at UT Southwestern. Dr. Zhang co-led the study with Xiaochen Bai, Ph.D., Associate Professor of Biophysics and Cell Biology at UT Southwestern, and their postdoctoral fellows Defen Lu and Guijun Shang. Dr. Zhang and Dr. Bai are members of the Harold C. Simmons Comprehensive Cancer Center.
STING, short for “stimulator of interferon genes,” is a central part of the innate immune system, which serves as the body’s first line of defense against viruses, bacteria, and cancers. After a sensor known as cGAS detects foreign DNA in cells, it generates a messenger molecule known as cyclic GMP-AMP (cGAMP) that activates STING. In turn, STING launches several signaling pathways that spur the production of inflammatory molecules and chemical signals that prompt cells to clean out detritus to eliminate invaders.
In collaboration with UT Southwestern researcher Zhijian “James” Chen, Ph.D., Professor of Molecular Biology and in the Center for Genetics of Host Defense, the Zhang lab and Bai lab previously reported the first images of STING taken with cryogenic electron microscopy (cryo-EM), a technique that freezes proteins in place to accurately assess their structure, in UTSW’s Cryo-Electron Microscopy Facility.
Although this work elucidated some of the fundamental mechanisms that control STING activity, exactly how this protein switches into an active form has been unclear. To answer this question, the Zhang and Bai labs mixed purified STING protein with cGAMP and used cryo-EM to image the resulting product. However, the researchers saw few activated STING molecules, and those that were present were unstable.
Hoping to increase the amount of activated STING available to image, the scientists added an investigational drug known as compound 53 (C53) that’s currently being tested as a STING activator for anti-cancer therapy. C53 was assumed to bind to the same site as cGAMP on STING.

In a new study at University of California, Irvine, researchers have revealed the impact of native lipids on rhodopsin signaling and regeneration, which may usher in a new paradigm for discovery of drugs that target G protein-coupled receptors (GPCRs).
GPCRs are cell surface receptors that respond to a variety of stimuli to activate signaling pathways across cell membranes. All GPCRs are membrane bound and have rarely been studied in their native membrane environments. Recent progress has yielded atomic structures of key intermediates and roles for lipids in in mediating the signaling. However, capturing signaling events of a wild-type receptor in real-time, across a native membrane to its downstream effectors, has remained elusive until now. These receptors by far represent the largest class of drug targets, and a vast number of approved drugs modulate their functions.
In this new study published today in Nature, titled, “Capturing a rhodopsin receptor signaling cascade across a native membrane,” the researchers, using mass spectrometry, probed the archetype class A GPCR, rhodopsin, directly in fragments of native disc membranes. They monitored real-time photoconversion of dark-adapted rhodopsin to opsin, delineating the stepwise isomerization of retinal and hydrolysis of the retinal-opsin adduct, further discovering that the reaction is significantly slower in its natural membrane environment than in artificial detergent micelles.
“Human diseases, ranging from cancer to cardiovascular diseases to blindness, are all highly impacted by the function of GPCRs. In addition to quantitative analysis of the signaling function, this novel technology, for the first time, has enabled direct detection of new potential targets of therapeutic value for the visual system, within the native membranes. I am convinced that analogous work will be done on many other GPCR systems, ” explained Krzysztof Palczewski, PhD, Donald Bren Professor of Ophthalmology at the UCI School of Medicine and co-corresponding author.
Considering the lipids ejected with rhodopsin from the membrane fragments in the mass spectrometer, researchers were able to demonstrate that opsin can be regenerated in the membranes through photoisomerized retinal-lipid conjugates, and to obtain evidence for increased association of rhodopsin with unsaturated long-chain phosphatidylcholine during signal transduction.
The team also captured the secondary steps of the signaling cascade following rhodopsin activation. Monitoring light activation of transducin (Gt), and dissociation of guanosine diphosphate (GDP) to generate intermediate apo trimeric G protein, they observed Gta.GTP subunits interacting with phosphodiesterase 6 (PDE6), found in cone and rod photoreceptor cells, which hydrolyzes the second messenger molecule cyclic guanosine monophosphate (cGMP).
“By applying rhodopsin-targeting compounds, we have shown how they either stimulate or dampen signaling via the rhodopsin-opsin and transducin signaling pathways,” said Palczewski. “Using instantaneous flashes of light, synchronized with recordings on a mass spectrometer, we were able to capture the signaling cascade and demonstrate roles for lipids and ligands in rhodopsin signaling. This work highlights new opportunities for drug discovery in native environments and may lead to a new way to investigate membrane-bound receptor pharmacology.”
Story Source:
Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

