Although radioresistant and circulating tumor cell survival has been attributed to altered metabolism, the metabolic impact of radiation therapy on stromal cells is unknown. Corn et al. demonstrate radiation-induced mitochondrial and metabolic changes in fibroblasts that are regulated by autophagy and drive growth in triple-negative breast cancer.
The importance of diet and lifestyle in maintaining overall health has long been recognised. MicroRNAs (miRNAs) have emerged as key players in the intricate interplay between health and disease. This study, including 305 participants, examined the role of miRNAs from capillary blood as indicators of individual physiological characteristics, diet, and lifestyle influences. Key findings include specific miRNAs associated with inflammatory processes and dietary patterns. Notably, miR-155 was associated with subjects with metabolic diseases and upregulated in age. Additionally, the study revealed diet-related miRNA expressions: high consumption of vegetables, fruits, and whole grains correlated with increased levels of miR-let-7a and miR-328, both implicated in anti-inflammatory pathways, and decreased expression of pro-inflammatory miR-21.
Here, Dolly Mehta & team find loss of ERG in endothelial cells alters neutrophil transcriptome towards inflammatory lineage via IL8/CXCR2 and CXCR2 blockade with Reparixin reduces inflammation, neutrophil infiltration, and improves survival in a pneumonia model.
The figure shows mouse lungs 30 minutes after antibody administration, with increased number of neutrophils (green) in Erg-null mice compared with Ergfl/fl mice. Endothelium (red).
1Department of Pharmacology and Regenerative Medicine, and.
2Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois Chicago, College of Medicine, Chicago, Illinois, USA.
Address correspondence to: Dolly Mehta, Department of Pharmacology and Regenerative Medicine, University of Illinois, Chicago, College of Medicine, 835 S. Wolcott Avenue, Chicago, Illinois 60,612, USA. Phone: 312.355.0236; Email: dmehta@uic.edu.
The immune system’s B cells create antibodies that can mount a response against just about anything—either destroying a pathogen or instructing the rest of the immune system to go after the offender. But what happens when these antibodies malfunction?
Researchers at Boston Children’s Hospital have identified the previously unknown mechanism for how immune cells can go back and self-edit the genes that code for these antibodies, essentially recycling them into newer versions.
The workings of this new mechanism, published in Nature, were uncovered in the laboratory of Frederick Alt, Ph.D., of the Program in Cellular and Molecular Medicine at Boston Children’s and a Howard Hughes Medical Center Investigator.
Among the many promising possibilities of using CRISPR-based therapeutics, their translational use in monogenic human genetic diseases has the potential to provide long-term therapy after a single treatment. Genetic disorders can be treated with the help of CRISPR by editing the defective (disease-causing) gene or by editing the enhancer or regulator of the defective gene. Numerous studies, which are summarized in the table below (Table ), have shown promising results by using these two approaches.
3. Examples of CRISPR-Based Therapeuticsfor the Treatment of Genetic Disorders.
DiseaseCRISPR targetapproachmajor outcome of the studyreferenceDuchenne muscular dystrophydystrophin gene (DMD)single or multiplexed sgRNAs were developedto restore thedystrophin reading frame by targeting the mutational hotspot at exons45–55 and introducing shifts within exons or deleting one ormore exonsdystrophin expression is restored in vitroOusterout et al. Huntington’sdiseaseHuntingtin gene (HTT)HTT 5′ UTR was targetedimpropermaturation of the transcript and reducing the expressionof the disease-causing alleleKolli et al.a dual sgRNA approachwas used in vitro toexcise a 44kb promoter region upstream of a mutant HTT gene to silence its expressionexpression of the Huntington’sdisease-causing variant wasablatedShin et al.glaucomamyocilin gene (MYOC)Knocked down the expression of mutant MYOC in a mouse model of primary open-angle glaucomareductionof ER stress, lower intraocular pressure, and thepreventability of further glaucomatous damage in mouse eyes was observed. The authors also demonstrated the feasibility of utilizing CRISPR/Cas9in human eyes with glaucomaJain et al.hereditary tyrosinemiatype Ifumarylacetoacetate hydrolase gene (FAH)HDR-mediated point mutation correction in mouse hepatocytes.a significant proportion of alleles were correctedVanLith et al. Leber congenital amaurosis type 10 (LCA10)centrosomalprotein 290 gene (CEP290)AAV5-basedtherapy (EDIT-101) encapsulates Staphylococcusaureus Cas9 (SaCas9) and two sgRNAs targeting genomic locationsupstream and downstream of the intronic CEP290 pointmutation. The two sgRNAs enable cutting around the mutation to induceits removal or inversionnormal splicing of CEP290 pre-mRNA was restoredMaeder et al. Noonan syndromeleucine zipper like post translational regulator 1 gene (LZTR1)intron 16 of LZTR1 was targetedthe gene editing process could overcomethe disease phenotypeassociated with Noonan syndrome-associated cardiomyopathy in iPSC-derivedcardiomyocytes in vitroHanses et al. Angelman syndromeUBE3A-ATS Inc. RNAUBE3A-ATS Inc. RNA was targetedin cultured human neurons andin a mouse model of the diseasetargeting of UBE3A-ATSablated its function, leading to expressionof the paternal UBE3A gene and rescuing the diseasephenotypeWolter et al.congenital muscular dystrophy type 1A (MDC1A)laminin subunit alpha 1 gene (LAMA1)CRISPR activator mediated gene upregulation3.6-foldupregulation of LAMA1 was observedKemaladevi et al.genetic deafnesstransmembrane channel like 1gene (TMC1)non-homologous end joining(NHEJ)-mediated mutant Tmc alleledisruptiondeafness was prevented in mouse models upto one year postinjectionGyörgy et al.
