Lipid Layer Research Articles

Evaluation of Therapeutic Capability of Emustil Drops against Tear Film Complications under Dry Environmental Conditions in Healthy Individuals.

Background and Objectives: Dry eye disease (DED) is a multifactorial ailment of the tears and ocular surface. The purpose of this study was to assess the tear film physiology under controlled dry environmental conditions and compare the efficacy of oil-in-water emulsion drops on tear film parameters in protection and relief treatment modalities under low-humidity conditions. Emustil eye drops were used after exposure to a low-humidity environment in the relief method, whereas, in the protection method, the drops were applied before exposure to low humidity. Materials and Methods: 12 normal male subjects (mean age 34.0 ± 7.0 years) were exposed to ultra-dry environmental conditions. A number of tear film measurements were carried out under desiccating environmental conditions in a controlled environment chamber (CEC), where the chamber temperature sat at 21 °C with a relative humidity (RH) of 5%. Keeler's TearScope Plus and an HIRCAL grid were used to assess the tear break-up time and lipid layer thickness (LLT), and the evaporation rate was evaluated using a Servomed EP3 Evaporimeter. Results: LLT measurements showed that the dry environment affected LLT significantly (p = 0.031). The median grade of LLT dropped from grade 3 (50-70 nm) at 40% RH to grade 2 (13-50 nm) at 5% RH. A significant increase in LLT was seen after both modes of treatment, with a median LLT grade of 3 when the Emustil was used for both protection (p = 0.004) and relief (p = 0.016). The mean tear evaporation rate in normal environmental conditions (40%) was 40.46 ± 11.80 g/m2/h (0.11 µL/min) and increased sharply to 83.77 ± 20.37 g/m2/h (0.25 µL/min) after exposure to the dry environment. A minimal decrease in tear film evaporation rate was seen in relief; however, statistical tests showed that the decrease in tear film evaporation rate was not significant. Mean NITBUT dropped from 13.6 s at 40% RH to 6.6 s at 5% RH (p = 0.002). All NITBUT measurements at 5% RH (with or without the instillation of Emustil) were significantly lower than those at 40%. The instillation of Emustil at 5% RH resulted in a significant improvement in NITBUT for protection (p = 0.016) but this was not the case for relief (p = 0.0.56). Conclusions: A control environmental chamber (CEC) enables the analysis of tear film parameters comparable to those found in dry eye patients. This enables us to examine the capability of oil in emulsion drops to manage tear film disruption in healthy individuals. This study suggests that using Emustil oil-in-water emulsion before exposure to a dry environment should be advocated for people who work in dry environments.

Skin Barrier Fine Tuning through Low-Temperature Lipid Chain Transition

The lipids in the mammalian stratum corneum (SC) adopt an unusually rigid arrangement to form a vital barrier preventing water loss and harmful environmental impacts. Just above the physiological temperature, a subset of barrier lipids undergoes a phase transition from a very tight orthorhombic to a looser hexagonal arrangement and vice versa. The purpose of this lipid transition in skin physiology is unknown. Permeability experiments on isolated human SC indicated that the transition affects the activation energy for a model compound that prefers lateral movement along lipid layers but not for water or a large polymer that would cross the SC through the pore pathway. The orthorhombic phase content of SC lipids, as determined by infrared spectroscopy, was also modulated by (de)hydration. Spontaneous rearrangement of human SC lipid monolayers into 10 nm higher multilamellar islets at 32-37 °C but not at room temperature was revealed by atomic force microscopy. Our findings add to our knowledge of fundamental skin physiology suggesting a fine temperature- and hydration-controlled switch from fluid lipids (required for lipid barrier assembly) to rigid and tightly packed lipids in the mature SC (necessary for the water and permeability barriers).

Cholesterol-Controlled Interaction of Ionic Liquids with Model Cellular Membranes.

