Join co-hosts Brandon Nappi and Hannah Black in an engaging episode of The Leaders Way as they sit down with Linn Tonstad, Professor of Theology, Religion, and Sexuality at Yale Divinity School. In this episode, Tonstad shares her unique perspective on queer theology and how it relates to potential for social transformation. Perfect for Pride Month, this episode challenges us to envision a world with "a little less violence."

54: Queer Theology with Linn Tonstad

In this episode, Dr. Yavor Metodiev delves into the anesthetic considerations that should be taken when caring for a patient with oncological disease during pregnancy. Dr. Metodiev and colleagues concisely summarize the complexities of treating patients with oncological disease, emphasizing the crucial balance between maternal and fetal safety. With the increasing incidence of oncological disease in pregnant women (1 in 2000), anesthetists are expected to encounter more of these cases, and we play a pivotal role in managing these patients during the peripartum period. 
 
https://pubmed.ncbi.nlm.nih.gov/39775436/

Anesthetic Management of oncological disease in pregnancy

There has been a lot of news and some confusion in recent months about the connection between alcohol consumption and cancer risk. In this episode, Dionisia Quiroga, DO, PhD, a James breast cancer specialist, explains the recent findings of the U.S. Surgeon General, what they mean and what people need to know to reduce their cancer risk. “One of the data findings was that most Americans don’t know alcohol is a risk factor for cancer development,” Dr. Quiroga said. “It’s important people know so they are empowered to make the right decisions for themselves.” Previous research indicated one alcoholic drink per day for women and two for men was a safe level of consumption. “When we look at the new data, it shows that any alcohol consumption can increase the risk,” Dr. Quiroga said. One of the theories about why alcohol consumption increases the cancer risk is that “alcohol in the system breaks down into substances that can cause DNA damage” that leads to cancer. “And alcohol can alter the hormones in the body and most cases of breast cancer are linked to some sort of hormone issue,” Dr. Quiroga said, adding this could also be a factor in prostate cancer risk. “Alcohol use is also tied to other types of cancer where alcohol passes through the body and is processed, such as head and neck cancer, colon cancer, and liver cancer since the liver breaks down alcohol.”

Episode 189: How Alcohol Impacts the Risk of Cancer, with Dr. Dionisia Quiroga

In this episode of Global Health Insights, host Dr. Sharon Chekijian sits down with Dr. Azita Emami, Dean of the Yale School of Nursing, to explore her remarkable journey across continents and disciplines in pursuit of health equity. From her early academic ambitions to leading three major nursing schools in the U.S., Dean Emami shares how her experiences shaped her commitment to global nursing leadership, immigrant health, and culturally responsive care. She discusses the importance of empowering nurses to practice to the full scope of their expertise, expanding primary care access, and developing equitable healthcare systems worldwide. She underscores the value of global citizenship, collaboration, and advocacy in transforming health outcomes.

Building Global Health Through Nursing Leadership: A Conversation with Dean Azita Emami

BUFFALO, NY — June 3, 2025 — A new #research paper was #published in  Aging (Aging-US) on May 1, 2025, as the #cover of Volume 17, Issue 5, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.”

In this study, researchers Arjun Sapkota, Sebok K. Halder, and Richard Milner from San Diego Biomedical Research Institute investigated how aging affects the brain’s vulnerability to low oxygen, or hypoxia. Using C57BL/6J mice ranging from 2 to 23 months of age, they identified specific oxygen levels that disrupt the blood-brain barrier (BBB)—a critical structure that protects brain tissue from harmful substances. The findings are important for understanding age-related cognitive decline and the potential risks faced by individuals with chronic oxygen-limiting conditions such as asthma, sleep apnea, emphysema, and heart disease.

The BBB is essential for maintaining brain health. In this study, mild and prolonged hypoxia—called chronic mild hypoxia—was found to compromise the BBB in mice. Older mice showed significantly more BBB disruption than younger ones. Notably, barrier weakening and blood vessel changes occurred at oxygen levels of just 15% in aged mice, compared to 13% in young mice. These data suggest that the aging brain is more sensitive to oxygen deprivation, even at levels that may be considered only mildly hypoxic.

