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1.
Int J Mol Sci ; 25(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892230

RESUMO

Marine natural products constitute a great source of potential new antidiabetic drugs. The aim of this study was to evaluate the role of phosphoeleganin (PE), a polyketide purified from the Mediterranean ascidian Sidnyum elegans, and its derivatives PE/2 and PE/3 on insulin sensitivity in human hepatocellular carcinoma (HepG2) cells. In our experiments, insulin stimulates the phosphorylation of its receptor (INSR) and AKT by 1.5- and 3.5-fold, respectively, whereas in the presence of PE, PE/2, and PE/3, the insulin induced INSR phosphorylation is increased by 2.1-, 2-, and 1.5-fold and AKT phosphorylation by 7.1-, 6.0-, and 5.1-fold, respectively. Interestingly, PE and PE/2 have an additive effect on insulin-mediated reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression. Finally, PE and PE/2, but not PE/3, decrease interleukin 6 (IL6) secretion and expression before and after palmitic acid incubation, while in the presence of high glucose (HG), only PE reduces IL6. Levels of other cytokines are not significantly affected by PE and its derivates. All these data suggest that PE and its synthetic-derived compound, PE/2, significantly decrease IL6 and improve hepatic insulin signaling. As IL6 impairs insulin action, it could be hypothesized that PE and PE/2, by inhibiting IL6, may improve the hepatic insulin pathway.


Assuntos
Carcinoma Hepatocelular , Insulina , Interleucina-6 , Neoplasias Hepáticas , Transdução de Sinais , Humanos , Interleucina-6/metabolismo , Insulina/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Células Hep G2 , Animais , Receptor de Insulina/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resistência à Insulina , Antígenos CD
2.
Int J Mol Sci ; 24(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37569266

RESUMO

PREP1 is a homeodomain transcription factor that impairs metabolism and is involved in age-related aortic thickening. In this study, we evaluated the role of PREP1 on endothelial function. Mouse Aortic Endothelial Cells (MAECs) transiently transfected with a Prep1 cDNA showed a 1.5- and 1.6-fold increase in eNOSThr495 and PKCα phosphorylation, respectively. Proinflammatory cytokines Tnf-α and Il-6 increased by 3.5 and 2.3-fold, respectively, in the presence of Prep1, while the antioxidant genes Sod2 and Atf4 were significantly reduced. Bisindolylmaleimide reverted the effects induced by PREP1, suggesting PKCα to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOSThr495, PKCα phosphorylation, and proinflammatory cytokines and increased Sod2 and Atf4 mRNA levels. The experiments performed on the aorta of 18-month-old Prep1 hypomorphic heterozygous mice (Prep1i/+) expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOSThr495 phosphorylation and a 45% reduction in Tnf-α levels, with no change in Il-6, compared to same-age WT mice. However, a significant decrease in Sod2 and Atf4 was observed in Prep1i/+ old mice, indicating the lack of age-induced antioxidant response. These results suggest that Prep1 deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.


Assuntos
Células Endoteliais , Proteínas de Homeodomínio , Camundongos , Animais , Resveratrol/farmacologia , Proteínas de Homeodomínio/genética , Células Endoteliais/metabolismo , Proteína Quinase C-alfa , Fator de Necrose Tumoral alfa/genética , Antioxidantes/farmacologia , Interleucina-6/genética , Citocinas , Aorta/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-31035698

RESUMO

Background: Immunization of healthcare workers (HCWs) and medical students for the hepatitis B virus (HBV) is a crucial part of the hospital infection control programs. The aim of our study was to evaluate the persistence of anti-HBV specific antibodies in HCWs vaccinated during infancy or adolescence. Methods: Medical records of 734 consecutive subjects born after 1980 (481 females, 65.5% and 253 males, 34.5%) who underwent serological testing for anti-hepatitis B surface antibodies (anti-HBs) were evaluated. Results: A non-protective titer (<10 mUI) was found in 88/734 (12.0%) subjects; 84 (47.8%) of them received a booster dose of anti-hepatitis B vaccine and the anti-HBs titer of 58 subjects was measured 1 month after administration. A protective titer (anti-HBs >10 mIU/mL) was observed in almost 90% of subjects receiving the booster dose. Conclusions: A substantial percentage of HCWs had a non-protective anti-HBs titer at the time of the first employment, especially those vaccinated at birth age. However, the response to the booster dose showed that in these subjects, an anti-HBs titer <10 mIU/mL was due to the physiological decline of antibodies over the years. Therefore, primary immunization in childhood is highly effective and provides lasting immunity against HBV infection.


Assuntos
Pessoal de Saúde , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Hepatite B/prevenção & controle , Estudantes de Medicina , Adolescente , Adulto , Criança , Feminino , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B/administração & dosagem , Vírus da Hepatite B/imunologia , Humanos , Imunização Secundária , Lactente , Itália , Masculino , Testes Sorológicos , Vacinação , Adulto Jovem
4.
PeerJ ; 6: e4154, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29362689

RESUMO

INTRODUCTION: Dental practitioners are exposed to different occupational hazards during the course of their professional activity, such as physical, chemical, biological, ergonomic factors. The ergonomic hazards, caused by strained posture and prolonged repetitive movements, can induce musculoskeletal disorders. It occurs in 54-93% of dental professionals and involve the spine, shoulder and hand-wrist tract. Through a systematic review of international literature, we analyzed specific ergonomic risk factors and preventive measures of musculoskeletal disorders in professional dental activity. METHODS: This systematic review is coherent with the PRISMA statement. The scientific research on the major online databases was based on the following keywords: dentist, prevention, ergonomic, dentistry, musculoskeletal, neck pain, posture, ergonomics, work and occupational. The studies included in this review focus on disorders related to ergonomics and on the most effective preventive measures to be adopted. No restrictions were applied for language or publication type. We excluded reports not related to ergonomic prevention in dentistry, reports of minor academic significance, editorial articles, individual contributions, and studies published in scientific conferences. RESULTS: Online research indicated 4188 references: PubMed (2919), Scopus (1257) e Cochrane Library (12). We excluded 3012 of these, because they were unrelated to ergonomics theme and 187 due to duplication. From the remaining 989 studies, 960 papers did not meet inclusion criteria and they were excluded. Therefore, we analyzed 29 articles, including 16 narrative reviews and 13 original article. The main risk factor for the development of musculoskeletal disorders found in our analysis is static posture adopted during work, highlighted in 87.5% of reviews and 84% of original articles. With regard to preventive measures, 75% of the reviews highlighted the importance of stretching after each working session and at the end of the working day, while 61.5% of the original articles emphasized the use of modern and ergonomic instruments. DISCUSSION: This review showed that static postures are strongly responsible in the etiology of musculoskeletal disorders. The awkward postures more frequently identified among dental professionals are: extreme forward-head and neck flexion; trunk inclination and rotation towards one side; lifting one or both shoulders; increased curvature of the thoracic vertebral column; incorrect positioning of the lower limbs with thigh-leg angle of less than 90°. It is really important to use of a modern workstation with appropriate ergonomic supports. Among the preventive ergonomic measures, literature has widely recognized the role of physical activity and of a neutral and balanced posture. The present review has some limits: a large part of the selected studies did not have a high methodological quality score and an inadequate statistical analysis.

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