While ionic liquids (ILs) are considered as prospective ingredients of new antimicrobial agents, it is important to understand the adverse effects of these molecules on human cells. Since cholesterol is the essential component of a human cell membrane, in the present study, the effect of an imidazolium-based IL has been investigated on the model membrane in the presence of cholesterol. The area per sphingomyelin lipid is found to reduce in the presence of the IL, which is quantified by the area-surface pressure isotherm of the lipid monolayer formed at the air-water interface. The effect is considerably diminished in the cholesterol-containing monolayer. Further, the IL is observed to decrease the rigidity of the cholesterol-free monolayer. Interestingly, the presence of cholesterol does not allow any change in this property of the layer at lower surface pressure. However, at a higher surface pressure, the IL increases the elasticity in the cholesterol-induced condensed phase of the lipid layer. The X-ray reflectivity measurement on a stack of cholesterol-free lipid bilayers proved the formation of IL-induced phase-separated domains in the matrix of a pure lipid phase. These domains are found to be formed by interdigitating the chains of the lipids, producing a thinner membrane. Such a phase is less intense in the cholesterol-containing membrane. All of these results indicate that the IL molecules may deform the cholesterol-free membrane of a bacterial cell, but the same may not be harmful to human beings as cholesterol could restrict the insertion in the cellular membrane of a human cell.

Rosacea Meibomian Gland Dysfunction Posterior Blepharitis May Be a Marker for Earlier Associated Dyslipidaemia and Inflammation Detection and Treatment with Statins.

Posterior blepharitis and dry eye are common disorders with meibomian gland dysfunction (MGD), a principal driver of their pathophysiology. Meibomian gland dysfunction is increasingly prevalent in older populations with contributory hormonal imbalances. The abnormal meibum in MGD has been documented to have an excess of cholesterol with a resultant disruption of the lipid layer of the tear film. This leads to tear film instability due to the inadequate trapping of the aqueous portion of the tear film with resultant evaporative dry eye. Significant morbidity may follow MGD with ocular surface inflammation disrupting both social and work function. Rosacea is a common chronic inflammatory condition of the central face but can have ocular and systemic inflammatory associations. It is especially prevalent in North European populations and can have onset at any age, but commonly presents between thirty and fifty years of age. In ocular rosacea, MGD is a recognised manifestation as is dyslipidaemia. Ocular rosacea can predate cutaneous disease. As yet, there is no directly reported evidence of the efficacy of the early identification and treatment of ocular rosacea with associated dyslipidaemia and systemic inflammation. We posit that MGD in ocular rosacea sufferers may be a marker for dysregulated cholesterol synthesis and inflammation, and that statins maybe a potential therapy. This article introduces potential strategies to utilise ocular rosacea MGD as a possible marker for ophthalmologists, cardiologists, and primary healthcare physicians to treat rosacea-associated dyslipidaemia and systemic inflammation. This could aid in overall cardiovascular morbidity and mortality control for rosacea sufferers, potentially at an earlier age, while also addressing their tear film de-stabilisation through cholesterol lowering and inflammation reduction.

Evaluation of the Clinical Characteristics of Dry Eye Secondary to Different Types of Liver Diseases.

This study compares the clinical characteristics of dry eye secondary to primary biliary cholangitis (PBC), drug-induced liver injury (DILI), and viral hepatitis B(HBV) to evaluate the ocular surface damage caused by different types of liver diseases. Thirty healthy people were included as control group. Sixty patients with dry eye secondary to different types of liver disease were included, including 19 cases of PBC, 18 cases of DILI, and 23 cases of HBV. All patients were evaluated by the SPEED questionnaire, corneal fluorescein staining (CFS), noninvasive tear breakup time (NIBUT), Schirmer I test (SIt), tear meniscus height test (TMH), the area of meibomian glands dropout (MG dropout), partial blinking rate (PBR), lipid layer thickness (LLT), meibum expressibility, and meibum quality. There are statistical differences in ophthalmic examination results between different types of liver diseases and normal people (P < 0.05). Compared with DILI and HBV groups, the CFS score of PBC group score was higher (P < 0.05), the PBR was higher (P < 0.05), and the SIt was lower (P < 0.01). The TMH of PBC and DILI groups were significantly lower than the HBV group, and the difference was statistically significant (P < 0.05). Compared with the PBC group, the LLT of the DILI group decreased (P < 0.01). The area of meibomian glands dropout of the three groups had mild-to-moderate defects, but there was no significant statistical difference between groups (P > 0.05).The Meibum quality score in the DILI group was significantly higher than the HBV group (P < 0.05). The PBC group was more prone to aqueous-deficient dry eye. The DILI group was more prone to obstructive meibomian gland dysfunction (MGD).The HBV group was more prone to nonobstructive MGD. The symptoms of dry eye in the PBC group are mild-to-moderate discomfort, but the degree of corneal damage is higher, indicating that the corneal sensitivity is reduced, which may be related to the high rate of partial blinking.

