Evaluation of Epigallocatechin-3-Gallate-Palmitate (EC16) in Nasal Formulations Against Human Coronavirus
Background: Chronic neurologic diseases are common sequelae of COVID. They severely impact the qu... more Background: Chronic neurologic diseases are common sequelae of COVID. They severely impact the quality of life and increase the burden on healthcare systems. The long COVID neurological symptoms are due to the robust replication of SARS-CoV-2 in the nasal neuroepithelial cells, leading to neuroinvasion and inflammation of the central nerve system (CNS). Currently used medications and vaccines do not inhibit the robust SARS-CoV-2 replication in the nasal epithelial cells. EGCG-palmitate (EC16), a multifunctional compound, has the potential to become a novel intranasal-delivered drug for minimizing post-COVID neurologic symptoms. Method: EC16-containing formulations were developed and tested in vitro against human β coronavirus OC43 (CoV-OC43) using a TCID50 assay following three test protocols differing in exposure sequence. Results: EC16 formulations in normal saline, phosphate buffered saline, and cell culture medium were found to effectively inhibit human β-coronavirus infection (...
Background: Osteoarthritis (OA) is a clinical syndrome characterized by joint failure that is acc... more Background: Osteoarthritis (OA) is a clinical syndrome characterized by joint failure that is accompanied by pain and functional limitations. OA is the leading cause of chronic disability in elderly and it is estimated that the United States spends $185 billion in management of OA annually. Although OA patients receive both pharmacologic and non-pharmacologic treatments, none of them provide long-lasting treatments. Since 1980s, autologous chondrocyte transplantation (ACT) has been used to regenerate cartilage within focal cartilage defects of young patients without pre-existing OA with increased functionality by 74% to 90%. In this technique, chondrocytes are removed from patients, multiplied in vitro, then implanted into the focal cartilage defect. Our review aimed to compare chondrocyte gene expression profiles of non-OA patients with OA patients to determine if OA-derived chondrocytes could be used for the ACT. Methods: An extensive literature search was conducted with following...
Cyanobacterial harmful algal blooms (CHAB), caused by eutrophication, are known to threaten both ... more Cyanobacterial harmful algal blooms (CHAB), caused by eutrophication, are known to threaten both wildlife and human health. Due to urbanization and land use changes, an increase of CHAB's at a more frequent rate within Barnegat Bay has been observed. In order to detect possible CHAB causing cyanobacteria, water samples were collected from 12 different locations within Barnegat Bay. Each sample was filtered through a 30-and 0.4-μm polycarbonate filter sequentially. Flow cytometry was carried out for the filtrate collected between 0.4-and 30-μm. Chelex DNA extraction, polymerase chain reaction (PCR), and gel electrophoresis were then performed for all sites using four primer sets (27F/785R, PSF/UR, CYA359F/CYA781R and MSF/MSR) designed to detect cyanobacteria. Flow cytometric results indicated the water samples contained a wide range of cyanobacteria, including M. aeruginosa, Cylindrospermum spp., Anabaena spp., and Synechococcus sp. IU 625 ranges from 3.16 to 8.17 × 10 7 cells•L −1. PCR-based assays suggest that general cyanobacteria as well as phytospecific species were present for all sites, but no toxin-producing Microcystis aeruginosa was detected. Plaque assays demonstrated the presence of cyanophages for S. IU 625, Anabaena spp., and M. aeruginosa at all sites, up to 10 5 PFU•ml −1 .
Nutraceuticals have been a rich source of prophylactic and therapeutic benefits to humans against... more Nutraceuticals have been a rich source of prophylactic and therapeutic benefits to humans against various diseases. Golden buckwheat (Fagopyrum dibotrys [F. dibotrys or F. dibityo]) has been used in Chinese traditional medicine and herbal medicine to treat inflammatory conditions. Extracts from the leaves and roots of the plant contain unique combinations of compounds that may have potential for future medications due to their anti-cancer, antioxidant, anti-inflammatory, anti-aging, and hepatoprotective properties. However, the potential antiviral activity of the plant extract has not been explored. The purpose of the current study is to investigate if Golden buckwheat or 5,7,3’,4’-tetrahydroxyflavan-3-ol C4-C8 dimer, the major compound of Golden buckwheat, possess antiviral activity against alcohol-resistant nonenveloped viruses such as norovirus and hepatitis A viruses. Methods used in the study include cytotoxicity assay (MTT assay), viral infection assays, and TCID50 assay. The ...
