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Introduction
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Publications (95)
Approximately 70–90% of drug candidates at the development stage are hydrophobic. These compounds often exhibit poor water solubility. Examples of hydrophobic drug candidates include quercetin, cannabidiol (CBD), tetrahydrocannabinol (THC), retinoic acid, tocotrienols, paclitaxel, and ivermectin. This physical property can limit the development of...
It is estimated that 70–90% of drug candidates at the development stage are hydrophobic, with poor water solubility. Examples of hydrophobic drug candidates include quercetin, cannabidiol (CBD), tetrahydrocannabinol (THC), retinoic acid, tocotrienols, and ivermectin. This physical property can limit the development of these molecules for new drug u...
It is estimated that 70–90% of drug candidates at the development stage are hydrophobic, with poor water solubility. Examples of hydrophobic drug candidates include quercetin, cannabidiol (CBD), tetrahydrocannabinol (THC), retinoic acid, tocotrienols, and ivermectin. This physical property can limit the development of these molecules for new drug u...
Following recovery from the acute infection stage of the SARS-CoV-2 virus (COVID-19), survivors can experience a wide range of persistent Post-Acute Sequelae of COVID-19 (PASC), also referred to as long COVID. According to the US National Research Action Plan on Long COVID 2022, up to 23.7 million Americans suffer from long COVID, and approximately...
Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinic...
A recent estimate indicates that up to 23.7 million Americans suffer from long COVID, and approximately one million workers may be out of the workforce each day due to associated symptoms, leading to a USD 50 billion annual loss of salary. Post-COVID (Long COVID) neurologic symptoms are due to the initial robust replication of SARS-CoV-2 in the nas...
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 (...
Background
Non-toxic hand hygiene and surface disinfectant products with virucidal activity against norovirus are in urgent need to aid in curtailing infections due to this alcohol-resistant non-enveloped virus.
Method
Alcohol-based formulations were made with epigallocatechin-3-gallate-palmitate (EC16), an FDA accepted food additive. Based on in-...
Objective:
Currently used alcohol-based hand sanitizers and surgical hand rubs are not effective against alcohol-resistant microorganisms. We reported previously that nontoxic antioxidant food additive compounds derived from green tea polyphenols, particularly epigallocatechin-3-gallate-palmitate (EC16), are suitable in alcohol formulations to eff...
SARS-CoV-2, the novel coronavirus responsible for the COVID-19 pandemic, caused >26 million cases in the United States and >437,000 deaths as of Jan 30, 2020. Worldwide by that date, there had been 102 million cases of infections, and deaths had climbed to 2.21 million. Mutated variants of SARS-CoV-2 that have emerged from the United Kingdom, Brazi...
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 U...
Endospores have the ability to withstand extreme temperature, desiccation, ultraviolet radiation and chemicals which make them a threat to the food and healthcare industry. Green tea polyphenols (GTP), contain anti-microbial and anti-spore properties but not stable. In this study, two modified lipophilic green tea polyphenols, epigallocatechin-3-ga...
Current non-toxic or “generally recognized as safe” (GRAS) countermeasures against viral entry into cells in the human body are often inadequate. The objective of this study was to evaluate ProtecTeaV, a novel alcohol-based instant hand sanitizer formulation containing lipophilic EGCG (derived from green tea extract), in comparison to commonly used...
Pathogenic viral infections pose major health risks to humans and livestock due to viral infection-associated illnesses such as chronic or acute inflammation in crucial organs and systems, malignant and benign lesions. These lead to large number of illnesses and deaths worldwide each year. Outbreaks of emerging lethal viruses, such as Ebola virus,...
Background:
Recent studies suggest that light in the UVA range (320-400 nm) activates signaling pathways that are anti-inflammatory, antioxidative and play a critical role in protection against cancer. These effects have been attributed to NF-E2-related factor (NRF2)-mediated up-regulation of 'phase 2' genes that neutralize oxidative stress and me...
Objective:
Previous animal studies indicated catechins from the tea plant (Camellia sinensis) may modulate salivary function and possess a therapeutic effect for xerostomia. The objective of this study was to evaluate a natural formulation containing tea catechins in 60 patients with xerostomia, including patients with Sjögren syndrome.
Study des...
We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR). Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE) dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose) on caspase-14 expres...