A new analysis suggests that most U.S. dog owners are unaware of — and do not follow — guidelines on safe pet food and dish handling from the Food and Drug Administration (FDA), but that better education and implementation of the guidelines could reduce contamination. Dr. Emily Luisana of North Carolina State University in Raleigh and colleagues present these findings in the open-access journal PLOS ONE on April 6, 2022.
Pet food and dish handling involves potential health risks for both dogs and people, especially those with compromised immune systems. Multiple outbreaks of bacterial illness among dogs and humans have occurred as a result of contaminated dog food. The FDA has issued guidelines on protocols for safe pet food and dish handling, available online, but the information is limited, and the effects of the recommendations have been unclear.
To help clarify, Dr. Luisana and colleagues surveyed 417 dog owners. They found that less than 5 percent were aware of the guidelines, and many owners did not follow many of the recommendations. For instance, only one third reported washing their hands after feeding, and only two thirds reported preparing dog food on separate surfaces from those used for human food. The latter fact is of potential public health importance, but is not addressed in the FDA recommendations.
To better understand the effects of the FDA recommendations, the researchers tested 68 household dog food dishes for bacterial contamination. After initial testing, they divided the owners into three groups with different instructions for implementing food handling guidelines, then tested the dishes again after 1 week. They found significantly reduced contamination of dishes from owners who instituted the FDA’s pet food handling guidelines, either alone or in combination with the FDA’s human food handling protocol, versus dishes from owners who were not asked to implement either protocol.
The researchers note that their study was small and that future research could clarify optimal hygiene strategies and ways to communicate them.
Nonetheless, on the basis of their findings, the researchers outline suggestions to reduce contamination in pet food dishes for owners, veterinarians, pet food sellers and manufacturers. These include ensuring household members who feed pets adhere to FDA guidelines and including written information on guidelines with pet food sales.
The authors add: “Most pet owners are unaware that pet food bowls can be a hidden source of bacteria in the household. Knowing how to mitigate this risk and practice proper pet food storage and hygiene may make for a happier, healthier household.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

Implantable bioelectronics are now often key in assisting or monitoring the heart, brain, and other vital organs, but they often lack a safe, reliable way of transmitting their data to doctors. Now researchers at Columbia Engineering have invented a way to augment implantable bioelectronics with simple, high-speed, low-power wireless data links using ions, positively or negatively charged atoms that are naturally available in the body.
Implantable bioelectronics are increasingly playing key roles in healthcare. For example, pacemakers can help ensure that a patient’s heart maintains a healthy beat, and neural interface devices can assist patients with epilepsy and other disorders by stimulating specific brain regions to reduce their neurological symptoms, or even link a paralyzed patient’s brain with robotic limbs. However, one major challenge that implanted bioelectronics face is how to communicate their data through the body to external devices for further analysis and diagnostics by physicians and scientists.
“From brain or muscle activity to hormone concentrations, these data need to be transmitted so that they can undergo advanced processing and review by experts before medical decision-making occurs,” said study co-senior author Dion Khodagholy, an associate professor of electrical engineering at Columbia University.
“This is especially important for conditions where there can be substantial fluctuations over time, such as in epilepsy or movement disorders,” added study co-senior author Jennifer Gelinas, an assistant professor of neurology at Columbia University Irving Medical Center. “One example of this is the NeuroPace device for epilepsy — the data from it needs to be downloaded for the clinician to adjust its stimulation protocols to better treat seizures.”
Although cables offer a simple way to quickly transmit data from implants to outside machines, the way they penetrate tissue limits their long-term use. At the same time, conventional wireless approaches using radio waves or visible light often do a poor job penetrating biological tissue.
“Safe, effective, long-term wireless communications with implanted devices is still lacking,” Khodagholy said.

