Biomimetic Curcumin-Loaded Liposomes for the Treatment of Dry Eyes and Meibomian Gland Dysfunction: An In Vivo Study.

Meibomian gland dysfunction (MGD) and dry eye syndrome (DES) are common eye diseases characterized by altered tear film stability and inflammation of the ocular surface, causing significant discomfort and possible visual impairment. This study aimed to investigate the efficacy of curcumin-loaded liposomes (Lipo@Cur) compared to cyclosporine A-loaded liposomes (Lipo@CycA) in experimental rabbit models of MGD and DES, with a focus on their ability to improve tear film stability and reduce ocular surface inflammation. MGD and DES were induced using complete Freund's adjuvant (CFA) and treated to evaluate the effect of liposomal formulations on tear break-up time (TBUT), clinical signs of inflammation (telangiectasia, conjunctival hyperemia, meibomian foramen occlusion), and corneal as well as conjunctival histological cells.

Small anticancer drug release by light: Photochemical internalization of porphyrin-β-cyclodextrin nanoparticles.

Aiming to engineer simple, neutral, strongly amphiphilic photoactive nanoparticles (NPs) to specifically target cancer cell lysosomes for drug transport and light-controlled release, new conjugates of β-cyclodextrin with highly hydrophobic triphenylporphyrin bearing different alkyl chains, were synthesized. Although differently sized, all conjugates self-assemble into ~60 nm NPs in water and display similar photoactivity. The NPs target selectively the lysosomes of breast adenocarcinoma MCF-7 cells, embedding in vesicular membranes, as experiments with model liposomes indicate.

5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action.

In a course of metabolic experiments, we determined that the addition of δ-aminolevulinic acid (5-ALA) to a panel of glioblastoma multiforme (GBM) cells caused a steep reduction in their glycolytic activity. This reduction was accompanied by a decrease in adenosine triphosphate (ATP) production from glycolysis. These results suggested that 5-ALA is an inhibitor of glycolysis; due to the structural similarity of 5-ALA to the established lactate dehydrogenase (LDH) inhibitors oxamate (OXM) and tartronate (TART), we initially investigated LDH inhibition by 5-ALA in silico.

Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy.

Background: Host immune response is a critical component in tumorigenesis and immune escape. Radiation is widely used for glioblastoma (GBM) and can induce marked tissue inflammation and substantially alter host immune response. However, the role of myeloperoxidase (MPO), a key enzyme in inflammation and host immune response, in tumorigenesis after radiotherapy is unclear.

Reactive Species from Two-Signal Activated Macrophages Interfere with Their Oxygen Consumption Measurements.

Metabolic modulation of macrophage activation has emerged as a promising strategy lately in immunotherapeutics. However, macrophages have a broad spectrum of functions and thus, understanding the exact metabolic changes that drive a particular immune response, is of major importance. In our previous work, we have reported a key role of nitric oxide (NO) in two(2)-signal activated macrophages [M(2-signals)].

Predictive biomarkers for 5-ALA-PDT can lead to personalized treatments and overcome tumor-specific resistances.

Background: Photodynamic therapy (PDT) is a minimally invasive, clinically approved therapy with numerous advantages over other mainstream cancer therapies. 5-aminolevulinic acid (5-ALA)-PDT is of particular interest, as it uses the photosensitiser PpIX, naturally produced in the heme pathway, following 5-ALA administration. Even though 5-ALA-PDT shows high specificity to cancers, differences in treatment outcomes call for predictive biomarkers to better stratify patients and to also diversify 5-ALA-PDT based on each cancer's phenotypic and genotypic individualities.

Photodynamic Efficacy of Cercosporin in 3D Tumor Cell Cultures.

In the present work, we study the photodynamic action of cercosporin (cerco), a naturally occurring photosensitizer, on human cancer multicellular spheroids. U87 spheroids exhibit double the uptake of cerco than T47D and T98G spheroids as shown by flow cytometry on the single cell level. Moreover, cerco is efficiently internalized by cells throughout the spheroid as shown by confocal microscopy, for all three cell lines.

Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production.

We demonstrate excitation of photosensitisers (PSs) by accelerated protons to produce fluorescence and singlet oxygen. Their fluorescence follows a pattern similar to the proton energy loss in matter, while proton-derived fluorescence spectra match the photon-induced spectra. PSs excited in dry gelatin exhibit enhanced phosphorescence, suggesting an efficient PSs triplet state population.

Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT-tamoxifen hybrid therapy.

Currently the greatest challenge in oncology is the lack of homogeneity of the lesions where different cell components respond differently to treatment. There is growing consensus that monotherapies are insufficient to eradicate the disease and there is an unmet need for more potent combinatorial treatments. We have previously shown that hypericin photodynamic therapy (HYP-PDT) triggers electron transport chain (ETC) inhibition in cell mitochondria.

Cytotoxic and Photocytotoxic Effects of Cercosporin on Human Tumor Cell Lines.

Cercosporin is a naturally occurring perylenequinone. Although other perylenequinones have been extensively studied as photosensitizers in photodynamic therapy of cancer (PDT), cercosporin has been studied in this light only within the remits of phytopathology. Herein, we investigated the photocytotoxicity of cercosporin against two glioblastoma multiforme (T98G and U87) and one breast adenocarcinoma (MCF7) human cell lines.

Molecular Mechanisms of UVA-Induced Melanoma.

Cutaneous melanoma is a deadly skin cancer, resulting from malignant transformation of melanocytes. Long-wave ultraviolet radiation (315-400 nm) is able to damage DNA, cause mutations, and induce melanoma. However, the exact mechanisms of UVA-induced cutaneous melanoma remain a matter of debate.