Antimicrobial, antioxidant, and in silco studies of divalent metal complexes of novel aminopyrimidine Schiff base chelators

The amino-pyrimidine-based imine-chelators, 1-((pyrimidin-2-ylimino)methyl)naphthalene-2-ol(HL1), 2-(((2-hydroxynaphthalen-1-yl)methylene)amino)pyrimidine-4,6-diol(HL2) and 1-(((4,6-dimethylpyrimidin-2-yl)imino)methyl)naphthalen-2-ol(HL3) have been synthesized by facile reaction of 2‑hydroxyl-1-naphthaldehyde with 2-aminopyrimidine, 2-amino-4,6-dihydroxypyrimidine, and 2-amno-4,6-dimethypyrimidine respectively. The chelators were coordinated with Fe(II) sulfate and Cu(II) acetate to afford the corresponding complexes which were fully characterized. The Cu(II) complex exhibited superlative antimicrobial activity with an inhibitory growth zone reaching 26.5 mm outperforming both the chelators and the Fe(II) complexes. Thus Cu(II) complex has potential significance in new antibacterial drug designs and isolation. The impressive activity was due chelation which increased the lipophilic feature of the Cu(II) complex, thereby favouring its infiltration through the lipid layers of the bacterial membranes. However, compared to other samples, Fe-L2 has the best antifungal performance activity against Aspergillus niger, Aspergillus flevus, and Rhizopus stolonifer with inhibition zone of 29±1.4, 19±2.1 and 22±1 respectively. The C18H12N5O6 antioxidant result confirmed that Cu-L2 had the highest scavenging ability (99.80%) at 200 μg/mL. Interestingly, Cu-L2 exhibited the highest antioxidant actions both in vitro and in silco evaluations, hence can serve as a potential antioxidant agent. Molecular docking determinations displayed a substantial binding affinity with the drug targets suggesting that the metallic compounds could be exploited for drugs design.

Relations between nonmotor manifestations and motor disorders in patients with benign essential blepharospasm.

To evaluate the relations between nonmotor manifestations (dry eye, mood disorders, and sleep disturbance) and motor disorders in patients with benign essential blepharospasm (BEB), and to determine whether relieving motor disorders by botulinum neurotoxin can improve the nonmotor manifestations. In this prospective case series study, 123 BEB patients were enrolled for evaluations. Among them, 28 patients underwent botulinum neurotoxin therapy and attended another two postoperative visits at 1month and 3months. Motor severity was measured with Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI). We assessed dry eye using OSDI questionnaire, Schirmer test, tear break-up time (TBUT), tear meniscus height, lipid layer thickness (LLT) and corneal fluorescence staining. Zung's Self-rating Anxiety and Depression Scale (SAS, SDS) and Pittsburgh Sleep Quality Index (PSQI) were for mood status and sleep quality evaluations. Patients with dry eye or mood disorders had higher JRS scores (5.78 ± 1.13, 5.97 ± 1.30) than those without (5.12 ± 1.40, 5.50 ± 1.16; P = 0.039, 0.019, respectively). BSDI values of patients with sleep disturbance (14.61 ± 4.71) was higher than those without (11.89 ± 5.44, P = 0.006). Correlations were found between JRS, BSDI and SAS, SDS, PSQI, OSDI, TBUT. Botulinum neurotoxin effectively relieved JRS, BSDI and improved PSQI, OSDI, TBUT, LLT (8.11 ± 5.81, 21.77 ± 15.76, 5.04 ± 2.15s, 79.61 ± 24.11nm) at the 1-month visit compared to baseline (9.75 ± 5.60, 33.58 ± 13.27, 4.14 ± 2.21s, 62.33 ± 22.01nm; P = 0.006, < 0.001, = 0.027, < 0.001, respectively). The BEB patients with dry eye, mood disorders, or sleep disturbance had more severe motor disorders. Motor severity was associated with the severity of the nonmotor manifestations. Relieving motor disorders by botulinum neurotoxin was effective in improving dry eye and sleep disturbance.

