Prevalence of anxiety, depression, and suicidal ideation symptoms among university students: a systematic review / Prevalência de sintomas ansiedade, depressão e ideação suicida entre estudantes universitários: uma revisão sistemática

Several studies have suggested an increase in the prevalence of mental disorders and suicidal ideation among university students. This review aims to determine the current prevalence of university students identified with anxiety, depression, and suicidal ideation symptoms worldwide. After the survey in five electronic databases utilizing the PRISMA guidelines, 48 articles involving 40 countries and 56,816 students were selected. The results showed a prevalence of 24.5% for anxiety symptoms, 26.1% for depression symptoms, and 18.8% for suicidal ideation. Moreover, the prevalence of all these situations was higher in health students than in the general university population. The high prevalence of mental disorders in university students highlights the importance of strategies for prevention, diagnosis and treatment in this population

Exposure of cultured fibroblasts to the peptide PR-11 for the identification of induced proteome alterations and discovery of novel potential ligands.

The PR-11 peptide corresponds to the N-terminal and active region of the endogenously synthesized PR-39 molecule, of porcine origin. It is known to possess various biological effects including antimicrobial properties, angiogenic and anti-inflammatory activities. Apart from its reported activity as a proteasome inhibitor, a more comprehensive understanding of its function, at the molecular level, is still lacking. In this study, we used a label-free shotgun strategy to evaluate the proteomic alterations caused by exposure of cultured fibroblasts to the peptide PR-11. This approach revealed that more than half of the identified moleculeswere related to signalling, transcription and translation. Proteins directly associated to regulation of angiogenesis and interaction with the hypoxia-inducible factor 1-? (HIF-1?) were significantly altered. In addition, at least three differentially expressed molecules of the NF-?B pathway were detected, suggesting an anti-inflammatory property of PR-11. At last, we demonstrated novel potential ligands of PR-11, through its immobilization for affinity chromatography. Among the elutedmolecules, gC1qR, a known complement receptor, appearedmarkedly enriched. This provided preliminary evidence of a PR-11 ligand possibly involved in the internalization of this peptide. Altogether, our findings contributed to a better understanding of the cellular pathways affected by PR-39 derived molecules

Avaliação proteômica e caracterização do potencial angiogênico do peptídeo PR-11 e análogos.

Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa de Pós Graduação, Universidade Federal de Ouro Preto.O proteassoma tem sido considerado um potencial alvo farmacológico devido ao seu envolvimento em processos vitais relacionados à proteólise celular, sendo a mais importante entre as vias de degradação. A literatura demonstra que estruturas análogas ao peptídeo PR-11 (RRRPRPPYLPR), que corresponde aos 11 primeiros aminoácidos da porção N-terminal do peptídeo natural PR-39, apresentam uma forte inibição sobre o proteassoma 20S. Inicialmente descoberto por suas propriedades antimicrobianas, os peptídeos desta classe desempenham importantes efeitos anti-inflamatórios e angiogênicos. Apesar da ampla atividade biológica, os estudos moleculares são predominantemente limitados à inibição do proteassoma por estes peptídeos. Dessa forma, este trabalho teve como principais objetivos: avaliar o proteoma de culturas de fibroblastos expostas ao PR-11; identificar possíveis alvos desse peptídeo por sua imobilização em coluna de afinidade e caracterizar o perfil angiogênico do PR-11 e moléculas análogas por meio de implantes subcutâneos de esponjas em camundongos. Os peptídeos PR-11, F12 e C8C15 foram sintetizados empregando-se a estratégia Fmoc em fase sólida, purificados em sistema HPLC e identificados por espectrometria de massas. A estratégia shotgun label-free foi utilizada para avaliar as alterações proteômicas causadas pela exposição de culturas de fibroblastos ao PR-11 a 1 μM durante 2, 6 e 10 horas. Esta abordagem revelou que mais da metade das proteínas diferencialmente expressas identificadas estão relacionadas à sinalização celular, transcrição e tradução. Proteínas diretamente associadas à angiogênese pela regulação ou interação com o HIF-1α foram significativamente alteradas. Além disso, ao menos três proteínas diferencialmente expressas da via do NF-κB relacionam-se a uma resposta anti-inflamatória. Em paralelo, a interação do PR-11 imobilizado com extrato solúvel de fígado de ratos permitiu a identificação de novos ligantes ao peptídeo, destacando-se a gC1qR. Esta proteína está envolvida na internalização celular do peptídeo CGKRK, o qual assemelha-se ao segmento N-terminal do PR-11. Nossos resultados apresentam evidências preliminares de que a proteína gC1qR possa mediar a internalização celular do PR-11. De modo geral, a avaliação histológica das esponjas dos animais tratados com os peptídeos PR-11, F12 e C8C15 demonstra um aumento do perfil proliferativo e maturação do processo angiogênico. Por fim, os dados obtidos neste trabalho apresentam importantes informações para a elucidação dos mecanismos moleculares envolvidos nas atividades biológicas promovidas pelo PR-11 e moléculas similares.The proteasome has been considered a potential pharmacologic target due to its participation in various processes related to intracellular protein turnover. It was recently demonstrated that analogues of the PR-11 peptide (RRRPRPPYLPR), which corresponds to the first 11 amino acids of the PR-39 molecule, exhibit a potent inhibition over the 20S proteasome. It is known to possess various biological effects including antimicrobial properties, angiogenic and anti-inflammatory activities. Apart from its reported activity as a proteasome inhibitor, a more comprehensive understanding of its function, at the molecular level, is still lacking. Thus, this present work aimed to evaluate the proteomic alterations caused by exposure of cultured fibroblasts to the peptide PR-11; to identify novel potential ligands of this peptide by affinity chromatography and to characterize the angiogenic profile of PR-11 derived molecules using subcutaneous implants of sponges in mice. The peptides PR-11, F12 and C8C15 were synthesized through the Fmoc strategy in solid phase, purified by HPLC and identified by mass spectrometry. A label-free shotgun strategy was used to analyze the proteomic alterations caused by exposure of 1 μM PR-11 during 2, 6 and 10 hours. This approach revealed that more than half of the identified molecules were related to signalling, transcription and translation. Proteins directly associated to regulation of angiogenesis and interaction with the hypoxia-inducible factor 1-α (HIF-1α) were significantly altered. In addition, at least three differentially expressed molecules of the NF-κB pathway were detected, suggesting an anti-inflammatory property of PR-11. In parallel, we demonstrated novel ligands of PR-11, through its immobilization for affinity chromatography. Among the eluted molecules, gC1qR, a known complement receptor, appeared markedly enriched. This provided preliminary evidence of a PR-11 ligand possibly involved in the internalization of this peptide. In general, the histological evaluation of the sponges of treated mice with PR-11, F12 and C8C15 peptides demonstrates an increase in the proliferative profile and maturation of angiogenesis. Altogether, our findings contributed to a better understanding of the cellular pathways affected by PR-11 and similar molecules

Síntese de peptídeos ricos em prolina e arginina e atividade inibitória sobre o complexo proteolítico proteassoma 20s de mamíferos e do parasito Schistosoma mansoni.

