Characteristics of stable Vitiligo skin disease

A new study, led by researchers from the University of California, Irvine, reveals the unique cell-to-cell communication networks that can perpetuate inflammation and prevent repigmentation in patients with vitiligo disease.
The study, titled, “Multimodal Analyses of Vitiligo Skin Identifies Tissue Characteristics of Stable Disease,” was published today in JCI Insight.
“In this study, we couple advanced imaging with transcriptomics and bioinformatics to discover the cell-to-cell communication networks between keratinocytes, immune cells and melanocytes that drive inflammation and prevent repigmentation caused by vitiligo,” said Anand K. Ganesan, MD, PhD, professor of dermatology and vice chair for dermatology research at UCI School of Medicine. “This discovery will enable us to determine why white patches continue to persist in stable vitiligo disease, which could lead to new therapeutics to treat this disease.”
Vitiligo is an autoimmune skin disease that is characterized by the progressive destruction of melanocytes, which are mature melanin-forming cells in the skin, by immune cells called autoreactive CD8+ T cells that result in disfiguring patches of white depigmented skin. This disease has shown to cause significant psychological distress among patients. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but until now, why the white patches in stable disease persist was poorly understood.
“Until now, the interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools,” said Jessica Shiu, MD, PhD, assistant professor of dermatology and one of the first authors of the study. “By combining non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq), we identified distinct subpopulations of keratinocytes in lesional skin of stable vitiligo patients along with the changes in cellular compositions in stable vitiligo skin that drive disease persistence. In patients that responded to punch grafting treatment, these changes were reversed, highlighting their role in disease persistence.”
MPM is a unique tool that has broad applications in human skin. MPM is a noninvasive imaging technique capable of providing images with sub-micron resolution and label-free molecular contrast which can be used to characterize keratinocyte metabolism in human skin. Keratinocytes are epidermal cells which produce keratin.
Most studies on vitiligo have focused on active disease, while stable vitiligo remains somewhat of a mystery. Studies are currently underway to investigate when metabolically altered keratinocytes first appear and how they may affect the repigmentation process in patients undergoing treatment.
The findings of this study raise the possibility of targeting keratinocyte metabolism in vitiligo treatment. Further studies are needed to improve the understanding of how keratinocyte states affect the tissue microenvironment and contribute to disease pathogenesis.
This work was made possible, in part, through access to the Genomics High Throughput Facility Shared Resource of the Cancer Center Support Grant at the University of California, Irvine and three National Institutes of Health shared instrumentation.
The study was funded by the National Institutes of Health, the National Science Foundation, the Simons Foundation, National Institute of Arthritis and Musculoskeletal and Skin diseases, and the National Cancer Institute.
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Materials provided by University of California – Irvine. Note: Content may be edited for style and length.

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Cannabis products demonstrate short-term reduction in chronic pain, little else, review finds

Evidence behind the effectiveness of cannabis-related products to treat chronic pain is surprisingly thin, according to a new systematic evidence review by researchers at Oregon Health & Science University.
The federally funded review, which will be updated on an ongoing basis, was published today in the Annals of Internal Medicine.
Researchers did find evidence to support a short-term benefit in treating neuropathic pain — caused by damage to peripheral nerves, such as diabetic neuropathy resulting in pain described as burning and tingling, involving two FDA-approved synthetic products with 100% tetrahydrocannabinol, or THC: dronabinol (under the trade name Marinol) and nabilone (Cesamet). Both products also lead to notable side effects including sedation and dizziness, according to the review.
Another product, a sublingual spray of equal parts THC and cannabidiol, or CBD, extracted from the cannabis plant, known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain, although that product is not available in the U.S. This product also led to side effects, such as nausea, sedation and dizziness.
“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, Pharm.D., emeritus professor of medical informatics and clinical epidemiology in the OHSU School of Medicine. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.
“Unfortunately, there is very little scientifically valid research into most these products,” she said. “We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”
Voters in Oregon, Washington and 20 other states have legalized medical and recreational marijuana, however the researchers found many of the products now available at U.S. dispensaries have not been well studied.

