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Letters to the Editor Issue 307

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listed in letters to the editor, originally published in issue 307 - December 2025

Epigenetic “Scars”: Unveiling How Childhood Trauma Affects Our Genes

Researchers identify molecular markers in children and adolescents, revealing how child maltreatment stress alters DNA, brain development, and mental health

Childhood trauma has often been linked to adverse mental health outcomes, but its impact on genetic changes often goes unnoticed. A new study at University of Fukui identified “epigenetic scars” in DNA, leading to structural alterations of brain regions related to emotional regulation, memory retrieval, and social cognition. Findings suggest that these biological markers may enable early detection, personalized treatment, and prevention of these effects—offering hope for breaking the intergenerational cycle of child abuse.

Child maltreatment, which includes abuse and neglect, is one of the most serious public health concerns worldwide. These adversities leave a lasting impact on the emotional well-being, memory, and social development of affected individuals. The problem, however, reaches far beyond its psychological impact, affecting the brain and biological processes through genetic changes, which have remained unclear until now.

A recent study led by Senior Asst. Professor Shota Nishitani and Professor Akemi Tomoda from the Research Center for Child Mental Development at University of Fukui, Japan, in collaboration with Professor Masataka Nagao from the Department of Forensic Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan, reveals that child maltreatment leaves measurable biological “scars” on children’s DNA, leading to long-term alterations in the brain. The findings of the study were published in Molecular Psychiatry on September 16, 2025.[1]

Their research builds on earlier findings from Prof. Tomoda’s group, which had revealed that child maltreatment can alter DNA. Unlike previous studies that focused on specific candidate genes, this current work employed a broader genome-wide approach, revealing novel molecular markers and directly linking them to brain structure.

Briefly, the researchers conducted a detailed analysis of the epigenome (a set of chemical “switches” on our DNA that regulate gene activity) across three different groups to identify biological markers linked to childhood maltreatment as trauma. Participants included those in judicial autopsy cases, as well as toddlers and adolescents who had undergone protective interventions, with the adolescents also undergoing brain MRI scans.

“We identified four DNA methylation sites that were consistently associated with child maltreatment, namely ATE1, SERPINB9P1, CHST11, and FOXP1,” explains lead author, Senior Asst. Professor Nishitani.

DNA methylation sites are key players in genetic regulation, as they can regulate the gene expressions without changing the underlying DNA sequence. While the researchers identified four different sites, the site FOXP1 was particularly significant as it acts as a “master switch” for the genes involved in brain development. The researchers found that hypermethylation of FOXP1 was linked to changes in gray matter volume in the orbitofrontal cortex, cingulate gyrus, and occipital fusiform gyrus of the brain regions which are responsible for emotional regulation, memory retrieval, and social cognition. This highlights the biological link between early trauma, brain development, and later mental health outcomes.

“Childhood trauma is not only a painful psychological experience but also leaves lasting biological marks at the molecular and brain levels,” explains Prof. Tomoda. “By identifying these epigenetic markers, we hope to develop new tools that can enable the detection and support of at-risk children as early as possible.”

To use their discovery for predictive analysis, the researchers created a methylation risk score (MRS) using the four identified DNA methylation sites. The score could successfully distinguish individuals with and without a history of maltreatment using external data independent of their own, suggesting its potential as an objective screening tool for identifying childhood trauma.

The significance of this discovery extends to multiple fields, including healthcare, forensic medicine, and public health policies. In healthcare, these biomarkers could help improve early diagnosis and personalized trauma-informed treatment approaches. While in forensics, it could help support investigations and support child welfare. Furthermore, the screening tools may also drive preventive care, reducing the long-term societal impact of maltreatment.

With these implications, the study also reflects the mission of the Division of Developmental Support Research at the University of Fukui, which integrates neuroscience, clinical practice, and community-based approaches to promote resilience and well-being for children and families. The center is dedicated to advancing the science and practice of child development and mental health, and focuses on early detection, intervention, and prevention of developmental and mental health issues.

“Childhood should be a time of safety and growth,” emphasizes Prof. Tomoda. “Understanding how childhood trauma affects us biologically can lead to better strategies for prevention, treatment, and support, helping break the cycle of maltreatment.”

Reference

  1. Nishitani, S., Fujisawa, T.X., Takiguchi, S. et al. Multi-epigenome-wide analyses and meta-analysis of child maltreatment in judicial autopsies and intervened children and adolescents. Mol Psychiatry . https://doi.org/10.1038/s41380-025-03236-1. 2025.

