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Archive - 2019

November 5th

Blood Test for CA125 Level Can Help General Practitioners Spot Ovarian Cancer in Women with Suspicious Symptoms

Testing for levels of CA125 in the blood is a useful tool for gauging the likelihood of ovarian cancer and could help detect other types of cancer among patients in primary care, according to research presented at the 2019 National Cancer Research Institute (NCRI) Cancer Conference in Glasgow, UK (November 3-5). Although the CA125 test is already in use in countries around the world, this is the first large study to look at how well it performs in general practice for testing women who have possible symptoms of ovarian cancer. Researchers say their results could guide women and their general practitioners (GPs) on whether more invasive tests are needed to check for ovarian and other cancers. They also say that clinical guidelines could now be improved to ensure urgent referrals are made for women most at risk. The research was led by Dr. Garth Funston (photo), a Clinical Research Fellow at the University of Cambridge, UK. He said: "Less than half of women with ovarian cancer survive for five years following diagnosis. The majority of women are not diagnosed until the disease is advanced, which makes it more difficult to cure. It's important that GPs have effective tools to detect ovarian cancer early and ensure patients are referred appropriately. While CA125 is widely used in general practice in the UK and internationally, prior to this study, it was unclear how effective a test it really was in general practice." The research included data on 50,780 women who visited GPs in England with possible signs of ovarian cancer, such as persistent bloating or abdominal pain, and were tested for levels of CA125 in their blood between May 2011 and December 2014.

Critical Protein (ZBP1) That Could Spur West Nile/Zika Virus Treatments Is Identified

A protein that is critical in controlling replication of West Nile and Zika viruses -- and could be important for developing therapies to prevent and treat those viruses -- has been identified by a Georgia State University (GSU) biologist and his research group. The researchers found Z-DNA binding protein 1 (ZBP1) is a sensor that plays a significant role in triggering a robust immune response when it detects a viral infection within cells. The Georgia State study, published online on September 11, 2019 in the journal Frontiers in Microbiology, found that ZBP1 is essential for restricting both West Nile and Zika virus replication, and that it prevents West Nile-associated encephalitis (inflammation of the brain) in mice. The article is titled “"Z-DNA-Binding Protein 1 Is Critical for Controlling Virus Replication and Survival in West Nile Virus Encephalitis.” The absence of ZBP1 in mice leads to 100 percent mortality when mice are infected with even a non-disease-producing strain of West Nile Virus, the study found. "It's significant because you take a virus that has never been shown to kill anything and, if you block this protein, the virus will just kill everything," said Mukesh Kumar, PhD, Assistant Professor of Biology at GSU, and senior author of the study. "We discovered that when cells are infected with viruses such as Zika and West Nile, they respond by triggering necroptosis, a form of programmed cell death, via ZBP1 signaling. This inhibits viral replication and spread, allowing the immune system to clear the virus." Dr. Kumar said the findings could present new treatment strategies for viruses that can infect the central nervous system by modulating ZBP1 expression. Subsequent research by Dr. Kumar's team will explore effectiveness against similar viruses such as Eastern equine encephalitis and Powassan virus.

November 4th

From Cone Snail Venom to Pain Relief; One Conotoxin (Prialt) Has Been Approved by FDA As Treatment for Sever Chronic Pain and Is 1,000 Times More Potent Than Morphine & Triggers No Dedpendence

