Overview of Cell Death Mechanisms Induced by Rose Bengal Acetate-Photodynamic Therapy

Photodynamic Therapy (PDT) is a non-invasive treatment for different pathologies, cancer included, using three key components: non-toxic light-activated drug (Photosensitizer, PS), visible light, and oxygen. Their interaction triggers photochemical reactions leading to Reactive Oxygen Species (ROS) generation, that mediate cytotoxicity and cell death. In the present paper, the most important findings about the synthetic dye Rose Bengal Acetate (RBAc), an emerging photosensitizer for its efficient induction of cell death, will be reported with the aim to integrate RBAc phototoxicity to novel therapeutic PDT strategies against tumour cells. After its perinuclear intracellular localization, RBAc causes multiple subcellular organelles damage, that is, mitochondria, Endoplasmic Reticulum (ER), lysosomes, and Golgi complex. Indeed, RBAc exerts long-term phototoxicity through activation of both caspase-independent and- dependent apoptotic pathways and autophagic cell death. In particular, this latter cell death type may promote cell demise when apoptotic machinery is defective. The deep knowledge of RBAc photocytotoxicity will allow to better understand its potential photomedicine application in cancer

Powerful Properties of Ozonated Extra Virgin Olive Oil

Extra virgin olive oil has been mainly produced and consumed in Mediterranean countries since ancient times; olive oil is one of the principal ingredients in the Mediterranean diet, and it constitutes the main source of nutritional fat. Aside from the high nutritional content of olive oil, it is also known for its cosmetic and therapeutic properties. In 1956, Thiers obtained satisfactory results in the treatment of scleroderma, stating that olive oil and its derivatives could be considered “a new group of therapeutic agents.” Hincky reported the beneficial properties of olive oil in the treatment of dry, senescent and sensitive skins. This has opened a new perspective for the use of the olive fruit, thus contributing to the increase in research about new applications. One such application is ozonized olive oil, which combines the properties of ozone with those of olive oil, to obtain a peerless compound. The composition of olive oil makes it a suitable vehicle for cutaneous absorption, as it is able to stabilize ozone, which is a highly reactive molecule. The oxidant power of ozone has interesting effects on microorganism and on wound healing

Chronic Treatment with Ethanolic Extract of the Leavesof Azadirachta indica Ameliorates Lesions of Pancreatic Islets in Streptozotocin Diabetes

Botanical drugs are complementary therapies in the management of diabetes mellitus. In this work, we studied the effects of chronic treatment of diabetic rats with A. indica (neem) on blood glucose, pancreatic islet histopathology, and oxidative status of the pancreas. Fifty-four Wistar rats (5-8 weeks old) were randomly assigned to 5 treatment groups. Hyperglycemia was induced in 34 fasted rats with a single i.p. injection of STZ (70 mg/kg bw/d). Ethanolic extract of A. indica leaves (500 mg/kg bw/d) was given orally to diabetic rats (n=12) for 50d. Glibenclamide was given (p.o) at 600 µg/ kg bw/d. In each group, blood glucose, islet histopathology, and pancreatic oxidative status, were assessed. All hyperglycemic rats in the neem-treated group had become normoglycemic at the end of week 2. By 50d, the number of viable b cells was highest in the neem-treated diabetic rats (compared with the diabetic and glibenclamide groups). Similarly, islet histology showed marked improvement in this group, in addition to improved oxidative stress. Our findings confirmed the hypoglycemic effect of neem. Besides, the improved islet morphology and oxidative status in neem-treated diabetic rats suggest the potential of this herb at improving lesions of the pancreatic islet in diabetes mellitus. Los medicamentos a base de plantas son terapias complementarias en el manejo de la diabetes mellitus. En este trabajo se estudiaron los efectos del tratamiento crónico de ratas diabéticas con A. indica (Neem) sobre la glucosa de la sangre, la histopatología de los islotes pancreáticos, y el estado oxidativo del páncreas. Cincuenta y cuatro ratas Wistar (5-8 semanas de edad) fueron asignadas aleatoriamente a 5 grupos de tratamiento. La hiperglucemia fue inducida en 34 ratas en ayunas con una única inyección IP de STZ (70 mg/kg peso corporal/d). El extracto etanólico de hojas de A. indica (500 mg/kg de peso corporal/día) fue administrado por vía oral a ratas diabéticas (n=12) por 50d. Glibenclamida fue dada (PO) a 600 mg/kg peso corporal/d. En cada grupo, la glucosa en la sangre, la histopatología de los islotes, y el estado oxidativo de páncreas, se evaluaron. Todas las ratas de hiperglucemia en el grupo tratado con el Neem se habían convertido en normoglucémicas al final de la semana 2. Por 50d, el número de células b viables fue mayor en el Neem ratas tratadas con diabetes (en comparación con los grupos de diabéticos y glibenclamida). Del mismo modo, la histología de los islotes mostró una notable mejoría en este grupo, además de mejorar el estrés oxidativo. Nuestros resultados confirman el efecto hipoglucemiante de Neem. Además, la mejora de la morfología de los islotes y el estado de oxidación en el neem tratados con ratas diabéticas sugieren el potencial de esta hierba en la mejora de las lesiones de los islotes pancreáticos en la diabetes mellitus

Morphological and Biochemical Profiles of the Gonadal Cycle in the Sea Urchin Paracentrotus lividus: Wild Type vs. Bred

