Ocular hypertension in myopia: analysis of contrast sensitivity

Purpose: we evaluated the evolution of contrast sensitivity reduction in patients affected by ocular hypertension and glaucoma, with low to moderate myopia. We also evaluated the relationship between contrast sensitivity and mean deviation of visual field. Material and methods: 158 patients (316 eyes), aged between 38 and 57 years old, were enrolled and divided into 4 groups: emmetropes, myopes, myopes with ocular hypertension (IOP≥21 ±2 mmHg), myopes with glaucoma. All patients underwent anamnestic and complete eye evaluation, tonometric curves with Goldmann’s applanation tonometer, cup/disc ratio evaluation, gonioscopy by Goldmann’s three-mirrors lens, automated perimetry (Humphrey 30-2 full-threshold test) and contrast sensitivity evaluation by Pelli-Robson charts. A contrast sensitivity under 1,8 Logarithm of the Minimum Angle of Resolution (LogMAR) was considered abnormal. Results: contrast sensitivity was reduced in the group of myopes with ocular hypertension (1,788 LogMAR) and in the group of myopes with glaucoma (1,743 LogMAR), while it was preserved in the group of myopes (2,069 LogMAR) and in the group of emmetropes (1,990 LogMAR). We also found a strong correlation between contrast sensitivity reduction and mean deviation of visual fields in myopes with glaucoma (coefficient relation = 0.86) and in myopes with ocular hypertension (coefficient relation = 0.78). Conclusions: the contrast sensitivity assessment performed by the Pelli-Robson test should be performed in all patients with middle-grade myopia, ocular hypertension and optic disc suspected for glaucoma, as it may be useful in the early diagnosis of the disease. Introduction Contrast can be defined as the ability of the eye to discriminate differences in luminance between the stimulus and the background. The sensitivity to contrast is represented by the inverse of the minimal contrast necessary to make an object visible; the lower the contrast the greater the sensitivity, and the other way around. Contrast sensitivity is a fundamental aspect of vision together with visual acuity: the latter defines the smallest spatial detail that the subject manages to discriminate under optimal conditions, but it only provides information about the size of the stimulus that the eye is capable to perceive; instead, the evaluation of contrast sensitivity provides information not obtainable with only the measurement of visual acuity, as it establishes the minimum difference in luminance that must be present between the stimulus and its background so that the retina is adequately stimulated to perceive the stimulus itself. The clinical methods of examining contrast sensitivity (lattices, luminance gradients, variable-contrast optotypic tables and lowcontrast optotypic tables) relate the two parameters on which the ability to distinctly perceive an object depends, namely the different luminance degree of the two adjacent areas and the spatial frequency, which is linked to the size of the object. The measurement of contrast sensitivity becomes valuable in the diagnosis and follow up of some important eye conditions such as glaucoma. Studies show that contrast sensitivity can be related to data obtained with the visual perimetry, especially with the perimetric damage of the central area and of the optic nerve head

Therapeutic approaches with intravitreal injections in geographic atrophy secondary to age-related macular degeneration: current drugs and potential molecules

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory agents. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. Changes in the correct visual acuity and reduction in geographic atrophy progression were evaluated. Several new drugs have shown promising results, including those targeting the complement cascade and neuroprotective agents. The potential action of the two groups of drugs is to block complement cascade upregulation of immunomodulating agents, and to prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. Our analysis indicates that finding treatments for dry AMD will require continued collaboration among researchers to identify additional molecular targets and to fully interrogate the utility of pluripotent stem cells for personalized therapy