The researchers also determined when this vulnerability emerged. The BBB showed increased sensitivity to low oxygen not only in aged mice but also in mice as young as 2 to 6 months, with a second spike occurring between 12 and 15 months—equivalent to middle age in mice. These findings may reflect age-dependent changes in brain vascular function and remodeling capacity.

“Hypoxia-induced endothelial proliferation was relatively constant across the age range, but advanced age strongly enhanced the degree of BBB disruption (4-6-fold greater in 23 months vs. 2 months old).”

Another key focus was microglial activation, a sign of brain inflammation. Aged mice exhibited higher microglial activation across all oxygen levels, including normal conditions. Chronic microglial activation is closely linked to neuroinflammation and has been implicated in diseases such as Alzheimer’s. While the rate of blood vessel formation was constant across ages, the degree of BBB disruption increased sharply with age, suggesting that repair mechanisms may weaken over time.

These results may help explain why older adults with chronic hypoxia-related diseases are at higher risk for neurodegeneration and cognitive decline. The study also draws attention to the risks of high-altitude exposure for aging populations, where oxygen levels naturally drop.

Altogether, these findings underscore the importance of protecting brain health in older individuals by managing oxygen exposure and reducing hypoxia-related risks. The researchers emphasize the need to develop new therapies that support blood-brain barrier integrity, particularly in aging populations exposed to chronic or intermittent low-oxygen conditions.

DOI - https://doi.org/10.18632/aging.206241

Corresponding author - Richard Milner - rmilner@sdbri.org

Video short - https://www.youtube.com/watch?v=Nr6rTm7aJRo

Keywords - aging, blood-brain barrier integrity, endothelial, proliferation, microglia, chronic mild hypoxia, hypoxic threshold

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Aging (Aging-US)

Aging Increases Brain’s Sensitivity to Hypoxia and Blood-Brain Barrier Damage in Mice

BUFFALO, NY - June 3, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 19, 2025, titled “PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling."

In this study, led by first author Reem Ali and corresponding author Dindial Ramotar from Hamad Bin Khalifa University in Qatar, researchers discovered that a protein called PRDX1 helps maintain the stability of ATM, a key protein involved in repairing damaged DNA, especially when cells are under stress from arsenite exposure. The study found that without PRDX1, cells lose their ability to repair DNA and become more sensitive to chemotherapy. This finding suggests that targeting PRDX1 could improve the success of some cancer treatments.

PRDX1 is already known for its role in protecting cells from oxidative damage, but this study shows it also plays a role in the DNA repair process. ATM is an essential protein that detects breaks in DNA and starts the repair process. When PRDX1 is missing, ATM is rapidly lost, especially when cells are exposed to arsenite, a toxic substance found in the environment. Without ATM, the DNA repair system fails, leaving cells more vulnerable to damage.

By using both human cell lines and clinical samples from ovarian cancer patients, the team showed that high levels of PRDX1, along with ATM and MRE11 (another DNA repair protein), were linked to tumors' aggressive features and lower patient survival rates. This pattern suggests that tumors with high PRDX1 may resist chemotherapy by increasing their DNA repair capacity. On the other hand, removing PRDX1 weakened the repair system and made cancer cells more responsive to DNA-damaging platinum drugs.

The study also showed that combining low doses of arsenite with drugs that either block ATM or damage DNA caused a much higher rate of cancer cell death in cells that lacked PRDX1. These results suggest a new treatment approach: lowering PRDX1 levels to make cancer cells more sensitive to DNA-damaging platinum therapies already in use. This highlights PRDX1 not only as a protector of cell function but also as a potential weak point in cancer cells.

“As such, we propose that small molecule inhibitors of PRDX1, or single nucleotide polymorphisms that compromise PRDX1 function, in combination with low doses of arsenite can be exploited to treat chemo-resistant tumours.”

These findings open the door for the use of PRDX1 as a biomarker to predict treatment response and as a promising target for new combination therapies. For patients with ovarian cancer and potentially other tumors, adjusting PRDX1 levels may help overcome drug resistance and improve outcomes.

