305,354 research outputs found
Recent developments in the management of dry age-related macular degeneration
No full textElisa Buschini, Antonio M Fea, Carlo A Lavia, Marco Nassisi, Giulia Pignata, Marta Zola, Federico M Grignolo Ospedale Oftalmico, Ophthalmic Section, Department of Clinical Pathophysiology, University of Turin, Turin, Italy Abstract: Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy. Keywords: dry AMD, geographic atrophy, new AMD therap
Strategie di monitoraggio di rischio genotossico per una sorgente di inquinamento puntiforme: il forno inceneritotr R.S.U. di Parma
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Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Tumour suppressor role of Serine hydroxymethyltransferase in Drosophila melanogaster
No full textSerine hydroxymethyltransferase (SHMT) works in the one carbon
(1C) pathway to regulate essential cellular processes such as
nucleotide synthesis and epigenetic maintenance. SHMT catalyses
the reversible interconversion of serine and tetrahydrofolate (THF)
to glycine and 5,10-methyleneTHF (meTHF). The one carbon
units produced in this reaction are used by thymidylate synthase
enzyme (TS) to produce Thymidylate (dTMP) an essential
precursor of DNA. Therefore, it is expected that a depletion of
SHMT could reduce the biosynthesis of dTMP, thus increasing the
genome instability. To test this hypothesis, we depleted SHMT in
Drosophila melanogaster, using the RNA interference strategy,
which reduced the catalytic activity of SHMT of about 40%.
We showed that SHMT depletion resulted in chromosome damage
that was also produced by RNAi-mediated TS silencing.
Interestingly, dTMP supplementation reduced the chromosome
aberrations suggesting the SHMT depletion impacts on genome
integrity by impairing the folate cycle.
More interestingly, we found that the administration of pyridoxal
5’-phosphate (PLP), the enzymatic cofactor of SHMT was able to
rescue the chromosome damage. In contrast, the administration of
the PLP antagonist 4-deoxypyridoxine (4DP) exacerbated the CAB
phenotype, thus unveiling a gene-nutrient relationship between
SHMT and vitamin B6 which impacts on genome stability.
Several studies associated the overexpression of SHMT2 and, at
lesser extent SHMT1, to cancer indicating that this activity takes
part to metabolic reprograming by supplying cancer cells with
molecular building blocks essential for their rapid growth. On the
other hand, only a few studies have focused on the consequence of
reduced SHMT levels in cancer.
Dottorato di ricerca in Genetica e Biologia Molecolare
Pag. 9
In this thesis we exploited the RasV12DlgRNAi Drosophila cancer
model to test whether the RNAi-induced silencing of SHMT could
increase the malignancy of tumours induced by the expression of
the RasV12 oncogene combined to silencing of Disc large (Dlg)
polarity gene in larval eye discs. From this analysis it emerged that
SHMT depletion exacerbates cancer phenotype of RasV12DlgRNAi
tumours and causes genome instability by synergizing with the
tumour background. CABs induced by SHMT silencing were
rescued by dTMP supplementation that likewise rescued the
malignant phenotype of RasV12DlgRNAi larvae, thus linking genome
instability to tumours. Moreover, we provided evidence that the
levels of PLP can modulate the tumour phenotypes as well as the
genome instability resulting from SHMT silencing, thus suggesting
that the gene-nutrient interaction between SHMT and vitamin B6 is
able to impact on cancer through the genome damage.
We found that SHMT depletion in RasV12DlgRNAi cells promotes
the formation reactive oxygen species (ROS) due to the
overexpression of the NAPDH oxidase enzyme, suggesting that
ROS may contribute to CABs which, in turn, might be responsible
for promoting tumour phenotypes in the RasV12DlgRNAi cells
depleted of SHMT.
Taken together, our studies highlighted a clear tumour suppressor
role of SHMT that acts as a safeguard against the genome damage
and also showed, for the first time, how the interplay between
SHMT activity and the vitamin B6 availability can modulate the
cancer risk by impacting on genome integrity
Inquinanti genotossici nell'acqua
No full textL’inquinamento delle acque è un fenomeno globale entro il quale gli interrogativi posti dalla presenza di agenti mutageni, cancerogeni e teratogeni non possono essere considerati disgiuntamente da quelli relativi ad altri agenti tossici. I contaminanti genotossici presenti nell’ambiente acquatico possono essere individuati saggiando in vitro campioni ambientali e rilevando il danno genetico indotto dopo l’esposizione in organismi sentinella. Evidenze di questo tipo sono un segnale d’allarme per le potenziali conseguenze a lungo termine, definite dall’instaurarsi di cambiamenti nelle popolazioni, nelle specie e nelle comunità
degli organismi esposti. L’applicazione di biomarcatori di esposizione e di effetto in associazione alle
analisi chimiche può fornire le informazioni utili a individuare le fonti inquinanti e a stabilire adeguate misure
di protezione dei corpi idrici
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