-
1.
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.
-
2.
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.
-
3.
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.
-
4.
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.
-
5.
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.
-
6.
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.
-
7.
The controversial role of glucose in the diabetic kidney.
Fernandes, R
Porto biomedical journal. 2021;(1):e113
-
-
Free full text
-
Abstract
The kidneys play an important role in maintaining glucose homeostasis being the main mechanisms, the gluconeogenesis, renal glucose consumption and glucose reabsorption in the proximal tubules. In this review, we present the main research into the role of glycogen-the stored form of glucose, and how it accumulates in the cells, providing new information on the link between diabetes and diabetic kidney disease. In the last 10 years, research under the scope of renal insulin handling, glucose transport in the proximal tubules, renal gluconeogenesis and renal insulin resistance, made possible to relate the roles of glucose and glycogen in the kidney with other several organs, like the liver. On the one hand, insulin positively regulates kidney uptake and degradation, and there is probably a specific action and resistance to insulin at the renal site. Moreover, insulin regulates the bioavailability of the sodium-glucose co-transporters-SGLT2 inhibitor, and inhibits renal gluconeogenesis. Only the liver and kidneys can supply glucose to the circulation through the process of gluconeogenesis, which involves the synthesis of glucose again from non-glycemic substrates; and the decomposition of stored glycogen. In the mind of nephrologists, diabetologists and scientists, glucose metabolism in the kidney is the focus, with the relevant success of inhibitors in reducing kidney and cardiovascular diseases in individuals with diabetes. However, these new data led to the intriguing paradigm that many of the beneficial effects on the renal and cardiovascular system appear to be independent of the systemic glucose-lowering actions of these agents. The goal of this work puts in context a highly relevant research area for renal glucose metabolism, of glycogen accumulation and metabolism in the diabetic kidney.
-
8.
A state of the art review on the novel mediator asprosin in the metabolic syndrome.
Luís, C, Fernandes, R, Soares, R, von Hafe, P
Porto biomedical journal. 2020;(6):e108
-
-
Free full text
-
Abstract
Metabolic syndrome is a complex and heterogeneous pathology characterized by a cluster of biochemical, clinical, and metabolic factors that came together in raising the risk of cardiovascular diseases, type 2 diabetes mellitus, and all-cause mortality. Some of these features are well defined in this syndrome like: obesity, inflammation, hypertension, insulin resistance, atherosclerotic dyslipidemias, endothelial dysfunction, and inflammation. This circuit is intermediated by a complex network of hormones, cytokines, transcription factors, and adipokines, among others. Some like leptin, adiponectin, Plasminogen activator inhibitor-1, interleukin-6, Tumor necrosis factor, and their influence on the metabolic syndrome are well described in the literature and new players are described continuously. One novel player was described in 2016 by Romere et al as a fasting-induced glycogenic protein hormone named asprosin. In order to perform a state-of-the-art, nonsystematic review of asprosin, a study of the available literature was carried out in the main database (Pubmed) and the results were studied and correlated to better understand the mechanism of action of this hormone. Asprosin is not only associated with the metabolic syndrome features like glucose and lipid metabolism, insulin resistance, obesity and inflammation but also in other pathologies metabolic syndrome related like diabetic retinopathy, polycystic ovary syndrome and anorexia nervosa. A limited number of pathways were already unveiled although much more research is needed to better understand the therapeutical potential of asprosin in the metabolic syndrome.
-
9.
Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy.
Martins, B, Amorim, M, Reis, F, Ambrósio, AF, Fernandes, R
Antioxidants (Basel, Switzerland). 2020;(8)
Abstract
Diabetic retinopathy (DR) is a complex, progressive, and heterogenous retinal degenerative disease associated with diabetes duration. It is characterized by glial, neural, and microvascular dysfunction, being the blood-retinal barrier (BRB) breakdown a hallmark of the early stages. In advanced stages, there is formation of new blood vessels, which are fragile and prone to leaking. This disease, if left untreated, may result in severe vision loss and eventually legal blindness. Although there are some available treatment options for DR, most of them are targeted to the advanced stages of the disease, have some adverse effects, and many patients do not adequately respond to the treatment, which demands further research. Oxidative stress and low-grade inflammation are closely associated processes that play a critical role in the development of DR. Retinal cells communicate with each other or with another one, using cell junctions, adhesion contacts, and secreted soluble factors that can act in neighboring or long-distance cells. Another mechanism of cell communication is via secreted extracellular vesicles (EVs), through exchange of material. Here, we review the current knowledge on deregulation of cell-to-cell communication through EVs, discussing the changes in miRNA expression profiling in body fluids and their role in the development of DR. Thereafter, current and promising therapeutic agents for preventing the progression of DR will be discussed.
-
10.
Sweet Stress: Coping With Vascular Dysfunction in Diabetic Retinopathy.
Santiago, AR, Boia, R, Aires, ID, Ambrósio, AF, Fernandes, R
Frontiers in physiology. 2018;:820
Abstract
Oxidative stress plays key roles in the pathogenesis of retinal diseases, such as diabetic retinopathy. Reactive oxygen species (ROS) are increased in the retina in diabetes and the antioxidant defense system is also compromised. Increased ROS stimulate the release of pro-inflammatory cytokines, promoting a chronic low-grade inflammation involving various signaling pathways. An excessive production of ROS can lead to retinal endothelial cell injury, increased microvascular permeability, and recruitment of inflammatory cells at the site of inflammation. Recent studies have started unraveling the complex crosstalk between retinal endothelial cells and neuroglial cells or leukocytes, via both cell-to-cell contact and secretion of cytokines. This crosstalk is essential for the maintenance of the integrity of retinal vascular structure. Under diabetic conditions, an aberrant interaction between endothelial cells and other resident cells of the retina or invading inflammatory cells takes place in the retina. Impairment in the secretion and flow of molecular signals between different cells can compromise the retinal vascular architecture and trigger angiogenesis. In this review, the synergistic contributions of redox-inflammatory processes for endothelial dysfunction in diabetic retinopathy will be examined, with particular attention paid to endothelial cell communication with other retinal cells.