Bacterial spores are resistant to harsh environments and to currently used hand hygiene products.... more Bacterial spores are resistant to harsh environments and to currently used hand hygiene products. Infections caused by spore-forming bacteria, which often occur in healthcare settings, long-term care facilities, food and beverage industries, are associated with high morbidity and mortality in the United States. The current recommendation from the US Center for Disease Control and Prevention (CDC) to prevent the spread of bacterial spores is to wash hands with soap and water. However, it is known that soap and water do not inactivate bacterial spores, but rather remove them from the skin into the water drainage system. Although there is a trend towards a reduction of healthcare associated infections (HAI) in the United States, spore-forming bacteria, such as Clostridium difficile (C difficile) and Bacillus cereus (B. cereus), still pose significant risks to the population. Thus, hand hygiene methods with high sporicidal activity, yet without toxicity, are needed to better protect the general population from infections caused by spore-forming bacteria. We reported previously that derivatives of green tea polyphenols, especially lipid-soluble green tea polyphenols such as EGCG-acyl esters, exhibit potential as sporicidal agents without toxicity to humans or the environment. We hypothesize that alcohol (ethanol) formulated with lipid-soluble EGCG and other plantderived ingredients would achieve high sporicidal efficacy and become novel hand/surface disinfectants without toxicity. The objective of the current study was to determine if alcohol/EGCG-Palmitate (EGCG-P) formulations containing plant-derived ingredients are able to inactivate B. cereus spores effectively as a basis for future hand hygiene purposes. Methods used included suspension testing of different formulations against purified B. cereus spores and quantification of spore germination. The results demonstrated that several formulations containing only plant-derived ingredients were capable of reducing spore germination by greater than 10,000 fold (log 4 reduction) after 60-second exposure. Additional proof-of-concept studies are warranted to explore the suitability of these formulations for future hand hygiene products against spore-forming bacteria.
Theaflavin-3,3′-digallate (TFDG), a polyphenol derived from the leaves of Camellia sinensis, is k... more Theaflavin-3,3′-digallate (TFDG), a polyphenol derived from the leaves of Camellia sinensis, is known to have many health benefits. In this study, the antibacterial effect of TFDG against nine bacteria and the sporicidal activities on spore-forming Bacillus spp. have been investigated. Microplate assay, colony-forming unit, BacTiter-GloTM, and Live/Dead Assays showed that 250 µg/mL TFDG was able to inhibit bacterial growth up to 99.97%, while 625 µg/mL TFDG was able to inhibit up to 99.92% of the spores from germinating after a one-hour treatment. Binding analysis revealed the favorable binding affinity of two germination-associated proteins, GPR and Lgt (GerF), to TFDG, ranging from −7.6 to −10.3 kcal/mol. Semi-quantitative RT-PCR showed that TFDG treatment lowered the expression of gpr, ranging from 0.20 to 0.39 compared to the control in both Bacillus spp. The results suggest that TFDG not only inhibits the growth of vegetative cells but also prevents the germination of bacterial...
Cyanobacteria harmful algal blooms (CHABs) are primarily caused by man-made eutrophication and in... more Cyanobacteria harmful algal blooms (CHABs) are primarily caused by man-made eutrophication and increasing climate-change conditions. The presence of heavy metal runoff in affected water systems may result in CHABs alteration to their ecological interactions. Certain CHABs produce by-products, such as microcystin (MC) cyanotoxins, that have detrimentally affected humans through contact via recreation activities within implicated water bodies, directly drinking contaminated water, ingesting biomagnified cyanotoxins in seafood, and/or contact through miscellaneous water treatment. Metallothionein (MT) is a small, metal-sequestration cysteine rich protein often upregulated within the stress response mechanism. This study focused on zinc metal resistance and stress response in a toxigenic cyanobacterium, Microcystis aeruginosa UTEX LB 2385, by monitoring cells with (0, 0.1, 0.25, and 0.5 mg/L) ZnCl2 treatment. Flow cytometry and phase contrast microscopy were used to evaluate physiologic...
