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Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting research to identify additional mechanisms that may be involved in this two-directional talk. Here, we investigated whether and how 5-hydro-5-methylimidazolone (MG-H1), a specific methylglyoxal (MG)-derived advanced glycation end product (AGE), was a novel player in the dialogue between PCa and OB to drive PCa bone metastases. Conditioned medium from osteotropic PC3 PCa cells, pre-treated or not with a specific MG scavenger, was administrated to human primary OB and cell morphology, mesenchymal trans-differentiation, pro-osteogenic determinants, PCa-specific molecules, and migration/invasion were studied by phase-contrast microscopy, real-time PCR, western blot and specific assays, respectively. We found that PC3 cells were able to release MG-H1 that, by binding to the receptor for AGEs (RAGE) on OB, reprogrammed them into a less-differentiate phenotype, endowed with some PCa-specific molecular features and malignant properties, in a mechanism involving reactive oxidative species (ROS) production and NF-kB pathway activation. These findings provide novel insights into the mechanisms of PCa osteoblastic metastases and foster in vivo research toward new therapeutic strategies interfering with PCa/OB cross-talk.

Methylglyoxal (MG) is a potent precursor of glycative stress (abnormal accumulation of advanced glycation end products, AGEs), a relevant condition underpinning the etiology of several diseases, including those of the oral cave. At present, synthetic agents able to trap MG are known; however, they have never been approved for clinical use because of their severe side effects. Hence, the search of bioactive natural scavengers remains a sector of strong research interest. Here, we investigated whether and how oleuropein (OP), the major bioactive component of olive leaf, was able to prevent MG-dependent glycative stress in human dental pulp stem cells (DPSCs). The cells were exposed to OP at 50 µM for 24 h prior to the administration of MG at 300 µM for additional 24 h. We found that OP prevented MG-induced glycative stress and DPSCs impairment by restoring the activity of Glyoxalase 1 (Glo1), the major detoxifying enzyme of MG, in a mechanism involving the redox-sensitive transcription factor Nrf2. Our results suggest that OP holds great promise for the development of preventive strategies for MG-derived AGEs-associated oral diseases and open new paths in research concerning additional studies on the protective potential of this secoiridoid.

Oleuropein (OP) is a bioactive compound derived from plants of the genus Oleaceae exhibiting antitumor properties in several human cancers, including non-small-cell lung cancer (NSCLC). Recent evidence suggests that OP has proapoptotic effects on NSCLC cells via the mitochondrial apoptotic pathway. However, the exact molecular mechanisms behind the apoptogenic action of OP in NSCLC are still largely unknown. Glyoxalase 2 (Glo2) is an ancient enzyme belonging to the glyoxalase system involved in the detoxification of glycolysis-derived methylglyoxal. However, emerging evidence suggests that Glo2 may have also nonenzymatic roles in some malignant cells. In the present study, we evaluated whether and how Glo2 participated in the proapoptotic effects of OP in NSCLC A549 cells. Our results indicate that OP is able to induce apoptosis in A549 cells through the upregulation of mitochondrial Glo2 (mGlo2), mediated by the superoxide anion and Akt signaling pathway. Moreover, our data shows that the proapoptotic role of mGlo2, observed following OP exposure, occurs via the interaction of mGlo2 with the proapoptotic Bax protein. Conversely, OP does not alter the behavior of nonmalignant human BEAS-2B cells or mGlo2 expression, thus suggesting a specific anticancer role for this bioactive compound in NSCLC. Our data identify a novel pathway through which OP exerts a proapoptotic effect in NSCLC and suggest, for the first time, a novel, nonenzymatic antiapoptotic role for this ancient enzyme in NSCLC., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.