Abstract Sjogren's syndrome (SS) and type-1 diabetes are prevalent autoimmune diseases in the USA. We reported previously that epigallocatechin-3-gallate (EGCG) prevented and delayed the onset of autoimmune disease in non-obese diabetic (NOD) mice, a model for both SS and type-1 diabetes. EGCG also normalized the levels of proteins related to DNA r...
The submandibular salivary glands of non-obese diabetic (NOD) mice, a model for Sjogren's syndrome and type-1 diabetes, show an elevated level of proliferating cell nuclear antigen (PCNA), a protein involved in cell proliferation and repair of DNA damage. We reported previously that epigallocatechin-3-gallate (EGCG), the most abundant green tea cat...
We previously reported that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea leaves, reduced levels of PCNA (a marker for DNA repair) and normalized antioxidant enzyme peroxiredoxin 6 prior to the onset of autoimmune symptoms in a mouse model for primary Sjogren’s syndrome (NOD.B10.H2b). However, whether oxidative DNA dama...
Green tea polyphenol epigallocatechin gallate (EGCG) is a strong anti-oxidant that has previously been shown to reduce the number of plaques in HIV-infected cultured cells. Modified EGCG palmitoyl-EGCG (p-EGCG), is of interest as a topical antiviral agent for Herpes Simplex Virus (HSV-1) infections. This study evaluated the effect of p-EGCG on HSV-...
The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epig...
The purpose of this study was to evaluate caspase-14 expression in the retina under normal and diabetic conditions, and to determine whether caspase-14 contributes to retinal microvascular cell death under high glucose conditions.
Quantitative real-time polymerase chain reaction and western blot analysis were used to evaluate caspase-14 expression...
Primary Sjogren’s syndrome is a major autoimmune disorder characterized by xerostomia and xerophthamia. The pathogenesis of Sjogren’s syndrome (SS) likely involves both genetic and environmental factors. A major potential contributor to salivary dysfunction is glandular oxidative stress, which can cause DNA damage, leading to the activation of DNA...
The effects of a proprietary topical formulation containing EGCG-stearate in 100% glycerin USP were studied in two volunteer patients with recurrent herpes simplex (HSV) type 1. Application during early onset (prodromal stage) in a patient with herpes labialis prevented lesion progression. In a second patient with herpetic stomatitis, application o...
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Xerostomia has multiple causes (e.g., chronic medication, autoimmune disorders, cancer therapy, and metabolic diseases). It affects up to 30% of adult Americans, and the prevalence is higher in the population over 65 years old. A major contributor to salivary dysfunction is oxidative stress in the salivary gland tissues. We reported previously that...
OBJECTIVES: Our lab previously has shown that specific doses of blue light (400-500 nm) induce small amounts of reactive oxygen species (ROS), which then initiates cytoprotective signaling pathways. This study examined the effect of blue light treatment on the glutathione redox couple and the pro-survival protein FLIP25 in human keratinocytes. METH...
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Sjogren's syndrome (SS) involves glandular acinar cell dysfunction, but the underlying mechanisms are not fully understood. In the NOD animal model and Sjogren's syndrome patients, significantly increased PCNA expression is seen in salivary gland epithelial cells. We reported previously that epigallocatechin-3-gallate (EGCG), the most abundant gree...
Objectives: One of the key components in successful wound healing and regeneration depends on the ability to achieve an adequate blood supply. Implicated in the pathogenesis of impaired wound healing in diabetics may be an abnormal angiogenic response. The aim of this study was to identify the differential expression of angiogenesis-associated gene...
Objective: Previous studies in our laboratory have suggested that exposure to minimal doses of blue light (λ=400-500 nm) elicits production of small amounts of reactive oxygen species (ROS), and contributes to increased mitochondrial activity and cell growth in epithelial cells. In addition, cytoprotective mechanisms such as the Nrf-2-mediated phas...
Objectives: Short, discrete doses of blue light (400-500 nm) differentially alter Nrf2- and p53-mediated cell signaling and mitochondrial activity of normal keratinocytes, epidermoid carcinoma and metastatic oral tumor cells. This research compared the effects of blue light on a colon cancer cell line, HT-29, with responses from tumor cells derived...
Xerostomia affects 27% of the adult population in the United States. It lowers a person's quality of life, and causes oral complication such as dental caries, candidiasis, and oral mucosal soreness. Previous animal model studies showed that secretory gland dysfunction was strongly associated with expression of proliferative cell markers.