Heavy alcohol use increases the risk of Alzheimer’s Disease (AD); however, the underlying mechani... more Heavy alcohol use increases the risk of Alzheimer’s Disease (AD); however, the underlying mechanisms are not addressed. The key chemical of alcohol beverages is ethanol (EtOH), and acetaldehyde is its key toxic metabolite. QIAGEN Ingenuity Pathway Analysis (IPA) bioinformatics tool was used to investigate and compare the holistic impact of EtOH and acetaldehyde on AD. An extensively researched biomarker of AD pathologies is amyloid-beta of which the precursor is amyloid precursor protein (APP). Molecules associated with APP or EtOH were collected from the QIAGEN Knowledge Base, and 313 molecules were overlapping between the molecule sets. Using the “Pathway Explorer” tool, 40 of the 313 molecules were found to change due to EtOH exposure and influence APP and were compared with acetaldehyde-mediated molecule expression changes. A pathway analysis of the findings related to these 40 molecules showed that EtOH increases APP expression at a confidence of p = 0.056 (z-score = 1.91, two-...
Biofilm, a stress-induced physiological state, is an established means of antimicrobial tolerance... more Biofilm, a stress-induced physiological state, is an established means of antimicrobial tolerance. A perpetual increase in multidrug resistant (MDR) infections associated with high mortality and morbidity have been observed in healthcare settings. Multiple studies have indicated that the use of natural products can prevent bacterial growth. Recent studies in the field have identified that epigallocatechin gallate (EGCG), a green tea polyphenol, could disrupt bacterial biofilms. A modified lipid-soluble EGCG, epigallocatechin-3-gallate-stearate (EGCG-S), has enhanced the beneficial properties of green tea. This study focuses on utilizing EGCG-S as a novel synergistic agent with antibiotics to prevent or control biofilm. Different formulations of EGCG-S and selected antibiotics were used to study their combinatorial effects on biofilms produced by five potential pathogenic bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcusepidermidis, and Mycobac...
The diversity of bacterial species in the oral cavity makes it a key site for research. The close... more The diversity of bacterial species in the oral cavity makes it a key site for research. The close proximity of the oral cavity to the brain and the blood brain barrier enhances the interest to study this site. Changes in the oral microbiome are linked to multiple systemic diseases. Alcohol is shown to cause a shift in the microbiome composition. This change, particularly in the oral cavity, may lead to neurological diseases. Alzheimer’s disease (AD) is a common neurodegenerative disorder that may cause irreversible memory loss. This study uses the meta-analysis method to establish the link between binge drinking, the oral microbiome and AD. The QIAGEN Ingenuity Pathway Analysis (IPA) shows that high levels of ethanol in binge drinkers cause a shift in the microbiome that leads to the development of AD through the activation of eIF2, regulation of eIF4 and p70S6K signaling, and mTOR signaling pathways. The pathways associated with both binge drinkers and AD are also analyzed. This st...
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive loss of ... more Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive loss of cognitive functions in affected individuals. Brain tissue pathology is associated with the formation of senile plaques which result from the overproduction of amyloid β (Aβ), due to the cleavage of a membrane bound glycoprotein. It is unclear what causes AD and its associated pathologies, but age and genetic predisposition play an import role in the likelihood of disease development. Studies have shown that the reactivation of latent herpes simplex virus 1 (HSV-1) infection can lead to the neuropathy of acute herpes simplex encephalitis (HSE), which causes similar symptoms to AD. HSV-1 infection is a known risk factor for the development of AD, but no study has determined a definitive causal relationship. Using the Qiagen Ingenuity Pathway Analysis (IPA) tool, the inhibitory relationship between therapeutics for AD and HSV-1 were explored. Thirteen drugs developed to decrease Aβ buildup in AD and 32 drugs that act as HSV antivirals were retrieved from the data in the Qiagen Knowledge Base. These drugs were analyzed displayed as two separate networks. While many promising Aβ aggregation-targeting drugs have been discontinued due to lack of efficacy, HSV drugs could serve as potential therapeutics for those with AD. This review aims to describe new insights on how HSV-1 relates to the development of AD and highlight the mechanism of action of Aβ-related drugs and HSV drugs in the context of AD. With HSV-1 being a likely candidate for the causation of AD, there is a need to study the effects of HSV antiviral drugs on those who have AD.
Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. Th... more Antiviral drugs currently on the market primarily target proteins encoded by specific viruses. The drawback of these drugs is that they lack antiviral mechanisms that account for resistance or viral mutation. Thus, there is a pressing need for researchers to explore and investigate new therapeutic agents with other antiviral strategies. Viruses such as the human immunodeficiency virus (HIV) alter canonical signaling pathways to create a favorable biochemical environment for infectivity. We used Qiagen Ingenuity Pathway Analysis (IPA) software to review the function of several cellular kinases and the resulting perturbed signaling pathways during HIV infection such as NF-κB signaling. These host cellular kinases such as ADK, PKR, MAP3K11 are involved during HIV infection at various stages of the life cycle. Additionally IPA analysis indicated that these modified host cellular kinases are known to have interactions with each other especially AKT1, a serine/threonine kinase involved in multiple pathways. We present a list of cellular host kinases and other proteins that interact with these kinases. This approach to understanding the relationship between HIV infection and kinase activity may introduce new drug targets to arrest HIV infectivity.
