The cancers of the skin, melanoma and the keratinocyte cancers, basal cell andsquamous cell carcinomas (BCC and SCC), are among the most common cancersin white populations. While ultraviolet radiation (UVR) is their principal cause,links with non-UVR-related factors have also been noted. Ultimately, theinteraction of these elements results in malignancy however, understanding oftheir specific contributions remains incomplete. This thesis reports findings fromsix studies aiming to investigate gaps in current knowledge of the role of UVR andnon-UVR-related risk factors on skin cancer. The papers are groupedaccording to the aspects of skin cancer epidemiology and aetiology they address. The first two papers address the descriptive epidemiology of melanoma inEngland, a country with low ambient solar UVR. They arise from ecologicalstudies using national melanoma registration data and document rising trends inmelanoma incidence by anatomic site (Paper 1), and by region of residence andsocio-economic deprivation (Paper 2). Their findings were consistent with thesuggestion that increases in recreational UVR exposure are driving rises inmelanoma rates. These results emphasise both the need to closely monitor UVRexposure and melanoma trends and the importance of public health campaigns. The second group of three papers considers the assessment of associations ofnutritional factors with keratinocyte cancer. Two studies use data from aprospective cohort to evaluate the relationship between dietary intake (Paper 3)and blood concentrations (Paper 4) of omega-3 and omega-6 polyunsaturatedfatty acids (PUFA) in relation to BCC and SCC risk. Associations with both PUFAtypes were observed. In addition, Paper 5, a three-way correlational assessment,demonstrated that questionnaire and blood circulating levels of omega-3 PUFAwere highly correlated with measures of skin bioavailability. Collectively, thesestudies give evidence for associations of these nutrients with skin cancer and forthe utility of both intake and biomarker measures for assessing the relationships. The final paper explores the relationship between a widely cited non-UVR riskfactor, namely scars and cancers of the skin. It reports a systematic review of allpublished observational studies quantifying this association. While innumerablecase reports were found, quantitative analyses were rare. The review identifieda major gap in the literature where knowledge of scar malignancies is notevidence-based, but rather founded mainly on cumulative anecdotal reporting. Taken together, this body of published work highlights the largely unrecognisedcomplexity of the aetiology of cancers of the skin. Future research must bebroad in scope in order to advance understanding of the interaction betweenUVR and other risk factors and to provide a base for health messages aimed atreducing the burden of these malignancies.

Endocannabinoids are endogenous lipid mediators involved in various biological processes, and have immunomodulatory and anti-inflammatory activities. Anandamide (arachidonoyl ethanolamine, AEA) and 2-arachidonoyl glycerol (2-AG) are the main representatives of this group. The endocannabinoid receptors CB1 and CB2 with AEA have been found in human HaCaT keratinocytes and fibroblasts, but the metabolic pathway leading to endocannabinoid production in the skin has not been fully elucidated. This study aimed to investigate the profile of endocannabinoids and their main metabolizing enzymes in human skin cells and assess whether omega-3 polyunsaturated fatty acids (n-3 PUFA) altered these profiles. In addition, an investigation was carried out to check whether UV radiation could stimulate the production of endocannabinoids and N-acylethanolamines (NAE) in human skin cells. For this purpose HaCaT keratinocytes and 46RB.1N fibroblast cells were treated with 10 and 50µM of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or oleic acid (OA) in the presence or absence of UVR (15mJ/cm2). Data suggest that n-3 PUFA may both directly (by up-regulating NAPE-PLD levels) and indirectly (by decreasing FAAH levels) increased endocannabinoid and NAE levels in HaCaT keratinocytes and 46BR.IN fibroblasts. DHA treatment significantly decreased COX-2 expression in the absence of UVR and inhibited UVR-induced COX-2 overexpression in 46BR.IN fibroblasts. In contrast, DHA appeared to induce COX-2 up-regulation in the absence of UVR and did not prevent UVR induced COX-2 up-regulation in HaCaT keratinocytes. EPA appeared to induce COX-2 down-regulation in the absence of UVR and did not prevent UVR induced COX-2 up-regulation in both HaCaT keratinocytes and 46BR.IN fibroblasts. UVR did not have any significant effect on endocannabinoid and NAE biosynthesis. However, UVR induced endocannabinoid production in some experiments of this study. A clinical study was carried on 16 volunteers from two different ethnic groups and two different skin types. The purpose was to assess the effect of UVR on the serum endocannabinoids and NAE, therefore, the volunteers were subjected to multiple doses (1.3, SED/ 6 min) of UVR for 6 weeks. Data showed that UVR did not have major effect on human serum NAE in both skin phototypes II and V but increased 2-AG in human serum in both skin types but the more pronounced effect was evident in skin phototypes V rather than in skin phototypes II. Human serum docosahxaenoylethanolamide levels were found to be higher in White Caucasians group (skin phototypes II). Based on these it can be concluded that n-3 PUFA and UVR alter the endocannabinoids and NAE profile in HaCaT keratinocytes and 46BR.IN fibroblasts. In addition, results of the clinical study indicated that UVR has no major effects on serum endocannabinoids or NAE therefore, further studies are required to address this question in vivo.