Extensional flow of a free film of nematic liquid crystal with moderate elasticity

The human tear film is a multilayer structure in which the dynamics are often strongly affected by a floating lipid layer. That layer has liquid crystalline characteristics and plays important roles in the health of the tear film. Previous models have treated the lipid layer as a Newtonian fluid in extensional flow. Motivated to develop a more realistic treatment, we present a model for the extensional flow of thin sheets of nematic liquid crystal. The rod-like molecules of these substances impart an elastic contribution to the rheology. We rescale a weakly elastic model due to Cummings et al. [“Extensional flow of nematic liquid crystal with an applied electric field,” Eur. J. Appl. Math. 25, 397–423 (2014).] to describe a lipid layer of moderate elasticity. The resulting system of two nonlinear partial differential equations for sheet thickness and axial velocity is fourth order in space, but still represents a significant reduction of the full system. We analyze solutions arising from several different boundary conditions, motivated by the underlying application, with particular focus on dynamics and underlying mechanisms under stretching. We solve the system numerically, via collocation with either finite difference or Chebyshev spectral discretization in space, together with implicit time stepping. At early times, depending on the initial film shape, pressure either aids or opposes extensional flow, which changes the free surface dynamics of the sheet and can lead to patterns reminiscent of those observed in tear films. We contrast this finding with the cases of weak elasticity and Newtonian flow, where the sheet retains the same qualitative shape throughout time.

A rapid single-phase extraction for polar staphylococcal lipids.

The lipid membrane is gaining appreciation as a critical factor in the emergence of antibiotic resistance, both for antibiotics that target lipid synthesis or the membrane directly and for cell-wall-targeting antibiotics. The methods used to study the emergence of antibiotic resistance in vitro can generate a large number of samples that may be low in volume and in cell density. As in eukaryotic/mammalian lipidomics, two-phase liquid-liquid extractions are the most commonly used approach to recover lipids from bacteria. The need to separate the lipid layer is cumbersome for high-throughput applications and can be a source of poor reproducibility or contaminant introduction. While several single-phase extractions have been proposed for serum, tissue, and eukaryotic cells, there have been far fewer efforts to adapt or develop such methods for bacteria lipidomics. Here, we describe a simple, single-phase lipid extraction method based on methanol, acetonitrile, and water-the MAW method. The merits of the MAW method are evaluated against the Bligh & Dyer (B&D) method for the recovery of the major membrane lipids (phosphatidylglycerols, diglycosyldiacylglycerols, and lysyl-phosphatidylglycerols) in the Gram-positive pathogen Staphylococcus aureus. We demonstrate that the MAW method achieves recoveries that are comparable to that of the B&D extraction (≥ 85% for PG 15:0/d7-18:1). The benefits of the MAW method enable the detection of lipids from lower amounts of bacteria than the B&D method (0.57 vs 0.74 McFarlands for PG 32:0, respectively) and is easily scaled down to microplate volumes to facilitate high-throughput studies of bacterial lipids.

Enhancing STING activation by cyclic dinucleotide-manganese particles for systemic cancer immunotherapy.

