A collaborative approach to improving representation in viral genomic surveillance.

The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic.

A collaborative approach to improve representation in viral genomic surveillance.

Unlabelled: The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic.

Azithromycin Reduces Markers of Vascular Damage in Pediatric Patients With Sickle Cell Disease.

Background: Immunomodulatory effects of macrolides in chronic inflammation are well known. In this study, we tested our hypothesis that azithromycin (AZT) can decrease inflammation in pediatric patients with sickle cell disease (SCD).

Methods: The use of AZT as an anti-inflammatory agent was evaluated in double-blind, placebo-controlled, cross-over study for 8 weeks of treatment with 8 weeks of washout.

The cannabinoid receptor 2 agonist, β-caryophyllene, improves working memory and reduces circulating levels of specific proinflammatory cytokines in aged male mice.

Age-related cognitive decline has been associated with proinflammatory cytokines, yet the precise relationship between cognitive decline and cytokine load remains to be elucidated. β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB) agonist with established anti-inflammatory effects that is known to improve memory and increase lifespan. It is of interest to explore the potential of BCP to reduce age-related cognitive decline and proinflammatory cytokine load.

Using glycyrrhizic acid to target sumoylation processes during Epstein-Barr virus latency.

Cellular sumoylation processes are proposed targets for anti-viral and anti-cancer therapies. We reported that Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) dysregulates cellular sumoylation processes, contributing to its oncogenic potential in EBV-associated malignancies. Ginkgolic acid and anacardic acid, known inhibitors of sumoylation, inhibit LMP1-induced protein sumoylation; however, both drugs have adverse effects in hosts.

Treatment of Hematological Malignancies with Glycyrrhizic Acid.

The current study examined the effectiveness of glycyrrhizic acid (GA) in reducing cell viability and inducing apoptosis in human chronic myeloid leukemia (CML) in vitro and a mouse lymphoma in vivo. Additionally, we assessed GA as a candidate for combinational therapy in CML along with the current frontline treatment, imatinib (IM). Treatment of K562 CML cells with GA alone resulted in significant induction of apoptosis and loss of cell viability.

Inhibition of hyaluronic acid formation sensitizes chronic myelogenous leukemia to treatment with doxorubicin.

In the current study we examined the ability of 4-methylumbelliferone (4-MU), which can inhibit hyaluronic acid synthesis, to sensitize K562 chronic myelogenous leukemia (CML) cells to doxorubicin therapy. Exposure of K562 cells to doxorubicin led to increased hyaluronic acid synthase (HAS) gene expression and increased levels of cell surface hyaluronic acid. Furthermore, exposure of K562 cells to exogenous HA caused resistance to doxorubicin-induced cell death.

Treatment with the hyaluronic Acid synthesis inhibitor 4-methylumbelliferone suppresses LPS-induced lung inflammation.

Exposure to bacterial endotoxins, such as lipopolysaccharide (LPS), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for LPS-induced inflammation. In the current study, we investigated the potential use of the hyaluronic acid (HA) synthesis inhibitor 4-methylumbelliferone (4-MU) on LPS-induced acute lung inflammation.

Treatment with the hyaluronic acid synthesis inhibitor 4-methylumbelliferone suppresses SEB-induced lung inflammation.

Exposure to bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can lead to the induction of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). To date, there are no known effective treatments for SEB-induced inflammation. In the current study we investigated the potential use of the hyaluronic acid synthase inhibitor 4-methylumbelliferone (4-MU) on staphylococcal enterotoxin B (SEB) induced acute lung inflammation.

Targeting hyaluronic acid production for the treatment of leukemia: treatment with 4-methylumbelliferone leads to induction of MAPK-mediated apoptosis in K562 leukemia.

The current study examined the effect of modulation of hyaluronic acid (HA) synthesis on leukemia cell survival using the hyaluronic acid synthesis inhibitor 4-methylumbelliferone (4-MU). Treatment of CML cells with 4-MU led to caspase-dependent apoptosis characterized by decreased HA production, PARP cleavage, and increased phosphorylation of p38. Addition of exogenous HA, the pan caspase inhibitor Z-VAD-FMK or the p38 inhibitor SB203580 to 4-MU treated cells was able to protect cells from apoptosis.

Development of a novel treatment for leukemia directed at tumor-associated mRNA splicing.

This report describes a novel approach to cancer therapy that targets genes that are preferentially alternatively spliced and expressed in leukemia. We developed CD44v6 and CD44v8 splicing constructs fused with GFP or a humanized fragment of Pseudomonas aeruginosa exotoxin A (hPE24). Transfection of K562 leukemia cells with the GFP-linked splicing constructs led to subsequent production of detectable levels of GFP.

The role of hyaluronic acid in SEB-induced acute lung inflammation.

We investigated the role of the extracellular matrix component, hyaluronic acid (HA) in SEB-induced ALI/ARDS. Intranasal exposure of mice to SEB led to a significant increase in the level of soluble hyaluronic acid in the lungs. Similarly, in an endothelial cell/spleen cell co-culture, SEB exposure led to significant increases in soluble levels of hyaluronic acid, cellular proliferation, and cytokine production compared with SEB-exposed spleen cells or endothelial cells alone.

Fatigue in medical residents leads to reactivation of herpes virus latency.

The main objective of this study was to detect fatigue-induced clinical symptoms of immune suppression in medical residents. Samples were collected from the subjects at rest, following the first night (low-stress), and the last night (high-stress) of night float. Computerized reaction tests, Epworth Sleepiness Scale, and Wellness Profile questionnaires were used to quantify fatigue level.