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Your body is full of medicine. Researchers can now synthesize it

Northeastern University researchers have made a breakthrough drug discovery, developing the first synthetic endogenous cannabinoid compound, with repercussions for new therapeutics from pain and inflammation to cancer.

Spyros P. Nikas, an associate research professor in Northeastern’s Center for Drug Discovery, says that the discovery hinges on the distinction between two different kinds of cannabinoid chemicals, endogenous and exogenous. Exogenous cannabinoids are those produced outside the human body, like THC or CBD, both derived from the cannabis plant and present in marijuana.

Our own bodies, however, are also producing cannabinoids all the time. Called endogenous cannabinoids —or just “endocannabinoids”—these chemicals “modulate a wide range of physiological and pathophysiological responses,” Nikas says, processes that include mood, inflammation and even neurodegenerative disorders like Alzheimer’s and Parkinson’s. The research is published in the Journal of Medicinal Chemistry.

Transcutaneous Peripheral Nerve Stimulation for Essential Tremor: A Randomized Clinical Trial

Essential tremor (ET), the most common upper limb tremor, can impair daily activities. In a multicenter RCT, an artificial intelligence–driven transcutaneous peripheral nerve stimulation (TPNS) device reduced mADL scores by 6.9 points at 90 days, compared with a 2.7-point reduction in the sham group.

Question Is an artificial intelligence (AI)–driven TPNS device superior to a sham device in reducing essential tremor?

Findings In this randomized clinical trial that included 125 adults with essential tremor, use of the TPNS device reduced the modified Activities of Daily Living score of the Essential Tremor Rating Assessment Scale by a clinically meaningful 6.9 points at 90 days, significantly more than the 2.7-point reduction seen in the sham-treated group.

Meaning The TPNS device improved activities related to upper limb tremor at 90 days and could be an effective noninvasive treatment for essential tremor.

Association Between Choroid Plexus Morphological Alterations, Alzheimer Pathologies, and Cognitive ImpairmentA Longitudinal Study

Question What are the main predictors for high health care costs among patients with head and neck cancer?

Findings In this population-based cohort study, advanced cancer stage and receiving multiple treatment modalities were the strongest predictors of high health care costs. Female sex, older age, and lower socioeconomic status were associated with an increased likelihood for high health care costs, although with a weaker effect size.

Meaning Future research should focus on evaluating screening strategies and early diagnosis to assess their potential effects on cost reduction and improved outcomes for patients with head and neck cancer.

While studying the effects of glutamine deprivation, Boa Kim & team noticed dramatic clustering of glutaminase throughout endothelial cells

The team now report on a mechanism underlying kidney tumor cell growth involving the cancer-driving protein HIF2α that blocks clustering/activation of glutaminase—revealing a new therapeutic target in renal clear cell carcinoma:

The figure shows glutamine deprivation induces GLS1 clustering within mitochondria in HUVEC (top) and HELA (bottom) with mitochondrial protein (green) and GLS (red).

1Department of Medicine, Cardiovascular Institute, and Institute of Diabetes Obesity and Metabolism, and.

2The Abramson Family Cancer Research Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

3McAllister Heart Institute, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.

Cutaneous Melanoma: A Review

The incidence and prevalence of cutaneous melanoma in the US and worldwide have increased over the last 5 decades.

Cutaneous melanoma presents as a new, changing, or irregularly pigmented skin lesion. Risk factors for cutaneous melanoma include UV radiation exposure, skin type, presence of benign and atypical nevi, and personal or family history of melanoma.

This Review summarizes current evidence regarding the epidemiology, pathophysiology, diagnosis, and treatment of cutaneous melanoma.

Improvements in melanoma mortality over the last decade are attributed to the advent of multiple effective therapies,6 including immune checkpoint blockade with anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) antibodies (ipilimumab), anti–programmed cell death protein 1 (PD-1) antibodies (nivolumab, pembrolizumab), and anti–lymphocyte activation gene 3 protein (LAG-3) antibodies (relatlimab), as well as oral combination targeted therapy with B-Raf protein (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors (eg, encorafenib + binimetinib, vemurafenib + cobimetinib, dabrafenib + trametinib).

This review summarizes current evidence regarding epidemiology and risk factors, clinical presentation, diagnosis, and management of cutaneous melanoma (Box).

Dysfunctions of Circulating Adaptive Immune Cells in End-Stage Liver Disease

End-stage liver disease (ESLD) from acute liver failure to compensated advanced chronic liver disease and decompensated cirrhosis at different stages (chronic decompensation, acute decompensation with or without acute-on-chronic liver failure) has high disease severity and poor patient outcome. Infection is a common complication in patients with ESLD and it is associated with a high mortality rate. Multiple mechanisms are involved in this marked susceptibility to infections, noticeably the inadequate immune response known as immune paresis, as part of cirrhosis-associated immune dysfunction (CAID). Specifically in the adaptive immune arm, lymphocyte impairments—including inadequate activation, reduced ability to secrete effector molecules and enhanced immune suppressive phenotypes—result in compromised systemic immune responses and increased risk of infections.

Boosting One Mitochondrial Protein Increases Lifespan And Slows Aging in Mice

Tiny biological batteries known as mitochondria keep the body’s cells running smoothly, and their gradual decline is linked to a wide range of age-related diseases. Now scientists think they have found a way to keep mitochondria powered for longer.

A protein called COX7RP is key to this discovery from researchers at the Saitama Medical University and Chiba University in Japan. The protein is thought to help mitochondria form supercomplexes, structures that improve energy efficiency.

In the new study, male mice engineered to produce extra COX7RP showed a host of differences compared with controls, including a 6.6 percent increase in average lifespan and indicators of an extended healthspan – being able to live healthier for longer.

Molecular Switch for Repairing Central Nervous System disorders

A molecular switch has the ability to turn on a substance in animals that repairs neurological damage in disorders such as multiple sclerosis (MS), Mayo Clinic researchers discovered. The early research in animal models could advance an already approved Food and Drug Administration therapy and also could lead to new strategies for treating diseases of the central nervous system.

Research by Isobel Scarisbrick, Ph.D., published in the Journal of Neuroscience finds that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin, a fatty substance that coats and protects nerves.

“Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair,” says Dr. Scarisbrick, principal investigator and senior author. “This sets the stage for development of new clinically relevant myelin regeneration strategies.”

Consciousness May Be a Fundamental Force of the Universe, Not a Byproduct

You’ve probably grown up accepting that your thoughts, feelings, and inner awareness all emerge from the firing of neurons in your brain. It’s what science has taught us for decades. Your consciousness is simply what happens when billions of brain cells communicate. Simple enough, right?

What if you’ve been looking at this backwards the whole time? What if the entire universe has been trying to tell you something fundamentally different about the nature of reality itself?

A materials science professor from Uppsala University recently published a framework that proposes an entirely new theory of the origin of the universe. Here’s where things get interesting. This framework presents consciousness not as a byproduct of brain activity, but as a fundamental field underlying everything we experience, including matter, space, time, and life itself.

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