2571 Background: Activating the innate immune pathway of stimulator of interferon genes (STING) can elicit potent anti-tumor immunity via the production of type-I interferons (IFN-I). However, cyclic-dinucleotide (CDN) STING agonists have undesirable pharmacological properties. Most CDNs in clinical development are administered intratumorally, thus precluding their applications in treating metastasis, hematologic malignancies, and hard-to-reach solid tumors. Here, we report the development of a new nanoparticle system for the systemic delivery of CDN STING agonists with potent efficacy, favorable pharmaceutical properties, and acceptable safety profiles. Methods: Nutritional metal ions play crucial roles in modulating immune pathways, which could potentially be used for enhancing STING activation. We screened different metal ions and found that manganese ion (Mn2+) achieved strong synergy with CDN STING agonists for inducing IFN-I production. We further developed a new nanoparticle system for co-delivery of Mn2+ and CDN for systemic cancer immunotherapy. Results: Mn2+ induced up to 77-fold enhancement in CDN-mediated STING activation. Mixing CDNs with Mn2+ resulted in the self-assembly of nanocrystals, and the lipid layer coating led to uniform nanoparticles. The resulting STING-activating CDN-Mn nanoparticle (SNP) given intravenously elicited IFN-I responses, attenuated the suppressive functions of myeloid cells, remodeled the immunosuppressive tumor microenvironment, and expanded CD8+ T cells for sustained tumor control. Intravenous SNP therapy resulted in robust anti-tumor efficacy in multiple murine tumor models, including a genetically engineered mouse model of MMTV-PyMT triple-negative breast cancer. We have also demonstrated the robust anti-tumor efficacy of SNP against VX2 head and neck squamous cell carcinomas (HNSCC) in New Zealand white rabbits. Mechanistically, the efficacy of intravenous SNP therapy was dependent on the host STING expression but independent of the tumor STING expression. In addition, the anti-tumor efficacy of SNP was decreased in mice lacking Ifnar1 or Ifngr1 expression in the B16F10 melanoma model, showing the crucial effects of IFN-I and IFN-II responses. Lastly, SNP was effectively uptaken by human PBMCs and elicited IFN-I responses when injected into fresh human tumor biopsies derived from HNSCC patients. Conclusions: SNP empowers highly effective systemic cancer immunotherapy via nanotechnology. It also underscores the potential of utilizing metal ions for immune-mediated disease treatment.

Fluorescent head-labelled phospholipid coumarin bioconjugate as a chemical reporter for antioxidant protection in liposomes

The oxygen radical absorbance capacity (ORAC) assay is considered a valuable analytical tool for measuring the protection afforded by an antioxidant compound to a target probe. Fluorescein is the classical probe used in the ORAC assays. In addition to not being a biological target for oxidation, fluorescein acts as a free molecule within the reaction media. Moreover, the probe specific location is the aqueous medium where its oxidation occurs. Hence, fluorescein is not ideal for inferring about the interactions of radicals with biomimetic membrane models within the liquid-lipid interface or deeper in the bilayer system.The aim of the present work was to explore the use of POPE-COUM probe, a 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphoethanolamine labelled with 3-carboxycoumarin, to report the protection of antioxidants interacting with biomembranes using liposomes as a biomimetic model. The probe was obtained applying an improved bioconjugation by using continuous flow synthesis to afford the desired compound in just 5 min in 80% yield. The lipid peroxidation induced by 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH) derived radicals was monitored directly by the fluorescence intensity decay of the POPE-COUM, without resorting to any other reporter, in large unilamellar vesicles (LUVs). The results obtained showed a delay on the oxidation of the probe compared to aqueous phase fluorescein which might indicate that POPE-COUM is not accessible to the attack by the AAPH-derived radicals and is protected towards the inside of the vesicle. Hence, the access to the embedded probe only happens when alteration of the LUV structure occurs. Fluorescence lifetime imaging microscopy studies support the fact that the fluorescent POPE-COUM probe is restricted to the lipidic layers, and no background fluorescence was observed.Ultimately, these outcomes represent the proof-of-concept for the use of POPE-COUM in ORAC assays and its suitability as biomarker of the oxidation state and integrity of cellular membrane biomimetic systems such as liposomes.

Nanoliter Liquid Packaging in a Bioresorbable Microsystem by Additive Manufacturing and its Application as a Controlled Drug Delivery Device

AbstractPrecise packaging of nanoliter amounts of liquid in a microsystem is important for many biomedical applications. However, existing liquid encapsulation technologies have limitations in terms of liquid waste, evaporation, trapped bubbles, and liquid degradation. In this study, multiple additive manufacturing techniques for nanoliter liquid packaging in bioresorbable microsystems is used. Two‐photon photolithography is used for bioresorbable reservoir fabrication, while inkjet printing (IJP) is used for precise nanoliter liquid packaging. Dual IJP allows for micro‐reservoirs to be filled with precise amounts of drug solution and subsequently and rapidly sealed with a layer of lipids mixed with Fe3O4 nanoparticles. Combining these two printing techniques can overcome the previous limitations of liquid encapsulation technologies. To demonstrate the relevance of this technique, a wirelessly activated, bioresorbable multi‐reservoir microcapsule that can be used for controlled drug delivery is presented. The microcapsules and their content are shown to be stable during fabrication, storage, and operation. Multiple cargo release events are triggered independently by the local melting of the sealing layer, resulting from magnetically induced Fe3O4 nanoparticle heating. The operation of the capsule is demonstrated in tissue phantoms and in vitro cell cultures.