About University of Fukui, Japan

The University of Fukui is a preeminent research institution with robust undergraduate and graduate schools focusing on education, medical and science, engineering, and global and community studies. The university conducts cutting-edge research and strives to nurture human resources capable of contributing to society on the local, national, and global level.

Website: https://www.u-fukui.ac.jp/eng/

About Senior Asst. Professor Shota Nishitani from University of Fukui, Japan (Fiscal year 2019–2023)

Shota Nishitani, (Ph.D.), served as an Assistant Professor (Fiscal year 2019–2021) and a Senior Assistant Professor (Fiscal year 2022–2023) at the Research Center for Child Mental Development, University of Fukui, Japan. Prior to this role, he gained four years of extensive experience in epigenome-wide association studies as a Visiting Assistant Professor at Emory University (Fiscal year 2015–2018). His research aims to unravel the neurobiological mechanisms underlying child maltreatment and trauma. He addresses these questions by integrating computational approaches, such as epigenetic and neuroimaging bioinformatics, with experimental molecular biology techniques. He is now continuing his career as a Research Scientist at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine.

About Professor Akemi Tomoda from University of Fukui, Japan

Akemi Tomoda MD PhD, is a Professor and Director of the Division of Developmental Support Research at the Research Center for Child Mental Development, University of Fukui, Japan. Her areas of research interest include child psychiatry, neuroimaging of brain structure and function, attachment disorders, ADHD, and the effects of child maltreatment. Over her 35-year-long research career, she has published more than 140 peer-reviewed articles, along with multiple chapters, letters, and commentaries. Currently, her research focuses on child psychiatry, particularly on identifying the neurobiological and epigenetic consequences of child maltreatment.

Funding Information

The study was supported by

  1. Japan Agency for Medical Research and Development (AMED) (Grant JP20gk0110052)
  2. Japan Society for the Promotion of Science (JSPS) KAKENHI Scientific Research (A) (Grant JP19H00617)
  3. JSPS KAKENHI Scientific Research (C) (Grants JP20K02700, JP21K02352)
  4. Strategic Budget to Realize University Missions, University of Fukui
  5. Research Grants, University of Fukui (FY 2019 and 2020)
  6. Life Science Innovation Center, University of Fukui – Grants for Translational Research and Creative & Innovative Research (LSI20305, LSI22202)
  7. Grant for Life Cycle Medicine, Faculty of Medical Sciences, University of Fukui

Media contact Source and Further Information

Rddhi Chhabra <rddhi.chhabra@cactusglobal.com>

Yuuka Kawamoto, University of Fukui PR center <sskoho-k@ad.u-fukui.ac.jp>

 

Bioengineered Bone Marrow Model Successfully Used in Leukaemia Research

Scientists at the University of Glasgow have successfully used the first bioengineered bone marrow model to carry out vital cancer research, offering new insights into potential therapies for the disease.

The breakthrough is documented in a new study, published in the journal Biomaterials, and represents an important step forward in being able to carry out medical research without the use of animals.

The study details the efficacy of CAR T-cell therapy – a promising new blood cancer treatment – in targeting acute myeloid leukaemia (AML), the most common leukaemia in adults. Researchers say their new bioengineered model has been able to deliver the kind of human-relevant insights and information that current research methods that rely on animal models have so far been unable to achieve. 

Leukaemia cancers are caused by mutations in hematopoietic stem cells (HSCs), which then rely on interactions with the bone marrow for their growth and survival. However, studying these stem cells outside of the body is particularly challenging. Once removed from the bone marrow, HSCs quickly change or die, making them challenging, or impossible, to work with in laboratories. As a result, until now, research teams have had to rely on animal models to test new drugs that could target blood cancers.

Now, a team led by scientists at the University of Glasgow has been able to successfully carry out research on leukaemic HSCs by inserting them into bioengineered jelly-like substances, called hydrogels, that mimic the natural bone marrow environment. The team then targeted the cancer cells with CAR T-cell therapy to find out if it could effectively target the disease. While this is an early-stage study, the approach opens the door to more accurate pre-clinical testing, which - over the next decade - could help improve the development of safer and more effective therapies.

While CAR T-cell therapy has shown promise for other blood cancers, its application to AML has been hindered by a number of issues, including toxicity to local healthy cells

Researchers have suggested that combining CRISPR-Cas9 gene editing with CAR T-cell therapy might have the potential for selectively targeting AML cells while sparing healthy tissue, by essentially making healthy cells ‘invisible’ to CAR T cells. However, so far validating the effectiveness of this combination of treatments prior to clinical trial has been hampered by the differences between humans and animal models.

