The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to ...the optic neuropathy. Indeed, inflammation - involving the activation and proliferation of resident glial cells (astrocytes, Muller cells and microglia) and the release of a plethora of anti- and pro-inflammatory cytokines, chemokines and reactive oxygen species - has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. In view of this, therapies aimed at modulating the immune and inflammatory responses may represent a promising approach for limiting the optic nerve damage and the loss of retinal ganglion cells associated with glaucoma.
Autophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal-lysosomal pathway, is fundamental for neuronal homeostasis and its ...deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic-ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process. Ischemic insult triggered in the retina an acute induction of autophagy that lasted during the first hours of reperfusion. This early upregulation of the autophagic flux limited RGC death, as demonstrated by the increased neuronal loss observed in mice with genetic impairment of basal autophagy owing to heterozygous ablation of the autophagy-positive modulator Ambra1 (Ambra1
). Upregulation of autophagy was exhausted 24 h after the ischemic event and reduced autophagosomal turnover was associated with build up of the autophagic substrate SQSTM-1/p62, decreased ATG12-ATG5 conjugate, ATG4 and BECN1/Beclin1 expression. Animal fasting or subchronic systemic treatment with rapamycin sustained and prolonged autophagy activation and improved RGC survival, providing proof of principle for autophagy induction as a potential therapeutic strategy in retinal neurodegenerative conditions associated with hypoxic/ischemic stresses.
The aim of this work is the design, preparation and characterization of membranes based on cyclosporine A (CsA) and chitosan carboxylate (CC) to be used as an implantable subcutaneous medical device ...for a prolonged therapeutic effect in the treatment of breast cancer. The choice to use CsA is due to literature data that have demonstrated its possible antitumor activity on different types of neoplastic cells. To this end, CsA was bound to CC through an amidation reaction to obtain a prodrug to be dispersed in a chitosan-based polymeric membrane. The reaction intermediates and the final product were characterized by Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (
H-NMR). Membranes were analyzed by differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The data obtained showed the effective formation of the amide bond between CsA and CC and the complete dispersion of CsA inside the polymeric membrane. Furthermore, preliminary tests, conducted on MDA-MB-231, a type of breast cancer cell line, have shown a high reduction in the proliferation of cancer cells. These results indicate the possibility of using the obtained membranes as an interesting strategy for the release of cyclosporin-A in breast cancer patients.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The molecular target and mechanism by which d-limonene induces LC3 lipidation and autophagosome formation remain elusive. Here, we report that this monoterpene rapidly enhances Ca2+ levels in SH-SY5Y ...cells; yet this effect does not lead to calpain- or caspase-mediated proteolysis of α-spectrin, nor calpain activity is required for the established enhancement of LC3-II levels by d-limonene. However, d-limonene rapidly reduced vimentin levels, an unexpected effect also induced by the autophagy inhibitor chloroquine (CQ). The magnitude of vimentin reduction parallels accumulation of LC3-II caused by a brief incubation with d-limonene or CQ. For longer exposure (48 h), d-limonene does not reduce vimentin, nor it increases LC3-II levels; conversely, a clear reduction of vimentin along with a massive accumulation of LC3-II is evident in cells treated with CQ. Vimentin participates in organelle positioning and in other cellular processes that have linked this intermediate filament protein to various diseases, including cancer, inflammatory and autoimmune disorders, and to virus replication and internalization. Our findings suggest an inverse relationship between vimentin reduction and LC3-II accumulation, whose causal link needs to be examined. Further experiments are needed to dissect the role of vimentin reduction in the mechanisms through which CQ impairs fusion of autophagosome with lysosomes as well as in other effects of this drug.
Display omitted
•The mechanism by which d-limonene induces LC3 lipidation remains elusive.•d-Limonene rapidly enhances Ca2+ levels but not calpain activity in SH-SY5Y cells.•d-Limonene reduces vimentin levels rapidly but transiently.•The autophagy inhibitor chloroquine reduces vimentin levels in a long-lasting way.•Vimentin reduction and LC3-II accumulation appear to be inversely related.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plant extracts are a rich source of natural compounds with antimicrobial properties, which are able to prevent, at some extent, the growth of foodborne pathogens. The aim of this study was to ...investigate the potential of polyphenolic extracts from cladodes of
(L.) Mill. to inhibit the growth of some enterobacteria and the biofilm formation by
.