Authors describe 2 cases of likely iatrogenic cerebral amyloid angiopathy after cadaveric dura mater use for cardiac surgery during infancy. Both are remarkable for their early age at onset, lack of genetic risk factor, and demonstration of brain amyloidosis.
To alert on the risk of interhuman transmission of β-amyloid (Aβ) pathology leading to cerebral amyloid angiopathy (CAA) after non-neurosurgical procedures, here cardiovascular procedures, using cadaveric dura mater (DM) patches.
Millions of neurons branch throughout our bodies, keeping them in close communication with our brains. This peripheral network begins to take shape long before birth, as the cells of a growing embryo move into position and adopt their specialized roles. This crucial stage of human development can’t be monitored directly, but by examining genetic clues that linger in adult cells, scientists have now gained surprising insights into the developmental origins of the peripheral nervous system.
Researchers led by Xiaoxu Yang, Ph.D., at University of Utah Health, and Keng Ioi Vong, Ph.D., and Joseph Gleeson, M.D., at the University of California San Diego, have discovered that within the first few weeks of development, some of an embryo’s cells have already been selected to take on particular roles in the peripheral nervous system. Their findings, recently reported in the journal Nature, overturn longstanding assumptions in biology.
Their discovery could change the way scientists think about treatments for a variety of childhood diseases that begin in the cells of the peripheral nervous system.
Multiple myeloma is the second most common blood cancer in adults. It starts in the white blood cells that are responsible for creating antibodies that help the body fight infections. Once the myeloma cells begin to multiply, it makes it harder for the blood cells to function properly. There are effective treatments for multiple myeloma, including immunotherapies that can significantly extend survival; however, in some, the cancer cells become treatment resistant.
A University of Calgary study led by members of the Arnie Charbonneau Cancer Institute, published in Nature Medicine, takes a closer look at why patients often relapse after immunotherapy by studying how the myeloma cells adapt to treatment. By understanding how the cancer builds resistance, future treatments can be designed to take this into account with the goal of preventing another relapse.
“Multiple myeloma tumor cells are highly adaptable under therapeutic pressure,” says Dr. Holly Lee, MD, Ph.D., a clinical assistant professor at the Cumming School of Medicine and first author on the study. “A treatment could be incredibly effective, bringing disease bulk down from about 100% to about 1% to 2% but all it took was that one to two percent of the cells that were left to adapt and cause this relapse in patients.”
ForSight Robotics said it has completed what it described as the world’s first fully robot-assisted cataract surgery in a human patient, using its proprietary JASPER platform in a procedure the company says could mark a major step toward expanding access to eye surgery worldwide.
The Israel-based surgical robotics company said the operation was performed by Dr. Alexey Rapoport, with Dr. Robert Edward T. Ang of the Asian Eye Institute in Manila serving as principal investigator.
According to the company, the procedure was the first cataract surgery in a human patient to be completed from start to finish with robotic assistance and without the use of general anesthesia, which it said aligns with the standard practice for modern cataract procedures. The company said earlier ophthalmic robotic procedures had been limited to partial tasks during cataract surgery and had been performed under general anesthesia.