The antibiotic resistance profiles of Pseudomonas aeruginosa in the Asia Cornea Society Infectious Keratitis Study.

Purpose: To describe the prevalence and antibiotic resistance profiles of Pseudomonas aeruginosa isolated from the Asia Cornea Society Infectious Keratitis Study (ACSIKS).

Methods: All bacterial isolates from ACSIKS underwent repeat microbiological identification in a central repository in Singapore. Minimum inhibitory concentration (MIC) determination was conducted for isolates of P.

Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P.

Host Defense Peptides at the Ocular Surface: Roles in Health and Major Diseases, and Therapeutic Potentials.

Sight is arguably the most important sense in human. Being constantly exposed to the environmental stress, irritants and pathogens, the ocular surface - a specialized functional and anatomical unit composed of tear film, conjunctival and corneal epithelium, lacrimal glands, meibomian glands, and nasolacrimal drainage apparatus - serves as a crucial front-line defense of the eye. Host defense peptides (HDPs), also known as antimicrobial peptides, are evolutionarily conserved molecular components of innate immunity that are found in all classes of life.

Evaluation of Host Defense Peptide (CaD23)-Antibiotic Interaction and Mechanism of Action: Insights From Experimental and Molecular Dynamics Simulations Studies.

Host defense peptides (HDPs) have the potential to provide a novel solution to antimicrobial resistance (AMR) in view of their unique and broad-spectrum antimicrobial activities. We had recently developed a novel hybrid HDP based on LL-37 and human beta-defensin-2, named CaD23, which was shown to exhibit good antimicrobial efficacy against in a bacterial keratitis murine model. This study aimed to examine the potential CaD23-antibiotic synergism and the secondary structure and underlying mechanism of action of CaD23.

Hybrid derivative of cathelicidin and human beta defensin-2 against Gram-positive bacteria: A novel approach for the treatment of bacterial keratitis.

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3.

Mussel-Inspired Durable Antimicrobial Contact Lenses: The Role of Covalent and Noncovalent Attachment of Antimicrobials.

Contact lens is a major risk factor for microbial keratitis among contact lens wearers. Chemical strategies that can prevent microbial adhesion and biofilm formation are required to improve a wearer's hygiene and safety. Taking advantage of the material-independent properties of a polydopamine (pDA) coating, we investigated the role of covalent/noncovalent interactions of the antimicrobials and pDA in conferring long-term antimicrobial activities.

Dissecting the Molecular Mechanism of Colistin Resistance in -1 Bacteria.

Colistin or polymyxin B is the last resort antibiotic to treat infections of multidrug-resistant Gram-negative bacteria by disrupting their outer membranes. The recent emergence of Gram-negative bacteria that demonstrate colistin resistance, particularly plasmid-mediated mobile colistin resistance (), poses a big challenge to the treatment of multidrug resistance infections. Using molecular dynamics simulations, we explore the mechanism of colistin resistance in a model lipid A bilayer mimicking the Gram-negative -1 bacterial outer membrane.

Strategies in Translating the Therapeutic Potentials of Host Defense Peptides.

The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties.

Wound healing properties of magnesium mineralized antimicrobial nanofibre dressings containing chondroitin sulphate - a comparison between blend and core-shell nanofibres.

The development of antimicrobial nanofibre dressings that can protect the injured tissues from commensal pathogens while promoting tissue regeneration finds enormous potential in plastic and reconstructive surgery practices. To achieve this goal, we investigated the effect of chondroitin sulphate on the morphology, mechanical properties, wettability and biocompatibility of polydopamine crosslinked electrospun gelatin nanofibres containing mineralized magnesium. To extend the durability of dressings, we prepared composite dressings containing polycaprolactone (PCL) and gelatin as blend or core-shell nanofibres.

Increased Protein -Glutathionylation in Leber's Hereditary Optic Neuropathy (LHON).

Leber's hereditary optic neuropathy (LHON, MIM#535000) is the most common form of inherited optic neuropathies and mitochondrial DNA-related diseases. The pathogenicity of mutations in genes encoding components of mitochondrial Complex I is well established, but the underlying pathomechanisms of the disease are still unclear. Hypothesizing that oxidative stress related to Complex I deficiency may increase protein -glutathionylation, we investigated the proteome-wide -glutathionylation profiles in LHON ( 11) and control ( 7) fibroblasts, using the GluICAT platform that we recently developed.

Mechanism of polyamine induced colistin resistance through electrostatic networks on bacterial outer membranes.

Naturally occurring linear polyamines are known to enable bacteria to be resistant to cationic membrane active peptides. To understand this protective mechanism, molecular dynamics simulations are employed to probe their effect on a model bacterial outer membrane. Being protonated at physiological pH, the amine groups of the polyamine engage in favorable electrostatic interactions with the negatively charged phosphate groups of the membrane.

Rational Substitution of ε-Lysine for α-Lysine Enhances the Cell and Membrane Selectivity of Pore-Forming Melittin.

Here, we present a rational approach that enhances the membrane selectivity of a prolific pore-forming peptide, melittin, based on experimental observations that the cationic polymer, ε-polylysine, disrupts bacterial membranes with greater affinity over mammalian cells when compared to poly-l-lysine and poly-d-lysine. We systematically replaced three α-lysine residues in melittin with ε-lysine residues and identified key residues that are important for cytotoxicity. We then assessed the antimicrobial properties of the modified peptides which carry two or three ε-lysyl residues.

