A startup by prominent biochemist David Liu seeks to turn hollowed out viruses into CRISPR-delivery vehicles.
Category: biotech/medical – Page 722
Year 2023 đ
Data from patients with AMD, retinal dystrophies, and diabetic retinopathy indicate an important role of immune cells, including microglia, in the pathogenesis of these retinal diseases1. The accumulation of drusen components provides an environment rich in chemoattractants for microglia and leads to their translocation to the subretinal space in AMD2,4. The involvement of microglia in the activation of the NLRP3 inflammasome and the promotion of proinflammatory cytokine secretion has been confirmed in in vitro and animal studies11,12,14. In patients with retinal dystrophies like retinitis pigmentosa, it has been shown that microglia become activated in response to signals from degenerating rod photoreceptors and migrate to the outer retinal layers4. There, they participate in the phagocytosis of debris and dying cells and secrete proinflammatory factors. Mouse models of retinal degeneration (e.g. rd1, rd7, rd8, and rd10 models) confirm many of these conclusions9,10,13,15, but make it clear that the role of microglia may also be homeostatic, depending on both stimuli and anatomical location within the retina7,20. Activated microglia are observed at all the stages of human diabetic retinopathy3,8 and also feature prominently in many animal models of the disease44,45. Finally, accumulations of activated microglia are also seen in a variety of animal models of retinal degeneration, including light-induced retinal degeneration and models based on complement dysregulation34,46,47.
The pathways regulating immune surveillance, cell trafficking, and neuroinflammation in the retina are not well understood. A large number of molecules and processes have been implicated, ranging from chemokines involved in chemotaxis, cytokines involved in activation, factors that regulate oxidative stress and complement activation, and immunoregulatory proteins. In such a complex biological system, the unbiased nature of a forward genetics approach is particularly valuable in identifying genes affecting these immune cell processes. Furthermore, the accumulation of subretinal microglia, visible as or correlated with the accumulation of fundus spots, can serve as a marker for retinal pathology and thus as a screen for genes essential to retinal homeostasis. Our approach here has two important advantages relative to all prior forward genetics studies of the retina: 1. We are systematically applying a semiquantitative fundus spot scale to fundus photographs, and 2. Our pipeline is the only one in which all mice screened are G3 mice that have been pre-genotyped at all mutant loci. Our unbiased identification of 6 gene-phenotype associations to retinal pathology with strong literature support using our fundus spot scale screen is proof of concept supporting the efficacy of our approach. We identified other associations that had not been reported in the literature at the time of the screening. From those, we first concentrated our efforts on the gene Lipe, partly because the fundus spot scale was the only parameter leading to its identification.
In order to confirm our findings in ENU-mutagenized mice and also to explore the role of Lipe in retinal homeostasis, a CRISPR-generated Lipeâ/â mouse line was generated. Imaging of the retinas on these mice confirmed an early and prominent accumulation of fundus spots. Furthermore, we found a similar widespread accumulation of hyperautofluorescent spots in these mice. We were also able to show that Lipeâ/â mice have increased accumulation of subretinal Iba1+/CD16+/TMEM119+/CCR2â cells consistent with activated microglia. It can be argued that microglia migrating to the subretinal space are by definition showing some level of activation48,49,50. But our findings of well-accepted morphological signs of activation and co-staining with CD16, a marker of microglial activation10,34,51,52, further support this conclusion.
Crispr used in mice to reverse vision loss đ.
Qin and colleagues develop a genome-editing tool characterized by the versatility of prime editors and unconstrained PAM requirement of SpRY. In vivo gene corre.
Year 2020 Immortality in eyes achieved with Nad plus đđđ.
Glaucoma and age-related macular degeneration are leading causes of irreversible blindness worldwide with significant health and societal burdens. To date, no clinical cures are available and treatments target only the manageable symptoms and risk factors (but do not remediate the underlying pathology of the disease). Both diseases are neurodegenerative in their pathology of the retina and as such many of the events that trigger cell dysfunction, degeneration, and eventual loss are due to mitochondrial dysfunction, inflammation, and oxidative stress. Here, we critically review how a decreased bioavailability of nicotinamide adenine dinucleotide (NAD; a crucial metabolite in healthy and disease states) may underpin many of these aberrant mechanisms. We propose how exogenous sources of NAD may become a therapeutic standard for the treatment of these conditions.
While it has long been known that ultraviolet (UV) light can help kill disease-causing pathogens, the COVID-19 pandemic has put a spotlight on how these technologies can rid environments of germs. However, the excimer lamps and LEDs that can directly emit light in the required deep-UV wavelengths generally have low efficiency or suffer from short lifetimes. Moreover, UV light of the wrong wavelength can actually be harmful to human cells.
