Tag: medical research

Categories : Medical Research & Technology New Compounds and TreatmentsTags :

Combination Nanoparticle Therapy Shows Promise as Antiviral

On By ModernMedia

Researchers have developed a new nanoparticle combination as a broad-spectrum anti-RNA virus treatment. 

The results of their study have been published on the bioRxiv preprint server. Note that as a preprint, this paper has not yet been peer reviewed.
Non-specific antivirals offer a number of attractive advantages. Their broad spectrum activity suppresses mutations, and would they also readily be at hand for future outbreaks. Nanoparticles are one possibility, with reduced toxicity.

Silver nanoparticles (AgNPs) are well-established as antibacterial and antiviral agents, and are the subject of many exotic biomedical applications. The mechanism of AgNPs is thought to be through physiochemical destruction of the microbial surface, with internal disruption from free Ag+ ions and reactive oxide species. Graphene oxide (GO) also has anti microbial properties. With its high surface area, GO also acts as a drug carrier.

The researchers produced seven different material combinations using three different methods: reduction with silver salt, direct addition of Ag nanospheres, and direct addition of Ag nanospheres to thiolised graphene.
To test the materials against seasonal-type infections as well as the kind of virus that could be expected from a future pandemic, the researchers tested the nanoparticles with influenza A virus (IAV) and human coronavirus (HCoV) OC43. IAV is an enveloped virus of the orthomyxovirus family with a segmented single-stranded RNA genome; it causes flu pandemics. HCoV-OC43 is an enveloped betacoronavirus with a single-stranded RNA genome associated with the common cold in humans.

Two of the GO-AgNP materials showed rapid, potent antiviral activity in solution against the viruses. The remaining five materials possessed a range of modest to no antiviral effects against IAV, the researchers reported. They observed a synergistic effect between the AgNPs and GO, with mechanism of action possibly being rapid disruption of the viral envelope. With high levels of antiviral agents, the combination of AgNPs with GO was found to show greater antiviral performance and lower toxicity.

“Our finding that graphene oxide/silver nanoparticle ink can rapidly prevent in vitro infection with two different viruses is exciting, and suggests that the ink has the potential to be used in a variety of applications to help reduce the spread of viruses in the environment,” said co-author Dr Meredith J Crane.

Source: News-Medical.Net

Journal information: Graphene oxide/silver nanoparticle ink formulations rapidly inhibit influenza A virus and OC43 coronavirus infection in vitro, Meredith J. Crane, Stephen Devine, Amanda M. Jamieson, bioRxiv 2021.02.25.43

Categories : Diseases, Syndromes and ConditionsTags :

Bacteria in Cystic Fibrosis Use Slimy Shield to Ward off Drugs

On By ModernMedia

Research has revealed that a common bacteria found in the lungs of those with cystic fibrosis produces a slime that acts as a defence against a variety of therapeutic drugs.

Dr Laura Jennings, a research assistant professor in UM’s Division of Biological Sciences and an affiliate with the University’s Center for Translational Medicine, headed the research.

A life threatening-condition caused by a genetic mutation, cystic fibrosis causes persistent lung infections and gradually reduces a person’s breathing capacity. A common strain of bacteria, Pseudomonas aeruginosa, often thrives in the lungs of people with cystic fibrosis,  and when a P. aeruginosa infection is established, it can be extremely hard to remove.
The research showed that stubborn bacteria dwelling in the lungs of cystic fibrosis patients produce a carbohydrate slime, which both shields them against antibiotics and also mucus-reducing drugs.

“We found the first direct evidence that these carbohydrates are produced at the sites of infection,” Dr Jennings said. “We showed that one of the carbohydrates, called Pel, sticks to extracellular DNA, which is abundant in the thick mucus secretions prominent in cystic fibrosis lungs.

“This interaction makes a slimy protective layer around the bacteria, making them harder to kill,” she said. “As such, it reduces the pathogen’s susceptibility to antibiotics and drugs aimed at reducing the thickness of airway mucus by digesting DNA.”

She explained that the research supports a theory that these carbohydrates also support the aggregation of these bacteria in the lungs of cystic fibrosis patients.

“This is important because we know that physically breaking up bacterial aggregates can restore bacterial susceptibility to killing with antibiotics and cells of the immune system,” Jennings said. “Therefore, understanding the mechanisms that promote bacterial aggregation may facilitate new therapeutic approaches aimed at digesting the carbohydrates holding bacterial cells together.”

Source: Medical Xpress

Journal information: Laura K. Jennings et al. Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.108782

Categories : Cardiovascular DiseaseTags :

Only Smaller ‘Good’ Cholesterol Particles Reduce Heart Risk

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New research on cholesterol shows that ‘good cholesterol’ is not all good for the heart – only smaller particles reduce heart risk.

Higher levels of ‘good cholesterol’ or high-density lipoprotein cholesterol (HDL-c ) have been associated with better cardiovascular outcomes. In contrast, ‘bad cholesterol’ or low-density lipoprotein cholesterol (LDL-c ), deposits cholesterol on artery walls, increasing the risk of cardiovascular disease.

Medications that lowers LDL-c  also reduce cardiovascular risk, but medication that increases HDL-c does not decrease cardiovascular risk. This paradox calls into question the assumption that HDL-c is protective against cardiovascular risk.

Researchers analysed the size of HDL-c particles, which is determined by genetic characteristics, and compared this to the risk of myocardial infarction. The results showed that genetic characteristics for having large HDL-c particles were associated with increased heart attack risk. Characteristics for smaller HDL-c particles were linked to reduced heart attack risk.

“There is a positive causal relationship between the size of HDL cholesterol particles and the risk of heart attack, so although we have to increase the levels of good cholesterol in the blood, they must always be small particles,” explains the study’s principal investigator, Dr Robert Elosua, a researcher at the Hospital del Mar-IMIM, CIBERCV, and the University of Vic-Central University of Catalonia.

The HDL-c particles are more effective in transferring cholesterol to the liver for subsequent elimination. “If we need to do something in relation to HDL, it is to increase the number of small particles, which are those that adequately perform the function of eliminating cholesterol, those that really move it to the liver for removal, and do not allow it to accumulate in the arteries and cause cardiovascular disease,” said Dr Álvaro Hernáez.
There are currently no drugs that increase HDL-c and also reduce cardiovascular risk. “This study highlights new and potential therapeutic targets in the field of cardiovascular diseases, including several genes related to the qualitative aspects of HDL particles, which may contribute to cardiovascular prevention,” concluded first author Dr Albert Prats.

Source: Medical Xpress

Journal information: Albert Prats-Uribe et al, High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study, Metabolism (2020). DOI: 10.1016/j.metabol.2020.154351

Categories : Diseases, Syndromes and Conditions Medical Research & TechnologyTags :

Researchers Study Enzyme Processes for New Drugs

On By ModernMedia

Traditional discovery has produced drugs that effectively target proteins directly involved with disease, but options are starting to run out and researchers are looking to more complex and obscure interactions for drug targets.

So far, drug discovery has used the ‘small molecule’ approach, where a specific protein is targetted in a cancer cell to shut it down and bring down the cancer cell as a whole. Up until this point, traditional drugs have only been able to target proteins that are involved in the disease that also have activities that are amenable to the small molecule approach, leaving a vast number of proteins unaddressed. Many of these other proteins may be involved in disease processes behind the scenes.

“It’s starting to get to the point where we’ve kind of taken traditional drug discovery as far as we can, and we really need something new,” explained University of Nevada, Las Vegas biochemist Gary Kleiger.

“Cancer cells are clever,” Kleiger said. “They can evolve very, very quickly. So, a drug might be working at first—targeting an enzyme and telling that enzyme, ‘stop doing your activity,’ which can stop the cancer cells from growing. Those cancer cells appear to lie dormant, but all the while there are still little things that happen that eventually enable those cancer cells to bypass that drug.” Therefore, in order to stay ahead of cancer’s capacity to evolve drug resistance, it is necessary to target many additional disease-causing proteins, and thus, limiting the landscape of druggable proteins is a serious disadvantage.

The new approach by investigated by Kleiger and collaborators uses a family of human enzymes called ubiquitin ligases found in human cells. Of about 20 000 known proteins in the human body, some 5-10% are enzymes.

Kleiger’s team uses cutting edge cryo electron microscopes that can image the ubiquitin ligases when they’re at work. To test their hypotheses, Kleiger and collaborators measure the activity of ‘mutated’ enzymes that should now be defective in their activities.

Kleiger compared the process to how a 50 000 year old society might view a bicycle. They could identify its purpose and general properties, but could test the importance of a certain gear; if it was bent, the bicycle would no longer function. “We can do that at the molecular level with the enzymes,” he said.

Source: Medical Xpress

Journal information: Daniel Horn-Ghetko et al, Ubiquitin ligation to F-box protein targets by SCF–RBR E3–E3 super-assembly, Nature (2021). DOI: 10.1038/s41586-021-03197-9