DOI - https://doi.org/10.18632/oncotarget.28720

Correspondence to: Dindial Ramotar - dramotar@hbku.edu.qa

Video short - https://www.youtube.com/watch?v=suOhF7mPlNQ

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Keywords - cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modification

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MEDIA@IMPACTJOURNALS.COM

Oncotarget

Blocking PRDX1 Protein May Improve Chemotherapy Response in Ovarian Cancer

BUFFALO, NY — June 4, 2025 — A new #editorial was #published in Aging (Aging-US) Volume 17, Issue 5, on May 29, 2025, titled “Rethinking healthcare through aging biology.”

In this scientific editorial, Aging (Aging-US) Editor-in-Chief Marco Demaria from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG) and the University of Groningen (RUG), advocates for healthcare reform that addresses the biological drivers of aging rather than individual chronic conditions. The article proposes that targeting the root causes of age-related diseases through aging biology could revolutionize preventive care, extend healthspan, and reduce long-term healthcare costs. This proactive approach aligns with a growing body of aging research focused on improving healthy longevity.

Dr. Demaria explains that today’s disease-focused model is inadequate for aging populations, who often suffer from multimorbidity—the presence of multiple chronic illnesses like cancer, heart disease, and type 2 diabetes. These overlapping conditions, rooted in common aging mechanisms, overwhelm healthcare systems and lead to complex treatments with limited success. The editorial suggests that identifying and intervening in the biological aging process could prevent such diseases before they emerge.

In the editorial, Dr. Demaria outlines three healthcare paradigms. The first is the existing system, which reacts to disease after symptoms appear. The second involves intervening once age-related damage begins, using new tools such as senolytics, which eliminate harmful senescent cells, and rapalogs, which regulate cellular metabolism. The third and most forward-looking model focuses on preventing aging-related damage before it starts. This strategy supports lifelong biological balance and seeks to avoid early molecular decline through continuous health maintenance.

Prevention is key in this model. Lifestyle choices—such as exercise, a healthy diet, quality sleep, and stress reduction—play a vital role in slowing the aging process. Dr. Demaria also points to the promise of biological age diagnostics—tools or tests that estimate a person’s biological age—which allow people to track their physiological aging and adopt personalized interventions. Additionally, optimizing maternal nutrition and early-life health can contribute to lifelong disease prevention.

To support this shift, the editorial calls for major changes in medical education. Physicians must be trained in geroscience, healthspan optimization, and personalized preventive care. This knowledge will prepare future clinicians not just to treat disease, but to delay or prevent it altogether. Collaboration among healthcare providers, researchers, and policymakers will be essential for building this new system.

​​“The third paradigm—preventing aging-related damage—demands a systemic shift toward predictive and preventative research, with an emphasis on multi-omic data, lifestyle interventions, and early-life interventions.”

By redefining medicine around the science of aging, Dr. Demaria’s editorial highlights the path toward healthier aging, longer life expectancy, and a more sustainable healthcare future.

DOI - https://doi.org/10.18632/aging.206262

Corresponding author - Marco Demaria - m.demaria@umcg.nl

Video short - https://www.youtube.com/watch?v=xR-16cjHnQY

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New Vision for Healthcare Focuses on Preventing Aging-Related Diseases

BUFFALO, NY - June 4, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 20, 2025, titled “Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells."

In this study, authors Shan Lu and Zhongyun Dong from the University of Cincinnati College of Medicine investigated how interfering with a protein interaction could reduce prostate cancer growth. Their study based on prostate cancer cells shows that blocking the link between PCNA, a protein important for DNA repair, and the androgen receptor (AR), which drives prostate cancer growth, can slow down cancer cell multiplication. This discovery could lead to a new treatment for patients with advanced prostate cancer, particularly those no longer responding to hormone therapy.

Prostate cancer is one of the most common cancers in men. Many patients eventually become resistant to hormone treatment. In this advanced stage, called castration-resistant prostate cancer (CRPC), tumors continue to grow by using either the full-length androgen receptor (AR-FL) or altered versions called AR variants (AR-Vs). This study shows that the interaction between AR and PCNA helps both AR-FL and AR-Vs remain active, supporting cancer cell survival and growth.

The researchers identified a new region in the AR that binds to PCNA. They developed a small peptide, R9-AR-PIP, to mimic this region and block the AR-PCNA connection. They found that this peptide reduced AR’s ability to bind DNA and lowered the levels of key genes involved in cancer cell growth. Importantly, the peptide was effective against both types of AR, including the variant forms that are especially challenging in CRPC.