Conotoxins are bioactive peptides found in the venom that marine cone snails produce for prey capture and defense. These peptides are used as pharmacological tools to study pain signaling and have the potential to become a new class of analgesics. To date, more than 10,000 conotoxin sequences have been discovered. Associate Professor Markus Muttenthaler, PhD, from the Faculty of Chemistry at the University of Vienna and his colleagues from the University of Queensland in Australia are experts in the field of venom drug discovery and have now provided an overview on the status quo of conotoxin research in the top-of-its-class journal "Chemical Reviews” (https://pubs.acs.org/doi/abs/10.1021/acs.chemrev.9b00207). That article, published on Octobder 21, 2019 is titled “Conotoxins: Chemistry and Biology.” In another study accepted on October 16 for publication in the Australian Journal of Chemistry, the authors describe an “On-Resin Strategy to Label Α-Conotoxins: Cy5-Rgia(https://www.publish.csiro.au/CH/justaccepted/CH19456), the researchers have furthermore developed fluorescently labeled conotoxin versions to visualize pain receptors in cells. The marine predatory cone snail is well-known for its effective envenomation strategy, which helps the relatively slow-moving animal to catch their prey such as fish or molluscs and to defend itself. The cone snail paralyzes and kills its prey with the help of a very selective and potent cocktail of venom peptides, which is injected into prey through a harpoon-like needle. "Cone snails can control their venom composition depending if they hunt or defend themselves," says Dr. Muttenthaler.

Commonly Used Diabetes Drug (Pioglitazone) Relieves Symptoms of Nicotine Withdrawal; May Provide New Strategy in Efforts to Help Individuals Stop Smoking

A drug commonly used to treat Type II diabetes abolishes the characteristic signs of nicotine withdrawal in rats and mice, according to new research published on November 4, 2019 in the Journal of Neuroscience. The finding may offer an important new strategy in the battle to end smoking. The article is titled “Activation of PPARγ attenuates the expression of physical and affective nicotine withdrawal symptoms through mechanisms involving amygdala and hippocampusneurotransmission.” Smokers trying to quit face potent side effects from nicotine withdrawal, including cravings, increased appetite, restlessness, anxiety, irritability, and depression. Even though they may want to quit, many smokers continue to smoke simply because the withdrawal experience is so unpleasant. The diabetes drug, pioglitazone, targets a specific form of the peroxisome proliferator-activated receptors in the nucleus. This receptor, PPARγ, is found in areas of the brain involved in drug addiction. In their current work, Esi Domi(photo), PhD, post-doc at the Center for Social and Affective Neuroscience-Linköping University (Sweden), and colleagues have demonstrated that direct injections of pioglitazone into the hippocampi of male mice reduced the signs of physical nicotine withdrawal, including paw tremors, chattering, and head shakes. Injecting pioglitazone into the amygdala of male mice ameliorated signs of anxiety associated with nicotine withdrawal. Nicotine abusers face a 30% higher risk of developing Type II diabetes. The researchers suggest pioglitazone may help diabetic smokers quit by lessening the physical and emotional withdrawal symptoms while reducing insulin resistance.

Simple Blood Test for Tumor-Associated Antigens My Be Effective for Early Detection of Breast Cancer; Similar Test Being Assessed in Soctland for Lung Cancer

Breast cancer could be detected up to five years before there are any clinical signs of it, using a blood test that identifies the body's immune response to substances produced by tumor cells, according to new research presented on November 3 at the 2019 National Cancer Research Institute (NCRI) Conference (November 3-5)(https://www.ncri.org.uk/events/2019-ncri-cancer-conference/) in Glasgow. The work was presented in poster #2966, entitled “Clinical Utility of Autoantibodies in Early Detection of Breast Cancer.” Cancer cells produce proteins called antigens that trigger the body to make antibodies against them - autoantibodies. Researchers at the University of Nottingham (UK) have found that these tumor-associated antigens (TAAs) are good indicators of cancer, and now the scientists have developed panels of TAAs that are known already to be associated with breast cancer to detect whether or not there are autoantibodies against them in blood samples taken from patients. In a pilot study, the researchers, who are part of the Centre of Excellence for Autoimmunity in Cancer (CEAC) group at the School of Medicine, University of Nottingham, took blood samples from 90 breast cancer patients at the time they were diagnosed with breast cancer and matched them with samples taken from 90 patients without breast cancer (the control group). The researchers used screening technology (protein microarray) that allowed them to screen the blood samples rapidly for the presence of autoantibodies against 40 TAAs associated with breast cancer, and also 27 TAAs that were not known to be linked with the disease.