Introduction: The rise in antibiotic resistant cases has caused a global concern. Researchers aro... more Introduction: The rise in antibiotic resistant cases has caused a global concern. Researchers around the world are trying to find a novel alternative to combat this issue. Green tea with its many health benefits, including antibacterial and antiviral activity, has shown to be one of the most promising candidates to be used as an agent to solve this problem. Objective: This study focuses on evaluating the synergistic effects of antibiotics and two green tea polyphenols: epigallocatechin gallate (EGCG), and its modified lipophilic form epigallocatechin gallate stearate (EGCG-S). Methods: In this study, twelve antibiotics and eight bacteria: Gram-positive Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis) and Bacillus megaterium (B. megaterium); Gram-negative Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Serratia marcescens (S. marcescens), and Enterobacter aerogenes (E. aerogenes); and acid-fast Mycobacterium smegmatis (M. smegmatis) were used. Antibacterial synergism profiling of EGCG, EGCG-S and antibiotics has been established using a disk diffusion assay. Results: The results revealed that both 1% of EGCG and 1% EGCG-S enhanced the antimicrobial activities on antibiotics in various bacteria. Antimicrobial susceptibility study indicated that EGCG-S was able to enhance some antibiotics from the resistant category to intermediate or susceptible and/or from intermediate category to susceptible. Both EGCG and EGCG-S worked comparably on Gram-positive bacteria; in S. aureus, both compounds enhanced 5 antibiotics (AM10, CF30, C30, S10 and TE30) activities while EGCG-S had higher efficiency. B. megaterium were susceptible to most of the antibiotic treatment, thus the impact of EGCG and EGCG-S was insignificant. EGCG-S worked better than EGCG on Gram-negative bacteria; converted 9 antibiotics susceptibility in E. coli and P. aeruginosa, and 8 antibiotics in E. aerogenes. EGCG and EGCG-S also showed synergism on acid-fast bacteria M. smegmatis with EGCG-S has much higher efficiency than EGCG.
Background: Drug-ethanol interaction can result in hepatotoxicity. The liver is capable of metabo... more Background: Drug-ethanol interaction can result in hepatotoxicity. The liver is capable of metabolizing both acetaminophen and ethanol; however, severe acute or moderate chronic simultaneous exposure can cause cell and tissue damage. Therapeutic doses can become harmful if gene activity is altered via competition for metabolic pathways. Simultaneous intake of ethanol and acetaminophen results in overactive CYP2E1 and depletion of glutathione, leaving NAPQI to build up in the liver. NAPQI is a hepatotoxic substance typically neutralized by glutathione. Methods: Bioinformatics tools including PharmGKB, Chemical Annotation Retrieval Toolkit, Transcriptome Analysis Console 4.0 (TAC), wikipathways, STRING, and Ingenuity Pathway Analysis (IPA) were used to explore interactive metabolic pathways of ethanol-acetaminophen exposure as a proof of concept for assessing drug-drug or drug-alcohol interactions. Results: As the ethanol-acetaminophen comparison indicates, bioinformatics tools may be...
Eutrophication is a process that occurs due to the excessive accumulation of nutrients, primarily... more Eutrophication is a process that occurs due to the excessive accumulation of nutrients, primarily nitrogen and phosphorus, from natural and anthropogenic sources. This phenomenon causes cyanobacterial overgrowth, which over time leads to cyanobacterial harmful algal blooms (CHABs) that affect public drinking water sources and water sites with recreational usage. The rapid detection of bloom-forming cyanobacteria in freshwater bodies is critical in order to implement prevention strategies. Cyanobacteria contain phycobiliproteins such as phycoerythrin and allophycocyanin as part of the phycobilisome that allows autofluorescence. In this study, samples from 36 freshwater bodies in 14 New Jersey counties were collected and analyzed using flow cytometry with forward-scatter phycoerythrin and allophycocyanin parameters. Pure cultures of Synechococcus sp. IU 625, Cylindrospermum spp. and Microcystis aeruginosa were used as references. The results revealed that 17 out of the 36 analyzed sit...
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