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Warning labels could help customers identify hidden sugar in restaurant menus

Do you really want to order a soda with your burger? Just one soda can have more added sugar than the entire daily limit recommended for most adults.
Seeing a warning icon on a restaurant menu may help consumers identify the high amounts of added sugar hidden in menu items — and it may even convince them to reach for healthier items like water.
Those are the observations recorded in a new University of California, Davis, study. In a national survey sampling more than 1,300 adults, researchers found that added-sugar warnings with icons plus text, or icons only, were effective at getting a “high added sugar” warning message across to people. The survey took place in 2021.
“Excess added sugar in our food supply is a leading driver of Type 2 diabetes, which is predicted to affect about half of all U.S. adults in their lifetime,” said the study’s lead author, Desiree Sigala, UC Davis postdoctoral researcher in the Department of Molecular Biosciences.
The study, published online in the July issue of the journal Preventive Medicine, is believed to be the first of its kind to design and test the effects of added-sugar warnings for restaurant menus. And while the United States Food and Drug Administration requires large chain restaurants to make some nutrition information available in restaurants, there is currently no requirement for added sugar to be publicly disclosed for restaurant foods, researchers said.
This leaves consumers in the dark about the high levels of added sugar in their meals, which can contribute to negative health outcomes, researchers said. New York City recently sought to address this problem by passing a law requiring added-sugar warnings on prepackaged restaurant menu items. Policymakers across the country are considering similar warnings for added sugar on restaurant menus.

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Gene variation may be early indicator for gastric cancer

Researchers at the University of Arizona Health Sciences are hoping to catch stomach cancer before it develops in at-risk patients. In a paper published in Gastroenterology, researchers identified a genetic variation that could help identify when patients with Helicobacter pylori are more likely to develop stomach cancer.
The National Cancer Institute cites infection with H. pylori as the primary identified cause of certain types of stomach cancer. H. pylori is a bacterium that grows in the mucosa, or membrane layer that lines the stomach.
“This study is proposing that if you are carrying this particular allele, you are more likely to have an aggressive type of response to the bacteria that can result in complications,” said the study’s senior author, Juanita L. Merchant, MD, PhD, Regents Professor of Medicine and chief of the Division of Gastroenterology at the UArizona College of Medicine — Tucson.
In the United States, H. pylori is more prevalent in Hispanics, African Americans and the elderly. Dr. Merchant cited data suggesting that 1-3% of people with H. pylori will develop gastric cancer and that the cure rate is around 30%, which is low compared with some other types of cancer.
Current diagnosis of stomach or gastric cancer requires the patient to undergo an upper endoscopy, where a doctor looks for signs of cancer and takes a tissue sample for analysis.
For years, Dr. Merchant and colleagues have been investigating new ways to diagnose stomach cancer in its earliest possible stages. In 2020, they published research on a promising biomarker that appears in some patients before stomach cancer develops.

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COVID-19 increases risk of psychiatric diagnoses in the months after infection, study finds

A recent Oregon State University study found that COVID-19 patients had a roughly 25% increased risk of developing a psychiatric disorder in the four months following their infection, compared with people who had other types of respiratory tract infections.
The findings support previous research on psychiatric disorders among post-COVID patients, though the current study found a smaller effect than the earlier studies, said co-author Lauren Chan, a Ph.D. student in nutrition in OSU’s College of Public Health and Human Sciences.
For the current study, published in World Psychiatry, researchers used data from the National COVID Cohort Collaborative (N3C) to match 46,610 COVID-19 positive individuals with control patients who were diagnosed with a different respiratory tract infection so they could compare how COVID specifically affected patients’ mental health.
They looked at the rate of psychiatric diagnoses for two time periods: from 21 to 120 days after patients’ COVID diagnosis, and from 120 to 365 days after diagnosis, limited to patients with no previous mental illness.
Researchers found that COVID patients had a 3.8% rate of developing a psychiatric disorder compared with 3.0% for other respiratory tract infections. The 0.8% difference amounts to about a 25% increased relative risk.
They looked specifically at anxiety disorders and mood disorders and found a minor but significant increase in risk for anxiety disorders and no change in risk for mood disorders.

