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1.
TRAP1 Is Expressed in Human Retinal Pigment Epithelial Cells and Is Required to Maintain their Energetic Status.
Ramos Rego, I, Silvério, D, Eufrásio, MI, Pinhanços, SS, Lopes da Costa, B, Teixeira, J, Fernandes, H, Kong, Y, Li, Y, Tsang, SH, et al
Antioxidants (Basel, Switzerland). 2023;(2)
Abstract
Age-related macular degeneration (AMD) is the leading cause of severe vision loss and blindness in elderly people worldwide. The damage to the retinal pigment epithelium (RPE) triggered by oxidative stress plays a central role in the onset and progression of AMD and results from the excessive accumulation of reactive oxygen species (ROS) produced mainly by mitochondria. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone that contributes to the maintenance of mitochondrial integrity by decreasing the production and accumulation of ROS. The present study aimed to evaluate the presence and the role of TRAP1 in the RPE. Here, we report that TRAP1 is expressed in human adult retinal pigment epithelial cells and is located mainly in the mitochondria. Exposure of RPE cells to hydrogen peroxide decreases the levels of TRAP1. Furthermore, TRAP1 silencing increases intracellular ROS production and decreases mitochondrial respiratory capacity without affecting cell proliferation. Together, these findings offer novel insights into TRAP1 functions in RPE cells, opening possibilities to develop new treatment options for AMD.
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2.
Association between dietary patterns and biomarkers in connection with diabetes mellitus in adolescents: A systematic review.
Barboza, BP, Tureck, C, Bricarello, LP, de Almeida Alves, M, Retondario, A, de Moura Souza, A, Fernandes, R, de Assis Guedes de Vasconcelos, F
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2023;(4):685-697
Abstract
AIMS: To perform a systematic review to investigate the association between adolescents' a posteriori dietary patterns with diabetes-related biomarkers (fasting blood glucose, fasting insulinemia, glycated hemoglobin and homeostatic model assessment insulin resistance index (HOMA-IR)). DATA SYNTHESIS Review registered with PROSPERO under number CRD42020185369. Studies with adolescents aged 10-19 years that identified dietary patterns by a posteriori methods were included. The databases used included: PubMed, SCOPUS, Web of Science, Food Science and Technology Abstracts, CINAHL, SPORTDiscus, Lilacs/BVS, The Cochrane Central Register of Controlled Trials, ProQuest Dissertations&Theses Global and Capes Theses Bank and Brazilian Digital Library of Theses and Dissertations. Risk of bias was assessed via the Agency for Healthcare Research and Quality tool. Eight cross-sectional studies that evaluated 6438 adolescents (55.5% females) were included. For fasting blood glucose, the results were inconsistent and some studies found no association for the dietary patterns called traditional (57%), Western (42%) and healthy (28%). For the fasting insulinemia and HOMA-IR outcomes, the Western dietary pattern showed a positive association or higher means in 60% and 50% of the studies, respectively. No studies that evaluated glycated hemoglobin were found. CONCLUSION Fasting insulinemia and HOMA-IR outcomes were positively associated with the Western dietary patterns. The studies reviewed did not present consistent evidence of an association with western, healthy and traditional dietary patterns with fasting blood glucose, as the results were conflicting or did not show statistical significance.
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3.
Immune Fingerprint in Diabetes: Ocular Surface and Retinal Inflammation.
Amorim, M, Martins, B, Fernandes, R
International journal of molecular sciences. 2023;(12)
Abstract
Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye's immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system's main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.
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4.
The Influence of Adipocyte Secretome on Selected Metabolic Fingerprints of Breast Cancer Cell Lines Representing the Four Major Breast Cancer Subtypes.
Luís, C, Guerra-Carvalho, B, Braga, PC, Guedes, C, Patrício, E, Alves, MG, Fernandes, R, Soares, R
Cells. 2023;(17)
Abstract
Molecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.
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5.
Advances in Vitreoretinal Surgery.
Ribeiro, L, Oliveira, J, Kuroiwa, D, Kolko, M, Fernandes, R, Junior, O, Moraes, N, Vasconcelos, H, Oliveira, T, Maia, M
Journal of clinical medicine. 2022;(21)
Abstract
Advances in vitreoretinal surgery provide greater safety, efficacy, and reliability in the management of the several vitreoretinal diseases that benefit from surgical treatment. The advances are divided into the following topics: scleral buckling using chandelier illumination guided by non-contact visualization systems; sclerotomy/valved trocar diameters; posterior vitrectomy systems and ergonomic vitrectomy probes; chromovitrectomy; vitreous substitutes; intraoperative visualization systems including three-dimensional technology, systems for intraoperative optical coherence tomography, new instrumentation in vitreoretinal surgery, anti-VEGF injection before vitrectomy and in eyes with proliferative diabetic retinopathy, and new surgical techniques; endoscopic surgery; the management of subretinal hemorrhages; gene therapy; alternative techniques for refractory macular hole; perspectives for stem cell therapy and the prevention of proliferative vitreoretinopathy; and, finally, the Port Delivery System. The main objective of this review is to update the reader on the latest changes in vitreoretinal surgery and to provide an understanding of how each has impacted the improvement of surgical outcomes.
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6.
Scientific evidence of the association between oral intake of OMEGA-3 and OMEGA-6 fatty acids and the metabolic syndrome in adolescents: A systematic review.