Objectiv...
The pathogenesis of autoimmune diseases is multifaceted, and the complexity of symptoms, diagnosis and treatment options associated with these diseases reflects this. Sjogren's syndrome (SS) is an autoimmune disorder affecting up to 4 million Americans, and results from autoimmune reactions in secretory glands (primary SS) and other tissues (second...
In vivo anti-tumor effects of DSPP-silencing in OSC2 cells. (A) The anti-tumor effect of DSPP-silencing in OSC2 cells shows small tumor size (volume) for L2 derived tumor (left flank) compared with shC control derived tumors (right flank). Tumor size was measured weekly over a period of 6 weeks. (B) Histologic evaluation of hematoxylene and eosin (...
We determined recently that dentin sialophosphoprotein (DSPP), a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins, is highly upregulated in human oral squamous cell carcinomas (OSCCs) where upregulation is associated with tumor aggressiveness. To investigate the effects of DSPP-silencing on...
Objective: Cisplatin resistance remains a major challenge to successful chemotherapy in head and neck squamous cell carcinomas (HNSCCs), including oral squamous cell carcinomas (OSCCs); being effective in only about 20% of patients. Upregulation of Dentin sialophosphoprotein (DSPP), a member of the SIBLINGs (Small Integrin-Binding Ligand N-linked G...
Objective: The SIBLINGs (Small Integrin Binding Ligands N-linked Glycoproteins), bone sialoprotein (BSP) and dentin silaophosphoprotein (DSPP) are upregulated in several cancers. In oral squamous cell carcinoma (OSCC), BSP expression is confined to well-differentiated tumors, while DSPP is expressed across the spectrum of well- to poorly-differenti...
Xerostomia is associated with severe oral complications and a negative impact on quality of life. Major causes of xerostomia include Sjogren's syndrome (SS), cancer therapy, chronic medication, and diabetes. We hypothesize that glandular hyperproliferation and reduced antioxidant capacity associated with inflammation are important contributors to s...
Objectives: This study aimed to verify the relationship between dentin sialophosphoprotein (DSPP) and caspase-14 expression in oral squamous cell carcinoma (OSCC). DSPP, a member of the Small Integrin-Binding Ligand N-linked Glycoproteins (SIBLINGs) is highly up-regulated in a number of epithelial cancers, including OSCC. DSPP upregulation in OSCC...
Xerostomia results from many causal factors, such as Sjogren's syndrome (SS), radiation/chemotherapy, chronic drug use, and diabetes. Approximately 30% of American seniors experience xerostomia, and the number of cases is increasing. Elevated oxidative stress in the salivary glands (induced by lymphocytes infiltration, cancer therapies, and chronic...
Autoimmune disorders, the third most common group of diseases in the United States, affect about 8% of the population. Among them, Sjogren's syndrome (SS) and type 1 diabetes are prevalent autoimmune disorders. We previously reported that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea leafs, reduced the severity of sympt...
Objectives: Sjgren's Syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of the salivary glands, causing gland dysfunction. Animal studies demonstrated that green tea polyphenols (GTP) exert protective effects on salivary glands against SS-like autoimmune disorders. GTP, specifically epigallocatechin-3-gallate (EGCG),...
Current therapeutic approaches to salivary gland cancer are often associated with severe disfigurement and loss of glandular function, which are traumatic to the patients. Exploration of novel treatment approaches, such as gene therapy, is needed.
The human salivary gland cancer cell line HSG was transiently transfected with full length human caspa...
Oral cancer is an aggressive malignancy with a mortality rate consistently at 50%. Treatment of oral cancer frequently causes disfigurement. Therefore, novel therapies need to be explored. We reported previously that caspase-14, a green tea polyphenol-targeted gene expressed during terminal differentiation of certain epithelial cells, induces tumor...
Objectives: Our lab previously has shown that exposure to short, discrete doses of blue light (400-500 nm) significantly slows the growth of human A431 epidermoid tumor xenografts in vivo. We hypothesized that blue light treatment stimulates cell signaling pathways that enhance apoptosis or inhibit cell cycle progression.
Methods: Cultured A431 h...
Objective: We determined recently that dentin sialophosphoprotein (DSPP), a member of the SIBLING (Small Integrin Binding LIgands N-linked Glycoproteins) gene family is highly up-regulated in human oral squamous cell carcinomas (OSCC), and DSPP expression is associated with tumor aggressiveness. To investigate the role of DSPP in human OSCC, endoge...
