Potential pro-inflammatory impact of scleral lens midday fogging on human corneal epithelial cells: An in vitro study.

Purpose: Midday fogging (MDF) occurs when particulate material accumulates in the fluid reservoir (FR) beneath scleral lenses (SL), and its impact on epithelial cells is unknown. This study examines the in vitro pro-inflammatory effect of the FR on human corneal epithelial cells in varying degrees of MDF.

Methods: Normal SL neophytes were recruited to wear SL 8 h daily for 4 days.

Simultaneous submission of seven CTSA proposals: UM1, K12, R25, T32-predoctoral, T32-postdoctoral, and RC2: strategies, evaluation, and lessons learned.

Translation is the process of turning observations in the research laboratory, clinic, and community into interventions that improve people's health. The Clinical and Translational Science Awards (CTSA) program is a National Center for Advancing Translational Sciences (NCATS) initiative to advance translational science and research. Currently, 64 "CTSA hubs" exist across the nation.

A Low-Fat/Sucrose Diet Rich in Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation.

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks.

Anti-inflammatory and wound healing potential of medicinal maggot excretions/secretions at the ocular surface.

Purpose: In the skin, Lucilia sericata maggot excretions/secretions (ES) accelerate wound healing and limit inflammation. This study aimed to determine whether ES have similar beneficial effects at the ocular surface.

Methods: Human corneal epithelial cells (HCEC) were cultured with ES and cell viability was determined by the MTT assay.

Changes in tear glucose and insulin concentrations following an oral glucose tolerance test.

Clinical Relevance: Tear glucose and insulin are responsible for the health of the ocular surface; thus, it is important for clinicians to detect the tear glucose and insulin using point-of-care methods.

Aim: To determine if changes in blood glucose and insulin levels following an oral glucose tolerance test are reflected in the tears and to test the association between gene expression and tear insulin and glucose.

Methods: Twenty healthy young adults were enrolled.

Impact of Low Humidity on Damage-associated Molecular Patterns at the Ocular Surface during Dry Eye Disease.

Significance: Dry eye is one of the leading causes for individuals to seek eye care, whereas the pathogenesis is poorly understood. One mechanism in which dry eye inflammation may ensue is by the release of damage-associated molecular patterns (DAMPs) by damaged cells to stimulate the production of cytokines and matrix metalloproteinases. Examining DAMP levels on the ocular surface during dry eye disease (DED) will increase our understanding of their potential involvement in the pathogenesis of DED.

Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation.

Dry eye disease (DED) affects hundreds of millions of people worldwide. It is characterized by the production of inflammatory cytokines and chemokines as well as damaging matrix metalloproteinases (MMPs) at the ocular surface. While proteoglycan 4 (PRG4), a mucin-like glycoprotein present at the ocular surface, is most well known as a boundary lubricant that contributes to ocular surface integrity, it has been shown to blunt inflammation in various cell types, suggesting a dual mechanism of action.

Scleral lens wear: Measuring inflammation in the fluid reservoir.

Purpose: To measure inflammatory mediators in the scleral lens fluid reservoir (FR) in healthy eyes and to compare them to basal tear samples after 8-hs (8h) and 4-days (4d) of scleral lens (SL) wear.

Methods: Fifteen normal, habitual soft contact lens wearers were fitted with 14.8- or 15.

MyD88 Deficiency Protects Against Dry Eye-Induced Damage.

Purpose: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation. Toll-like receptors (TLRs) are integral in the initiation of inflammatory signaling. Therefore, we evaluated the effect of TLR-deficiency on dry eye-related ocular surface damage and inflammation using a mouse model of experimental dry eye (EDE).

High-Mobility Group Box 1 in Dry Eye Inflammation.

Purpose: To determine high-mobility group box 1 (HMGB1) expression during experimental dry eye (EDE) and dry eye-like culture conditions and elucidate its role in corneal dry eye-related inflammation.

Methods: EDE was induced in 8- to 12-week-old C57BL/6 mice. Corneal tissue sections and lysates from EDE and untreated mice were evaluated for HMGB1 expression by immunostaining and quantitative real-time PCR (qPCR).

MyD88 contribution to ocular surface homeostasis.

