Day: February 16, 2023

Categories : Regenerative MedicineTags : Leave a comment

Can Progressive Hearing Loss be Reversed?

On By ModernMedia
Photo by Dylann Hendricks on Unsplash

In humans, hearing loss from exposure to loud noises is progressive because the primary cells which detect sound, cochlear hair cells, cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss, though it can happen to anyone over time.

On the other hand, birds and fish can regenerate these hair cells, and now researchers report their advances in promoting this effect in mammals. Their work is published in Frontiers in Cellular Neuroscience.

“We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn’t fully understand why,” said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighbouring stem cells to become new sensory hair cells.

“This new study tells us how that activation is happening – a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals,” said White.

Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signalling) with similar cells that lacked such signalling. They found the growth gene, ERBB2, promoted stem cell-like development by initiating the expression of multiple proteins – including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.

“When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells,” said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. “This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults.”

“We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal,” said White.

Source: University of Rochester Medical Center

Categories : Diet and NutritionTags : Leave a comment

Brown Rice has a Cell-protecting Compound

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Photo by Łukasz Rawa on Unsplash

Among its many health benefits, brown rice has long been known to protect against oxidative stress – but it was not known which compound was responsible for this. Researchers in Japan have identified the compound that confers this protective effect, with their findings published in the International Journal of Molecular Sciences.

In a recent study led by Professor Yoshimasa Nakamura from the Graduate School of Environmental and Life Science, Okayama University, researchers from Japan have identified cycloartenyl ferulate (CAF) as the main “cytoprotective” or cell-protecting compound in brown rice. CAF is a unique compound owing to its hybrid structure. As Professor Nakamura explains, “CAF is a hybrid compound of polyphenol and phytosterol and is expected to be a potent bioactive substance with various pharmacological properties, such as antioxidant effect and blood fat-lowering effect.”

In this study, the researchers provide evidence of CAF’s antioxidant properties by demonstrating that it can protect cells from stress caused by hydrogen peroxide. Although hydrogen peroxide is a by-product of a cell’s metabolic processes, abnormal amounts of the compound can be toxic to cells and cause irreversible damage. Treatment of cells with CAF increased their resistance to toxic stress induced by hydrogen peroxide. Moreover, CAF provided greater protection from hydrogen peroxide-induced stress compared to alpha-tocopherol and gamma-tocopherol, two other prominent antioxidant compounds that were earlier speculated to be major contributors to the antioxidant capacity of brown rice.

According to the study’s estimates, the amount of CAF in the whole grain of brown rice is five-fold higher than that of other antioxidant compounds found in brown rice. Further, CAF increases the concentration of heme oxygenase-1 or HO-1, an enzyme that facilitates the production of antioxidants. “We demonstrated here that CAF significantly increased the mRNA level of HO-1, the small molecular weight antioxidant-producing enzyme, at concentrations similar to that required for cytoprotective effects in resistance to oxidative damage,” Professor Nakamura explains.

The researchers further explored this mechanism of action through experiments where blocking HO-1 activity using inhibitors reduced the antioxidant effect of CAF considerably. The high abundance and unique mechanism of action are evidence that CAF is the major contributing antioxidant in brown rice.

Through this study, the researchers have not only uncovered the secret to the health benefits of brown rice, but also locked down on the component that is majorly responsible for these benefits. This will allow the use of CAF in the development of better novel supplements and food products focused on consumer health. As an optimistic Professor Nakamura observes, “Our study can help in the development of new functional foods and supplements based on the functionality of CAFs, like CAF-based nutraceuticals.”

Source: Okayama University

Categories : Diseases, Syndromes and Conditions Immune SystemTags : Leave a comment

Iron Holds a Clue to New Lupus Treatments

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Source: Wikimedia CC0

A new approach for treating systemic lupus erythematosus (SLE) could lie in targeting iron metabolism in immune system cells. Researchers found that blocking an iron uptake receptor reduces disease pathology and promotes the activity of anti-inflammatory regulatory T cells in a mouse model of SLE. The findings were published in the journal Science Immunology.

Treatments for lupus aim to control symptoms, reduce immune system attack of tissues, and protect organs from damage. Only one targeted biologic agent has been approved for treating SLE, belimumab in 2011.

“It has been a real challenge to come up with new therapies for lupus,” said Jeffrey Rathmell, PhD, Vanderbilt University professor. “The patient population and the disease are heterogeneous, which makes it difficult to design and conduct clinical trials.”

Rathmell’s group has had a long-standing interest in lupus as part of a broader effort to understand mechanisms of autoimmunity.

When postdoctoral fellow Kelsey Voss, PhD, began studying T cell metabolism in lupus, she noticed that iron appeared to be a “common denominator in many of the problems in T cells,” she said. She was also intrigued by the finding that T cells from patients with lupus have high iron levels, even though patients are often anaemic.

“It was not clear why the T cells were high in iron, or what that meant,” said Voss.

To explore T cell iron metabolism in lupus, Voss and Rathmell drew on the expertise of other investigators at VUMC.