Green tea polyphenols (GTPs), also referred to as green tea catechins, possess properties that can provide unique health benefits to humans. As indicated in other chapters of this book, studies using molecular, cellular, and animal models, and in human subjects, have demonstrated that these phytochemicals from non-oxidized tea leaves have anti-canc...
Nickel-containing alloys are used in dentistry because of their low cost, but poor corrosion behavior increases their risk of causing adverse biological responses. Intraorally, nickel-containing alloys accumulate bacterial plaque that triggers periodontal inflammation via toxins such as lipopolysaccharide (LPS). Recent evidence suggests that in mon...
Protection of glandular cells from autoimmune-induced damage would be of significant clinical benefit to Sjogren's syndrome (SS) patients. Epigallocatechin-3-gallate (EGCG) possesses anti-apoptotic, anti-inflammatory, and autoantigen-inhibitory properties.
To investigate if EGCG protects against certain autoimmune-induced pathological changes in th...
Blue light curing units (wavelengths of 400-500 nm) are a mainstay of restorative dentistry, and several high-intensity light sources have been developed to polymerize resin composites more rapidly. The biological safety of visible light has been assumed, but some reports of adverse biological effects of blue light in non-dental contexts support fu...
The current study investigated the protective effects of green tea polyphenols (GTPP) on TBT-induced oxidative damage. The results showed that reactive oxygen species (ROS) production and malondialdehyde content of the liver in mice exposed to TBT were reduced in the GTPP-treated group compared to the untreated group. The intracellular ROS level wa...
The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene expression differentially in tumor and normal cells. In normal human primary epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in NHEK, but not in epithelial cancer cells....
Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. The expression and proteolytic processing of caspase 14, a member of the caspase family which is associated with epithelial cell diff...
Sjogren's syndrome (SS) is a relatively common autoimmune disorder. A key feature of SS is lymphocytic infiltration of the salivary and lacrimal glands, associated with the destruction of secretory functions of these glands. Current treatment of SS targets the symptoms but is unable to reduce or prevent the damage to the glands. We reported previou...
The green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) possesses anti-carcinogenic properties and was found to induce terminal differentiation in epidermal keratinocytes. Caspase-14, a member of the caspase family associated with epithelial cell differentiation, planned cell death, and barrier formation, is induced by EGCG in normal human e...
Nickel is a component of biomedical alloys that is released during corrosion and causes inflammation in tissues by as yet unknown mechanisms. Recent data show that Ni(II) at concentrations of 10-50 microM amplifies lipopolysaccharide-triggered, NFkappaB-mediated cytokine secretion from monocytes. In the current study, we tested the hypothesis that...
The current study tested the hypothesis that the extracellular environment mediates mitochondrial suppression of oral epithelial cells and fibroblasts by blue light.
We exposed Balb fibroblasts (Balb), normal human epidermal keratinocytes (NHEK), and oral squamous carcinoma cells (OSC2) to blue light (30-120J/cm2) in different cell-culture media an...
Sjogren's syndrome (SS) is an autoimmune disorder that affects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary SS is associated with other autoimmune disorders such as systemic rheumatic diseases and systemic lupus erythematosis (SLE), which can affect multiple organs, including the epiderm...
Blue light from dental photopolymerization devices has significant biological effects on cells. These effects may alter normal cell function of tissues exposed during placement of oral restorations, but recent data suggest that some light-induced effects may also be therapeutically useful, for example in the treatment of epithelial cancers. Reactiv...
Autoimmune disorders, characterized by inflammation and apoptosis of target cells leading to tissue destruction, are mediated in part by autoantibodies against normal cellular components (autoantigens) that may be overexpressed. For example, antibodies against the autoantigens SS-A/Ro and SS-B/La are primary markers for systemic lupus erythematosus...
Blue light of high intensity is commonly used in dentistry to activate polymerization of resin restorative materials. Other than its effects on the retina, the biological effects of blue light (380-500nm wavelengths) are poorly studied. Limited evidence suggests that blue light acts by forming intracellular reactive oxygen species (ROS) that then a...
Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and pa...
Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that...
Blue light (lambda = 380-500 nm) historically has been used to initiate polymerization of biomaterials and recently has been proposed as a therapeutic agent. New evidence suggests that cell-type-specific responses result from redox changes induced by exposure to blue light. Cultured cells were exposed to defined doses of blue light, equivalent to e...