Shaping membrane interfaces in lipid vesicles mimicking the cytoplasmic leaflet of myelin through variation of cholesterol and myelin basic protein contents

Myelin basic protein (MBP) is an intrinsically disordered protein and in the central nervous system (CNS) mainly responsible for connecting the cytoplasmic surfaces of the multilamellar, compact myelin. Increased posttranslational modification of MBP is linked to both, the natural development (from adolescent to adult brains) of myelin, and features of multiple sclerosis. Here, we study how a combination of this intrinsically disordered myelin protein with varying the natural cholesterol content may alter the characteristics of myelin-like membranes and interactions between these membranes. Large unilamellar vesicles (LUVs) with a composition mimicking the cytoplasmic leaflet of myelin were chosen as the model system, in which different parameters contributing to the interactions between the lipid membrane and MBP were investigated. While we use cryo-transmission electron microscopy (TEM) for imaging, dynamic light scattering (DLS) and electrophoretic measurements through continuously-monitored phase-analysis light scattering (cmPALS) were used for a more global overview of particle size and charge, and electron paramagnetic resonance (EPR) spectroscopy was utilized for local behavior of lipids in the vesicles' membranes in aqueous solution. The cholesterol content was varied from 060 % in these LUVs and measurements were performed in the presence and absence of MBP. We find that the composition of the lipid layers is relevant to the interaction with MBP. Not only the size, the shape and the aggregation behavior of the vesicles depend on the cholesterol content, but also within each membrane, cholesterol's freedom of movement, its environmental polarity and its distribution were found to depend on the content using the EPR-active spin-labeled cholesterol (CSOSL). In addition, DLS and EPR measurements probing the transition temperatures of the lipid phases allow a correlation of specific behavior with the human body temperature of 37 °C. Overall, our results aid in understanding the importance of the native cholesterol content in the healthy myelin membrane, which serves as the basis for stable and optimum protein-bilayer interactions. Although studied in this specific myelin-like system, from a more general and materials science-oriented point of view, we could establish how membrane and vesicle properties depend on cholesterol and/or MBP content, which might be useful generally when specific membrane and vesicle characteristics are sought for.

Evaluation of different treatment modalities on the efficacy of hydroxypropyl Guar (HP-Guar) formulation on tear film stability (TFS) in subjects exposed to adverse environmental conditions

The study aimed to assess the efficacy of hydroxypropyl guar (HP) formulation (Systane) to protect tear film parameters under desiccating environment using protection and relief treatment modalities. The subjects were exposed to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C and screened for Tear break-up time (TBUT), Tear film evaporation rate (TFER) and lipid layer thickness (LLT) using the HIRCAL grid, Servomed EP3 Evaporimeter and Keeler’s TearScope-Plus respectively. Significant improvement in LLT was noticed in the protection modality. The mean tear film evaporation rate doubled after exposure to the humidity of 5% to a value of 105.37 g/m2/h (0.29 µl/min). All subjects displayed a significant reduction in non-invasive tear break-up time (NITBUT) with a mean NITBUT of 7.7 s after exposure to a desiccating environment for 15 min. A significant increase in NITBUT after the instillation of the drops was recorded in both methods. The results obtained from this study showed that a solution containing HP-Guar significantly improves tear film parameters under a desiccating environment. Apart from the tear evaporation rate, all tear parameters showed improvement after the use of HP-Guar eye drops. It is evident that tear film parameters respond differently to the management modalities and using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Synthesis, Physicochemical, and Antimicrobial Activity of Copper and Zinc Complexes with N, O - Bidentate Schiff Base