Using their bioengineered stem cell model the team were able to provide key new information on the efficacy and safety of CAR T-cell therapy for AML. They found that, conventional testing methods - typically cells in a Petri dish - both overestimated the effectiveness of CAR T-cell therapy and failed to predict its harmful effects on healthy cells – issues that were detected using the bioengineered tissue model. The new findings have clear implications not only for future research on CAR T-cell therapy for AML, but also on approaches to pre-clinical CAR T-cell testing.

Dr Hannah Donnelly, one of the lead authors of the study and research fellow at the University of Glasgow said: “There is a major translational gap in cell therapy development – conventional, over-simplified testing methods often fail to predict how therapies will behave in humans. This gap leads to high failure rates in clinical trials, driving up costs and delaying treatments for patients. By using human cells combined with hydrogels to mimic the complex structure of the bone marrow in the lab, we’ve shown that it’s possible to assess both the effectiveness of therapies and detect off-target effects much earlier – well before they reach the expensive clinical trial stage.

“Our results highlight the potential of non-animal technologies for studying and developing new leukaemia therapies. This approach could reduce reliance on animal models in drug testing over time, ultimately paving the way for more efficient and effective development of therapies for patients.”

The study, ‘Synthetic peptide hydrogels as a model of the bone marrow niche demonstrate efficacy of a combined CRISPR-CAR T-cell therapy for acute myeloid leukaemia’ is published in Biomaterials.[1]This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC).

Reference

  1. Sebastian Doherty-Boyd et al. Synthetic peptide hydrogels as a model of the bone marrow niche demonstrate efficacy of a combined CRISPR-CAR T-cell therapy for acute myeloid leukaemia. Biomaterials 328: May 2026, 123803. https://www.sciencedirect.com/science/article/pii/S0142961225007227  

Further Information 

For more information contact Elizabeth McMeekin or Ali Howard in the University of Glasgow Communications and Public Affairs Office on Elizabeth.mcmeekin@glasgow.ac.uk  or ali.howard@glasgow.ac.uk

 

 

Hanyang University Researchers Explore Role of Time-Restricted Eating in Controlling MASLD

A new study explored the benefits of time-restricted eating (TRE) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)

Time-restricted eating (TRE), a form of intermittent fasting, helps with improving weight loss, insulin resistance, and body composition. These factors are the functional changes associated with metabolic dysfunction-associated steatotic liver disease (MASLD). The results of this study explore the efficacy and safety of TRE in patients with MASLD. The study results suggest that TRE can effectively reduce hepatic steatosis and can serve as a practical dietary strategy for MASLD management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition where excess fat builds up in the liver due to metabolic risk factors. The cornerstone for treating MASLD is managing the underlying metabolic risk factors through a healthy diet and physical activity. 

A group of researchers from Hanyang University, under the guidance of Professor Dae Won Jun, explored the effect of time-restricted eating (TRE) in managing MASLD. TRE is a form of intermittent fasting focused on eating all the daily calories within a specific daily window. “What is the most effective and sustainable dietary approach for patients with MASLD? We wanted to find an answer to this question,” mentioned Professor Jun while talking about the motivation behind the study. The study was published online on June 19, 2025, in the Journal of Hepatology [1]

For the study, patients with overweight or obesity and MASLD were randomized into three groups: standard of care (SOC) group, or the control group; the calorie restriction (CR) group; and the TRE group. Improvement in hepatic steatosis and changes in physical, physiological and biochemical parameters were analyzed.

Participants in both the TRE and CR groups showed a significant decrease in hepatic steatosis, body weight, and visceral fat. Serious adverse events were not reported in either the TRE group or the CR group. Notably, TRE participants achieved these benefits simply by limiting eating hours while maintaining their usual meals, without adopting specific diets such as the Mediterranean diet. “Our study suggests that TRE may be more practical and easier to follow, especially for Asian populations,” said Dr Joo Hyun Oh, a researcher associated with the study. Changes in blood glucose, cholesterol, and sleep duration were similar between CR and TRE. This suggests that while TRE effectively improves liver fat and function, it may not provide additional metabolic or sleep-related advantages beyond CR.

