Power of cancer drugs may see boost by targeting newly identified pathway

Proteins labeled with colored tags fill the main compartment — but not the nuclei (blue) — of human cervical cancer cells. Green cells contain the protein TRPV2, red cells contain STING, and yellow and orange cells contain a mixture of both. The proteins are part of a newly discovered DNA-protection pathway that potentially could be targeted to improve cancer therapies, according to researchers at Washington University School of Medicine in St. Louis.
Image Credit: Lingzhen Kong

Cells zealously protect the integrity of their genomes, because damage can lead to cancer or cell death. The genome — a cell’s complete set of DNA — is most vulnerable while it is being duplicated before a cell divides. Cancer cells constantly are dividing, so their genomes are constantly in jeopardy.

Researchers at Washington University School of Medicine in St. Louis has identified a previously unknown signaling pathway cells use to protect their DNA while it is being copied. The findings, published in the journal Molecular Cell, suggest that targeting this pathway potentially could boost the potency of cancer therapeutics.

“A cell that can’t protect its genome is going to die,” said senior author Zhongsheng You, a professor of cell biology and physiology. “This entire pathway we found exists to protect the genome so the cell can survive in the face of replication stress. By combining inhibitors of this pathway with chemotherapy drugs that target the DNA replication process, we potentially could make such drugs more effective.”

Pioneering approach advances study of CTCF protein in transcription biology

Scientists at St. Jude collaborated to better understand CTCF. L to R: Beisi Xu, PhD, Chunliang Li, PhD; Judith Hyle; Mohamed Nadhir Djekidel, PhD.
Photo Credit: St. Jude Children's Research Hospital

Scientists at St. Jude Children’s Research Hospital used the auxin-inducible degron 2 system on CTCF, bringing the novel approach to bear on a fundamental protein.

CTCF is a critical protein known to play various roles in key biological processes such as transcription. Scientists at St. Jude Children’s Research Hospital used a next-generation protein degradation technology to study CTCF. Their work revealed the superiority of the approach in addition to providing functional insights into how CTCF regulates transcription. The study, published today in Genome Biology, paves the way for more clear, nuanced studies of CTCF.

Transcription is an essential biological process where DNA is copied into RNA. The process is the first required step in a cell to take the instructions housed in DNA and ultimately translate that code into the amino acid or polypeptide building blocks that become active proteins. Dysregulated transcription plays a role in many types of pediatric cancer. Finding ways to modify or target aspects of the transcriptional machinery is a novel frontier in the search for vulnerabilities that can be exploited therapeutically.

While the biology of CTCF has been extensively studied, how the different domains (parts) of CTCF function in relation to transcription regulation remains unclear.

Risk of developing heart failure much higher in rural areas vs. urban

Photo Credit: Tumisu

Large NIH-supported study showed that rural-dwelling Black men are at greatest risk.

Adults living in rural areas of the United States have a 19% higher risk of developing heart failure compared to their urban counterparts, and Black men living in rural areas have an especially higher risk – 34%, according to a large observational study supported by the National Institutes of Health.

The study, one of the first to look at the link between living in rural America and first-time cases of heart failure, underscores the importance of developing more customized approaches to heart failure prevention among rural residents, particularly Black men. The study was largely funded by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, and the findings, produced in collaboration with Vanderbilt University Medical Center, Nashville, Tennessee, published today in JAMA Cardiology.

“We did not expect to find a difference of this magnitude in heart failure among rural communities compared to urban communities, especially among rural-dwelling Black men,” said Véronique L. Roger, M.D., M.P.H., the study’s corresponding author and a senior investigator with the Epidemiology and Community Health Branch in NHLBI’s Division of Intramural Research. “This study makes it clear that we need tools or interventions specifically designed to prevent heart failure in rural populations, particularly among Black men living in these areas.”

No link between IVF-assisted conception and school-age childhood development outcomes

Researchers say the study offers important reassurance for clinicians and families.
Photo Credit: Yan Krukau

A comprehensive study of more than 400,000 children - with over 11,000 conceived via in-vitro fertilization (IVF) - has found no link between IVF conception and adverse developmental outcomes for school-age children.

Published today in PLOS Medicine, the study involved collaboration between the three major IVF units in Victoria - Melbourne IVF, Monash IVF and City Fertility Centre, and incorporated data on over 400,000 children born between 2005 and 2013, 11,059 of whom were conceived via IVF.