First, Voss used a CRISPR genome editing screen to evaluate iron-handling genes in T cells. She identified the transferrin receptor, which imports iron into cells, as critical for inflammatory T cells and inhibitory for anti-inflammatory regulatory T cells.

The researchers found that the transferrin receptor was more highly expressed on T cells from SLE-prone mice and T cells from patients with SLE, which caused the cells to accumulate too much iron.

“We see a lot of complications coming from that – the mitochondria don’t function properly, and other signalling pathways are altered,” Voss said.

An antibody that blocks the transferrin receptor reduced intracellular iron levels, inhibited inflammatory T cell activity, and enhanced regulatory T cell activity. Treatment of SLE-prone mice with the antibody reduced kidney and liver pathology and increased production of the anti-inflammatory factor, IL-10.

“It was really surprising and exciting to find different effects of the transferrin receptor in different types of T cells,” Voss said. “If you’re trying to target an autoimmune disease by affecting T cell function, you want to inhibit inflammatory T cells but not harm regulatory T cells. That’s exactly what targeting the transferrin receptor did.”

In T cells from patients with lupus, expression of the transferrin receptor correlated with disease severity, and blocking the receptor in vitro enhanced production of IL-10.

Since the transferrin receptor mediates iron uptake in many cell types, the researchers want to develop transferrin receptor antibodies that bind specifically to T cells, to minimise off-target effects. They are also interested in studying the details of their unexpected discovery that blocking the transferrin receptor enhances regulatory T cell activity.

Source: Vanderbilt University Medical Center

Categories : Mental Health Obstetrics & GynaecologyTags : Leave a comment

During Pregnancy, Experiencing Racism Worsens Depression

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Photo by Shvets Productions on Pexels

In a recent study published in The Journal of Advanced Nursing that included pregnant Black women from multiple US states, feeling upset by experiences of racism in the 12 months prior to delivery was associated with significantly higher odds of depression during pregnancy.

Perinatal depression is defined as major or minor depressive episodes that occur during pregnancy or in the first 12 months after birth. Mothers with perinatal depression often report symptoms including depressed mood; loss of interest or pleasure in daily activities; changes in weight, appetite and sleep; poor concentration; feelings of hopelessness; and suicidal ideations. Non-Hispanic Black women are twice as likely to experience symptoms of depression and suicidal ideations during the perinatal period than White women.

For this study, 7328 women answered survey questions. The findings showed that 11.4% of respondents reported feeling upset due to experiences of racism, and 11.4% reported experiencing depression during pregnancy. After adjusting for confounding factors, respondents who reported feeling upset due to the experience of racism had over two-fold higher odds of experiencing depression during pregnancy compared with respondents who did not report feeling upset due to the experience of racism.

“Our findings reinforce the importance of respectful maternity care, given the mental health impacts of experiences of racism during the perinatal period,” the authors wrote. “Racism is a powerful structural determinant of health with roots in a historical system of oppression that persists today in health care practices and policies. Perinatal health care providers, in collaboration with public health and other health disciplines, are ideally positioned to address inequities in maternal and child health that are rooted in racism.”

Source: Wiley

Categories : CancerTags : Leave a comment

Greater Precision with MRI-guided Prostate Cancer Radiotherapy

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Credit: Darryl Leja / National-Human-Genome Research Institute / National Institutes of Health

Men undergoing MRI-guided radiotherapy for localised prostate cancer, had fewer toxicities and better quality of life, according to new research published in JAMA Oncology. This was the first randomised phase III clinical trial to directly compare MRI-guided stereotactic body radiotherapy (SBRT) with the same therapy guided by CT.

“MRI guidance offers several advantages over standard CT guidance, most notably the ability to dramatically reduce planning margins, providing more focused treatment with less injury to nearby normal tissues and organs,” said lead author Amar Kishan, MD, a radiation oncologist. “MRI technology is more costly than CT, both in terms of upfront equipment expenses and longer treatment times, which is one reason our study set out to determine if MRI-guided technology offers tangible benefits for patients.”

SBRT for prostate cancer usually delivers radiation in five or fewer precisely targeted doses. It is an established and generally well tolerated form of treatment, but it can cause toxicities resulting in urinary, bowel and sexual dysfunction. This UCLA-led clinical trial included 154 analysable patients with prostate cancer who were randomised to either a CT-guidance arm (76 patients) or an MRI-guidance arm (78 patients).

This study included assessment by both physicians and patients. From both perspectives, MRI-guided therapy was associated with fewer side effects and better quality of life over at least three months of follow-up.

“In this trial, we demonstrated that the reduction in treatment volumes facilitated by MRI guidance leads to a significant reduction in moderate physician-scored toxicity and to a reduction in the proportion of patients noting significant decrements in patient-reported outcome metrics in the near term,” said Dr Kishan. “Although additional studies will need to confirm these benefits over time, we’re hopeful that these results will lead to better outcomes for men with prostate cancer.”

The 2mm margin used with MRI-guidance in the trial is narrower than has been used in any previous large study. Unlike CT, MRI technology can monitor prostate motion directly, and it offers improved soft tissue contrast, improving the accuracy of alignment prior to radiation.

Source: University of California – Los Angeles Health Sciences