Paracentrotus lividus gonads represent a valued gourmet delicacy, particularly appreciated in Europe and in Japan. Their commercial value is generally associated to their size, freshness, colour and texture. Diet, gametogenesis and environmental conditions have a marked influence, promoting the indispensable mechanisms of synthesis, selective storage and mobilization of the bioactive compounds, as lipids, proteins and carbohydrates of gonads in order to obtain nutrients. The objective of this work is to compare the morphological and biochemical profiles of reproductive life cycle of the gonads of adult P. lividus in its marine natural environment and adult captured sea urchins breeding into a fish aquaculture system. The reproductive cycle of male and female wild and breeding P. lividus was characterized during 1 year by analysing variations of the gonadal content of lipids, proteins and carbohydrates of animals captured at four different locations of the south-western coast of Salento, Italy, with the animals grown in a fish farm and fed with four different types of diet. The gonadal and repletion indexes were determined before the specimen dissection for evaluation of sex, development stages and physiological aspects. Gonads were processed for histological and biochemical analysis. The gonadal content of lipids, proteins and carbohydrates was performed by the gas chromatography-mass spectrometry (GC-MS) and by spectrometry, respectively

Synthesis and in vitro cytotoxicity of glycans-capped silver nanoparticles

Silver nanostructures were successfully synthesized through a simple and "green" method using saccharides as reducing and caping agent. Transmission electron microscopy (TEM) and UV-Vis absorption were used to certify the quality of the silver nanoparticles obtained: firstly, size and dispersion. In this work Silver NanoParticles (AgNPs) cytotoxicity related to saccharides capping (Glucose and (GlucoseSucrose) was explored in human epithelia cervix carcinoma cells (HeLa). The cells were incubated with increasing AgNPs number/cell and HeLa cells viability was monitored for a period of 48 h compared with the positive and negative controls. We observed that the toxicity increases with incubation time and with AgNPs number/cell. In particular, the different cytotoxic degree of the AgNPs, i.e. AgNP-G are more toxic than AgNP-GS, suggest that the cytotoxic effects are largely depended on the capping agent. The highest concentration of AgNP-G number/cell is able to induce extensive cell death of HeLa cells soon after 1hr of incubation; conversely the lowest concentration of AgNP-GS number/cell, surprisingly, is able to induce cell proliferation

Micro and Nanoplastics Identification: Classic Methods and Innovative Detection Techniques

Micro and nanoplastics are fragments with dimensions less than a millimeter invading all terrestrial and marine environments. They have become a major global environmental issue in recent decades and, indeed, recent scientific studies have highlighted the presence of these fragments all over the world even in environments that were thought to be unspoiled. Analysis of micro/nanoplastics in isolated samples from abiotic and biotic environmental matrices has become increasingly common. Hence, the need to find valid techniques to identify these micro and nano-sized particles. In this review, we discuss the current and potential identification methods used in microplastic analyses along with their advantages and limitations. We discuss the most suitable techniques currently available, from physical to chemical ones, as well as the challenges to enhance the existing methods and develop new ones. Microscopical techniques (i.e., dissect, polarized, fluorescence, scanning electron, and atomic force microscopy) are one of the most used identification methods for micro/nanoplastics, but they have the limitation to produce incomplete results in analyses of small particles. At present, the combination with chemical analysis (i.e., spectroscopy) overcome this limit together with recently introduced alternative approaches. For example, holographic imaging in microscope configuration images microplastics directly in unfiltered water, thus discriminating microplastics from diatoms and differentiates different sizes, shapes, and plastic types. The development of new analytical instruments coupled with each other or with conventional and innovative microscopy could solve the current problems in the identification of micro/nanoplastics

Autophagy in development and regeneration: role in tissue remodelling and cell survival

Morphogenetic events that occur during development and regeneration are energy demanding processes requiring profound rearrangements in cell architecture, which need to be coordinated in timely fashion with other cellular activities, such as proliferation, migration and differentiation. In the last 15 years, it has become evident that autophagy, an evolutionarily-conserved catabolic process that mediates the lysosomal turnover of organelles and macromolecules, is an essential "tool" to ensure remodelling events that occur at cellular and tissue levels. Indeed, studies in several model organisms have shown that the inactivation of autophagy genes has a significant impact on embryogenesis and tissue regeneration, leading to extensive cell death and persistence of unnecessary cell components. Interestingly, the increased understanding of the mechanisms that confers selectivity to the autophagic process has also contributed to identifying development-specific targets of autophagy across species. Moreover, alternative ways to deliver materials to the lysosome, such as microautophagy, are also emerging as key actors in these contexts, providing a more complete view of how the cell component repertoire is renovated. In this review, we discuss the role of different types of autophagy in development and regeneration of invertebrates and vertebrates, focusing in particular on its contribution in cnidarians, platyhelminthes, nematodes, insects, zebrafish and mammals

Molecular Characterization of Temozolomide-Treated and Non Temozolomide-Treated Glioblastoma Cells Released Extracellular Vesicles and Their Role in the Macrophage Response

Extracellular vesicles (EVs) are widely investigated in glioblastoma multiforme (GBM) for their involvement in regulating GBM pathobiology as well as for their use as potential biomarkers. EVs, through cell-to-cell communication, can deliver proteins, nucleic acids, and lipids that are able to reprogram tumor-associated macrophages (TAMs). This research is aimed to concentrate, characterize, and identify molecular markers of EVs subtypes released by temozolomide (TMZ)-treated and non TMZ-treated four diverse GBM cells. Morphology, size distribution, and quantity of small (sEVs) and large (lEVs) vesicles were analyzed by cryo-TEM. Quality and quantity of EVs surface markers were evaluated, having been obtained by Western blotting. GBM cells shed a large amount of EVs, showing a cell line dependent molecular profile A comparative analysis distinguished sEVs and lEVs released by temozolomide (TMZ)-treated and non TMZ-treated GBM cells on the basis of quantity, size and markers expression. Finally, the GBM-derived sEVs and lEVs, irrespective of TMZ treatment, when challenged with macrophages, modulated cell activation toward a tendentially M2b-like phenotype