cladodes at two stages of development were analysed for total phenolic content and antioxidant activity by Oxygen Radical Absorbance Capacity (ORAC) and Trolox equivalent antioxidant capacity (TEAC) (in vitro assays) and by cellular antioxidant activity in red blood cells (CAA-RBC) (ex vivo assay). The Liquid Chromatography Time-of-Flight Mass Spectrometry (LC/MS-TOF) analysis of the polyphenolic extracts revealed high levels of piscidic acid, eucomic acid, isorhamnetin derivatives and rutin, particularly in the immature cladode extracts.
cladodes extracts showed a remarkable antioxidant activity (in vitro and ex vivo), a selective inhibition of the growth of Gram-positive bacteria, and an inhibition of
biofilm formation. Our results suggest and confirm that
cladode extracts could be employed as functional food, due to the high polyphenolic content and antioxidant capacity, and used as natural additive for food process control and food safety.
Abstract only
Glaucoma, a progressive age‐related optic neuropathy characterized by retinal ganglion cell degeneration and alteration of the optic nerve head, is a leading cause of irreversible ...blindness worldwide. Elevated intraocular pressure (IOP) is one of the main and the only known modifiable risk factor. However, despite lowering IOP, glaucomatous damage still progresses in a relevant percentage of patients.
Neuroprotection in glaucoma refers to any non‐IOP related treatments that can prevent or delay neurodegeneration. Metformin (1,1‐dimethylbiguanide hydrochloride) is one of the first‐line anti‐hyperglycemic drugs for type 2 diabetes mellitus. In recent years, several studies have investigated the neuroprotective effect of metformin in a variety of neurodegenerative diseases, revealing that this drug is able to regulate energy metabolism, prevent oxidative stress, reduce neuroinflammation and trigger autophagy.
The autophagy‐lysosome system, which is responsible for breaking down cellular components, preserving cellular homeostasis and preventing accumulation of protein aggregates and damaged organelles, is often dysregulated in neurodegenerative pathologies.
Here we show that the neurodegeneration observed in experimental models of glaucoma is associated with autophagy and mitophagy dysregulation, and describe the neuroprotective effects of treatment with metformin as autophagy modulator. To explore the possibility of the clinical translation of our findings, we performed a retrospective pilot study documenting for the first time a putative neuroprotective effect of metformin in glaucomatous diabetic patients.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is ...recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma.
Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that ...carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Glaucoma, a progressive age-related optic neuropathy characterized by the death of retinal ganglion cells, is the most common neurodegenerative cause of irreversible blindness worldwide. The ...therapeutic management of glaucoma, which is limited to lowering intraocular pressure, is still a challenge since visual loss progresses in a significant percentage of treated patients. Restricted dietary regimens have received considerable attention as adjuvant strategy for attenuating or delaying the progression of neurodegenerative diseases. Here we discuss the literature exploring the effects of modified eating patterns on retinal aging and resistance to stressor stimuli.
Glaucoma, a leading cause of irreversible blindness worldwide, is an age‐related neurodegenerative disease characterized by progressive alterations of the optic nerve head and degeneration of retinal ...ganglion cells (RGCs). Although elevated intraocular pressure (IOP) has been identified as the main and the only modifiable risk factor, the pathogenesis of the disease is still unclear. Indeed, lowering IOP is often insufficient to prevent the damage progression leaving unmet the therapeutic need of IOP‐independent pharmacological targets.
Autophagy, and the more selective mitophagy, are responsible for breaking down cellular components, preserving cellular homeostasis and preventing the accumulation of altered and aggregated proteins and damaged organelles.
Several evidence have shown that modulation of autophagy is a recurrent and functional response of RGCs to IOP‐dependent or independent glaucoma‐related insults. However, in RGCs, autophagy has been found to take part to either neuroprotection as well as neuronal death, depending on the experimental setting (i.e. animal model, timing of the experiments, drugs/doses used to modulate the pathway).
Here we describe the dynamic changes of autophagy flux and the modulation of mitophagy related proteins in a model of acute glaucoma induced in C57BL/6J mice by transient elevation of intraocular pressure (IOP). We also report and discuss experimental evidence supporting the pro‐survival role of autophagy and mitophagy induction in mice subjected to ocular hypertension suggesting the possibility to targeting autophagy to achieve retinal neuroprotection in glaucoma.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