Methylglyoxal (MG) is a potent inducer of advanced glycation end products (AGEs). MG, long considered a highly cytotoxic molecule with potential anticancer value, is now being re-evaluated to a protumorigenic agent in some malignancies. Anaplastic thyroid cancer (ATC) is an extremely aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Successful therapeutic intervention in ATC is undermined by our poor understanding of its molecular etiology. In the attempt to understand the role of MG in ATC aggressiveness, we used immunohistochemistry to examine the level of MG protein adducts in ATC and slow-growing papillary thyroid cancer (PTC). We detected a high level of MG adducts in ATC compared to PTC ones, suggesting a protumor role for MG-mediated dicarbonyl stress in ATC. Accordingly, MG adduct accumulation in ATC cells in vitro was associated with a marked mesenchymal phenotype and increased migration/invasion, which were both reversed by aminoguanidine (AG)-a scavenger of MG-and resveratrol-an activator of Glyoxalase 1 (Glo1), the key metabolizing enzyme of MG. Our study represents the first demonstration that MG, via AGEs, acts as a tumor-promoting factor in ATC and suggests that MG scavengers and/or Glo1 activators merit investigations as potential therapeutic strategies for this malignancy.

Because Sertoli cells (SCs) play a central role in germ cell survival, their death may result in marked germ cell loss and infertility. SCs are the only somatic cells within the seminiferous tubules and are essential for regulating spermatogenesis. Factors that enhance or diminish the viability of SCs may have profound effects on spermatogenesis. Yet the mechanisms underlying the maintenance of SC viability remain largely unknown. Glyoxalase 1 (Glo1) detoxifies methylglyoxal (MG), a highly reactive carbonyl species mainly formed during glycolysis, which is a potent precursor of cytotoxic advanced glycation end products (AGEs). Hydroimidazolone (MG-H1) and argpyrimidine (ArgPyr) are AGEs resulting from MG-mediated post-translational modification of arginine residues in various proteins. The role of Glo1 and MG-derived AGEs in regulating the fate of SCs has never been investigated. By using gene silencing and the specific MG scavenger, aminoguanidine, the authors demonstrate that Glo1, under testosterone and follicle-stimulating hormone control, sustains viability of porcine neonatal SCs through a mechanism involving the NF-κB pathway. Glo1 knockdown induces a mitochondrial apoptotic pathway driven by the intracellular accumulation of MG-H1 and ArgPyr that desensitizes NF-κB signaling by modifying the inhibitor of NF-κB kinase, IKKß. This is the first report describing a role for Glo1 and MG-derived AGEs in SC biology, providing valuable new insights into the potential involvement of this metabolic axis into spermatogenesis., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the correlation between the degree of anisometropia with depth of amblyopia and presence of stereopsis., Methods: A retrospective chart review of 119 patients treated during 1995-2004 was carried out. All patients had undergone a full ophthalmological examination. Inclusion criteria were: anisometropia >1 diopter (spherical and/or cylindrical), age at first examination between 2 and 8 years, no previous optical correction, absence of ocular and neurological disorders, absence of ocular motility disorders, and minimum follow-up of 2 years (mean 7.9 +/- 4.3). Optical correction was prescribed at first visit and, at a second visit, the need for patching or penalization was evaluated., Results: The results show a correlation between the degree of anisometropia and visual acuity at first visit (p < 0.001). There were, however, several subjects with good levels of visual acuity despite considerable anisometropia, and also subjects where mild or moderate anisometropia was sufficient to induce a severe amblyopia. Compared to other types of anisometropia, anisomyopic patients appeared to have a higher degree of binocular vision recovery when corrected optically. First evaluation with the presence of good stereoacuity seems to be a prognostic indicator for amblyopic recovery., Conclusions: This study demonstrates the difficulty of developing a guideline for screening and treatment of anisometropia. Even though there seems to be a correlation between type and degree of anisometropia in a majority of patients, there is also a significant number of cases that do not follow this pattern. Another important observation is the presence of binocular vision at the first evaluation as a good prognostic indicator for visual recovery with optical correction alone, even without penalization therapy.

Background: Strabismus is one of the most common visual disorders in infancy. While there is a great attention on the effects of the timing of surgery as to the development of binocular vision, little is known about the possible influence of congenital strabismus on perceptual-motor and more generally, on neuromotor development., Aims: Aim of this study was to investigate perceptual-motor and motor coordination abilities of 19 children with essential congenital esotropia who underwent a late surgery (after 4 years), compared to 23 age-matched controls., Methods: Children were tested using the Movement Assessment Battery for Children (Movement ABC) that were performed both 1-week before surgery (T1) and about 3 months (+/-2 weeks) after surgery (T2)., Results and Conclusions: At T1, abnormal or borderline results were found in more than half of the children with strabismus, as opposed to only about 17% of the controls. At T2 none of the children showed abnormal Movement ABC total scores and there was no difference in global scores between the study and the control group. The two groups also did not show any significant difference in individual items of the movement ABC with the exception of those assessing ball skills. Our results suggest that surgical correction of strabismus, even when performed after the 4th year of life, appears to be effective in improving perceptual-motor and motor function.