Now, a team led by researchers from Osaka University has shown how an optical device made of aluminum nitride can be used to generate deep-UV light in a method wholly different from previous approaches. The team made use of a process called âsecond harmonic generation,â which relies on the fact that the frequency of a photon, or particle of light, is proportional to its energy. The study is published in the journal Applied Physics Express.
Most transparent materials are considered âlinearâ with respect to their response to light, i.e., photons cannot interact with each other. However, inside certain ânonlinearâ materials, two photons can be combined into a single photon with twice the energy, and thus, twice the frequency.
Artificial intelligence (AI) is the term used to describe the use of computers and technology to simulate intelligent behavior and critical thinking comparable to a human being. John McCarthy first described the term AI in 1956 as the science and engineering of making intelligent machines.
This descriptive article gives a broad overview of AI in medicine, dealing with the terms and concepts as well as the current and future applications of AI. It aims to develop knowledge and familiarity of AI among primary care physicians.
PubMed and Google searches were performed using the key words âartificial intelligenceâ. Further references were obtained by cross-referencing the key articles.
More than half of all cardiovascular diseases worldwide have been found to be directly connected to five classic cardiovascular disease risk factors, with high blood pressure being the most significant factor related to heart attacks and strokes. Dr. Christie Ballantyne, professor of medicine, and Dr. Vijay Nambi, associate professor of medicine, both with Baylor College of Medicine, are co-authors along with a large group of scientists who make up the Global Cardiovascular Risk Consortium who recently published these findings in the New England Journal of Medicine.
The consortium, under the leadership of the University of Heart & Vascular Center of the Medical Center of Hamburg-Eppendorf and the German Center for Cardiovascular Research, used data from 112 studies consisting of 1.5 million people from 34 different countries.
The group reports that two conclusions can be made from these findings: The first, that more than half of all heart attacks and strokes can be prevented by understanding, treating or preventing the five classic risk factors: weight, high blood pressure, high cholesterol, smoking and diabetes. The second, that the other half of heart attacks and strokes cannot be explained with these risk factors and more work and research is needed to find additional causes.
Gastrointestinal (GI) disorders account for about 10% of all consultations in primary care and have a major impact on quality of life and health care resources. Gastro-oesophageal reflux disease (GERD), H. pylori infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), coeliac disease, antibiotic-associated diarrhea (ADA), infectious diarrhea, are some common GI disorders.
The efficacy of probiotics in preventing and treating gastrointestinal disorders has received considerable attention in recent years. This article will shed light on how probiotics are more or less effective in treating different gastrointestinal disorders.
Indian Burden and Factors Affecting GI Disorders The prevalence of self-reported gastrointestinal disorders in India is around 18%. Whereas the prevalence of gastroesophageal reflux disease (GERD) ranges from 2.5% to 7.1% in most population-based studies in Asia.
Malaria is one of the most widespread and devastating infectious diseases across the globe. This mosquito-borne parasitic disease killed approximately 619,000 people in 2021 alone, many of them children in Africa. In one of the deadliest forms of malaria, known as cerebral malaria, the patient experiences severe neurological symptoms, such as seizures and coma. Although only a small fraction of people who fall ill with malaria also experience cerebral malaria, the condition is lethal without treatment. Among hospitalized patients with the condition, death rates range between 15 and 20%. In a new paper, recently published in Science Translational Medicine, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, and their colleagues studied children with cerebral malaria in Malawi to better understand the underlying causes of these devastating symptoms in the hope of developing improved treatments.
Researchers know that the symptoms of cerebral malaria are caused when the brain swells within the confines of the skull, eventually impinging upon the brainstem, which causes breathing to stop. However, researchers have been unsure how malaria infection leads to brain swelling. Some researchers hypothesized that the main cause was a weakening of the blood-brain barrier, which would allow fluid to seep into the brain and cause it to swell. Others speculated that the primary driver behind the swelling was inside the blood vessels themselves. Red blood cells infected with P. falciparum, the parasite which causes malaria, can become âsticky,â adhering to the walls of blood vessels. Partial blockages inside the cerebral veins could slow the flow of blood leaving the brain, causing the blood vessels themselves to become engorged and expand the brain from within.
To distinguish between these two hypotheses, NIAID researchers and their collaborators used non-invasive imaging techniques to study the flow of blood within the brains of 46 children who had been hospitalized for cerebral malaria at the Pediatric Research Ward of Queen Elizabeth Central Hospital in Blantyre, Malawi. As a comparison, they also studied 33 children with uncomplicated malaria and 26 healthy children from the local region. By using a light-based external monitoring tool (called near-infrared spectroscopy, or NIRS) the researchers were able to measure the amount of hemoglobin in the childrenâs brains. They reasoned that if excess fluid was the cause of brain swelling, then the hemoglobin concentration would be low, due to dilution. Alternatively, if the blood vessels were engorged with blood, then the hemoglobin concentration would be high.
Commercial platforms for protein therapeutics are being built on academic research that has expanded the genetic code behind cell-based translation.