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Phase separation found in immune response within cells

Protein complexes that play a critical role in launching an immune response assemble in droplets that form within the liquid environment in cells much like oil droplets in water, UT Southwestern scientists report in a new study. The findings, published in Molecular Cell, could lead to new interventions to regulate immunity in individuals with overactive or underactive immune responses.
“These droplets basically function as microreactors that concentrate proteins and their substrates within. It’s like forming compartments without needing membranes to surround them,” said study leader Zhijian “James” Chen, Ph.D., Professor of Molecular Biology and Director of the Center for Inflammation Research at UTSW, a Howard Hughes Medical Institute Investigator, and winner of the 2019 Breakthrough Prize in Life Sciences.
More than two decades ago, the Chen lab discovered that a protein called ubiquitin assembles into chains inside cells when the cells are exposed to inflammatory molecules, such as interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα). Dr. Chen and his colleagues showed that the chains are key for promoting an immune response and can activate a group of proteins known as the IκB complex (IKK), which includes a component known as NEMO. This complex in turn triggers a protein called NF-κB to move to the nucleus and turn on hundreds of immune-related genes. But how the polyubiquitin chains, NEMO, and IKK come together has been unclear.
To answer this question, Dr. Chen’s team mixed ubiquitin and NEMO in test tubes with a protein called TRAF6, which promotes ubiquitin to assemble into chains. They saw that NEMO and the polyubiquitin chains assembled into liquid droplets that stayed separate from the liquid medium in the test tubes. Experiments in human cells showed that NEMO and the polyubiquitin chains displayed the same “phase separation” behavior after the cells were exposed to IL-1β or TNFα. When IKK entered these droplets, it became activated and triggered NF-κB to move to the nucleus. The longer the polyubiquitin chains, the larger the droplets they formed with NEMO and the stronger the immune response they triggered, Dr. Chen explained.
The team further studied this process using NEMO that was altered by mutations associated with a rare disease known as NEMO deficiency syndrome, which severely blunts immune response to bacterial infections. NEMO that carried these mutations could not effectively condense into droplets with polyubiquitin chains, preventing the cascade of events that triggers an immune response.
Dr. Chen noted that better understanding of this liquid phase separation phenomenon could eventually lead to treatments for NEMO deficiency syndrome and interventions to counteract overactive or underactive immunity, the root cause of autoimmune disorders and increased susceptibility to infection, respectively.
Dr. Chen is a George L. MacGregor Distinguished Chair in Biomedical Science and a member of the National Academy of Sciences.
Mingjian Du, Ph.D., a postdoctoral fellow in the Chen lab, is lead author of this study. Other UTSW researchers who contributed to this study include Chee-Kwee Ea and Yan Fang.
This research was supported by grants from the Cancer Prevention and Research Institute of Texas (RP180725, RP210041) and The Welch Foundation (I-1389).
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Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

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How a knee replacement impacts the planet

