Identification of Inhibitors of virus nsP2 ATPase.

Non-structural protein 2 (nsP2), which plays an essential role in replication of CHIKV, contains a protease, helicase, and methyltransferase-like domain. We executed a simple a screen using malachite green to detect compounds that decreased ATP hydrolysis and tested a library of diverse compounds to find inhibitors of CHIKV nsP2 helicase.

Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.

Sonic hedgehog (Shh) is a morphogen with important roles in embryonic development and in the development of a number of cancers. Its activity is modulated by interactions with binding partners and co-receptors including heparin and heparin sulfate proteoglycans (HSPG). To identify antagonists of Shh/heparin binding, a diverse collection of 34,560 chemicals was screened in single point 384-well format.

Identification of Novel GANT61 Analogs with Activity in Hedgehog Functional Assays and GLI1-Dependent Cancer Cells.

Aberrant activation of hedgehog (Hh) signaling has been implicated in various cancers. Current FDA-approved inhibitors target the seven-transmembrane receptor Smoothened, but resistance to these drugs has been observed. It has been proposed that a more promising strategy to target this pathway is at the GLI1 transcription factor level.

The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines.

The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed.

GC/HRMS Analysis of E-Liquids Complements In Vivo Modeling Methods and can Help to Predict Toxicity.

Tobacco smoking is a major risk factor for disease development, with the user inhaling various chemicals known to be toxic. However, many of these chemicals are absent before tobacco is "burned". Similar, detailed data have only more recently being reported for the e-cigarette with regards to chemicals present before and after the e-liquid is "vaped.

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain.

B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain.

Carbon-TiO Hybrid Quantum Dots for Photocatalytic Inactivation of Gram-Positive and Gram-Negative Bacteria.

Carbon-semiconductor hybrid quantum dots are classical carbon dots with core carbon nanoparticles doped with a selected nanoscale semiconductor. Specifically, on those with the nanoscale TiO doping, denoted as C-Dots, their synthesis and thorough characterization were reported previously. In this work, the C-Dots were evaluated for their visible light-activated antibacterial function, with the results showing the effective killing of not only Gram-positive but also the generally more resistant Gram-negative bacteria.

Vaping-Dependent Pulmonary Inflammation Is Ca Mediated and Potentially Sex Specific.

Here we use the SCIREQ InExpose system to simulate a biologically relevant vaping model in mice to investigate the role of calcium signaling in vape-dependent pulmonary disease as well as to investigate if there is a gender-based difference of disease. Male and female mice were vaped with JUUL Menthol (3% nicotine) using the SCIREQ InExpose system for 2 weeks. Additionally, 2-APB, a known calcium signaling inhibitor, was administered as a prophylactic for lung disease and damage caused by vaping.

Differential diagnosis of mild cognitive impairment of Alzheimer's disease by Simoa p-tau181 measurements with matching plasma and CSF.

Alzheimer's disease (AD) is characterized by a long preclinical phase. Although late-stage AD/dementia may be robustly differentiated from cognitively normal individuals by means of a clinical evaluation, PET imaging, and established biofluid biomarkers, disease differentiation between cognitively normal and various subtypes of mild cognitive impairment (MCI) remains a challenging task. Differential biomarkers for early-stage AD diagnosis with accessible biofluid samples are urgently needed.

A novel cross-institutional college internship program to train future diverse leaders in clinical research with data-driven approaches to assess impact.

The field of Clinical Research, like many other scientific disciplines, has struggled to recruit and retain talented researchers from diverse communities. While there is a strong history of documenting the problem, having a diverse and inclusive workforce is hindered by the lack of data-driven approaches, cross-institutional partnerships, access to mentors, and positive immersive experiences for people from underrepresented groups. Here, we describe a novel initiative for North Carolina Central University Clinical Research Sciences Program (NCCU-CRSP) student interns to partner with Duke University to have immersive clinical and pre-clinical research training in a 15-week internship as the culminating experience towards their degree for a Bachelor of Science in Clinical Research.

Small molecule screen identifies pyrimethamine as an inhibitor of NRF2-driven esophageal hyperplasia.

Objective: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2 ESCC.

Carbon Dots: Classically Defined versus Organic Hybrids on Shared Properties, Divergences, and Myths.

