Mayo Clinic scientists used DNA aptamers to tag senescent “zombie” cells, opening new paths for anti-aging and disease therapies.
Category: biotech/medical – Page 26
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 cell division, 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.
Rejuvenating aged haematopoietic stem cells by targeting RhoA
In their nucleus, as they replicate, blood stem cells can accumulate mutations and lose epigenetic marks that used to keep DNA well-arranged, ultimately increasing mechanical tension on the nuclear envelope. This study figured out RhoA is a mechanosensor activated by such tension and conducts a key role in the stem cell ageing process. Researchers subsequently proved its rejuvenating potential: after ex vivo treatment of blood stem cells with the drug Rhosin, a RhoA inhibitor, they observed an improvement in aged-related markers.
As study co-author summarizes: “Overall, our experiments show that Rhosin did rejuvenate blood stem cells, increased the regenerative capacity of the immune system and improved the production of blood cells once transplanted in the bone marrow.”
Ageing is defined as the deterioration of function overtime, and it is one of the main risk factors for numerous chronic diseases. Although ageing is a complex phenomenon affecting the whole organism, it is proved that the solely manifestation of ageing in the haematopoietic system affects the whole organism.
A research team previously revealed the significancy of using blood stem cells to pharmacologically target ageing of the whole body, thereby suggesting rejuvenating strategies that could extend healthspan and lifespan. Now, in a Nature Ageing publication, they propose rejuvenating aged blood stem cells by treating them with the drug Rhosin, a small molecule that inhibits RhoA, a protein that is highly activated in aged haematopoietic stem cells. This study combined in vivo and in vitro assays together with innovative machine learning techniques.
Blood stem cells, or hematopoietic stem cells, are located in the bone marrow, a highly dynamic and specialised tissue within the cavity of long bones. They are responsible for the vital function of continuously producing all types of blood cells: red blood cells (oxygen transporters), megakaryocytes (future platelets) and white blood cells (immune cells, lymphocytes and macrophages). Over time, however, stem cells also do age, they lose their regenerative capacity and generate fewer and lower quality immune cells. This has been linked to immunosenescence, chronic low grade inflammation and certain chronic diseases.