This paper is intended to prepare new antimicrobial complexes with proven efficiency. The Schiff base, through the condensation process of salicylaldehyde and p-toludine, and its Cu and Zn complexes were successfully synthesized. The Schiff base and its complexes were characterized using molar conductivity, Ultraviolet-visible (UV-Vis), atomic absorption spectroscopy (AAS), and Fourier transform infrared (FTIR) techniques. Accordingly, these characterizations not only confirmed that the synthesized Schiff base acted as N,O bidentate ligand (through azomethine nitrogen and phenoxide oxygen) and chelated with Cu(II) and Zn(II) in the metal-to-ligand ratio of 1:2 but also revealed the characteristic electronic-transition of π→π*/n→π* of the ligand, and ligand-metal charge transfer and d-d of the metal complexes. Moreover, both Cu and Zn complexes recorded weak molar conductance of 54.12 and 51.41 S cm2 mol-1, respectively. Further, their antibacterial activities were evaluated by disc diffusion assay against Staphylococcus aureus (gram-positive), Escherichia coli (gram-negative), and Bacillus cereus (gram-negative) bacteria. For all microbial, the metal complexes recorded higher activities than the parent ligand; such increased activity of the complexes may be due to the chelation of the metal ion in the complexes, which enhances the lipophylic character favoring its permeation through the lipid layer of the cell membrane. Such metal complexes can therefore be explored in the future as an option for decreasing the pathogenic potential of infecting bacteria.

Analysis of postoperative ocular surface changes and intervention effect after pars plana vitrectomy in meibomian gland dysfunction dry eye patients.

To observe ocular surface changes after phacovitrectomy in patients with mild to moderate meibomian gland dysfunction (MGD)-type dry eye and track clinical treatment response using a Keratograph 5M and a LipiView interferometer. Forty cases were randomized into control group A and treatment group B; the latter received meibomian gland treatment 3d before phacovitrectomy and sodium hyaluronate before and after surgery. The average non-invasive tear film break-up time (NITBUTav), first non-invasive tear film break-up time (NITBUTf), non-invasive measured tear meniscus height (NTMH), meibomian gland loss (MGL), lipid layer thickness (LLT) and partial blink rate (PBR) were measured preoperatively and 1wk, 1 and 3mo postoperatively. The NITBUTav values of group A at 1wk (4.38±0.47), 1mo (6.76±0.70), and 3mo (7.25±0.68) were significantly lower than those of group B (7.45±0.78, 10.46±0.97, and 11.31±0.89; P=0.002, 0.004, and 0.001, respectively). The NTMH values of group B at 1wk (0.20±0.01) and 1mo (0.22±0.01) were markedly higher than those of group A (0.15±0.01 and 0.15±0.01; P=0.008 and P<0.001, respectively); however, there was no difference at 3mo. The LLT of group B at 3mo [91.5 (76.25-100.00)] significantly exceeded that of group A [65.00 (54.50-91.25), P=0.017]. No obvious intergroup difference was found in MGL or PBR (P>0.05). Mild to moderate MGD dry eye worsens in the short term after phacovitrectomy. Preoperative cleaning, hot compresses, and meibomian gland massage as well as preoperative and postoperative sodium hyaluronate promote the rapid recovery of tear film stability.

Global trend in exosome isolation and application: an update concept in management of diseases.

Extracellular vesicles (EVs) secreted by various cells offer great potential for use in the diagnosis and treatment of disease. EVs are heterogeneous membranous vesicles. Exosomes are a subtype of EVs, 40-150nm spherical vesicles with a lipid layer derived from endosomes. Exosomes, which are involved in signal transduction and maintain homeostasis, are released from almost all cells, tissues, and body fluids. Although several methods exist to isolate and characterize EVs and exosomes, each technique has significant drawbacks and limitations that prevent progress in the field. New approaches in the biology of EVs show great potential for isolating and characterizing EVs, which will help us better understand their biological function. The strengths and limitations of conventional strategies and novel methods (microfluidic) for EV isolation are outlined in this review. We also present various exosome isolation techniques and kits that are commercially available and assess the global market demand for exosome assays.

A Retrospective Analysis of Tear Film and Blink Parameters in Patients With Ocular Surface Disease.