Led by Dr Amber Kennedy and Dr Anthea Lindquist, the study assessed childhood developmental and educational outcomes using the Australian Early Development Census (AEDC) and the National Assessment Program for Literacy and Numeracy (NAPLAN).

Dr Kennedy said: “We found no difference in performance across the five domains of the AEDC, nor in NAPLAN scores, between children who were born after IVF-assisted conception and those who were conceived without assistance.

Where you live and what cardiometabolic conditions you have affects risk of developing dementia

Image Credit: Gerd Altmann

People in the United States and England who have multiple cardiometabolic conditions such as diabetes and high systolic blood pressure are more likely to develop dementia than their peers who are relatively healthy, according to new research from the University of Surrey.

The study also found that people living in China have an increased risk of developing dementia if they have obesity and hypertension when compared to those in their country who are relatively healthy.

Panagiota Kontari, a post-graduate researcher in the School of Psychology at the University of Surrey, said:

“Dementia affects 55 million people worldwide and there is currently no cure, so prevention is key. Cardiometabolic conditions have been shown to increase likelihood of developing the syndrome due to their link with vascular, biological and neurodegenerative diseases, which might accelerate brain ageing and cognitive decline.

“Understanding how cardiometabolic conditions are clustered and which particular combination of them leads to a greater risk of dementia across the world is important as such knowledge could help design tailored prevention strategies that target varying risk factors in different countries.”

Propionic acid protects nerve cells and supports their regeneration

Thomas Grüter and Kalliopi Pitarokoili (right) from the study team in St. Josef Hospital.
Photo Credit: RUB, Marquard

Some autoimmune diseases attack the nerves in the arms and legs. Researchers from Bochum are taking a new approach to counteract this damage.

In laboratory tests, researchers from St. Josef Hospital Bochum showed that propionate, the salt of a short-chain fatty acid, can protect nerves and help with their regeneration. The findings could be useful for the treatment of autoimmune diseases that damage nerve cells, such as chronic inflammatory demyelinating polyneuropathy (CIDP). Propionate naturally arises in the intestine when fiber is broken down. In previous studies, a team from the same department from St. Josef Hospital Bochum, clinic of the Ruhr University Bochum, has already proven that people with multiple sclerosis (MS) have a lack of propionate and can benefit from additional propionate intake. Accordingly, the substance could also be useful for patients with CIDP.

A group led by Dr. Thomas Grüter and private lecturer Dr. Kalliopi Pitarokoili from the Neurological University Clinic on St. Josef Hospital (Head of Prof. Dr. Ralf Gold), in the journal Proceedings of the National Academy of Sciences.

A soybean protein blocks LDL cholesterol production, reducing risks of metabolic diseases

Graduate student Jennifer Kusumah, center; postdoctoral researcher Erick Damian Castañeda-Reyes, right; and undergraduate student Elen Huang, left; examine the antioxidant effects of soybean proteins that can decrease LDL cholesterol storage in human liver cells, potentially curtailing the development of metabolic diseases such as fatty liver disease and atherosclerosis. 
Photo Credit: Fred Zwicky

A protein in soybeans blocks the production of a liver enzyme involved in the metabolism of triglycerides and low-density lipoprotein, scientists found in a recent study.

Consuming soy flour rich in the protein B-conglycinin has the potential to reduce LDL cholesterol levels and lower the risk of metabolic diseases such as atherosclerosis and fatty liver disease, said Elvira de Mejia, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign and the corresponding author of the study.

Published in the journal Antioxidants, the study was co-written by Neal A. Bringe, a food scientist with Benson Hill Company; and Miguel Rebollo Hernanz, who at the time of the research was a visiting scholar at the U. of I. Rebollo Hernanz is the first author of the paper.

Scientists have long known of soybeans’ cholesterol-lowering properties and lipid-regulating effects, and the current project investigated two soy proteins thought to be responsible for these outcomes – glycinin and B-conglycinin – and found the latter to be particularly significant.

New Tool Uses Ultrasound ‘Tornado’ to Break Down Blood Clots

Ultrasonic Tornado
Illustration Credit: Xiaoning Jiang / Courtesy of North Carolina State University

Researchers have developed a new tool and technique that uses “vortex ultrasound” – a sort of ultrasonic tornado – to break down blood clots in the brain. The new approach worked more quickly than existing techniques to eliminate clots formed in an in vitro model of cerebral venous sinus thrombosis (CVST).

“Our previous work looked at various techniques that use ultrasound to eliminate blood clots using what are essentially forward-facing waves,” says Xiaoning Jiang, co-corresponding author of a paper on the work. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront.