Purpose: The purpose of this study was to investigate the evolution of refraction and visual function in patients with myopic anisometropia., Design: A retrospective study on a selected population., Methods: Forty-six anisomyopic patients underwent a complete ophthalmologic examination (cycloplegic refraction, visual acuity, ocular movement and fundus examination)., Results: The results show two different patterns of changes in refraction between the two eyes; in the same patient, the less myopic eye tends to get more myopic, while the more ametropic eye shows a more stable refraction. Furthermore, a recovery of binocular vision and amblyopia can be obtained by occlusion and full-time refractive correction., Conclusions: The evolution of refraction seems to be different in eyes with anisometropia and it is still to be understood whether it is fixation or reduced fixation that leads to a myopic shift.

The wide-spread use of video display units in many work places has led to an increase in ophthalmologic examinations of the operators. For this reason, instruments for visual test screening (for example Visotest) have become widely used. Nevertheless, the literature does not seem to offer any clarification about the utility of these instruments as epidemiological tools. The costs and benefits of visual screening programmes were estimated in relation to specific visual deficit prevalence in a differently age-structured population. Via epidemiological calculation, it was demonstrated that positive and negative predictive values, which are directly related to deficit prevalence, are more important than sensitivity and specificity calculations. In view of the disorders screened, a visual test with a low positive predictive value is more expensive than one with a low negative predictive value. A visual test for visual deficits screening does not appear to be advisable in young populations, where the true positives/false positives ratio is 1:4, whereas in older populations the ratio is 2:1.

The authors describe the methods of recording the visual evoked potentials and of their utilization for investigations in amblyopia. The characteristics of VEP have been analyzed in an amblyopic and a normal eye; analyzed further on were the reciprocal dependencies between an uniocular and binocular records, the phenomenon of suppression and sensitivity to contrast. The authors confirm the suitability of the VEP for objective evaluation of the progress of treatment and for elucidation of the physiopathology of amblyopia.

This report concerns a patient whom, on the basis of clinical data and instrumental findings, we diagnosed as suffering from Acute Multifocal Posterior Pigment Epitheliopathy (AMPPE). We found the comparison of the angiographic findings and of the automated perimetry performed with the Octopus quite interesting since the literature does not contain reports of such comparisons. The results of perimetry were also of considerable interest. The test revealed serious impairment of retinal luminous sensitivity. The comparison of angiography and automated perimetry of the lesions of the pigmented epithelium was quite useful for providing a better clinical picture and understanding of the functional state.

114 subjects with esotropia and blockage syndrome were observed. Diagnosis was based upon clinical and EOGraphical data. Tendon lengthening with fascia lata was performed mono or bilaterally on medical recti, with or without associated resection of the external recti. The residual angle of strabismus and the effect on the blockage were measured to evaluate the results. Those seemed to be generally favourable. The AA. discuss upon the action of this kind of surgery on the muscular dynamic.

This retrospective study shows the clinical data of 81 patients with elevation in adduction. The relationships between the elevation in adduction and various ocular anomalies, such as horizontal deviations, refractive errors, nystagmus, torticollis, superior oblique muscle paralysis and dissociated vertical deviation, have been studied in order to specify the clinical characteristics of this phenomenon. The age of onset of the elevation in adduction and of the dissociated vertical deviation has also been considered, and a typical temporal progression of these symptoms has been found. In this sequence, we first noticed the onset of the horizontal deviation, then the appearance of the elevation in adduction, and finally the appearance of the dissociated vertical deviation. Although the elevation in adduction is frequently found in association with the complex syndromic pattern of congenital esotropia, this phenomenon may also accompany other types of anomalies of ocular motility.