Tureck, C, Barboza, BP, Bricarello, LP, Retondario, A, Alves, MA, de Moura Souza, A, Fernandes, R, de Vasconcelos, FAG
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2022;(12):2689-2704
Abstract
AIMS: To conduct a systematic review of the literature on the scientific evidence of the oral intake of omega-3 and omega-6 FAs and metabolic syndrome (MS) in adolescents. DATA SYNTHESIS The study was registered in PROSPERO (number 42020185370). Studies were carried out with adolescents aged 10-19 years, who presented as intervention/exposure the oral intake of omega-3 and/or omega-6 fatty acids (FAs), in the databases PubMed, Scopus, Web of Science, LILACS, CENTRAL, and PQDT Global e BDTD. The tools used to assess the risk of bias were RoB 2.0, Agency for Healthcare Research and Quality (AHRQ), and Newcastle-Ottawa Scale. Fifteen papers retrieved published from 2010 to 2019 were included (n = 3534); nine were randomized studies and controlled clinical trials, four were cross-sectional studies, one was a retrospective cohort study, and one case-control study. No studies have evaluated the effect or association of omega-3 and/or of omega-6 FAs with actual MS, only with its components. The randomized clinical trials identified the effects of omega-3 FA on the decrease in blood pressure (n = 1 out of six), glycemia (n = 2 out of seven), and triglycerides (n = 5 out of eight), and the increase in HDL-c (n = 2 out of eight) considering the comparison between the group that received omega-3 FA and the control group. CONCLUSIONS Scientific evidence is controversial on the association between oral intake of omega-3 FAs and MS in adolescents, due to the heterogeneity between studies and the divergence of results for the same MS component.
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7.
The Impact of Metabolic Syndrome and Type 2 Diabetes Mellitus on Prostate Cancer.
Sousa, AP, Costa, R, Alves, MG, Soares, R, Baylina, P, Fernandes, R
Frontiers in cell and developmental biology. 2022;:843458
Abstract
Prostate cancer (PCa) remains the second most common type of cancer in men worldwide in 2020. Despite its low death rate, the need for new therapies or prevention strategies is critical. The prostate carcinogenesis process is complex and multifactorial. PCa is caused by a variety of mutations and carcinogenic events that constitutes the disease's multifactorial focus, capable of not only remodeling cellular activity, but also modeling metabolic pathways to allow adaptation to the nutritional requirements of the tumor, creating a propitious microenvironment. Some risk factors have been linked to the development of PCa, including Metabolic Syndrome (MetS) and Type 2 Diabetes Mellitus (T2DM). MetS is intrinsically related to PCa carcinogenic development, increasing its aggressiveness. On the other hand, T2DM has the opposite impact, although in other carcinomas its effect is similar to the MetS. Although these two metabolic disorders may share some developmental processes, such as obesity, insulin resistance, and dyslipidemia, their influence on PCa prognosis appears to have an inverse effect, which makes this a paradox. Understanding the phenomena behind this paradoxical behavior may lead to new concepts into the comprehension of the diseases, as well as to evaluate new therapeutical targets. Thus, this review aimed to evaluate the impact of metabolic disorders in PCa's aggressiveness state and metabolism.
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8.
Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.
Marques-Gomes, J, Salt, MJ, Pereira-Neto, R, Barteldes, FS, Gouveia-Barros, V, Carvalho, A, d'Arminio-Monforte, A, De-la-Torre-Rosas, A, Harris, A, Esteves, C, et al
HIV medicine. 2022;(6):639-649
Abstract
OBJECTIVES HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.
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9.
Underestimated Prediabetic Biomarkers: Are We Blind to Their Strategy?
Luís, C, Soares, R, Baylina, P, Fernandes, R
Frontiers in endocrinology. 2022;:805837
Abstract
Type 2 Diabetes (T2D) is currently one of the fastest growing health challenging, a non-communicable disease result of the XXI century lifestyle. Given its growing incidence and prevalence, it became increasingly imperative to develop new technologies and implement new biomarkers for early diagnosis in order to promote lifestyle changes and thus cause a setback of the disease. Promising biomarkers have been identified as predictive of T2D development; however, none of them have yet been implemented in clinical practice routine. Moreover, many prediabetic biomarkers can also represent potential therapeutical targets in disease management. Previous studies have identified the most popular biomarkers, which are being thoroughly investigated. However, there are some biomarkers with promising preliminary results with limited associated studies; hence there is still much to be understood about its mechanisms and associations in T2D pathophysiology. This work identifies and discusses the promising results of Galectin-3, Ophthalmate and Fetuin-A.
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10.
Lab-on-a-chip technologies for minimally invasive molecular sensing of diabetic retinopathy.
Vieira, M, Fernandes, R, Ambrósio, AF, Cardoso, V, Carvalho, M, Weng Kung, P, Neves, MAD, Mendes Pinto, I
Lab on a chip. 2022;(10):1876-1889
Abstract
Diabetic retinopathy (DR) is the most common diabetic eye disease and the worldwide leading cause of vision loss in working-age adults. It progresses from mild to severe non-proliferative or proliferative DR based on several pathological features including the magnitude of blood-retinal barrier breakdown and neovascularization. Available pharmacological and retinal laser photocoagulation interventions are mostly applied in the advanced stages of DR and are inefficient in halting disease progression in a significantly high percentage of patients. Yet, recent evidence has shown that some therapies could potentially limit DR progression if applied at early stages, highlighting the importance of early disease diagnostics. In the past few decades, different imaging modalities have proved their utility for examining retinal and optic nerve changes in patients with retinal diseases. However, imaging based-methodologies solely rely on morphological examination of the retinal vascularization and are not suitable for recurrent and personalized patient evaluation. This raises the need for new technologies to enable accurate and early diagnosis of DR. In this review, we critically discuss the potential clinical benefit of minimally-invasive molecular biomarker identification and profiling of diabetic patients who are at risk of developing DR. We provide a comparative overview of conventional and recently developed lab-on-a-chip technologies for quantitative assessment of potential DR molecular biomarkers and discuss their advantages, current limitations and challenges for future practical implementation and continuous patient monitoring at the point-of-care.