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In a new study, researchers from the Jackson Laboratory and UConn Health not only show how cancer hijacks this tightly regulated RNA splicing and rearrangement, but also propose a potential therapeutic strategy to slow down or even shrink aggressive and hard-to-treat tumors. The discovery could change the way people treat aggressive cancers, such as triple-negative breast cancer and certain brain tumors, for which current treatment options are limited.
Stem cells are immature cells that have a fundamental regenerative role in almost all tissues. They are usually in a quiescent, slowly dividing state. But after injury, they can repair damaged tissues by switching to an activated state so that they can rapidly proliferate and become mature, functional cells. For example, hematopoietic stem cells mostly reside in the bone marrow and remain quiescent until they are stimulated or "mobilized" into the blood.
In the microscopic cellular universe, a protein called PTEN (Phosphatase and tensin homolog) is like a precise molecular brake, constantly regulating cell proliferation and survival. This "life guardian" with only 403 amino acids plays a key role in embryonic development, synaptic plasticity and even tumor suppression by antagonizing the PI3K/AKT/mTOR signaling pathway. However, surprisingly, although 30% of cancers and various neurodevelopmental diseases (such as autism and epilepsy) are closely related to PTEN dysfunction, researchers have long lacked tools to directly observe its dynamics in living tissues-until the emergence of this breakthrough study in Nature Methods ("Genetically encoded biosensor for fluorescence lifetime imaging of PTEN dynamics in the intact brain").
Promoting liver regeneration and inhibiting fibrosis is an attractive strategy for treating human liver diseases, and hepatic stellate cells (HSCs) are very important for both processes. Recently, in a research report entitled "Lhx2 specifically expressed in HSCs promotes liver regeneration and inhibits liver fibrosis" published in the international journal Hepatology, scientists from the Chinese Academy of Sciences identified the transcription factor Lhx2 (LIM homeobox protein 2) as a key regulator of hepatic stellate cells (HSCs). Lhx2 can simultaneously promote liver regeneration and inhibit liver fibrosis.
Recently, the latest research results published by researchers from the Saint Louis University School of Medicine in the journal Science Translational Medicine showed that cancer cells can produce tumor-derived extracellular vesicles (tEVs) containing PD-L1, causing PD-L1 to activate CREB and STAT signals, leading to lipid metabolism reprogramming of T cells. This induces T cell senescence and achieves immunosuppression. Blocking this process is expected to improve the sensitivity of solid tumors to immunotherapy such as PD-L1 inhibitors.
Pancreatic cancer is the deadliest of all cancers. Only 12% of men diagnosed with pancreatic cancer are alive five years after diagnosis; 14% of women. In pancreatic cancer, symptoms are usually not obvious and usually appear later in its progression. Once this cancer spreads, it is difficult to treat because it cannot be completely removed by surgery.
A small but promising clinical study led by Memorial Sloan-Kettering Cancer Center suggests that adding a personalized mRNA vaccine to standard treatment may bring new hope to pancreatic cancer patients. The study followed 16 pancreatic cancer patients. Specifically, in addition to standard treatments such as surgery and chemotherapy, these patients received a customized mRNA vaccine designed using their own tumors. Unlike vaccines that are originally designed to prevent disease, this vaccine is designed to help the patient's own immune system fight cancer.
The blood-brain barrier (BBB) refers to the barrier between plasma and brain cells formed by the walls of brain capillaries and glial cells, and the barrier between plasma and cerebrospinal fluid formed by the choroid plexus, which only allows specific types of molecules to enter brain neurons and other surrounding cells from the bloodstream. The existence of the blood-brain barrier is of great significance in preventing harmful substances from entering the brain from the blood. However, it also prevents the transfer of most small and large molecule drugs (such as peptides, proteins and nucleic acids), severely limiting the treatment of central nervous system diseases (such as neurodegenerative diseases, brain tumors, brain infections and strokes). Although some progress has been made in this field in recent years, we still urgently need technologies that can cross the blood-brain barrier and improve the delivery of biomacromolecule-based therapies to the central nervous system (CNS) through systemic administration.
As an RNA therapy tool, circular mRNA has higher stability and durability than linear mRNA. However, its translation efficiency is low and it mainly relies on the internal ribosome entry site (IRES) to initiate translation. But the IRES-mediated translation efficiency is generally low, which severely limits the application of circular mRNA in therapy.
The CRISPR-Cas system is an adaptive immune system of bacteria and archaea that can resist the invasion of viruses and mobile genetic elements. Although the DNA targeting mechanisms of CRISPR-Cas9 and CRISPR-Cas12 systems have been widely studied, the evolutionary origin of the RNA-targeted CRISPR-Cas13 system is still unclear.