The cornea must maintain homeostasis, enabling rapid response to injury and microbial insult, to protect the eye from insult and infection. Toll-like receptors (TLRs) are critical to this innate immune response through the recognition and response to pathogens. Myeloid differentiation primary response (MyD88) is a key signaling molecule necessary for Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R)-mediated immune defense and has been shown to be necessary for corneal defense during infection.

Tumor-selective cytotoxicity of a novel pentadiene analogue on human leukemia/ lymphoma cells.

Background: A novel series of structurally divergent 1,5-diaryl-3-oxo-1,4-pentadiene analogues - displayed marked cytotoxic potencies towards a number of human leukemia/lymphoma cells.

Objective: To identify novel selective cytotoxic compounds that induce apoptosis.

Methods: The Differential Nuclear Staining (DNS) screening protocol was utilized to measure the cytotoxicity of all experimental dienones on several cancerous cells.

Validation of N-myristoyltransferase as Potential Chemotherapeutic Target in Mammal-Dwelling Stages of Trypanosoma cruzi.

Background: Trypanosoma cruzi causes Chagas disease, an endemic and debilitating illness in Latin America. Lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. The two clinically available drugs for the chemotherapy of Chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance.

Functions of Peptidoglycan Recognition Proteins (Pglyrps) at the Ocular Surface: Bacterial Keratitis in Gene-Targeted Mice Deficient in Pglyrp-2, -3 and -4.

Purpose: Functions of antimicrobial peptidoglycan recognition proteins (Pglyrp1-4) at the ocular surface are poorly understood. Earlier, we reported an antibacterial role for Pglyrp-1 in Pseudomonas aeruginosa keratitis. Here we investigated functions of three other related genes Pglyrp-2, -3 and -4 in a mouse model of P.

Dry eye modulates the expression of toll-like receptors on the ocular surface.

We aimed to determine if toll-like receptor (TLR) expression is modulated in response to dry eye-associated conditions and in dry eye syndrome (DES). Primary human corneal epithelial cells (HCEC), an SV40 HCEC cell line or a normal human conjunctival epithelial cell line (IOBA-NHC) were cultured under hyperosmolar stress (HOS) (400-500 mOsm/kg) or with DES associated cytokines (IL-1α/β, TNFα or TGFβ) at concentrations ranging from 1 to 1000 ng/ml for up to 24 h. Epithelial cells were harvested from a human cornea organ culture model following 24 h of desiccation.

Arsenic-exposed Keratinocytes Exhibit Differential microRNAs Expression Profile; Potential Implication of miR-21, miR-200a and miR-141 in Melanoma Pathway.

Long-term exposure to arsenic has been linked to cancer in different organs and tissues, including skin. Here, non-malignant human keratinocytes (HaCaT) were exposed to arsenic and its effects on microRNAs (miRNAs; miR) expression were analyzed miRCURY LNA array analyses. A total of 30 miRNAs were found differentially expressed in arsenic-treated cells, as compared to untreated controls.

The gender of cell lines matters when screening for novel anti-cancer drugs.

Current reports indicated that the gender origin of cells is important in all facets of experimental biology. To explore this matter using an anticancer high throughput screening platform, seven male- and seven female-derived human cell lines, six from cancer patients in each group, were exposed to 81 novel cytotoxins. In this screen, the findings revealed that 79 out of 81 of the compounds consistently inflicted higher levels of toxicity towards male derived cells, emphasizing that there is indeed a gender-related difference in cell sensitivity to these anti-neoplastic agents.

Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: structure-activity relationships and potent antileukemic and antilymphoma cytotoxicity.

Novel clusters of 3,5-bis(benzylidene)-4-oxo-1-piperidinyl dimers 3-5 were evaluated against human Molt4/C8 and CEM T-lymphocytes and human HeLa cervix adenocarcinoma cells as well as murine L1210 leukemia neoplasms. Several of these compounds demonstrated IC50 values in the submicromolar and low micromolar range and compounds possessing 4-fluoro, 4-chloro and 3,4,5-trimethoxy substituents in the series 3 and 4 were identified as potent molecules. A heat map revealed the very high cytotoxic potencies of representative compounds against a number of additional leukemic and lymphoma cell lines and displayed greater toxicity to these cells than nonmalignant MCF10A and Hs-27 neoplasms.

The cytotoxic effect of 2-acylated-1,4-naphthohydroquinones on leukemia/lymphoma cells.