Carbon dots are defined as small carbon nanoparticles with effective surface passivation via organic functionalization. The definition is literally a description of what carbon dots are originally found for the functionalized carbon nanoparticles displaying bright and colorful fluorescence emissions, mirroring those from similarly functionalized defects in carbon nanotubes. In literature more popular than classical carbon dots are the diverse variety of dot samples from "one-pot" carbonization of organic precursors.

Advancing workforce diversity by leveraging the Clinical and Translational Science Awards (CTSA) program.

Clinical trials continue to disproportionately underrepresent people of color. Increasing representation of diverse backgrounds among clinical research personnel has the potential to yield greater representation in clinical trials and more efficacious medical interventions by addressing medical mistrust. In 2019, North Carolina Central University (NCCU), a Historically Black College and University with a more than 80% underrepresented student population, established the Clinical Research Sciences Program with support from the Clinical and Translational Science Awards (CTSA) program at neighboring Duke University.

Hexameric Aggregation Nucleation Core Sequences and Diversity of Pathogenic Tau Strains.

Tau aggregation associates with multiple neurodegenerative diseases including Alzheimer's disease and rare tauopathies such as Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. The molecular and structural basis of tau aggregation and related diverse misfolded tau strains are not fully understood. To further understand tau-protein aggregation mechanisms, we performed systematic truncation mutagenesis and mapped key segments of tau proteins that contribute to tau aggregation, where it was determined that microtubule binding domains R2 and R3 play critical roles.

Lead/Drug Discovery from Natural Resources.

Natural products and their derivatives have been shown to be effective drug candidates against various diseases for many years. Over a long period of time, nature has produced an abundant and prosperous source pool for novel therapeutic agents with distinctive structures. Major natural-product-based drugs approved for clinical use include anti-infectives and anticancer agents.

E-cigarette Flavors, Sensory Perception, and Evoked Responses.

The chemosensory experiences evoked by flavors encompass a number of unique sensations that include olfactory stimuli (smell), gustatory stimuli (taste, i.e., salty, sweet, sour, bitter, and umami (also known as "savoriness")), and chemesthesis (touch).

A high throughput proliferation and cytotoxicity assay for co-cultured isogenic cell lines.

PTEN is a well-known tumor suppressor that is inactivated or suppressed at a high frequency in cancer. We sought an assay to screen compounds for ones that differentially inhibited proliferation or induced cytotoxicity in PTEN mutated cancer cells. We employed the isogenic pair of cell lines MCF10-A breast cell line (wild type, WT) and the same cell line with PTEN knocked out (KO) by CRISPR.

An olive-derived elenolic acid stimulates hormone release from L-cells and exerts potent beneficial metabolic effects in obese diabetic mice.

Insulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent.

A plant-based mutant huntingtin model-driven discovery of impaired expression of GTPCH and DHFR.

Pathophysiology associated with Huntington's disease (HD) has been studied extensively in various cell and animal models since the 1993 discovery of the mutant huntingtin (mHtt) with abnormally expanded polyglutamine (polyQ) tracts as the causative factor. However, the sequence of early pathophysiological events leading to HD still remains elusive. To gain new insights into the early polyQ-induced pathogenic events, we expressed Htt exon1 (Htt) with a normal (21), or an extended (42 or 63) number of polyQ in tobacco plants.

Obesity and Breast Cancer Metastasis across Genomic Subtypes.

Background: Obese women have higher risk of aggressive breast tumors and distant metastasis. However, obesity has rarely been assessed in association with metastasis in diverse populations.

Methods: In the Carolina Breast Cancer Study Phase 3 (2008-2013), waist-to-hip ratio (WHR), body mass index (BMI), and molecular subtype [PAM50 risk-of-recurrence (ROR) score] were assessed.

Selective Detection of Misfolded Tau From Postmortem Alzheimer's Disease Brains.

Tau aggregates are present in multiple neurodegenerative diseases known as "tauopathies," including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. Such misfolded tau aggregates are therefore potential sources for selective detection and biomarker discovery. Six human tau isoforms present in brain tissues and both 3R and 4R isoforms have been observed in the neuronal inclusions.

Inactivation of Vesicular Stomatitis Virus with Light-Activated Carbon Dots and Mechanistic Implications.

The prevention of viral transmission is an important step to address the spread of viral infections. Using the enveloped vesicular stomatitis virus (VSV) as a model, this study explored the antiviral functions of the specifically designed and prepared carbon dots (CDots). The CDots were prepared using small carbon nanoparticles with surface functionalization-passivation by oligomeric polyethylenimine (PEI).