KDM4 Involvement in Breast Cancer and Possible Therapeutic Approaches

Breast cancer (BC) is the second leading cause of cancer death in women, although recent scientific and technological achievements have led to significant improvements in progression-free disease and overall survival of patients. Genetic mutations and epigenetic modifications play a critical role in deregulating gene expression, leading to uncontrolled cell proliferation and cancer progression. Aberrant histone modifications are one of the most frequent epigenetic mechanisms occurring in cancer. In particular, methylation and demethylation of specific lysine residues alter gene accessibility via histone lysine methyltransferases (KMTs) and histone lysine demethylases (KDMs). The KDM family includes more than 30 members, grouped into six subfamilies and two classes based on their sequency homology and catalytic mechanisms, respectively. Specifically, the KDM4 gene family comprises six members, KDM4A-F, which are associated with oncogene activation, tumor suppressor silencing, alteration of hormone receptor downstream signaling, and chromosomal instability. Blocking the activity of KDM4 enzymes renders them “druggable” targets with therapeutic effects. Several KDM4 inhibitors have already been identified as anticancer drugs in vitro in BC cells. However, no KDM4 inhibitors have as yet entered clinical trials due to a number of issues, including structural similarities between KDM4 members and conservation of the active domain, which makes the discovery of selective inhibitors challenging. Here, we summarize our current knowledge of the molecular functions of KDM4 members in BC, describe currently available KDM4 inhibitors, and discuss their potential use in BC therapy

Diabetic retinopathy, oxidative stress and sirtuins: an in depth look in enzymatic patterns and new therapeutic horizons

Diabetic retinopathy (DR) is one of the leading causes of blindness in the world. DR represents the most common microvascular complication of diabetes, and its incidence is constantly rising. The complex interactions between inflammation, oxidative stress, and the production of free oxygen radicals caused by prolonged exposure to hyperglycemia determine the development of DR. Sirtuins (SIRTs) are a recently discovered class of 7 histone deacetylases involved in cellular senescence, regulation of cell cycle, metabolic pathways, and DNA repair. SIRTs participate in the progress of several pathologies such as cancer, neurodegenerative and metabolic diseases. In DR, sirtuins 1,3,5 and 6 play an important role as they regulate the activation of the inflammatory response, insulin sensibility, and both glycolysis and gluconeogenesis. A wide spectrum of direct and indirect activators of SIRTs pathways (e.g. antagomiR, resveratrol, or glycyrrhizin) is currently being developed to treat the inflammatory cascade occurring in DR. We focuse on the main metabolic and inflammatory pathways involving SIRTs and DR, as well as recent evidence on SIRTs activators that may be employed as novel therapeutic approaches to DR

X-linked dominant RPGR gene mutation in a familial Coats angiomatosis

Background: Retinitis Pigmentosa (RP) is the most frequent retinal hereditary disease and every kind of transmission pattern has been described. The genetic etiology of RP is extremely heterogeneous and in the last few years the large application of Next Generation Sequencing (NGS) approaches improved the diagnostic yield, elucidating previously unexplained RP causes and new genotype-phenotype correlations. The objective of this study was to reevaluate a previously reported family affected by Coats’-type RP without genetic diagnosis and to describe the new genetic findings. Case presentation: Cohort, prospective, and single-center observational family case. Three individuals of a family, consisting of a mother and four sons, with a Coats phenotype were revaluated after 25 years of clinical follow-up using visual acuity tests, ophthalmoscopy, Goldmann visual field, electroretinography (ERG), and spectral domain-optical coherence tomography (SD-OCT). Specifically, a RP NGS panel was performed on one member of the family and segregation analysis was required for the other affected and unaffected members. NGS analysis disclosed a RPGR (Retinitis Pigmentosa GTPase Regulator) gene truncating variant segregating with the phenotype in all the three affected members. RPGR mutations are reported as causative of an X-linked RP. Conclusions: This is the first reported family with a Coats’-type RP associated to a RPGR mutation and segregating as a dominant X-linked disease, confirming the hypothesis of the genetic origin of this condition and expanding the phenotypic spectrum of diseases caused by RPGR gene mutations. The Authors suggest RPGR gene screening mutations in patients presenting this phenotype

Waste recovery and circular economy: a resource from orange peels deriving from production of orange juice

