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Archive - May 31, 2020

Study Shows Ketamine Combats Depression by Targeting Serotonin 1B Receptors, Increasing Their Number, and Increasing Dopamine Levels

The anaesthetic drug ketamine has been shown, in low doses, to have a rapid effect on difficult-to-treat depression. Researchers at the Karolinska Institutet in Sweden now report that they have identified a key target for the drug: specific serotonin receptors in the brain. Their findings, which were published online on June 1, 2020 in Translational Psychiatry, give hope of new, effective antidepressants. The open-access article is titled “A Randomized Placebo-Controlled PET Study of Ketamine´s Effect on Serotonin1b Receptor Binding in Patients with SSRI-Resistant Depression.” Depression is the most common psychiatric diagnosis in Sweden, affecting one in ten men and one in five women at some point during their lives. Between 15 and 30 per cent of patients are not helped by the first two attempts at therapy, in which case the depression is designated difficult to treat. Studies have shown that low doses of the anaesthetic drug ketamine are rapid-acting on certain sufferers, but exactly how it works is unknown. A nasal spray containing ketamine has recently been approved in the USA and EU for patients with treatment-resistant depression. Researchers at the Karolinska Institutet have now imaged the brains of study participants using a PET (positron emission tomography) camera in connection with ketamine treatment.

New Understanding of mRNA/microRNA Interactions May Enable New Approaches to Treating Cancer

Research from Sweden’s Karolinska Institutet, published on March 27, 2020 in Nature, shows that an RNA molecule involved in preventing tumor formation can change its structure and thereby control protein production in the cell. The article is titled “Base-Pair Conformational Switch Modulates miR-34a Targeting of Sirt1 mRNA.” The finding may have important clinical implications as it [suggests the possibility of new strategies to treat different types of cancer. Short RNA molecules in our cells, called microRNAs, are important regulators of messenger RNAs (mRNAs) – the molecules that code for the building blocks of our body, the proteins. The exact mechanism of this regulation remains elusive, but it is known that microRNAs can silence mRNA molecules and thereby prevent protein production. Therefore, they have the potential to be used as tools or targets for drugs. “It’s important to increase our understanding of how microRNA regulates protein production because this process is disturbed in many different types of diseases, including cancer,” says Katja Petzold, PhD, Associate Professor in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet, who led the study. “We show for the first time that a microRNA-mRNA complex has a structure that changes and that this movement has an effect on the biological outcome, i.e., the amount of protein produced in the cell.” The researchers studied a microRNA known as miR-34a, which plays an important role in cancer by indirectly regulating the activity of the p53 protein, known as the “guardian of the genome” for its ability to prevent cancer formation. Changes in the function of p53 are very common in human cancers. miR-34a downregulates the mRNA that codes for Sirt1, a protein that deactivates p53.

Modified Adenoviruses Better Able to Target and Kill Cancer Cells Due to Addition of AU-Rich Elements That Hasten mRNA Breakdown in Normal Cells, But Which Result in Stabilized mRNA in Cancer Cells, Thus Enhancing Cancer Cell-Specific Killing by the Virus

Hokkaido University scientists have made an adenovirus (graphic image of an adenovirus) that specifically replicates inside and kills cancer cells by employing special RNA-stabilizing elements. The details of the research were published online on May 11, 2020 in the journal Cancers. The open-access article is titled “Conditionally Replicative Adenovirus Controlled by the Stabilization System of AU-Rich Elements Containing mRNA.” Much research in recent years has investigated genetically modifying adenoviruses to kill cancers, with some of these modified viruses currently being tested in clinical trials. When injected, these adenoviruses replicate inside cancer cells and kill them. Scientists are trying to design more efficient viruses, which are better able to target cancer cells, while leaving normal cells alone. Hokkaido University molecular oncologist Fumihiro Higashino, PhD, led a team of scientists to make two new adenoviruses that specifically target cancer cells. To do this, they used ‘adenylate-uridylate-rich elements’ (AREs or AU-rich elements), which are signals in RNA molecules known to enhance the rapid decay of messenger RNAs (mRNAs) in human cells. “AREs make sure that mRNAs don’t continue to code for proteins unnecessarily in cells,” explains Dr. Higashino. “Genes required for cell growth and proliferation tend to have AREs.” Under certain stress conditions, however, ARE-containing mRNAs can become temporarily stabilized allowing the maintenance of some necessary cell processes. ARE-mRNAs are also stabilized in cancer cells, supporting their continuous proliferation. Dr. Higashino and his team inserted AREs from two human genes into an adenovirus replicating gene, making the new adenoviruses: AdARET and AdAREF.

SARS-CoV-2 May Ultimately Be a Blood Vessel Disease, Which Might Explain Everything

In April 2020, blood clots (https://coronavirus.medium.com/doctors-want-to-know-could-blood-thinners...) emerged as one of the many mysterious symptoms attributed to COVID-19, a disease that had initially been thought to largely affect the lungs in the form of pneumonia. Quickly after this, came reports of young people dying due to coronavirus-related strokes. Next it was COVID toes — painful red or purple digits. What do all of these symptoms have in common? An impairment in blood circulation. Add in the fact that 40% of deaths (https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.120.317055) from COVID-19 are related to cardiovascular complications, and the disease starts to look like a vascular infection instead of a purely respiratory one. Months into the pandemic, there is now a growing body of evidence to support the theory that the novel coronavirus can infect blood vessels, which could explain, not only the high prevalence of blood clots, strokes, and heart attacks, but also provide an answer for the diverse set of head-to-toe symptoms that have emerged. “All these COVID-associated complications were a mystery.

FDA Publishes Comprehensive Review of What’s Known to Date on SARS-CoV-2; Outlines Roadmap for Effective Treatment of COVID-19; Proposes Range of Existing Drugs That Might Be Repurposed to Treat the Disease

Due to the devastating worldwide impact of COVID-19, the illness caused by the SARS-CoV-2 virus, there have been unprecedented efforts by clinicians and researchers from around the world to quickly develop safe and effective treatments and vaccines. Given that COVID-19 is a complex new disease with no existing vaccine or specific treatment, much effort is being made to investigate the repurposing of approved and available drugs, as well as those under development. In an article published online on May 29, 2020 in Frontiers in Immunology (https://www.frontiersin.org/articles/10.3389/fimmu.2020.01131/full) , a team of researchers from the U.S. Food and Drug Administration (FDA) review all of the COVID-19 clinical and research findings to date. They provide a breakdown of key immunological factors underlying the clinical stages of COVID-19 illness that could potentially be targeted by existing therapeutic drugs. The open-access review is titled “Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation.” Montserrat Puig (photo) (https://www.fda.gov/science-research/fda-science-jobs-and-scientific-pro...), PhD, of the FDA, senior author of the review, stated that "there are multiple factors involved in determining if the patient's immune response will be insufficient or successful in combating the infection. Our review is an overview of these factors and how they can be considered to define the context in which medications currently used for other diseases, or development of novel agents, can be utilized to prevent, ameliorate, or cure COVID-19." We know that during the early stage of COVID-19 people can show no symptoms or mild symptoms, and, for many, the disease resolves.