Memoria para optar al Título Profesional de Médico Veterinario / El objetivo del estudio fue evaluar el efecto de suplementar con Ácidos Grasos Poliinsaturados omega 3 (AGPI -3) la dieta de cerdas reproductoras sobre su rendimiento reproductivo, reflejado en su futura camada. Por 30 días a partir de 3 días previos al parto, 90 cerdas, 45 del Grupo Control (GC) fueron alimentadas con una dieta de lactancia y otras 45, Grupo Tratamiento (GT), con la dieta control más 5 g/kg de AGPI -3 (Crandon S.A., Chile). Registrándose consumo de alimento diario y el rendimiento reproductivo de las cerdas en el parto siguiente. El consumo de alimento fue menor en GT durante la primera semana (P = 0,002). En cerdas jóvenes (< 4 partos), GT presentó mayor número de lechones nacidos totales (P = 0,002) y nacidos vivos (P = 0,001) que GC. No hubo diferencias (P > 0,05) en el número de fetos momificados ni de ballicos entre grupos. En cerdas viejas (> 5 partos), se obtuvo un menor número de ballicos en GT en comparación a GC (P = 0,021). Sin embargo, el número de nacidos muertos fue mayor en GT que en GC (P = 0,026). Posteriormente, GT presentó una elevada mortalidad nacimiento-destete, no existiendo diferencias en el número de kilos destetados entre grupos, sin obtenerse un beneficio económico para GT. Los resultados demuestran que la suplementación con AGPI -3 tuvo efecto sobre los parámetros productivos de las cerdas jóvenes; siendo necesario esclarecer dicho aspecto en futuros estudios en el tema.

Orientador: Maria Cristina Cintra Gomes Marcondes / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-27T06:12:33Z (GMT). No. of bitstreams: 1 Miyaguti_NataliaAngelodaSilva_M.pdf: 7149513 bytes, checksum: e738b40c2027a8507e7b5ae2e65321e8 (MD5) Previous issue date: 2015 / Resumo: O Resumo poderá ser visualizado no texto completo da tese digital / Abstract: The Abstract is available with the full electronic digital document / Mestrado / Fisiologia / Mestra em Biologia Funcional e Molecular

Syfte: Syftet med studien var att genom en litteraturstudie undersöka om tillskott av omega-3 har någon positiv påverkan på torra ögon och ögats främre delar. Kan denna fleromättade fettsyra lindra symtomen samt de kliniska tecknen av torra ögon? Metod: Artiklarna i litteraturstudien baserades på tidigare kliniska studier och vetenskapliga publikationer. De sökmotorer som användes var PubMed och Web of Science, sökningarna utfördes mellan 2020-03-30 och 2020-04-15. För att göra urvalsprocessen sattes inklusionskriterier och exklusionskriterier upp. Begränsningarna var att artiklarna skulle finnas tillgängliga i fulltext och vara publicerade från år 2015-2020. Sökorden som användes var “dry eye + omega” och “dry eye and omega”. Litteraturstudier/reviews exkluderades samt studier med färre än 50 deltagare. Utifrån resultatet av sökningarna valdes de fem mest relevanta artiklarna ut för att ingå i studien. Resultat: Studierna involverade totalt 2569 deltagare. Tillskotten som användes i studierna var omega-3 i olika sammansättningar. De subjektiva mätningarna gjordes med Ocular Surface Disease Index (OSDI) och Dry Eye Questionnaire and Scoring System (DESS) och visade statistiskt signifikant förbättring på symtompoäng i tre av fem studier. De objektiva mätningarna visade statistiskt signifikant förbättring på bland annat TBUT i fyra av fem studier och Schirmertest i två av fem studier. Slutsats: Det finns en positiv effekt på torra ögon, torra ögonsymtom och främre ytan av ögat med ett dagligt tillskott av omega-3-fettsyror, men en viss placeboeffekt kan inte uteslutas. Fler studier med fler deltagare under en längre period krävs för att fastställa den optimala dosen, behandlingsperioden samt sammansättningen av tillskottet av omega-3. / The aim of this study was through a literature review, investigate whether a dietary supplement of omega-3 has a positive effect on dry eye symptoms and the anterior surface of the eye. Can this polyunsaturated fatty acid relieve the symptoms and the clinical signs of dry eyes? The articles included in the literature study were based on previous clinical studies and scientific publications. The search engines used were PubMed and Web of Science. The searches were conducted between 2020-03-30 and 2020-04-15. Inclusion criteria and exclusion criteria were determined in advance. The restrictions were that the articles should be available in full text and be published from 2015-2020. The keywords used were “dry eye + omega” and “dry eye and omega”. Other literature reviews were excluded as well as studies with fewer than 50 participants in the randomized clinical trials (RCTs). Based on the results on the searches, 30 articles were selected that related to the topic dry eyes and omega-3. Subsequently, the articles abstracts were reviewed, and the least relevant articles were excluded. The remaining 13 articles were read in more detail and of these, the 5 most relevant articles were selected to be included in the study. The five selected studies involved a total of 2569 participants. The supplements used in the studies contained omega-3 in various compositions. The subjective measurements were made using the Ocular Surface Disease Index (OSDI) and the Dry Eye Questionnaire and Scoring System (DESS) and showed statistically significant improvement in symptom scores in three out of five studies. The objective clinical tests showed statistically significant improvement on for example TBUT in four out of five studies and Schirmer’s test in two out of five studies. The conclusion is that there is a positive effect on dry eyes, dry eye symptoms and the ocular surface of the eye with a daily supplement of omega-3 fatty acids, however a placebo effect cannot be ruled out. More studies with more participants over a longer period of time are required to determine the optimal dose, treatment period and composition of the supplement of omega-3.

Orientador: Rejane Maira Góes / Resumo: O câncer de próstata (CaP) é um dos tipos mais recorrentes de câncer em homens e o consumo excessivo de lipídeos saturados favorece o seu desenvolvimento. Ao contrário, dietas ricas em ácidos graxos poli-insaturados (PUFA) tipo ômega-3 (n-3) tem sido associadas com menor incidência do CaP. O presente trabalho avaliou as repercussões do consumo de ácidos graxos PUFAs n-3 da série marinha, ácido docosahexaenoico (DHA) e ácido eicosapentaenoico (EPA), sobre a progressão tumoral na próstata ventral de camundongos transgênicos para o adenocarcinoma de próstata (TRAMP). Camundongos TRAMP foram alimentados com dieta padrão e eutanasiados com 8 (C8), 12 (C12) e 20 (C20) semanas de vida ou então alimentados com uma dieta rica em óleo de peixe (10% óleo de peixe) a partir da oitava semana de vida e então eutanasiados com 12 (T12) ou 20 semanas (T20). Os resultados adquiridos demonstraram o aumento na proliferação celular bem como na expressão tecidual do receptor de andrógeno (AR) e glicocorticoide (GR) e no número de linfócitos T na próstata dos grupos controles conforme o aumento da idade e da agressividade das lesões. A intervenção dietética com PUFAs n-3 proporcionou a preservação do microambiente glandular levando a uma menor frequência de lesões proliferativas, indicando um atraso na progressão tumoral, onde foi observado níveis de proliferação celular, da expressão tecidual de AR e GR e de linfócitos T inferiores que seus controles de mesma idade. Ainda, o consumo de DHA/EPA pro... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Prostate cancer (PCa) is one of the most frequent cancers among male individual and saturated lipid intake is linked to its development. However, diets rich in omega-3 (n-3) polyunsaturated fatty acid (PUFA) have been associated to lower PCa development risk. The present study assessed the outcome of the marine n-3 PUFA intake, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), upon tumor progression at the transgenic adenocarcinoma of the mouse prostate (TRAMP). TRAMP mice were chow-fed and euthanized at 8 (C8), 12 (C12) and 20th (C20) week of age or fed with a fish oil-enriched diet from 8 to 12 (T12) or 20th (T20) week of age and then euthanized. The results indicated an increase in proliferation rate, tissue expression of androgen receptor (AR) and glucocorticoid receptor (GR) and the number of T-cells at the prostate of the control groups according to the increase of age and aggressiveness of the lesions. Dietary intervention with n-3 PUFA led to the maintenance of the glandular microenvironment, highlighted by a reduction of the frequency of proliferative lesions, indicating a delay in PCa progression whereas the levels of cell proliferation, tissue expression of AR and GR and the number of T-cells were lower than the control groups of the same age. Also, DHA/EPA intake promoted a lowering effect of serum triglycerides and cholesterol, improving the metabolic profile of these animals. Thereby incorporation o DHA/EPA on diet is capable of decrease the severity o... (Complete abstract click electronic access below) / Mestre