Rabbit Fungal Keratitis Model of Fusarium solani Tested Against Three Commercially Available Antifungal Drugs.

Objectives: The purpose of this study was to develop a reproducible preclinical Fusarium solani keratitis model, which would allow comparative testing of currently available antifungals (NATACYN [Alcon, Fort Worth, TX], voriconazole 1%, and amphotericin B 0.1%) as well as efficacy testing of new antifungals for translation into clinical practice in the future.

Methods: The rabbit F.

A serum metabolomics study of patients with nAMD in response to anti-VEGF therapy.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the current standard of treatment for choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD), but there are no diagnostic tools to predict response of these therapies. We hypothesize that differences in baseline metabolic profiles of patients with nAMD may influence responsiveness to anti-VEGF therapy, and thus provide prognosticating information for these patients. A prospective study was performed on 100 patients with nAMD treated with anti-VEGF therapy.

Biological Mechanisms of Atropine Control of Myopia.

Myopia is a global problem that is increasing at an epidemic rate in the world. Although the refractive error can be corrected easily, myopes, particularly those with high myopia, are susceptible to potentially blinding eye diseases later in life. Despite a plethora of myopia research, the molecular/cellular mechanisms underlying the development of myopia are not well understood, preventing the search for the most effective pharmacological control.

Surface Immobilization of Nano-Silver on Polymeric Medical Devices to Prevent Bacterial Biofilm Formation.

Bacterial biofilm on medical devices is difficult to eradicate. Many have capitalized the anti-infective capability of silver ions (Ag) by incorporating nano-silver (nAg) in a biodegradable coating, which is then laid on polymeric medical devices. However, such coating can be subjected to premature dissolution, particularly in harsh diseased tissue microenvironment, leading to rapid nAg clearance.

Protective Action of Linear Polyethylenimine against Colonization and Exaggerated Inflammation and .

Increased evolution of multidrug resistant pathogens necessitates the development of multifunctional antimicrobials. There is a perceived need for developing new antimicrobials that can interfere with acute inflammation after bacterial infections. Here, we investigated the therapeutic potential of linear polyethylenimine (LPEI) and .

Age-associated changes in human tear proteome.

Background: Prevalence of many eye and ocular surface diseases increases with age. While the clinical characteristics and pathophysiologic mechanisms of these conditions are often either known or extensively studied, the effects of normal aging on tear film and ocular surface have not been as widely researched.

Methods: In order to examine the effects of aging on tear fluid proteomics, tear fluid samples were collected preoperatively from 115 subjects undergoing strabismus or refractive surgery using glass microcapillary tubes.

Mediators of Corneal Haze Following Implantation of Presbyopic Corneal Inlays.

Purpose: To identify protein mediators of corneal haze following presbyopic corneal inlay surgery.

Methods: Tears were collected from eyes with corneal haze following surgery with a shape-changing corneal inlay. Samples were subjected to quantitative proteomic analysis using iTRAQ and proteins significantly increased or decreased (1.

Combating Microbial Contamination with Robust Polymeric Nanofibers: Elemental Effect on the Mussel-Inspired Cross-Linking of Electrospun Gelatin.

Designing biocompatible nanofibrous mats capable of preventing microbial colonization from resident and nosocomial bacteria for an extended period remains an unmet clinical need. In the present work, we designed antibiotic free durable antimicrobial nanofiber mats by taking advantage of synergistic interactions between polydopamine (pDA) and metal ions with varying degree of antimicrobial properties (Ag, Mg, Ca, and Zn). Microscopic analysis showed successful pDA-mediated cross-linking of the gelatin nanofibers, which further improved by the inclusion of Ag, Mg, and Ca ions as supported by mechanical and thermal studies.

Mathematical models of amino acid panel for assisting diagnosis of children acute leukemia.

Background: The altered concentrations of amino acids were found in the bone marrow or blood of leukemia patients. Metabolomics technology combining mathematical model of biomarkers could be used for assisting the diagnosis of pediatric acute leukemia (AL).

Methods: The concentrations of 17 amino acids was measured by targeted liquid chromatograph-tandem mass spectrometry in periphery blood collected using dried blood spots.

Repurposing the anticancer drug cisplatin with the aim of developing novel infection control agents.

Antibiotic resistance threatens effective treatment of microbial infections globally. This situation has spurred the hunt for new antimicrobial compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen .

Tear Proteins Calcium binding protein A4 (S100A4) and Prolactin Induced Protein (PIP) are Potential Biomarkers for Thyroid Eye Disease.

There are no reliable biomarkers to predict thyroid eye disease (TED) in patients with autoimmune thyroid disease (AITD) currently. Several evidences support the involvement of the lacrimal gland in TED. The aim of our study was to quantitatively correlate the changes in tear protein profile with increasing severity of TED.

Recent advances in the applications of metabolomics in eye research.

Metabolomics, the identification and quantitation of metabolites in a system, have been applied to identify new biomarkers or elucidate disease mechanism. In this review, we discussed the application of metabolomics in several ocular diseases and recent developments in metabolomics regarding tear fluids analysis, data acquisition and processing.

The penetration and distribution of topical atropine in animal ocular tissues.

Purpose: To conduct a multi-tissue investigation on the penetration and distribution of topical atropine in myopia treatment, and determine if atropine is detectable in the untreated contralateral eye after uniocular instillation.

Methods: Nine mature New Zealand white rabbits were evenly divided into three groups. Each group was killed at 5, 24 and 72 hr, respectively, following uniocular instillation of 0.