Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: biotech/medical – Page 391

A power move in the study of sepsis-associated acute kidney injury

Using a new strategy for quantifying mitochondrial DNA, Mark L. Hepokoski & team show the release of mtDNA from the kidney directly contributes to interleukin-6 release during sepsis associated AKI.

1VA San Diego Healthcare System, San Diego, California, USA.

2Division of Pulmonary and Critical Care and Sleep Medicine, UCSD, La Jolla, California, USA.

3Department of Critical Care Medicine, Yantai Yuhuangding Hospital, Affiliated with Medical College of Qingdao University, Yantai, Shandong, China.

Exercise slows tumor growth in mice by shifting glucose uptake to muscles

It’s well known that exercise is good for health and helps to prevent serious diseases, like cancer and heart disease, along with simply making people feel better overall. However, the molecular mechanisms responsible for preventing cancer or slowing its progression are not well understood. But, a new study, published in the Proceedings of the National Academy of Sciences, reveals how exercise can increase glucose and oxygen uptake in the skeletal and cardiac muscles, instead of allowing it to “feed” tumors.

Reduced tumor growth in exercised mice To study how exercise-induced metabolic changes affect tumor growth, the research team injected mice with breast cancer cells and fed some of the mice a high-fat diet (HFD), consisting of 60% calories from fat, while others were fed a normal diet as a control. The HFD mice were given running wheels for exercise, although exercise was voluntary. The team used stable isotope tracer studies [U-13C6] glucose and [U-13C5] glutamine to track metabolic changes.

After 4 weeks of wheel running, the team found a significant difference in tumor sizes between mice that chose to exercise, compared to those that did not—even when they were fed the same diet.

Characterizing Fibroblast Heterogeneity in Diabetic Wounds Through Single-Cell RNA-Sequencing

DDX3X acts as a selective dual switch regulator of mRNA translation in acute ER stress.

Shawky et al. show that DDX3X selectively promotes or represses mRNA translation in a stress-dependent manner. This bidirectional regulation involves position-specific binding to the mRNA 5′ UTR and early coding region, reflecting distinct mechanisms, including initiation control during 48S scanning and translational repression associated with ac4C post-transcriptional modification.

Early Alpha-Fetoprotein Response Predicts Sustained Tumor Response Following Immune Checkpoint Inhibitors Combined with Targeted Therapy in Liver Cancer

Background: Although immune checkpoint inhibitors (ICI) have revolutionized liver cancer treatment, some patients experience early tumor progression after therapy, missing the window for other potential treatments, such as neoadjuvant therapy. Therefore, identifying the predictive factors for early progression is critical for timely therapeutic adjustment and the optimization of patient outcomes. Methods: This retrospective study enrolled patients with liver cancer who received their first ICI combined with targeted therapy at the Fifth Medical Center of the PLA General Hospital between June 2022 and December 2023. Early tumor progression was defined as tumor progression within 6 months of therapy initiation.

Reversing treatment resistance in prostate cancer

Scientists at the Herbert Irving Comprehensive Cancer Center (HICCC) have discovered a key mechanism that makes prostate cancer cells resistant to the latest drugs used to treat them. Their findings, reported in the current issue of Nature, solve a longstanding puzzle in tumor biology and present preclinical data on a drug compound that could soon enter the clinic.

The work grew out of decades of prostate cancer research by Michael Shen, Ph.D., co-leader of the Tumor Biology and Microenvironment research program at the HICCC. Shen’s research focuses on lineage plasticity, the ability of cancer cells to reprogram themselves to impersonate other types of cells.

“Plasticity is a hallmark of cancer in general and a very important feature of advanced prostate cancer, particularly when it comes to the emergence of treatment resistance,” says Shen. Treatment with androgen receptor inhibitors, which have become the standard of care in recent years, often stimulate prostate tumor cells to adopt neuroendocrine characteristics, rendering them resistant to the drugs.

Non-opioid ‘pain sponge’ therapy shows promise for chronic pain relief and halting cartilage degeneration

SereNeuro Therapeutics, a preclinical biotechnology company developing non-opioid pain therapies, has unveiled new data on a novel approach to chronic pain management and joint tissue preservation. The data highlight SN101, a first-in-class induced pluripotent stem cell (iPSC)-derived therapy.

The announcement was made at the International Society for Stem Cell Research (ISSCR) Symposium Accelerating PSC-Derived Cell Therapies: Starting with the End in Mind.

‘Mob breaker’ TRIM37 prevents abnormal cell division by eliminating extra spindle poles

In 2000, researchers discovered that mutations that inactivate a gene known as TRIM37 cause a developmental disease called Mulibrey nanism. The extremely rare inherited disorder leads to growth delays and abnormalities in several organs, causing afflictions of the heart, muscles, liver, brain and eyes. In addition, Mulibrey nanism patients exhibit high rates of cancer and are infertile.

In 2016, UC San Diego School of Biological Sciences researchers in the labs of Professors Karen Oegema and Arshad Desai began understanding how TRIM37, when operating normally, plays a key role in preventing conditions that lead to Mulibrey nanism. They linked TRIM37 to spindles, which separate chromosomes during , and centrosomes, the spherical organizing structures at each end of spindles.

The image above shows a normal mitotic cell (left) compared to a cell lacking TRIM37 (right), with spindle microtubules (green), centrosomal protein centrobin (magenta) and DNA (white). Normal cells have two spindle poles that ensure proper cell division. Cells lacking TRIM37 frequently have extra spindle poles, containing a cluster of centrobin molecules that disrupt proper cell division. Patients with Mulibrey nanism lack TRIM37 and their cells show similar extra spindle poles.

Genome-wide association study of proteomic aging reveals shared genetic architectures with longevity, early life development, and age-related diseases

There is still relatively little known about the genetic underpinnings of proteomic aging clocks. Here, we describe a genome-wide association study of proteomic aging in the UK Biobank (n=38,865), identifying 27 loci associated with participants’ proteomic age gap (ProtAgeGap). ProtAgeGap exhibits a strong genetic correlation with longevity (rg = −0.83), and in FinnGen a ProtAgeGap polygenic score (PGS) was associated with significantly increased odds of achieving longevity (n=500,348; OR = 1.43). Additional PGS analyses in All of Us (n=117,415), China Kadoorie Biobank (n=100,640), and ABCD Study (n=5,204) demonstrate reproducible associations across biobanks of ProtAgeGap PGS with obesity, cardiometabolic disease, and osteoarthritis in adults, and with developmental timing in children. Finally, colocalization analysis identified FTO as an obesity-related mechanism uniting diverse aging traits. Our results demonstrate a shared genetic architecture across the life course of ProtAgeGap with longevity, early developmental biology, and cardiometabolic and musculoskeletal diseases.

### Competing Interest Statement.

The authors have declared no competing interest.

/* */