Here, we tested seven 2-acylated-1,4-hydronaphthoquinones for their cytotoxic effects on a panel of cancer lymphoma/leukemia cells and compared to a non-cancer origin cell line. Several naphthohydroquinones exhibited selective cytotoxic effects on lymphoma/leukemia cells with lowest activity on non-cancer cells. The mode of cell death induced by an acylated naphthohydroquinone, which has a long alkyl chain, was found to be via apoptosis.

Synthesis, surface properties, and biocompatibility of 1,2,3-triazole-containing alkyl β-D-xylopyranoside surfactants.

We are interested in the development of surfactants derived from hemicellulosic biomass, as they are potential components in pharmaceuticals, personal care products, and other detergents. Such surfactants should exhibit low toxicity in mammalian cells. In this study we synthesized a series of alkyl or fluoroalkyl β-xylopyranosides from azides and an alkyne using the copper-catalyzed azide-alkyne (CuAAC) 'click' reaction in 4 steps from xylose.

Synthesis, thermal properties, and cytotoxicity evaluation of hydrocarbon and fluorocarbon alkyl β-D-xylopyranoside surfactants.

Alkyl β-d-xylopyranosides are highly surface active, biodegradable surfactants that can be prepared from hemicelluloses and are of interest for use as pharmaceuticals, detergents, agrochemicals, and personal care products. To gain further insights into their structure-property and structure-activity relationships, the present study synthesized a series of hydrocarbon (-C(6)H(13) to -C(16)H(33)) and fluorocarbon (-(CH(2))(2)C(6)F(13)) alkyl β-d-xylopyranosides in four steps from d-xylose by acylation or benzoylation, bromination, Koenigs-Knorr reaction, and hydrolysis, with the benzoyl protecting group giving better yields compared to the acyl group in the Koenigs-Knorr reaction. All alkyl β-d-xylopyranosides formed thermotropic liquid crystals.

Bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides: a novel class of potent cytotoxins.

The principal objective of this study was the examination of the theory of cytotoxic synergism. In this exploratory study, we tested the hypothesis that doubling the number of sites available for thiol alkylation in a series of candidate cytotoxins increases potency more than two-fold. This concept was verified in one-third of our comparisons using human Molt 4/C8 and CEM T-lymphocytes and murine L1210 cells.

Differential nuclear staining assay for high-throughput screening to identify cytotoxic compounds.

As large quantities of novel synthetic molecules continue to be generated there is a challenge to identify therapeutic agents with cytotoxic activity. Here we introduce a Differential Nuclear Staining (DNS) assay adapted to live-cell imaging for high throughput screening (HTS) that utilizes two fluorescent DNA intercalators, Hoechst 33342 and Propidium iodide (PI). Since Hoechst can readily cross cell membranes to stain DNA of living and dead cells, it was used to label the total number of cells.

Arene-Ru(II)-chloroquine complexes interact with DNA, induce apoptosis on human lymphoid cell lines and display low toxicity to normal mammalian cells.

The complexes [Ru(eta(6)-p-cymene)(CQ)Cl(2)] (1), [Ru(eta(6)-benzene)(CQ)Cl(2)] (2), [Ru(eta(6)-p-cymene)(CQ)(H(2)O)(2)][BF(4)](2) (3), [Ru(eta(6)-p-cymene)(en)(CQ)][PF(6)](2) (4), [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF(4)](2) (5) (CQ = chloroquine base; CQDP = chloroquine diphosphate; en = ethylenediamine) interact with DNA to a comparable extent to that of CQ and in analogous intercalative manner with no evidence for any direct contribution of the metal, as shown by spectrophotometric and fluorimetric titrations, thermal denaturation measurements, circular dichroism spectroscopy and electrophoresis mobility shift assays. Complexes 1-5 induced cytotoxicity in Jurkat and SUP-T1 cancer cells primarily via apoptosis. Despite the similarities in the DNA binding behavior of complexes 1-5 with those of CQ the antitumor properties of the metal drugs do not correlate with those of CQ, indicating that DNA is not the principal target in the mechanism of cytotoxicity of these compounds.

MicroRNAs and their implications in toxicological research.

MicroRNAs (miRNAs) are non-coding regulatory RNA molecules that bind target messenger RNAs (mRNA) and suppress their translation into proteins. When an organism is exposed to a toxic compound, cells respond by altering the pattern of gene expression, including miRNAs. Altered miRNA expression affects protein translation, which in turn alters cellular physiology causing adverse biological effects.