We had two objectives: (1) to investigate differences in tear film and blink parameters in patients with six ocular surface diseases (OSD): ocular graft versus host disease (oGVHD), Stevens-Johnson syndrome (SJS), lax eyelid syndrome, meibomian gland dysfunction (MGD), obstructive sleep apnea, and dry eye disease; and (2) to characterize the relationships between lipid layer thickness (LLT), meiboscore, Schirmer I test, and three blink parameters: partial blink rate (PBR), interblink interval (IBI), and interpalpebral fissure height (IPFH) in this group of patients. This is a single-site retrospective analysis of 228 patients (456 eyes) with six different primary OSD at Loyola University Medical Center between January 2018 and July 2020. Objective parameters included: LLT, IBI, PBR, IPFH, Pult meiboscore, and Schirmer I score. Linear mixed effects models were used to analyze the relationships between these parameters. The meiboscore was highest in patients with SJS compared with the other five groups. There was significant variability in IPFH across different groups, with patients with oGVHD having the smallest height. An increase in IPFH was associated with increases in IBI, PBR, and Schirmer score. Patients with no partial blinks demonstrated a statistically significant higher IBI than patients who showed 1%-50% partial blinks. Finally, no statistically significant relationship was found between the following: (1) meiboscore and LLT, (2) OSDI and IPFH, (3) Schirmer score and IBI, or (4) LLT and IBI. There were fewer than anticipated differences in objective tear film and blink parameters between patients with six different OSD. A statistically significant association was found between IPFH and Schirmer score and IPFH and IBI, representing new findings in tear film research. Further investigation of the relationship between IPFH and IBI is needed.

Thermal effect on eyelid and tear film after low-level light therapy and warm compress

ABSTRACT Clinical relevance The warming effect of low-level light therapy may contribute to its therapeutic mechanism which is beneficial for dry eye management. Background Low-level light therapy is proposed to work via cellular photobiomodulation and a potential thermal effect in dry eye management. This study examined the change in eyelid temperature and tear film stability after low-level light therapy compared to warm compress. Methods Participants with no to mild dry eye disease were randomised into control, warm compress, and low-level light therapy groups. The low-level light therapy group was treated with Eyelight mask (633 nm) for 15 minutes, the warm compress group with Bruder mask for 10 minutes, and the control group with an Eyelight mask having inactive LEDs for 15 minutes. Eyelid temperature was measured using the FLIR One® Pro thermal camera (Teledyne FLIR, Santa Barbara, CA, USA), and clinical measures of tear film stability were evaluated before and after treatment. Results Thirty-five participants (mean age ± SD, 27.3 ± 4.3 years) completed the study. Eyelid temperatures for external upper, external lower, internal upper and internal lower eyelids were significantly greater in the low-level light therapy and warm compress groups immediately after treatment compared to the control group (all p < 0.001). No difference in temperature was observed between the low-level light therapy and warm compress groups at all time points (all p > 0.05). Tear film lipid layer thickness was significantly greater after treatment (mean (95% CI), 13.1 nm (5.3 to 21.0), p < 0.005) but not different between groups (p > 0.05). Conclusion A single treatment of low-level light therapy increased eyelid temperature immediately after treatment, but the increase was not significantly different from warm compress. This suggests that thermal effects may in part contribute to the therapeutic mechanism of low-level light therapy.

Meibomian Gland Dysfunction in Primary Acquired Nasolacrimal Duct Obstruction.

This study was designed to investigate the influence of primary nasolacrimal duct obstruction (PANDO) on the structure and function of the Meibomian gland and to examine whether it is related to functional failure after dacryocystorhinostomy surgery. Medical records of patients diagnosed as PANDO from August 2021 to February 2022 were retrospectively studied. Results of slit lamp examination, lacrimal drainage test, tear break-up time, anterior segment optical coherence tomography, and meibography were collected. Tear meniscus height, tear break-up time, meiboscore, and lipid layer thickness of tear membrane were parameters compared between the eyes with complete PANDO and the control group. Medical records of 44 patients, therefore 88 eyes were collected, and there were 28 eyes with complete PANDO (total obstruction group), while normal eyes (control group) were 30. Mean tear meniscus height was significantly higher than that of the control group ( P value<0.001), but tear break-up time ( P value=0.322), lipid layer thickness ( P value=0.755), and meiboscore ( P value=0.268) were not significantly different. However, in the cases with moderate and severe meibomian gland destruction, the lipid layer thickness of the total obstruction group was significantly thinner than the control group. Lipid secretion of meibomian glands was less in eyes with PANDO than in eyes without PANDO, under moderate to severe meibomian gland destruction. It can lead to persistent epiphora after dacryocystorhinostomy due to a compensatory response against evaporative dry eye disease. Patients should be educated before the decision to undergo surgeries about the possibilities of persistent epiphora. Further studies are needed to prove the mechanism of meibomian gland function disturbance in PANDO.