A team led by University of Minnesota Twin Cities engineering researchers analyzed the fundamental properties and structures of lung surfactant — a naturally occurring substance that helps human and animal lungs expand and contract — providing insight that could eventually help scientists develop better treatments for respiratory illnesses.
The paper is published in Science Advances, a peer-reviewed, multidisciplinary scientific journal published by the American Association for the Advancement of Science.
Both human and animal lungs naturally produce a surfactant, a substance consisting of lipids and proteins that coats the lungs and decreases the surface tension as we inhale and exhale, making it easier to breathe.
Respiratory illnesses like pneumonia or COVID-19 can impede the lung surfactant from working properly, leading to complications in breathing. A similar issue occurs in pre-term babies, who sometimes haven’t yet developed the ability to produce the substance and suffer from Neonatal Respiratory Distress Syndrome. Right now, treatments consist of giving humans replacement surfactant taken from animal lungs, but researchers have been working to create synthetic surfactants to treat these conditions for years.
“The main purpose of lung surfactant is to minimize the amount of energy required to breathe,” said Cain Valtierrez-Gaytan, lead author on the paper and a Ph.D. student in the University of Minnesota Department of Chemical Engineering and Materials Science. “As scientists, we want to determine how the various components of the surfactant interact with each other at a fundamental level so we can know what to include in a potential synthetic surfactant.”
While lung surfactant comprises many different materials, the University of Minnesota team was initially intrigued by the role of cholesterol, a type of lipid that occurs naturally in animal and human cells.
Using a Langmuir trough along with a high-resolution optical microscope, the researchers took images of a few of the lipids that make up lung surfactant — dipalmitoylphosphatidylcholine, hexadecanol or palmitic acid, and dihydrocholesterol — at the monolayer level, or a film consisting of one layer of molecules at the interface between air and water. By testing how the monolayers behaved at different temperatures and pressures, they uncovered two previously unconfirmed phenomena that align with fundamental theories in materials science.
For one, the researchers found that the surfactants organize as equilibrium structures, meaning that if the crystalline parts of the molecules change shape and grow as pressure increases, they have the ability to go back to their original shape if that pressure is removed. This is a fairly rare occurrence, as monolayers typically don’t return to their original structure once it’s altered.
The microscope images also showed that when the pressure is increased, the crystalline parts of the monolayers “finger” or elongate. This is due to a chemical instability, the same instability that causes ice to splay out in fractals when a snowflake is formed. Knowing both of these properties helps the researchers better understand how fast the surfactant spreads across the lungs and how it reduces surface tension in the lungs.
“We can use basic materials science theories, like instabilities and equilibrium, to try to understand how the lung surfactant actually works,” said Joe Zasadzinski, senior author on the paper and a professor in the University of Minnesota Department of Chemical Engineering and Materials Science. “Then we can make predictions based on fundamental physics as to how these materials are going to organize, which will ultimately help us formulate the next generation of clinical surfactant materials.”
In addition to Valtierrez-Gaytan and Zasadzinski, the research team included former University of Minnesota Twin Cities alumni Mitchell Kohler (B.S. ChemE ’21) and Khanh Kieu (B.S. ChemE ’21), Augsburg University and University of Minnesota adjunct professor Ben Stottrup, and University of California, Santa Barbara postdoctoral researcher Joseph Barakat.
This research was funded by the National Institutes of Health.

Infants carry a vast assemblage of bacteria, viruses and fungi in their guts. Combined, these microbes make up a complex ecology known as the gut microbiome, which plays a major role in health and disease throughout life. The initial source of these billions of microbes is the mother’s breast milk.
In a new study, Efrem Lim and his colleagues use next-generation sequencing to investigate the breast milk microbiome from HIV positive women in Kenya. Lim is a researcher with the Biodesign Center for Fundamental and Applied Microbiomics at Arizona State University and an assistant professor with ASU’s School of Life Sciences. The study compares breast milk samples from women who received antibiotic treatment with those receiving combined anti-retroviral therapy. The results showed that antiretroviral therapy alone causes no disruption to the normal breast milk in terms of microbiome richness, diversity or bacterial composition, while the use of antibiotics produces distinct changes in the microbiome.
The research appears in the current issue of the journal Microbiology Spectrum.
Breast milk provides developing infants with a nutritious blend of essential microbes, antibodies, and human milk oligosaccharides, (a form of carbohydrate). Nursing infants use breast milk to establish the suite of microbes that begin to develop in their gut immediately after birth. Microbes acquired from the mother’s breast milk can be detected in infant stool samples.
Disruptions in the breast milk microbiome are a serious concern, due to the potential negative effect on infant health and subsequent development. Previous studies have implicated alterations in the infant microbiome in a broad range of chronic disorders, including Crohn’s disease, diabetes mellitus and obesity. The new study suggests that babies of HIV positive mothers on combined antiretroviral therapy can enjoy the many benefits associated with breast feeding without adverse effects to their microbiome.
Story Source:
Materials provided by Arizona State University. Original written by Richard Harth. Note: Content may be edited for style and length.