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Archive - Aug 16, 2017

Study of Exosome miRNA in Canine Mitral Valve Disease & Congestive Heart Failure Provides Clues to Target Therapies in Dogs and Human Mitral Valve Prolapse

esearchers at the Cummings School of Veterinary Medicine at Tufts University have discovered important biomarkers in extracellular vesicles in dogs with myxomatous mitral valve disease and congestive heart failure. This is the first biomarker discovery based on extracellular vesicles in a veterinary disease. The genomic material (microRNA, or miRNA) was isolated from small extracellular vesicles called exosomes, which are released from cells and can circulate in blood. These findings could provide important insight into the molecular basis, diagnosis, and therapies for myxomatous mitral valve disease in dogs, as well as mitral valve prolapse, a similar disease in humans. The results were published online on July 12, 2017 in the Journal of Extracellular Vesicles. The open-access article is titled “Circulating Exosome MicroRNA Associated With Heart Failure Secondary to Myxomatous Mitral Valve Disease in a Naturally Occurring Canine Model.” In their analysis of circulating exosome miRNA (Ex-miRNA), researchers found that the expressions not only change with disease progression and development of heart failure in dogs with myxomatous mitral valve disease but also exhibit changes solely on the basis of aging in dogs. Additionally, they found that Ex-miRNA expression level changes appear to be more specific to disease states than the measure of miRNA from plasma without attention to the isolation of Ex-miRNA. This suggests that Ex-miRNA may offer a novel approach that improves upon current established methods of monitoring patients with heart disease and other diseases, yet relies on readily available samples such as blood and urine.

Scientists Develop Blood Test That Spots Tumor-Derived DNA in People with Early-Stage Cancers; Hopkins-Developed Test Targets 58 Cancer-Associated Genes Using Deep Sequencing Technology

In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center, and colleagues, report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early-stage colorectal, breast, lung, and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumors and other altered DNA that can be mistaken for cancer biomarkers. A report on the research, performed on blood and tumor tissue samples from 200 people with all stages of cancer in the U.S., Denmark, and the Netherlands, appears in the August 16, 2017 issue of Science Translational Medicine. The open-access article is titled “Direct Detection of Early-Stage Cancers Using Circulating Tumor DNA.” "This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high-accuracy sequencing method is a promising approach to achieve this goal," says Victor Velculescu (photo), MD, PhD, Professor of Oncology at the Johns Hopkins Kimmel Cancer Center. Blood tests for cancer are a growing part of clinical oncology, but they remain in the early stages of development. To find small bits of cancer-derived DNA in the blood of cancer patients, scientists have frequently relied on DNA alterations found in patients' biopsied tumor samples as guideposts for the genetic mistakes they should be looking for among the masses of DNA circulating in those patients' blood samples. To develop a cancer screening test that could be used to screen seemingly healthy people, scientists had to find novel ways to spot DNA alterations that could be lurking in a person's blood but had not been previously identified.

Micromotors Deliver Drugs to Treat Bacterial Infection in Stomach; New Results in Animals Open Door to Use of Synthetic Motors As Active Delivery Platforms for In Vivo Treatment of Diseases

Nanoengineers at the University of California San Diego have demonstrated, for the first time, the use of micromotors to treat a bacterial infection in the stomach. These tiny vehicles, each about half the width of a human hair, move rapidly throughout the stomach while neutralizing gastric acid, and then release their cargo of antibiotics at the desired pH. The researchers published their findings on August 16, 2017 in Nature Communications. The open-access article is titled “Micromotor-Enabled Active Drug Delivery for In Vivo Treatment of Stomach Infection.” This micromotor-enabled delivery approach is a promising new method for treating stomach and gastrointestinal tract diseases with acid-sensitive drugs, researchers said. The effort is a collaboration between the research groups of nanoengineering professors Joseph Wang (photo) and Liangfang Zhang at the UC San Diego Jacobs School of Engineering. Dr. Wang and Dr. Zhang pioneered research on the in vivo operation of micromotors and this study represents the first example of drug-delivering micromotors for treating bacterial infection. Gastric acid can be destructive to orally administered drugs such as antibiotics and protein-based pharmaceuticals. Drugs used to treat bacterial infections, ulcers, and other diseases in the stomach are normally taken with additional substances, called proton pump inhibitors, to suppress gastric acid production. But when taken over longer periods or in high doses, proton pump inhibitors can cause adverse side effects including headaches, diarrhea, and fatigue. In more serious cases, they can cause anxiety or depression.

Compounds in Desert Creosote Bush Could Be Used to Treat Giardia and “Brain-Eating” Amoeba Infections

Researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego and the University of Colorado Anschutz Medical Campus have found that compounds produced by the creosote bush, a desert plant common to the southwestern United States, exhibit potent anti-parasitic activity against the protozoa responsible for giardia infections and an amoeba that causes an often-lethal form of encephalitis. The findings, published online on August 9, 2017 in PLOS Neglected Tropical Diseases, offer a starting point for widening the arsenal of antimicrobial agents, effective against deadly parasitic infections, scientists said. The open-access article is titled “Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.” The World Health Organization estimates that giardiasis, a diarrheal illness, is linked to approximately 846,000 deaths around the world each year. Infection usually occurs through ingestion of contaminated water or food. Though rarely lethal in the U.S., it's estimated there are more than 1 million cases of giardiasis in the country annually. Standard treatment usually involves antibiotics and anti-parasitic drugs. "The significance and intrigue of our study is that it shows the value of prospecting for new medicines from plants traditionally used by indigenous people as medicine," said co-principal investigator Anjan Debnath, PhD, an Assistant Adjunct Professor at Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego. The creosote bush (Larrea tridentata), also known as greasewood, or gobernadora in Spanish, is a tough evergreen bush with small waxy leaves, yellow flowers, and a distinctive turpentine-like scent. Native Americans in both the U.S.