A total knee replacement can greatly improve a patient’s quality of life, but first the procedure itself will create nearly 30 pounds of waste, about half of which presents a biohazard and requires energy-intensive treatment for safe disposal.
A cataract surgery can give the gift of clear sight, but only after releasing the equivalent of 181.8 kilograms of carbon dioxide, about the same as a car traveling 315 miles.
Though healthcare is one of the largest sectors in the U.S., its environmental impacts tend to fly under the radar: It accounts for 10 percent of the nation’s greenhouse gas emissions, and operating rooms generate 20-33 percent of total hospital waste. Researchers are only just beginning to track and understand the sector’s environmental impacts.
Among those researchers are a team at the University of Pittsburgh whose work quantifies the effects of healthcare on the environment, and in this case specifically focuses on a particularly waste-heavy and energy-intensive specialty: orthopedic surgery. The researchers from Pitt’s School of Medicine and the Swanson School of Engineering reviewed existing literature and found that while data is still sparse, efforts to reduce the carbon footprint of orthopedic surgery could make a huge impact.
“Surgical suites have a high environmental impact, partially because so many of the items they rely on are single-use, disposable products, like gowns, gloves, surgical instruments, and packaging,” explained coauthor Melissa Bilec, co-director of Mascaro Center for Sustainable Innovation and William Kepler Whiteford Professor of Civil and Environmental Engineering. “We’re just beginning to find out the impacts of the field, but we know the impacts are there. We also know that more research is needed to really define the best practices to reduce environmental impacts, climate change, and work toward a circular economy.”
A circular economy focuses on reusing items and material to keep them in circulation rather than relegating them to a landfill at the end of their lifecycle. Bilec is leading an NSF-funded project that brings together a five-university, cross-disciplinary team to utilize convergence research to address the complex challenge of global waste and creating a circular economy.

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New technology protects authenticity of engineered cell lines

Advances in synthetic biology and genome editing have led to a growing industry to develop customized cell lines for medical research. These engineered cell lines, however, can be vulnerable to misidentification, cross-contamination and illegal replication.
A team of University of Texas at Dallas researchers has developed a first-of-its-kind method to create a unique identifier for each copy of a cell line to allow users to verify its authenticity and protect the manufacturer’s intellectual property (IP). The engineers demonstrated the method in a study published online May 4 and in the May 6 print edition of Science Advances.
The patent-pending technology is the result of an interdisciplinary collaboration between UT Dallas faculty members. The study’s co-corresponding authors are Dr. Leonidas Bleris, a professor of bioengineering who specializes in genetic engineering, and Dr. Yiorgos Makris, a professor of electrical and computer engineering who is an expert on electronics hardware security.
Custom cell lines are used in the development of vaccines and targeted therapies for a range of diseases. The global cell-culture market is projected to reach $41.3 billion by 2026, an increase from $22.8 billion in 2021, according to a forecast by market research company MarketsandMarkets.
The UT Dallas engineers’ research to develop unique identifiers for genetically engineered cells was inspired by what are called physically unclonable functions (PUFs) in the electronics industry. A PUF is a physical characteristic that can serve as a unique “fingerprint” for a semiconductor device such as a microprocessor. In semiconductors, PUFs are based on natural variations that occur during the manufacturing process and must meet three requirements: They must have a unique fingerprint, produce the same fingerprint each time they are measured and be virtually impossible to replicate.
To apply that concept to engineered cells, the researchers developed a two-step process that takes advantage of a cell’s ability to repair damaged DNA, which is made up of sequences of small molecules called nucleotides.

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Small package, big potential to help cell-based therapies

