Lifeboat Foundation

HOUSTON, June 2, 2020 /PRNewswire/ — Cellenkos Inc., a privately held, clinical stage biotech company announced today that the US Food & Drug Administration (FDA) has cleared the way to initiate a Phase 1 clinical trial of CK0802 (Cryopreserved Cord Blood Derived T-Regulatory Cells) for treatment of COVID-19 associated acute respiratory distress syndrome (ARDS). The trial is designed as a randomized, double-blinded, placebo-controlled study to assess safety and preliminary efficacy in this hospitalized patient population.

“We appreciate FDA’s expedited review of our plans to evaluate CK0802 in critically ill, intubated patients suffering from ARDS, a deadly complication of COVID-19”, said Elizabeth J Read, MD, Chief Technology Officer, Cellenkos Inc. “Preliminary observations in two intubated COVID-19 ARDS patients, who received cryopreserved cord blood T-regulatory cells under FDA Emergency Use Authorization after failing tociluzumab, were promising. In the forthcoming Phase 1 randomized trial, CK0802 will be assessed for both toxicity and 28-day treatment success, as co-primary outcomes.”

“Use of allogeneic, off-the-shelf cord blood-derived T-regulatory cells has emerged as a promising therapeutic strategy for the treatment of inflammatory disorders, specifically in terms of interrupting and arresting the cytokine storm unleashed by COVID-19 infection,” said Dr Siddhartha Mukherjee, MD, PhD, Columbia University, New York, scientific advisor and collaborator on the multi-center clinical trial. “Rather than indiscriminate therapy with a drug such as an inhibitor of single cytokine such as IL-6, the T-regulatory cells can potentially calm inflammation exactly where it is most active, without causing a more general “global” immunosuppression that would be harmful in a virally infected patient. Planned correlative assays during the clinical trial will provide insights into the mechanism of action of CK0802 and its relation to clinical outcomes.”

Chronic stress has long been associated with the pathogenesis of psychological disorders such as depression and anxiety. Recent studies have found chronic stress can cause neuroinflammation: activation of the resident immune cells in the brain, microglia, to produce inflammatory cytokines. Numerous studies have implicated the inflammatory cytokine, interleukin-1 (IL-1), a master regulator of immune cell recruitment and activity in the brain, as the key mediator of psychopathology. However, how IL-1 disrupts neural circuits to cause behavioral and emotional problems seen in psychological disorders has not been determined.

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The research team previously detailed how psychosocial stress results in peripheral immune activation, increased levels of circulating monocytes, and robust neuroimmunological responses in the brain. These responses include increases in IL-1 and other inflammatory cytokines, activation of brain glial cells and movements of peripheral immune cells to the brain, along with enhanced activity of specific neuronal pathways. The work makes it clear that inflammatory-related effects of stress are not just global effects, but are associated with increased IL-1 signaling within specific brain circuits.

The study shows for the first time that neuronal IL-1Rs in the hippocampus, a brain structure connected to learning and memory, is necessary and sufficient to mediate some of the behavioral deficits caused by chronic stress, pointing to a critical neuroimmune mechanism for the etiology of these types of disorders. Findings from the study augment the understanding of IL-1R signaling in physiological and behavioral responses to stress and also suggest that it may be possible to develop better medications to treat the consequences of chronic stress by limiting inflammatory signaling not just generally, which may not be beneficial in the long run, but to specific brain circuits.

Continue reading “Chronic stress? Limiting inflammatory signaling to specific brain circuits” »

Undifferentiated human stem cells have been coaxed to develop into skin-like structures in vitro. When engrafted onto mice, the structures produce hair — highlighting the potential of the approach for regenerative therapies. Hair-follicle organoids that have a full complement of skin cells.

The discovery of the Dead Sea Scrolls had an incomparable impact on the historical understanding of Judaism and Christianity. ‘Piecing together’ scroll fragments is like solving jigsaw puzzles with an unknown number of missing parts. Because most of the 2,000-year-old scrolls were written on processed animal skin, an international team of researchers used DNA sequencing to ‘fingerprint’ fragments based on their genetic signature.

Three-dimensional graphene network is a promising structure for improving both the mechanical properties and functional capabilities of reinforced polymer and ceramic matrix composites. However, direct application in a metal matrix remains difficult due to the reason that wetting is usually unfavorable in the carbon/metal system. Here we report a powder-metallurgy based strategy to construct a three-dimensional continuous graphene network architecture in a copper matrix through thermal-stress-induced welding between graphene-like nanosheets grown on the surface of copper powders. The interpenetrating structural feature of the as-obtained composites not only promotes the interfacial shear stress to a high level and thus results in significantly enhanced load transfer strengthening and crack-bridging toughening simultaneously, but also constructs additional three-dimensional hyperchannels for electrical and thermal conductivity. Our approach offers a general way for manufacturing metal matrix composites with high overall performance.

Researchers detail the unusual workings of Tycoon ransomware — which appears to be designed to stay under the radar as much as possible.

Understanding of these mechanisms is critical to the development of ultracompact particle accelerators and light sources.

Gail Overton

Sometimes, breaking rules is not a bad thing. Especially when the rules are apparent laws of nature that apply in bulk material, but other forces appear in the nanoscale.

“Nature knows how to go from the small, atomic scale to larger scales,” said Melik Demirel, professor of engineering science and mechanics and holder of the Lloyd and Dorothy Foehr Huck Chair in Biomimetic Materials. “Engineers have used mixing rules to enhance properties, but have been limited to a single scale. We’ve never gone down to the next level of hierarchical engineering. The key challenge is that there are apparent forces at different scales from molecules to bulk.”

Composites, by definition, are composed of more than one component. Mixture rules say that, while the ratios of one component to another can vary, there is a limit on the physical properties of the composite. According to Demirel, his team has broken that limit, at least on the nanoscale.

Scientists have found a new method to strategically add deuterium to benzene, an aromatic compound commonly found in crude oil. When applied to the active ingredient of drugs to incorporate deuterium, it could dramatically improve the drugs’ efficacy and safety and even introduce new medicines.

To validate the method, which was published in Nature, a team led by W. Dean Harman of the University of Virginia worked with Xiaoping Wang at the Oak Ridge National Laboratory’s Spallation Neutron Source. Wang successfully verified the exact position of deuterium atoms that resulted from the selective deuteration of benzene molecules using single crystal neutron diffraction.

“Because the high sensitivity of neutrons to hydrogen and its deuterium isotope, we were able to quantitatively assign not only the positions of the deuterium atoms at the atomic level, but also determine precisely how many were added on each side of the benzene molecule,” Wang said. “This is important in designing new therapeutic drugs.”