As obesity is now a global issue, a clear, evidence-based guidance on finding the right diet is crucial. This research work can help in correcting misconceptions regarding unproven dietary trends. As TRE and CR are similarly effective in managing MASLD, individuals should choose an eating pattern suitable for their lifestyle. In the following years, the insights from this study can guide the development of personalized dietary strategies, tailored to each individual’s daily routine, cultural background, and biological needs. This can help in achieving sustainable weight management and preventing metabolic diseases.

Reference

  1. Joo Hyun Oh et al. Efficacy and safety of time-restricted eating in metabolic dysfunction-associated steatotic liver disease Journal of Hepatology. June 19, 2025. DOI: 1016/j.jhep.2025.06.005   https://www.journal-of-hepatology.eu/article/S0168-8278(25)02272-X/abstract

About Hanyang University

Hanyang University traces its roots back to 1939 when the Dong-A Engineering Institute was established. By 1948, the institute had transformed into the nation’s first private university, evolving into Hanyang University in 1959. At its core, Hanyang University upholds the Founding Philosophy of “Love in Deed and Truth,” and its mission is to provide practical education and professional training to future experts and leaders. With a rich history spanning nearly a century, Hanyang University continues to uphold its core values while adapting to the evolving landscape of education and research, both domestically and internationally.

 https://www.hanyang.ac.kr/web/eng

About Professor Dae Won Jun

Prof Dae Won Jun is a clinician-scientist based in Korea, specializing in steatotic liver disease (SLD). He is a professor at the College of Medicine, Department of Internal Medicine, Hanyang University. He completed his bachelor's and master's in medicine from Hanyang University. His research integrates clinical studies with translational approaches to identify new therapeutic targets for SLD and metabolic liver diseases. He leads nationwide SLD databases and collaborates on the development of small-molecule and RNA-based therapies aimed at improving outcomes in patients with metabolic and alcohol-associated liver diseases.

 

 

Chlorine Dioxide Wonder Drug

There is a helpful substance that anyone can make, good for infections and inflammations, an elegant molecule used to clean millions of tons of public water in the United States every day. Brazil wants to start using it now, and so should you. However, you cannot claim to be treating any of your diseases with it because then the FDA SWAT teams will hunt you down, but if you keep your mouth shut, you can use it for your health.

It is powerful and safe. I use it as a morning mouthwash and for sublingual absorption. I do that first thing every day, and it wipes out any viruses, bacteria, or fungus that might accumulate during the night. Dentists use it legally to treat bad breath, which is not a disease, so it’s legal. They also use it for the oral disorders that chemotherapy and radiation therapy cause in the mouth. I also use it because of its effect on my blood; it basically acts like a healthy blood thinner, because it unclumps red blood cells from each other.

It could be explored for cancer treatment, but that would break the back of Big Pharma, and then where would all the politicians get their money from? We can’t have that, but a doctor from China and some clinics in Germany inject it directly into tumours with a significant effect.

No pathogen survives chlorine dioxide, and no toxicity has been detected. Those who call it bleach might as well say salt is bleach, since it also contains an atom of Cl. Proper use cases, no harm cannot say that about pharmaceuticals, and all the repurposed drugs that some doctors get hysterical about. It truly is a wonderful drug, and I use it only in CDS form, which is chlorine dioxide gas dissolved in water. At 73, one big swig a day ensures the few teeth I still have stay in my mouth.

Curious Outlier, I know his real name is the best source of information about chlorine dioxide. If one is new to chlorine dioxide, please do yourself a favour and visit his site. The name of his site https://theuniversalantidote.com comes from NASA, which in 1987 named chlorine dioxide The Universal Antidote, and it is.

Chlorine dioxide is a selective oxidizer often used as a water purifier. Still, it has gained widespread recognition for its effectiveness in treating a range of diseases, from the simplest to the most complex. It is activated by mixing a sodium chlorite solution (often labelled as MMS: Miracle Mineral Solution) with an acid activator, such as HCl or citric acid, producing MMS1 (chlorine dioxide solution) for consumption. I never take it that way, but I use the same chemicals to make a gas, then throw them down the drain. Purer that way and easier on the stomach, but not quite as strong as the MMS. Autism kids need the extra kick that MMS gives.

The critical thing to note is that autism is avoidable, treatable, and reversible. Since we know what causes autism, it is not impossible to reverse it. Kerri Rivera has written several books on her protocol that has reversed autism. Here are links to the book and her website. The website is www.kerririvera.com , and the link to her book is at   https://www.barnesandnoble.com/w/kerri-rivera-protocol-kerri-rivera/1148200698

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Media Source and Further Information

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