The cyclin-dependent kinase inhibitor p21WAF1 participates in cell growth, differentiation, and apoptosis. p21WAF1 can be induced by green tea polyphenol EGCG in several cancer cell types, but its role in the oral cancer cell response to EGCG is not known. We found that EGCG upregulates p21WAF1 in an oral carcinoma cell line, OSC2, by cDNA microarr...
Tubular damage by cisplatin leads to acute renal failure, which limits its use in cancer therapy. In tubular cells, a primary target for cisplatin is presumably the genomic DNA. However, the pathway relaying the signals of DNA damage to tubular cell death is unclear. In response to DNA damage, the tumor suppressor gene p53 is induced and is implica...
Dysfunction of salivary glands is often associated with aging and cancer therapy. Green tea polyphenols were previously found to protect normal epithelial cells from reactive oxygen species, and to induce apoptosis in tumor cells. The current study investigated whether -(-) epigallocatechin-3-gallate (EGCG), the major green tea polyphenol, protects...
Oral cancer is one of the most disfiguring types of cancer, since the surgical removal of the tumor may result in facial distortion. Oral cancer is also known to exhibit "field cancerization", resulting in the development of a second primary tumor. Furthermore, the five-year survival rate of this disease has remained approximately 50% during the pa...
Previous studies have reported that blue light (400-500 nm) inhibits cell mitochondrial activity. We investigated the hypothesis that cells with high energy consumption are most susceptible to blue-light-induced mitochondrial inhibition. We estimated cell energy consumption by population doubling time, and cell survival and growth by succinate dehy...
The green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) possesses promising anticancer potential. Although in vivo studies unveiled the metabolic routes and pharmacokinetics of EGCG and showed no adverse effects, in vitro studies at high concentrations demonstrated oxidative stress. EGCG causes differential oxidative environments in tumor ve...
Green tea polyphenols (GTPPs) are considered beneficial to human health, especially as chemopreventive agents. Recently, cytotoxic reactive oxygen species (ROS) were identified in tumor and certain normal cell cultures incubated with high concentrations of the most abundant GTPP, (-)-epigallocatechin-3-gallate (EGCG). If EGCG also provokes the prod...
Plant-derived phenolic compounds, including polyphenols (e.g., tannins), flavonoids, and phenolic acids, have been under investigation for their anticancer therapeutic and chemoprevention properties. Recently, certain mechanisms underlying the differential effects of green tea polyphenols (GTPPs) on tumor versus normal cells have been determined. T...
The most abundant green tea polyphenol, epigallocatechin-3-gallate (EGCG), was found to induce differential effects between tumor cells and normal cells. Nevertheless, how normal epithelial cells respond to the polyphenol at concentrations for which tumor cells undergo apoptosis is undefined. The current study tested exponentially growing and aged...
Induction of apoptosis by green tea polyphenols has been observed in various tumor cell systems, but whether green tea polyphenol-induced apoptosis requires caspase 3 for execution has not been confirmed. We previously reported that green tea polyphenol-induced apoptosis involved Apaf-1 accumulation and caspase 3 activation in the cytosol. In the c...
Green tea polyphenols (catechins) are known to induce cell death in many types of tumor cells, but how normal epithelial cells survive in the presence of polyphenols is unknown. We recently reported that green tea polyphenols potently induced a cyclin-dependent kinase inhibitor, p57/(KIP2), only in normal human epithelial cells. In this study, we i...
A human oral tumour progression model was established that consists of normal epithelial cells and three cell lines representing stages from dysplastic to metastatic cells. To investigate the impact of exogenous transforming growth factor-β1 on this model system, we analysed the responsiveness of those cells to transforming growth factor-β1 and exp...
Green tea has been a popular beverage for many centuries. Only recently, however, has the anti-cancer power of green tea constituents been unveiled. Green tea polyphenols are found to induce apoptosis (programmed cell death) in many types of tumor cells, including oral cancer cells. However, mechanisms that enable normal cells to evade the apoptoti...
Green tea polyphenols are known to induce apoptosis in certain types of tumor cells. However, the mechanism(s) that enables normal cells to evade the apoptotic effect is still not understood. In this study, Western blot analysis combined with cycloheximide treatment was used to examine the effects of green tea polyphenols on the expression levels o...