Syfte. Syftet med denna litteraturstudie var att undersöka om orala tillskott av omega-3 har någon effekt på torra ögon. Metod. Den här litteraturstudien baserades på fem utvalda artiklar som söktes fram via sökmotorn Pubmed den 28 mars. Sökorden var “omega 3 supplement AND dry eye”. Olika begränsningar gjordes såsom tidsgräns för utgivning: mellan år 2015 till 2022 och Peer-reviewed randomiserad kontrollerade studier. Artiklar som inte gick i linje med den här litteraturstudiens syfte valdes bort, kvar fanns fyra artiklar. Den sista utvalda artikeln var en av tre ”given som förslag på citatmatchning” av sökmotorn Pubmed, vid angiven sökning ovan. Resultat. Av de fem artiklarna kunde två artiklar stödja en främjande effekt av omega-3 på dry eye disease (DED) och en artikel visade en statistisk signifikant positiv effekt på symtom i OSDI poäng i en subgrupp med svåra DED-symtom ≥ 52. Två av artiklarna kunde inte som slutsats stödja en positiv effekt av omega-3 på DED trots positiva effekter på korneal infärgning, Schirmer´s test, konjunktival infärgning samt TBUT, så var de inte statistiskt signifikanta, jämfört med placebogruppen. I de två artiklarna där en främjande effekt av omega-3 sågs på DED kunde det ses en positiv statistisk signifikant effekt på Ocular Surface Disease Index (OSDI) poäng, tårosmolaritet, TBUT med mera. Mängden deltagare varierade mellan studierna, även ålder, region, sammansättningen på fettsyrorna och biotillgängligheten av supplementen varierade, vilket kan ha påverkat studiernas resultat.Slutsats. Effekten av omega-3 på DED varierade mellan studierna. Själva sammansättningen på fettsyrorna påverkade resultaten där ökad biotillgänglighet hos omega-3, i återförestrad form och i form av krillolja (triglyceridform) visades ha en större effekt än omega-3 i etylesterform vid DED. Även addition av GLA till omega-3 supplementen hade en positiv effekt på symtom hos personer med svåra DED symtom. Fler studier behövs för en fullständig förståelse vad gäller dos och form av omega-3 samt för att utreda vilken svårighetsgrad av DED som kan dra nytta av omega-3-behandling. Framtida studier behöver även undersöka huruvida individanpassad terapi med Omega-3 kan användas vid DED. / Purpose. This literature study aimed to investigate whether oral omega-3 supplements affect dry eyes. Method. This literature review was based on five selected articles from the search engine Pubmed on 28 March. The keywords were "omega 3 supplement AND dry eye". There was inclusion criteria such as articles published between the years 2015 and 2022 and the articles needed to be Peer-reviewed randomized controlled trials. Articles in line with the purpose of this literature study were selected, and the outcome was four articles. The last article selected was one out of three included in the “suggestions for citation matching” by Pubmed, using the above-mentioned criteria. Results. Of the five articles, two articles could support a promoting effect of omega-3 on DED. One article showed a statistically significant positive impact on symptoms in OSDI scores in a subgroup with severe symptoms ≥ 52. In the two articles that could support a promoting effect of omega-3 on DED, a positive, statistically significant impact could be seen on OSDI scores, tear osmolarity, TBUT, and more. Two of the articles could not support a positive effect of omega-3 on DED. Even though there were positive effects on corneal staining, Schirmer´s test, conjunctival staining, and TBUT, they were not statistically significant compared with the placebo group. However, the number of participants varied between studies, which also varied for age, region, the composition of the fatty acids, and bioavailability of the supplement.Conclusion. The effect of omega-3 on DED varies between studies. The actual composition of the fatty acids seems to impact the result where increased bioavailability of omega-3, which is in re-esterified form, and krill oil that is in triglyceride form has a more significant effect than omega-3 in ethyl ester form. The addition of GLA to the omega-3 supplement also positively impacted symptoms in people with severe symptoms. More studies are needed to thoroughly understand the dose and form of omega-3, and severity of DED. But studies are also required to learn about individualized therapy, and if it can be applicable using omega-3 on DED.