“In other words, the ultrasound is swirling as it moves forward,” says Jiang, who is the Dean F. Duncan Professor of Mechanical and Aerospace Engineering at North Carolina State University. “Based on our in vitro testing, this approach eliminates blood clots more quickly than existing techniques, largely because of the shear stress induced by the vortex wave.”

“The fact that our new technique works quickly is important, because CVST clots increase pressure on blood vessels in the brain,” says Chengzhi Shi, co-corresponding author of the work and an assistant professor of mechanical engineering at Georgia Tech. “This increases the risk of a hemorrhage in the brain, which can be catastrophic for patients.

Stanford Medicine researchers measure thousands of molecules from a single drop of blood

A single drop of blood can yield measurements for thousands of proteins, fats and other biomarkers, researchers at Stanford Medicine found.
Photo Credit: PublicDomainPictures

Researchers at Stanford Medicine have shown they can measure thousands of molecules — some of which are signals of health — from a single drop of blood.

The new approach combines a microsampling device — a tool used to self-administer a finger prick — with “multi-omics” technologies, which simultaneously analyze a vast array of proteins, fats, by-products of metabolism and inflammatory markers.

“Even more importantly, we’ve shown you can collect the blood drop at home and mail it into the lab,” said Michael Snyder, PhD, director of the Center for Genomics and Personalized Medicine and senior author on the research, which was published in Nature Biomedical Engineering on Jan. 19.

Unlike finger-prick testing for diabetes, which measures a single type of molecule (glucose), multi-omics microsampling gives data about thousands of different molecules at once.

The research sounds similar to a well-known approach promoted in the past for testing a single drop of blood, but there are important differences: While the earlier approach was based on replicating existing diagnostic tests, multi-omic microsampling uses a different type of data analysis based on a technology called mass spectrometry, which sorts molecules based on their mass and electronic charge. In addition, the data analysis is performed in a lab, not in a portable box.

Getting under your skin for better health

UC College of Engineering and Applied Science professor Jason Heikenfeld in his Novel Devices Lab.
 Photo Credit: Andrew Higley/UC Marketing + Brand

The next frontier of continuous health monitoring could be skin deep.

Biomedical engineers at the University of Cincinnati say interstitial fluid, the watery fluid found between and around cells, tissues or organs in the body, could provide an excellent medium for early disease diagnosis or long-term health monitoring.

In a paper published in the journal Nature Biomedical Engineering, they outlined the potential advantages and technological challenges of using interstitial fluid.

“Why we see it as a valuable diagnostic fluid is continuous access. With blood, you can’t easily take continuous readings,” said UC doctoral graduate Mark Friedel, co-lead author of the study.

“Can you imagine going about your day with a needle stuck in your vein all day? So, we need other tools.”

MIT researchers develop an AI model that can detect future lung cancer risk

Caption:Researchers from Massachusetts General Hospital and MIT stand in front of a CT scanner at MGH, where some of the validation data was generated. Left to right: Regina Barzilay, Lecia Sequist, Florian Fintelmann, Ignacio Fuentes, Peter Mikhael, Stefan Ringer, and Jeremy Wohlwend
 Photo Credit: Guy Zylberberg.

The name Sybil has its origins in the oracles of Ancient Greece, also known as sibyls: feminine figures who were relied upon to relay divine knowledge of the unseen and the omnipotent past, present, and future. Now, the name has been excavated from antiquity and bestowed on an artificial intelligence tool for lung cancer risk assessment being developed by researchers at MIT's Abdul Latif Jameel Clinic for Machine Learning in Health, Mass General Cancer Center (MGCC), and Chang Gung Memorial Hospital (CGMH).

Lung cancer is the No. 1 deadliest cancer in the world, resulting in 1.7 million deaths worldwide in 2020, killing more people than the next three deadliest cancers combined. 

"It’s the biggest cancer killer because it’s relatively common and relatively hard to treat, especially once it has reached an advanced stage,” says Florian Fintelmann, MGCC thoracic interventional radiologist and coauthor on the new work. “In this case, it’s important to know that if you detect lung cancer early, the long-term outcome is significantly better. Your five-year survival rate is closer to 70 percent, whereas if you detect it when it’s advanced, the five-year survival rate is just short of 10 percent.” 

Coating bubbles with protein results in a highly stable contrast agent for medical use

Bacteria produce gas vesicles
Image Credit: Aalto University

Inspired by the bubbles bacteria create inside their cells, researchers developed a similar system by coating tiny gas vesicles with protein. The resulting bubbles are safe, highly stable, and function as contrast agent in medical applications. They could be used to diagnose, for example, cardiological issues, blood flow, and liver lesions.