November 2nd

Researchers Engineer Insulin-Producing Cells Activated by Light for Diabetes

Tufts University researchers have transplanted engineered pancreatic beta cells into diabetic mice, then caused the cells to produce more than two to three times the typical level of insulin by exposing them to light. The light-switchable cells are designed to compensate for the lower insulin production or reduced insulin response found in diabetic individuals. The study, published online on Septembr 13, 2019 in ACS Synthetic Biology, shows that glucose levels can be controlled in a mouse model of diabetes without pharmacological intervention. The article is titled “Amelioration of Diabetes in a Murine Model Upon Transplantation of Pancreatic Β-Cells with Optogenetic Control of Cyclic AMP.” Insulin is a hormone that plays a central role in precisely controlling levels of circulating glucose - the essential fuel used by cells -. Diabetes affects more than 30 million Americans according to the Centers for Disease Control and Prevention (CDC). In type II diabetes - the most common form of the disease - the cells of the body become inefficient at responding to insulin and as a consequence, glucose in circulation can become dangerously high (hyperglycemia) while the pancreas cannot produce enough insulin to compensate. In type I diabetes, the beta cells, which are the only cells in the body that produce insulin, are destroyed by the immune system resulting in complete lack of the hormone. Current treatments include the administration of drugs that enhance the production of insulin by pancreatic beta cells, or direct injection of insulin to supplement the naturally produced supply. In both cases, regulation of blood glucose becomes a manual process, with drug or insulin intervention conducted after periodic readings of glucose levels, often leading to spikes and valleys that can have harmful long-term effects.

Lymphatic System Found to Play Key Role in Hair Regeneration

Given the amount of wear and tear it's subjected to on a daily basis, the skin has a phenomenal ability to replenish itself. Spread throughout it are small reservoirs of stem cells, nested within supportive microenvironments called niches, which keep a tight rein on this repair process. Too much tissue might cause problems like cancer, while too little might accelerate aging. Until now, scientists were uncertain whether the stem cells themselves could instruct other stem cells to form new skin by reshaping their niche. But new research in Science, led by Elaine Fuchs, PhD, the Rebecca C. Lancefield Professor at the Rockefeller University, indicates that stem cells can indeed influence tissue regeneration. The open-access article, published online on October 31, 2019, is titled “Stem Cell–Driven Lymphatic Remodeling Coordinates Tissue Regeneration.” The study identifies a molecular coordination tool used by stem cells to signal across niches. The researchers also discovered a new component of the niche: a specialized type of vessel called lymphatic capillaries, which transport immune cells and drain excess fluids and toxins from tissues. These capillaries form an intimate network around the stem cell niche within each hair follicle, the study showed, thereby interconnecting all its niches. "By turning the skin completely transparent," says postdoctoral fellow Shiri Gur-Cohen, PhD, "we were able to reveal the complex architecture of this network of tubes." Hair-follicle stem cells control the behavior of lymphatic capillaries by secreting molecules that act as an on-off switch for drainage, the scientists found, enabling them to control the composition of fluids and cells in the surrounding locale and ultimately synchronize regeneration across the tissue.

November 1st

International Study Led by Harvard Scientists Reveals Surprising Amount of Gene Flow Among Butterfly Species, Even Between Some That Are Distantly Related

An international team of researchers analyzed the genomes of 20 butterfly species and discovered a surprisingly high amount of gene flow among them - even between species that are distantly related. The findings, published in the November1, 2019 issue Science, challenge conventional views about species and point to hybridization as a key process in the emergence of biological diversity. The article, which serves as the cover story of this issue of Science, is titled “Genomic Architecture and Introgression Shape A Butterfly Radiation.” Different species of passion vine butterflies (Heliconius) have similar color patterns that serve as warnings to predators. Scientists have previously found that one reason for their similarity is that they actually share parts of their DNA, thanks to hybridization that occurred at some point in their ancestry. The new findings suggest that this process of DNA sharing is far more common than previously thought. To understand how butterflies pass genes to other species by hybridizing, a process known as introgression, the researchers analyzed new genome assemblies of 20 Heliconius butterfly species. "DNA sharing had been shown in closely related species, but we wanted to probe deeper into the phylogenetic tree," said senior author James Mallet, Professor of Organismic and Evolutionary Biology in Residence and Associate of Population Genetics in the Museum of Comparative Zoology. "What we found is really astonishing: introgression even among species that are distantly related. "Species" are simply not what we thought they were, and now we have the data to show it.