Cell-based therapies have long been thought of as an alternative treatment option for patients with a range of diseases caused by organ and tissue failure, inclusive of heart attack, diabetes, corneal blindness, and cystic fibrosis. While great in theory, in practice, these therapies show limited clinical success in many applications due to low cell viability after injection, as well as poor retention at the injection site and engraftment into damaged tissue. Ongoing research led by BME’s Rachelle Palchesko and Adam Feinberg, is exploring the use of a new cell delivery method to help cells stick and stay where they’re needed most.
More than 50,000 cornea transplant procedures are performed in the United States annually, an impressive statistic that exceeds the number of transplants of all other solid organs combined. In new research published in Communications Materials, CMU and University of Pittsburgh researchers propose using a small package of shrink-wrapped corneal endothelial cells as a potential alternative to cornea transplant when low endothelial cell density is the cause of corneal blindness.
The corneal endothelium (CE) is a single layer of cells that lines the back surface of the cornea and is responsible for maintaining proper corneal thickness and clarity. Nearly half of all cornea transplants stem from failure of the CE, primarily due to a loss of cells that cannot replicate to repair damage or injury.
While some treatments for CE failure exist, chronic rejection and limited donor supply have motivated the development of new methods to inject CE cells to repopulate the corneal endothelium and restore function. Until now, most approaches have required the existing CE to be removed through scraping or cryogenic injury of the cornea to provide a place for the delivered cells to attach.
“You can imagine if you’re trying to take a healthy cell and put it in a hostile tissue, it doesn’t want to stay there,” explained Rachelle Palchesko, special faculty researcher of biomedical engineering. “We had a benchmark for effective application of shrink-wrapped cells in the cornea based on some work a group in Japan was doing, and we knew we could improve upon it. We’ve been able to show that we can package cells effectively and get them to integrate into high-density tissues, without inducing any injury or removing any cells. Our technology can improve cell therapies and help cells stick and stay where we want them to.”
The group’s technique utilizes shrink-wrapping micropatterned islands of corneal endothelial cells in a basement membrane-like layer of extracellular matrix that enables the cells to maintain their cell-cell junctions and cytoskeletal structure while in suspension. In a series of studies, the small packages of cells exhibited an ability to rapidly engraft into intact, high-density corneal endothelial monolayers in both in vitro and in vivo model systems.
“The bulk of my research has been in treating corneal blindness however we believe this technology has strong potential to be applied to other areas of the body,” said Palchesko. “Our group in the lab is investigating how to apply this technology to treat cystic fibrosis or deliver cells after a heart attack.”
“Imagine that organ failure could be prevented with a simple injection into the affected tissue instead of waiting for a transplant that may never come,” said Adam Feinberg, a professor of biomedical engineering and materials science and engineering. “This is the truly exciting potential of the technology as it is further developed and validated. And we are thankful for the support of the National Institutes of Health and Cystic Fibrosis Foundation in funding this research.”
Palchesko added, “This is a simple, effective technology — it’s not overly engineered; we’re just wrapping up these cells in little packages. I believe we can take it farther and help a lot of people.”
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Materials provided by College of Engineering, Carnegie Mellon University. Original written by Sara Vaccar. Note: Content may be edited for style and length.

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Chemists design chemical probe for detecting minute temperature shifts in the body

The noninvasive, life-saving technique known as magnetic resonance imaging works by aligning hydrogen atoms in a strong magnetic field and pulsing radiofrequency waves to convert the response of those atoms into an image.
The field of provenance for MRI, it could be argued, is chemistry – MRI works by exploiting the inherent magnetic properties of individual atoms. What if, instead of just creating images, an MRI machine could extract detailed information about the chemistry of the body — say, the pH levels in the vicinity of a tumor, or the temperature anomalies that occur around an injury? What if the physical principles of magnetic imaging could be applied to all sorts of chemical changes, down to the level of atoms and molecules, and could give us unparalleled new insights into human health and disease?
These “what if” questions drive the work of Department of Chemistry Assistant Professor Joseph Zadrozny and his team of students and researchers. An inorganic chemist who toes the line between chemistry and quantum physics, Zadrozny has built a lab at Colorado State University whose chief goal is to design molecules that allow magnetic resonance imaging to do things that it currently can’t. In doing so, the researchers are uncovering fundamental insights into how the magnetic properties of metal ion-containing molecules respond to their environments, whether that means extremely small shifts in temperature, pH or other metrics.
“We are living, breathing, talking chemical reactors,” Zadrozny said. “If you could image that chemistry, it would be really powerful.”
Nucleus that acts like an electron
In a breakthrough toward their goal of making new magnetic imaging probes with extreme temperature sensitivity, Zadrozny’s team has published a paper in the Journal of the American Chemical Society that describes a cobalt-based molecule they’ve engineered to be a noninvasive chemical thermometer. They’ve used their expertise in molecular design to make the cobalt complex’s nuclear spin – a workhorse, fundamental magnetic property – mimic the agile, but less stable sensitivity of an electron’s spin. “Spin” is what gives subatomic particles their magnetism.

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