Bacteria produce gas vesicles, tiny thin-walled sacs filled with air or fluid, to help them float. This phenomenon has captured the attention of scientists who see potential for similar bubble-based designs in fields like medicine. A team of researchers at Aalto University’s Department of Applied Physics, led by Professor Robin Ras, have now used the same idea to create a new kind of contrast agent for use in medical applications such as ultrasound imaging. The research was recently published in the Proceedings of the National Academy of Sciences.

Study indicates likely cause of common penis birth-defect

The prevalence of hypospadias has increased by 11.5% in recent decades, making it the most common genital malformation in newborn males.
Photo Credit: Carlo Navarro

An alarming increase in the occurrence of the most common genital malformation in male babies, hypospadias, is likely due to environmental factors, such as toxicant exposure, which alter epigenetic programming in a forming penis. 

That’s according to a new study in Scientific Reports that identified a direct link between hypospadias tissue samples and the presence of epigenetic alterations, or changes to the molecular factors and processes around DNA that determine how genes behave. Conversely, epigenetic alternations were not found in penile tissue samples taken from the foreskin of healthy babies without hypospadias, according to the Washington State University-led analysis. 

The research helps answer long-standing questions surrounding the increased frequency and potential root cause of hypospadias, a birth defect in which the opening of the urethra is located on the underside of the penis instead of the tip. 

New study to tackle role of environmental contamination in the growing problem of antibiotic resistance

Photo Credit: Volodymyr Hryshchenko

Environmental factors, including pollution, that might help ‘superbugs’ become resistant to antibiotics is set to be investigated by the University of Surrey. Findings will help address this serious public health problem by identifying trends and emerging areas that require further research.

During this new eighteen-month study, funded by the One Health European Joint Project, Surrey researchers will embark on work to catalogue the evidence of the effects of environmental factors on antibiotic resistance.  

Dr Giovanni Lo Iacono, Senior Lecturer in Biostatistics and Epidemiology at the University of Surrey, said:

“The World Health Organization has declared antimicrobial resistance as one of the top 10 global public health threats facing humanity. The danger of it cannot be underestimated as it limits treatment options for those who need it most and means that certain infections can become uncontrollable.”

Antibiotic resistance, which is a form of wider antimicrobial resistance, is the ability of bacteria to withstand antibiotics and has led to increasing treatment failure for commonplace infections. Misuse and overuse of antibiotics were previously believed to be the sole cause of this threat. However, the role of environmental factors such as contamination of water or soil by antibiotics, potentially impacting the food chain, is now being recognized.

Chemists Created a Substance with Potential Antitumor Activity

The new antitumor substance was synthesized at Ural Federal University's Scientific-educational and Innovation Center of Chemical and Pharmaceutical Technologies.
Photo Credit: Rodion Narudinov

New compound could be the basis of a drug for tumor cells

Chemists from the Ural Federal University and Volgograd State Medical University have created a compound that suppresses cancer cells. The powerful new substance could become the basis for antitumor drugs because it affects the pathology that leads to the development of malignant tumors, such as cancer of the breast, lung, prostate, and lymph nodes. The substance and the results of the experiments were published in the journal Molecules.

"Type 2 casein kinase (CK2) is known to suppress apoptosis in cells, but increased levels of type 2 casein kinase are observed in tumor cells, indicating that these cells are resistant to apoptosis compared to normal cells. If you block this protein, you can achieve tumor cell death. So, our team managed to develop a universal approach to the synthesis of new azolopyrimidines and obtain a library of corresponding heterocycles as potential inhibitors of casein kinase type 2," explains Grigory Urakov, an Engineer of the Scientific Laboratory of Medical Chemistry and Advanced Organic Materials at UrFU.

Highly accurate test for common respiratory viruses uses DNA as ‘bait’

Doctor examining a patient
Photo Credit: Thirdman

The test uses DNA ‘nanobait’ to detect the most common respiratory viruses – including influenza, rhinovirus, RSV and COVID-19 – at the same time. In comparison, PCR (polymerase chain reaction) tests, while highly specific and highly accurate, can only test for a single virus at a time and take several hours to return a result.

While many common respiratory viruses have similar symptoms, they require different treatments. By testing for multiple viruses at once, the researchers say their test will ensure patients get the right treatment quickly and could also reduce the unwarranted use of antibiotics.