“We identified a second PIP-box (PIP-box592) in the DNA binding domain of AR and found that dihydrotestosterone enhances the binding of full-length AR (AR-FL) but not a constitutively active variant (AR-V7) to PCNA.”

They also tested a small molecule, PCNA-I1S, which interferes with PCNA’s ability to move to the cell nucleus and interact with AR. This molecule showed similar effects as the peptide, reducing AR activity and stopping cancer cell growth. Together, these findings suggest that targeting PCNA/AR interactions could be a promising strategy to fight CRPC, especially in patients with limited treatment options.

One key result was that both the peptide and the small molecule reduced the levels of cyclin A2, a protein that helps cells divide and is often overexpressed in CRPC. Since this protein is linked to patients' poor outcomes, its reduction could be especially beneficial.

This study improves our understanding of how prostate cancer continues to grow even after hormone treatments fail. By blocking a crucial helper of the androgen receptor, researchers have uncovered a new way to potentially slow or stop the disease. Further studies in animal models are needed, but this approach could lead to more effective treatments for men with advanced prostate cancer.

DOI - https://doi.org/10.18632/oncotarget.28722

Correspondence to - Zhongyun Dong - dongzu@ucmail.uc.edu

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Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPC

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MEDIA@IMPACTJOURNALS.COM

Targeting PCNA-Androgen Receptor Interaction Suppresses Prostate Cancer Cell Growth

Researchers at Brown University have developed a combination treatment that significantly increases survival in mice with glioblastoma (GBM), a highly aggressive and treatment-resistant brain cancer. The approach uses a new class of drugs called imipridones along with radiation therapy and standard chemotherapy. This triple therapy, known as IRT, was recently detailed in a study published in Oncotarget.

Understanding Glioblastoma and the Need for Better Therapies

Glioblastoma is the most common and aggressive malignant brain tumor in adults. It grows quickly and is difficult to treat, often leading to poor outcomes. Most patients survive less than 15 months after diagnosis, even when treated with surgery, radiation, and the chemotherapy drug temozolomide (TMZ). This treatment may slow the disease, but it does not typically stop it.

Full blog - https://www.oncotarget.org/2025/06/04/experimental-triple-therapy-improves-survival-in-glioblastoma-mouse-model/

Paper DOI - https://doi.org/10.18632/oncotarget.28707

Correspondence to - Wafik S. El-Deiry - wafik@brown.edu

Video short - https://www.youtube.com/watch?v=Q_mXy8mana0

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Keywords - cancer, glioblastoma multiforme, IDH, ONC201, ONC206, MGMT, temozolomide, radiotherapy

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Experimental Triple Therapy Improves Survival in Glioblastoma Mouse Model

Buffalo, NY — June 4, 2025 — The Longevity & Aging Series has been honored with the Silver Award for “Excellence in Video/Film” at the inaugural EPIC Awards celebration on May 29, 2025, during the Society for Scholarly Publishing (SSP) 47th Annual Meeting in Baltimore, Maryland.

The EPIC Awards recognize the achievements of those who are advancing scholarly publishing through creativity, collaboration, and cutting-edge innovation. The Longevity & Aging Series, hosted by Aging (Aging-US) Editorial Board member Dr. Evgeniy Galimov, stood out for its impactful storytelling, production quality, and commitment to advancing understanding in the field of aging research.

The Longevity & Aging Series brings together leading experts to discuss the latest developments in the biology of aging, healthy longevity, and interventions to improve healthspan. Now in its third season, the series is a trusted resource for scientists, clinicians, and the broader public interested in the future of aging research.

For more information about the Aging (Aging-US) Longevity & Aging Series and to view the award-winning videos, please visit our show page or YouTube channel. If you are interested in becoming a guest or would like to know more about the series, please email us at media@impactjournals.com.

Longevity & Aging Series Show Page - https://www.aging-us.com/longevity

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Longevity & Aging Series Wins Silver Award for Excellence in Video/Film at SSP EPIC Awards

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Targeting PCNA-Androgen Receptor Interaction Suppresses Prostate Cancer Cell Growth

Oncotarget Podcast

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