Inhibition of the Dead Box RNA Helicase 3 Prevents HIV-1 Tat and Cocaine-Induced Neurotoxicity by Targeting Microglia Activation

AbstractHIV-1 Associated Neurocognitive Disorder (HAND) is a common and clinically detrimental complication of HIV infection. Viral proteins, including Tat, released from infected cells, cause neuronal toxicity. Substance abuse in HIV-infected patients greatly influences the severity of neuronal damage. To repurpose small molecule inhibitors for anti-HAND therapy, we employed MOLIERE, an AI-based literature mining system that we developed. All human genes were analyzed and prioritized by MOLIERE to find previously unknown targets connected to HAND. From the identified high priority genes, we narrowed the list to those with known small molecule ligands developed for other applications and lacking systemic toxicity in animal models. To validate the AI-based process, the selective small molecule inhibitor of DDX3 helicase activity, RK-33, was chosen and tested for neuroprotective activity. The compound, previously developed for cancer treatment, was tested for the prevention of combined neurotoxicity of HIV Tat and cocaine. Rodent cortical cultures were treated with 6 or 60  ng/ml of HIV Tat and 10 or 25 μM of cocaine, which caused substantial toxicity. RK-33 at doses as low as 1 μM greatly reduced the neurotoxicity of Tat and cocaine. Transcriptome analysis showed that most Tat-activated transcripts are microglia-specific genes and that RK-33 blocks their activat ion. Treatment with RK-33 inhibits the Tat and cocaine-dependent increase in the number and siz...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Most people know about the damaging effects that binge drinking can bring to someone’s life. Loss of enjoyment of life, losing family relationships, financial and career struggles, homelessness, and legal consequences are just the tip of the iceberg. However, it can be more difficult to realize the long-term effect of binge drinking on the body, because you cannot always see it. Frequent binge drinking poses many dangerous health risks, and many of them can lead to death. Facts on Long-Term Effect of Binge Drinking on the Body For men, binge drinking is defined as consuming five or more drinks within about two hour...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Alcohol Alcohol Rehab Information Alcoholism alcohol abuse alcohol dependence alcohol treatment alcohol treatment center binge binge drinking Source Type: blogs
Is your alcohol use turning into something you are worried about? It can be hard for many people to determine whether or not they have a problem with alcohol, but chances are, you’re not happy with your current drinking habits. If you’re wondering “do I have an alcohol problem?’, keep reading for a few tell-tale signs, what is involved with treatment, and what can happen if you leave your alcohol problem untreated. Ask Yourself These Questions If you are asking yourself, “do I have an alcohol problem?”, as yourself the following questions first. If you answer yes to most or all of them,...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Alcohol Alcohol Rehab Information Alcoholism Detox Resources for Alcohol and Drugs/Opiates alcohol abuse alcohol detox alcohol treatment Source Type: blogs
The dangers of alcohol begin at the first sip of the first drink. Although most responsible drinking habits shouldn’t be cause for major concern, everyone who drinks runs the risk of encountering the negative effects of alcohol. The Dietary Guidelines for Americans defines moderate drinking as up to 1 drink per day for women and up to 2 drinks per day for men.  A single drink is considered as: 12 ounces of beer (5% alcohol content) 8 ounces of malt liquor (7% alcohol content) 5 ounces of wine (12% alcohol content) 1.5 ounces of 80-proof (40% alcohol content) distilled spirits or liquor (e.g., gin, rum, vodka, ...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Alcohol Alcohol Rehab Information Alcoholism alcohol abuse alcohol dependence alcohol dependency alcohol detox alcohol treatment alcohol treatment center alcohol treatment facility Alcoholics Anonymous Source Type: blogs
This article shares 5 ways to help stop these uncomfortable morning feelings and also explains when it’s time to see a therapist. Ginny Fuchs Hopes to Emerge From OCD, Tearful Olympic Experience: Virginia “Ginny” Fuchs, an American flyweight boxer and Olympic hopeful, has struggled with obsessive compulsive disorder (OCD) since 5th grade. She expresses that boxing gives her hope against the disorder. “You’ve got to keep training to keep winning in boxing. So I’ve got to keep training my OCD thoughts and how to handle and manage it,” she says. “…I have this environment ...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Anxiety and Panic Disorders General Mental Health and Wellness Mindfulness OCD Psychology Around the Net Relationships Substance Abuse Trauma Violence and Aggression Addiction aging mothers caregiving Health Insurance Olympic Source Type: blogs
Right now, one in 12 children and adolescents in the US are severely obese. If that isn’t startling enough, consider this: among 12-to-15-year-olds, that number jumps to one in 10 — and among 16-to-19-year-olds, it is one in seven. According to the American Academy of Pediatrics (AAP), the best hope for many of these youths may be bariatric surgery. Bariatric surgery is surgery that helps with weight loss by making the stomach smaller and making other changes in the digestive system. It’s jarring to think about doing irreversible surgery on an adolescent — or a child, as the AAP discourages age limi...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Adolescent health Children's Health Diabetes Diet and Weight Loss Parenting Source Type: blogs
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Source: Cliffside Malibu - Category: Addiction Authors: Tags: Addiction Alcohol Alcoholism alcohol abuse alcohol dependence alcohol dependency alcohol detox alcohol treatment alcohol treatment center alcohol treatment facility alcohol use Alcoholics Anonymous Source Type: blogs
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Source: Cliffside Malibu - Category: Addiction Authors: Tags: Alcoholism alcohol abuse alcohol dependence alcohol dependency alcohol detox alcohol treatment alcohol treatment center alcohol treatment facility alcohol use risks Source Type: blogs
Cliffside Malibu does not condone the use of the term “addict” when referring to people suffering from the disorder of addiction. However, we do understand that others still may use the term in order to find information. Many people may find themselves asking the question, “am I an opioid addict?” if they feel as if their use has spiraled out of control. There are many ways to find out if you may have become addicted to opioids, as well as ways to get help and find treatment. How Opioid Addiction Begins Nearly 80% of heroin users started with prescription opioids, which puts prescription drugs and ...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Addiction Addiction to Pharmaceuticals addiction treatment opioid opioid crisis opioids pharmaceutical addiction pharmaceutical drug abuse treatment Source Type: blogs
On average, 130 Americans die from an opioid overdose every day. The Centers for Disease Control and Prevention (CDC) considers opioid overdose an epidemic in the United States, estimating it responsible for nearly 68 percent of 70,000 drug-related deaths in 2017. Understanding the effects of opioids can prevent opioid overdose, and knowing the opioid overdose signs can save lives. What Are Opioids? Opioids are a class of drugs naturally found in the opium poppy plant. Opioid drugs reduce pain by binding to opioid receptors in your brain, spinal cord and other areas of the body, creating morphine-like effects. The CDC ide...
Source: Cliffside Malibu - Category: Addiction Authors: Tags: Addiction Heroin Painkiller Substance Abuse drug overdose opiate opiate abuse opiate addiction opiates opioid opioids Source Type: blogs
Abstract Addiction in patients with cancer is not well described. Patients with substance use disorders (SUDs) and cancer experience worse outcomes; however, no guidelines exist for identifying and successfully managing these issues in oncology. With the goal to improve patient safety and outcomes, an interprofessional work group at a major academic cancer hospital initiated a trial screening process for identifying substance abuse issues in an oncology population. Simultaneously, guidelines for patients with cancer and SUDs were created. PMID: 31730608 [PubMed - in process]
Source: Clinical Journal of Oncology Nursing - Category: Nursing Authors: Tags: Clin J Oncol Nurs Source Type: research
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