In addition, the tests can be used in any setting, and can be easily modified to detect different bacteria and viruses, including potential new variants of SARS-CoV-2, the virus which causes COVID-19. The results are reported in the journal Nature Nanotechnology.

The winter cold, flu and RSV season has arrived in the northern hemisphere, and healthcare workers must make quick decisions about treatment when patients show up in their hospital or clinic.

Rapid cognitive decline uncommon in ageing people with HIV on stable treatment

We need to determine whether people with HIV may require additional care as a result of mental and cognitive health changes as they reach their 60s.
Photo Credit: Sabine van Erp

As with all chronic conditions, a focus on cognitive and mental health should be part of ongoing care.

With successful treatment, HIV has become a chronic health condition which can be managed with life-long care.

Treatment reduces the amounts of HIV in the blood to an undetectable level and most people with the infection who take their medication live as long as people without HIV.

While there have been successful developments in treating the virus, it’s important to understand how it may impact the long-term cognitive function of those ageing with HIV.

Associate Professor Lucette Cysique at the School of Psychology, UNSW Sydney, and her team conducted a long-term study of cognitive function in people who are ageing with chronic stable HIV infection, from 17 care facilities across Australia, published in eClinicalMedicine.

Excessive bed occupancy in hospitals leads to rising mortality

As shown in a new study by the University of Basel, individual empty beds do not necessarily mean a smaller burden on nursing staff.
Photo Credit: Gorden Murah Surabaya

Researchers have long suspected a link between bed occupancy and mortality in hospitals. Now, a study by the University of Basel has provided the missing data, revealing that smaller hospitals reach their capacity limit much earlier.

Since the outbreak of the coronavirus pandemic, if not before, we’ve got used to seeing figures relating to bed occupancy in Swiss hospitals in media reports. You might think that as long as there are free beds, there’s no problem. Now, a University of Basel study led by Professor Michael Simon has shown that, in some cases, the mortality rate in hospitals rises significantly before full capacity is reached.

For the study, the researchers analyzed data from over 1.1 million inpatient cases at 102 Swiss hospitals in order to investigate the relationship between bed occupancy and the 14-day mortality rate in hospitals. In other words, the cases were observed until the 14-day mark unless they were discharged earlier.

Joint study reveals how DNA unzipping machine works, shedding lights on cancer therapy

An initial open structure (IOS) is formed upon binding of human MCM double hexamer (hMCM-DH) to origin DNA.
Illustration Credit: Image modified from original illustration of Li et al, 2023 Cell 186, 1-14. Source/ Hong Kong University of Science and Technology

Scientists from The Hong Kong University of Science and Technology (HKUST), The University of Hong Kong (HKU) and Institut Curie, France have jointly uncovered a new mechanism of the human MCM2-7 complex in regulating replication initiation, which can be used as a novel and effective anticancer strategy with the potential for selective killing of cancer cells. The findings were recently published in the Cell journal.

Human life begins with a single fertilized egg in the mother’s womb. This egg propagates through cell divisions and develops into our multicellular body. During each cell division, our genome DNA, the blueprint of genetic information, is accurately replicated. Each cell carries roughly 2 meters of DNA organized into 23 pairs of chromosomes. In our lifetime (~70 years), our body will synthesize more than a light year’s length of DNA of ~1016 meters - the distance light travels in one year. The replication process requires the DNA duplex to be first melted and then separated into two single-stranded templates for DNA polymerases to synthesize as complement strands. Any misregulation of this process can cause dire consequences, such as tumorigenesis and inherited genetic disorders.

UC research shows people with latent tuberculosis infection are more prone to inflammation

Moises Huaman, MD, of the Division of Infectious Diseases in the Department of Internal Medicine at the UC College of Medicine
Photo Credit: University of Cincinnati

Study examines connection between inflammation, infection and cardiovascular risk

Newly published research from the University of Cincinnati finds that people with latent tuberculosis infection (LTBI) have more inflammation and could be at a higher risk for cardiovascular disease.

The research was published in Open Forum Infectious Diseases, a journal from the Infectious Diseases Society of America.

Roughly 25% of the world population has LTBI, a state where the individual has been exposed to tuberculosis but is not sick from it, says Moises Huaman, MD, of the Division of Infectious Diseases in the Department of Internal Medicine at the UC College of Medicine and corresponding author on the study.

“Developing countries have higher rates of LTBI,” says Huaman. “There are areas in the world where LTBI may affect 50% or so of the population. Here in the United States, the prevalence of LTBI is about 5%, which is still common. It is a global health problem.”