Indiana University-Purdue University Indianapolis (IUPUI) / Omega-3 polyunsaturated fatty acids (n-3 PUFAs) relieve the symptoms of a wide variety of chronic inflammatory disorders. Typically, they must be obtained in the diet from sources such as fish oils. Docosahexaenoic acid (DHA) is one of these n-3 PUFAs. As yet the structural mechanism responsible for the health benefits within the body is not completely understood. One model that has emerged from biochemical and imaging studies of cells suggests that n-3 PUFAs are taken up into phospholipids in the plasma membrane. Thus the focus here is on the plasma membrane as a site of potential structural modification by DHA. Within cellular membranes, the huge variety of molecules (called lipids) which constitute the membrane suggest inhomogeneous mixing, thus domain formation. One potential domain of interest is called the lipid raft, which is primarily composed of sphingomyelin (SM) and cholesterol (chol). Here the molecular organization of [2H31]-N-palmitoylsphingomyelin (PSM-d31) mixed with 1-palmitoyl-2-docosahexaenoylphosphatylcholine (PDPC) or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), as a monounsaturated control, and cholesterol (chol) (1:1:1 mol) in a model membrane was examined by solid state 2H NMR spectroscopy. Solid state 2H NMR spectroscopy extracts details of molecular orientation and anisotropy of molecular reorientation by analysis of the lineshape. This essentially non-invasive technique allows for a direct measurement of dynamics in bulk materials which has been extensively applied to biological materials. It is a niche area of NMR for which standard software often lack necessary features. Two software programs, “EchoNMR processor” and “EchoNMR simulator”, collectively known as “EchoNMR tools”, that were developed to quickly process and analyze one-dimensional solid-state NMR data, will be described along with some theoretical background of the techniques used. EchoNMR tools has been designed with a focus on usability and the open-source mindset. This is achieved in the in the MATLAB® programming environment which allows for the development of the graphical user interfaces and runs as an interpreter which allows the code to be open-source. The research described here on model membranes demonstrates the utility of the software. The NMR spectra for PSM-d31 in mixtures with PDPC or POPC with cholesterol were interpreted in terms of the presence of nano-sized SM-rich/chol-rich (raft-like) and PC-rich/chol-poor (non-raft) domains that become larger when POPC was replaced by PDPC. An increase in the differential in order and/or thickness between the two types of domains is responsible. The observation of separate signals from PSM-d31, and correspondingly from [3α-2H1]cholesterol (chol-d1) and 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31), attributed to the raft-like and non-raft domains enabled the determination of the composition of the domains. Most of the SM (84%) and cholesterol (88%) was found in the raft-like domain. There was also a substantial amount of PDPC (70%) in the raft-like domain that appears to have minimal effect on the order of SM. PDPC molecules sequestering into small groups to minimize the contact of DHA chains with cholesterol is one possible explanation that would also have implications on raft continuity. These results refine the understanding of how DHA may modulate the structure of raft domains in membranes.

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