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1.
Ocul Surf ; 26: 244-254, 2022 10.
Article in English | MEDLINE | ID: mdl-36130696

ABSTRACT

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. Additionally, mRNA expression of growth factors, antimicrobial peptides (AMPs) and cytokines was assessed by qPCR. ES ability to modulate TLR-induced IL-6 and IL-8 expression was determined by qPCR and ELISA. ES potential to promote corneal healing was evaluated in vitro by a migration assay in HCEC, and in vivo using a mouse model. RESULTS: ES did not impair HCEC viability up to 25 µg/ml. Among the factors evaluated, only hBD-2 was upregulated (2.5-fold) by 1.5 µg/ml ES after 6 hrs (P = 0.04). In HCEC, ES reduced Poly I:C-induced IL-6 and IL-8 mRNA (P ≤ 0.001) and protein (P ≤ 0.0001) expression. A similar effect was observed with Flagellin (TLR5 agonist) but it was less robust for FSL-1 (TLR2/6 agonist) and Pam3CSK4 (TLR1/2 agonist). The greatest in vitro migration effect was observed with 6.2 µg/ml ES after 44 hrs where gap area compared to vehicle was 53.3 ± 3.7% vs. 72.6 ± 5.4% (P = 0.001). In the mouse model, the maximum healing effect was present with 1.5 µg/ml ES after 12 hrs with a wound area of 19.0 ± 2.7% vs. 60.1 ± 21.6% (P = 0.003) or 77% reduction of the wound area compared to the negative control. CONCLUSIONS: ES significantly reduce in vitro TLR-induced production of inflammatory cytokines and promote corneal wound healing.


Subject(s)
Epithelial Cells , Larva , Animals , Humans , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Larva/chemistry , RNA, Messenger/genetics , Wound Healing , Epithelial Cells/drug effects , Cornea/cytology , Cells, Cultured
2.
Carbohydr Res ; 349: 12-23, 2012 Feb 15.
Article in English | MEDLINE | ID: mdl-22207000

ABSTRACT

Alkyl ß-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 ß-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 ß-d-xylopyranosides formed thermotropic liquid crystals. The phase transition of the solid crystalline phase to a liquid crystalline phase increased linearly with the length of the hydrophobic tail. The clearing points were near constant for alkyl ß-d-xylopyranosides with a hydrophobic tail ⩾8, but occurred at a significantly lower temperature for hexyl ß-d-xylopyranoside. Short and long-chain alkyl ß-d-xylopyranosides displayed no cytotoxicity at concentration below their aqueous solubility limit. Hydrocarbon and fluorocarbon alkyl ß-d-xylopyranosides with intermediate chain length displayed some toxicity at millimolar concentrations due to apoptosis.


Subject(s)
Glycosides/toxicity , Surface-Active Agents/toxicity , Temperature , Apoptosis/drug effects , Carbohydrate Conformation , Cell Survival/drug effects , Cells, Cultured , Crystallography, X-Ray , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Glycosides/chemical synthesis , Glycosides/chemistry , Humans , Models, Molecular , Structure-Activity Relationship , Surface-Active Agents/chemical synthesis , Surface-Active Agents/chemistry
3.
Cancer Sci ; 95(7): 596-601, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15245597

ABSTRACT

Human T-cell lymphotropic virus type 1 (HTLV-1) is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV-1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV-1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34-40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV-1-infected T-cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV-1 provirus load in peripheral blood lymphocytes on HTLV-1 carriers. We recruited 83 asymptomatic HTLV-1 carriers to examine HTLV-1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty-seven subjects were followed up for 5 months by measuring HTLV-1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real-time PCR quantification of HTLV-1 DNA revealed a wide range of variation of HTLV-1 provirus load among asymptomatic HTLV-1 carriers (0.2-200.2 copies of HTLV-1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV-1 provirus load as compared with the controls (P = 0.031). These results suggest that green tea drinking suppresses proliferation of HTLV-1-infected lymphocytes in vivo.


Subject(s)
Flavonoids/pharmacology , HTLV-I Infections/drug therapy , Human T-lymphotropic virus 1 , Lymphocytes/virology , Phenols/pharmacology , Proviruses , Tea/chemistry , Administration, Oral , Adult , Aged , Carrier State , DNA, Viral/analysis , Female , Humans , Leukemia-Lymphoma, Adult T-Cell/prevention & control , Leukemia-Lymphoma, Adult T-Cell/virology , Lymphocytes/physiology , Male , Middle Aged , Paraparesis, Tropical Spastic/prevention & control , Paraparesis, Tropical Spastic/virology , Polyphenols , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Viral Load
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