MtDNA depletion influences the transition of CD44 subtypes in human prostate cancer DU145 cells.

Our earlier study revealed that long-term ethidium bromide application causes mitochondrial DNA depletion in human prostate cancer DU145 cell line (DU145), and this DU145 subline appears to have expanded CD44 cell population than its parental wild type DU145 cells (DU145). Increasing evidence suggests that CD44 cells are highly cancer stem cell like, but it is not clear about their dynamic transition between CD44 and CD44 phenotypes in prostate cancer cells, and how it is affected by mitochondrial DNA depletion. To address these questions, four cell subpopulations were isolated from both DU145 and DU145 cell lines based on their CD44 expression level and mitochondrial membrane potential.

Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells.

One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout.

The influence of photodynamic therapy with 5-aminolevulinic acid on senescent skin cancer cells.

Background: Senescent cells, which are resistant to apoptosis, accumulate with age and after ultraviolet (UV) radiation, chemotherapy and radiation therapy. Preventing or eliminating senescent cells may be crucial for protection against skin cancer development and improving tumour treatment. The aim of the present study was to investigate the potential of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) to induce senescence in skin cancer cells and to eliminate senescent cells induced by chemotherapy (bleomycin) or UVA (315-400nm) exposure.

Phototherapy and vitamin D.

The skin is the site for the photosynthesis of vitamin D and is a target tissue for the active metabolite of vitamin D. An increasing body of evidence indicates that vitamin D produced during phototherapy may be responsible for the positive effects observed during treatment of some skin diseases. Topical or oral application of vitamin D derivatives are used alone or with phototherapy.

Layer Thickness of SPF 30 Sunscreen and Formation of Pre-vitamin D.

Background: Most studies have demonstrated that sunscreens with lower sun protection factor (SPF) do not prevent the production of vitamin D because much lower amount of sunscreen (SPF<30) is applied than recommended (2 mg/cm(2)) indicating that a significant amount of UV radiation can penetrate the skin. Since less sunscreen is applied, higher SPF sunscreens may be used to achieve the desired protection. However, there is little information regarding the application of high-SPF sunscreen and vitamin D formation.

Folic acid and its photoproducts, 6-formylpterin and pterin-6-carboxylic acid, as generators of reactive oxygen species in skin cells during UVA exposure.

Folic acid (FA) is the synthetic form of folate (vitamin B9), present in supplements and fortified foods. During ultraviolet (UV) radiation FA is degraded to 6-formylpterin (FPT) and pterin-6-carboxylic acid (PCA) which generate reactive oxygen species (ROS) and may be phototoxic. The aim of the present study was to investigate the production of ROS and phototoxicity of FA, FPT and PCA in skin cells during UVA exposure.

Daily, seasonal, and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer.

Background: Solar ultraviolet (UV) radiation varies with latitude, time of day, and season. Both spectral UV composition and ambient UV dose lead to different health outcomes at different latitudes. Finding the optimal time for sun exposure, whereby the positive effects of UV exposure (vitamin D) are facilitated and the negative effects (skin cancer, photoimmunosuppression) avoided are the most important consideration in modern skin cancer prevention programs.

Vitamin D and ultraviolet phototherapy in Caucasians.

Ultraviolet B (UVB) radiation increases vitamin D level, but the influence of different UV sources (broadband and narrowband UVB lamps, solar simulators and sunbeds) and exposure durations have not been well characterized. In this study the influence of different UV sources on serum 25-hydroxyvitamin-D3 (25(OH)D3) levels in humans are reviewed. Serum 25(OH)D levels before and after UV exposure, and UV doses were extracted from 18 papers published in the past eight years.

Influence of multiple UV exposures on serum cobalamin and vitamin D levels in healthy females.

Aims: Ultraviolet (UV) radiation is a major source for vitamin D production. Furthermore, UV destroys cobalamins (also called vitamin B12) in solution. However, data from humans are scarce.

The relationship between UV exposure and incidence of skin cancer.

Background: The incidence rates of skin cancer increase with decreasing latitude in most western countries. Ultraviolet (UV) radiation is a main risk factor for skin cancer.

Methods: We have studied the relationship between UV exposure and skin cancer incidence rates of squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and cutaneous melanoma (CM), and tried to fit different mathematical models to the experimental data.

Ultraviolet-radiation and health: optimal time for sun exposure.

Positive as well as negative health effects of exposure of human skin to UV radiation depend on spectra and fluence rates, both of which being dependent on latitude, time of the day and several other factors. The major positive effects are related to vitamin D photosynthesis and the major negative effect is skin cancer development. The action spectra for these effects are different.

Minimal and maximal incidence rates of skin cancer in Caucasians estimated by use of sigmoidal UV dose-incidence curves.

Background: Sigmoidal (S-shaped) dose-cancer incidence relationships are often observed in animal bioassays for carcinogenicity. Ultraviolet (UV) radiation is an established skin carcinogen. The aim of this study is to examine if S-shaped curves describe the relationship between solar UV doses and skin cancer incidences, and if such relationships can be used to estimate threshold levels of non-carcinogenic UV exposure, as well as maximal incidence rates.

Quantum entanglement in photoactive prebiotic systems.

This paper contains the review of quantum entanglement investigations in living systems, and in the quantum mechanically modelled photoactive prebiotic kernel systems. We define our modelled self-assembled supramolecular photoactive centres, composed of one or more sensitizer molecules, precursors of fatty acids and a number of water molecules, as a photoactive prebiotic kernel systems. We propose that life first emerged in the form of such minimal photoactive prebiotic kernel systems and later in the process of evolution these photoactive prebiotic kernel systems would have produced fatty acids and covered themselves with fatty acid envelopes to become the minimal cells of the Fatty Acid World.