October 31st

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Final Day (Day 5), Thursday, October 10

Thursday was the last day of the 2019 ASEMV meeting and a number of interesting topics were presented. Two are reported on here. Louis Laurent, MD, PhD, of the University of California-San Diego (UCSD), spoke on the “Discovery and Verfication of Extracelular miRNA Biomarkers for Non-Invasive Prediction of Preeclampsia in Asymptomatic Women.” Dr. Laurent said that she and colleagues performed small RNA-seq of maternal serum exRNAs to discover and verify miRNAs differentially expressed in patients who later developed preeclammpsia. Serum collected from 73 preeclampsia cases and 139 controls between 17-28 weeks gestational age, divided into separate Discovery and Verification cohorts, was analyzed by small RNA seq. Discovery and verification of univariate and bivariate miRNA biomarkers revealed that bivariate biomarkers verified at a markedly higher rate than univariate markers. The majority of verified biomarkers contained miR-155-5p, which has been reported to mediate the preeclampsia-associated repression of eNOS by TNF-alpha. Deconvolution analysis revealed that several verified miRNA biomarkers came from the placenta and were likely carried by placenta-specific EVs. Norman Haughey, PhD, Johns Hopkins University School of Medicine, presented a talk entitled “Astrocyte-Derived EVs Shed in Response to IL-1 Promote Stabilization of APP Translation Through Ligand-Independent Activation of the Wnt Pathway in Neurons.” In his introduction, Dr. Haughey noted that chronic inflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD) by upregulating amyloidogenic processing of APP. Based on previous findings that inflammatory stimuli modify the cargo of astrocyte-derived EVs (ADEV), Dr.

ASEMV 2019 Annual Meeting on Exosomes & Microvesicles—Day 4, Wednesday, October 9

Wednesday’s sessions of the annual ASEMV 2019 meeting at Asilomar,in Pacific Grove, California, featured multiple exciting presentations. Among the 19 talks of the day, we will focus on five of particular interest. Luis Rodriguez-Borlado, PhD, of Capricor Therapeutics, delivered as presentation titled “Extracellular Vesicles from Cardiosphere-Derived Cells (CDCs) Are Taken Up by Muscle Stem Cells and Increase Exercise Capability in a Duchenne Muscular Dystrophy Model.” Dr. Rodriguez-Borlada introduced his discussion by stating that Duchenne muscular dystrophy (DMD) patients infused with CDCs showed an improvement in PUL (pullulanase) activity, skeletal muscle activity, and a reduction in myocardial scarring when compared to placebo-treated patients. He noted that there is wide acceptance that most of the therapeutic effects observed in cell therapies using non-engrafting cells are caused by paracrine factors secreted by the delivered cells. In the current work, Dr. Rodriguez-Borlado said his group observed significant improvement in exercise capability in mdx mice (DMD model mice) treated wit CDC-EVs when compared with control-treated mice. EVs from immortal CDCs also showed immunomodulatory capabilities on macrophages and improved exercise capability in mdx mice, opening the possibility of developing consistent, robust, and affordable manufacturing process for producing clinical-grade EVs. Julia Saugstad, PhD, Oregon Health & Science University, presented work by a collaborative group and the presentation was titled “Establishing the Contributions of Extracellular miRNAs to Alzheimer’s Disease.” As background, Dr. Saugstad said that Alzheimer’s disease (AD) is the most common form of dementia, the sixth leading cause of death in the United States, and fifth-leading cause of death in those age 65 and older.