O proteassoma tem sido considerado um potencial alvo farmacológico devido ao seu envolvimento em processos vitais relacionados à proteólise celular, sendo a mais importante entre as vias de degradação. Recentemente, foi demonstrado que moléculas análogas ao peptídeo PR-11(RRRPRPPYLPR), que corresponde aos 11 primeiros aminoácidos da porção N-terminal do peptídeo PR-39, apresentam uma forte inibição sobre o proteassoma humano 20S, inibindo a atividade quimotripsina-símile em concentrações namolares (nM). Os peptídeos dessa classe desempenham importantes atividades anti-inflamatórias e angiogênicas. Novas moléculas envolvendo substituições conservativas de aminoácidos e sínteses de peptídeos cíclicos podem ser derivadas dessas estruturas, com o intuito de se encontrar melhores inibidores. Dessa forma, este trabalho teve como objetivos a síntese do peptídeo PR-11 e análogos para a realização de ensaios de atividade peptidásica in vitro, visando verificar o potencial inibitório dos peptídeos sintetizados em frações enriquecidas com proteassoma 20S de fígado de camundongos Swiss, eritrócitos humanos e vermes adultos de Schistosoma mansoni. Os peptídeos foram sintetizados empregando-se a estratégia Fmoc em fase sólida, purificados em sistema HPLC e identificados por espectrometria de massas. As frações com proteassoma 20S foram obtidas a partir de cromatografias de filtração molecular em Sephacryl S-400, as quais permitiram preparar satisfatoriamente enriquecidos de proteassoma livres de proteases de baixa massa molecular. Todos os análogos foram capazes de inibir a atividade quimotripsina-símile in vitro do proteassoma 20S das três espécies estudadas, utilizando a concentração final de 1μM de peptídeo. De um modo geral, as intensidades das atividades inibitórias foram similares para o proteassoma 20S de camundongos e humanos e menores para o de vermes adultos de Schistosoma mansoni. Os análogos cíclicos C8C15 e C9C15, quando comparados ao PR-11, apresentaram menor atividade sobre o proteassoma de humanos e atividade similar quanto à inibição em Schistosoma mansoni. Tal fato sugere que esse tipo de alteração estrutural possa ser útil na busca por inibidores mais seletivos para o proteassoma 20S do parasito.The proteasome has been considered a potential pharmacologic target due to its participation in various processes related to intracellular protein turnover. It was recently demonstrated that analogues of the PR-11 peptide (RRRPRPPYLPR), which corresponds to the first 11 amino acids of the PR-39 molecule, exhibit a potent inhibition over the human 20S proteasome. At the tissue level, these peptides display anti-inflammatory and angiogenic properties. Therefore, new molecules containing conservative amino acid substitutions as well as cyclic analogues could be designed towards the production of more suitable inhibitors. The present work aimed the synthesis of the PR-11 peptide and its various analogues followed by their use in peptidasic assays containing 20S proteasome enriched fractions obtained from mice liver, human erythrocytes and Schistosoma mansoni adult worms. Peptides were synthesized through the Fmoc strategy in solid phase, purified by HPLC and identified by mass spectrometry. Proteasome containing fractions were recovered after gel filtration in Sephacryl-S400. This resulted in fractions free of contaminating low molecular mass proteases. All PR-11 analogues were able to inhibit at 1μM the 20S proteasome chymotrypsin-like activities from the three investigated species. Overall the intensities of inhibitory activities were similar to 20S proteasomes from mice and human and comparatively lower for the S. mansoni complex. The cyclic analogues C8C15 and C9C15 exhibited decreased inhibitory activity over the human 20S proteasome compared to PR-11, however, a significant inhibition towards the parasite´s proteasome was observed. Altogether, our data suggest that cyclic PR-11 analogues represent interesting alternatives for the development of more selective proteasome inhibitors

Effect of storage on retinol content and total antioxidant capacity of human milk

The purpose of this paper is to evaluate the effect of different times and freezing temperatures on the antioxidant activity of raw human milk (HM) and the impact of light by different packaging on retinol level and the antioxidant activity of pasteurized HM. Donor milks were homogenized to form the pool of the experimental study characterized by the evaluation of the effects of time (0, 2, 4, 8 and 15 days) freezing temperatures (-3 degrees C, -8 degrees C and -18 degrees C) and the interference of the type of packaging on the antioxidant activity and retinol levels of HM. Findings The existing studies do not reveal the real impact of HM storage conditions adopted by human milk banks (HMB) in Brazil on their compounds, mainly in relation to the effects of temperature and freezing time and the incidence of light on retinol levels and antioxidant activity. In view of the already documented importance of these compounds for the growth, development and health of children, it is extremely important to assess their stability according to the procedures adopted by the banks. It has been observed in this study that lower freezing temperatures (-18 degrees C) further preserve the antioxidant activity. It was found that the amber and transparent vials wrapped with aluminum foil allowed for greater retinol stability of HM, with values of 2.501 +/- 0.757 mu mol/L and 4.991 +/- 0.825 mu mol/L, respectively. On the contrary, there was no significant influence on antioxidant activity. It is suggested that HMB store milk at lower temperatures and use glass jars that block the passage of light122260661