In the perspective of bio-sustainable development and renewable resource technologies, by-products and waste from agro-industrial sector represent a relatively cheap source of material suitable for several aims, which would reduce both the amount of waste and the related costs of disposal, while producing added-value nutritional products. The processing waste of oranges find various fields of application, in fact in addition to their use in agriculture as a fertilizer, orange peels can be used to produce candied fruit. Moreover, in a very recent application with the aim to recover these industrial residues, a chemical process that allows the processing of orange peel waste has been developed. This process is useful for obtaining a purified cellulose suitable for spinning, thus creating a truly innovative and sustainable fabric (Orange Fiber). In this work, the orange peels obtained from industrial processing waste were subjected to a first hydroalcoholic extraction which allowed to obtain an extract rich in essential oils that could be used in the food sector to produce liqueurs and/or aromas, but also in the cosmetic or pharmacological sectors. Subsequently, the peels after hydroalcoholic extraction were dried and this residue represents a valuable product rich in dietetic fiber useful in nutraceutical and pharmaceutical fields. Moreover, the same product could be used as fertilizer in agriculture. In lights of this, citrus fruit processing waste can be considerate as a sustainable and renewable energy source

Various applications of processing of olive leaves waste extracted with RSLDE: a green technology

There is no waste in nature. Everything that is produced has a purpose and everything that becomes waste can be transformed into a new resource, triggering a virtuous circuit that feeds itself. The circular economy of waste means a system in which the production-consumption-disposal process is overcome to replace it with a circular model, where the final waste product is re-introduced into the circulation as a secondary raw material. The logic to follow is that after consumption and before any disposal, it is necessary to activate virtuous processes such as reduce, reuse and recycling. This work focuses on the possible uses of a vegetable waste matrix, such as olive leaves. The olive tree (Olea europaea) is a fruit tree, cultivated for more than 3,500 years for its fruits and edible oil. However, just like oil, olive leaf contains a high amount of polyphenols, in particular oleuropein, one of the most powerful natural antioxidants known and hydroxytyrosol, which also has powerful antiseptic properties. Therefore, olive leaf extracts, thanks to the presence of oleuropein associated with hydroxytyrosol, represent a powerful natural antioxidant, a valid ally of the cardiovascular system. In addition, olive leaves are an excellent regulator of the digestive system: they regulate intestinal transit and above all eliminate fungi and other unwanted parasites from our body. Starting from these premises, in this work, a green extraction technique such as rapid solid liquid dynamic extraction (RSLDE) is compared with conventional maceration to obtain an olive leaf extract rich in antioxidants to be used in various sectors

Extraction and purification of phycocyanin from Arthrophira platensis microalgae using a green solid-liquid extraction technology (RSLDE)

Abstract. Spirulina is a blue alga belonging to the class of Cyanobacteria. This alga is characterized by a high content of phycocyanin, a blue photosynthetic pigment belonging to the phycobiliprotein family. Phycocyanin has a lot of industrial applications, in fact, it is used as a natural dye both in the cosmetic industry and in the food and textile sectors. It is also used in the biomedical field as a fluorescent marker. Anti-inflammatory, nephroprotective and hepatoprotective properties are also reported, probably related to its antioxidant activity. However, the extraction of phycobiliproteins from cyanobacteria is a very complicated procedure due to the extreme resistance of the wall of the cellular aggregates that make up spirulina. In literature, several procedures have been used to cause rupture of cell envelopes, through cycles of freezing/thawing, sonication and rupture of the cell wall with lysozyme. However, all these methods for cell breakdown do not guarantee a high quality of the extract, due to the complexity of the mixture obtained. In order to improve the yield of recovery of phycocyanin and to reduce the extraction process time, in this work, in combination with some experimental procedures for rupture of the membrane, a green extraction technique was used, the rapid solid liquid dynamic extraction (RSLDE). This technique can generate a pressure and a consequent depression on the matrix to be extracted. The extract obtained was immediately frozen at -20°C and then lyophilized. Analyzes such as UV-VIS spectrophotometric analysis and acrylamide gel electrophoresis were performed on the sample of lyophilizate to evaluate the efficiency of the extraction and purity of phycocyanin

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention