Maria João Martins

Bio: Maria João Martins is an academic researcher from University of Porto. The author has contributed to research in topics: Alkaline phosphatase & Oxidative stress. The author has an hindex of 17, co-authored 100 publications receiving 1022 citations.

11β-Hydroxysteroid dehydrogenase type 1: relevance of its modulation in the pathophysiology of obesity, the metabolic syndrome and type 2 diabetes mellitus.

Abstract: Recent evidence strongly argues for a pathogenic role of glucocorticoids and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in obesity and the metabolic syndrome, a cluster of risk factors for atherosclerotic cardiovascular disease and type 2 diabetes mellitus (T2DM) that includes insulin resistance (IR), dyslipidaemia, hypertension and visceral obesity. This has been partially prompted not only by the striking clinical resemblances between the metabolic syndrome and Cushing's syndrome (a state characterized by hypercortisolism that associates with metabolic syndrome components) but also from monogenic rodent models for the metabolic syndrome (e.g. the leptin-deficient ob/ob mouse or the leptin-resistant Zucker rat) that display overall increased secretion of glucocorticoids. However, systemic circulating glucocorticoids are not elevated in obese patients and/or patients with metabolic syndrome. The study of the role of 11β-HSD system shed light on this conundrum, showing that local glucocorticoids are finely regulated in a tissue-specific manner at the pre-receptor level. The system comprises two microsomal enzymes that either activate cortisone to cortisol (11β-HSD1) or inactivate cortisol to cortisone (11β-HSD2). Transgenic rodent models, knockout (KO) for HSD11B1 or with HSD11B1 or HSD11B2 overexpression, specifically targeted to the liver or adipose tissue, have been developed and helped unravel the currently undisputable role of the enzymes in metabolic syndrome pathophysiology, in each of its isolated components and in their prevention. In the transgenic HSD11B1 overexpressing models, different features of the metabolic syndrome and obesity are replicated. HSD11B1 gene deficiency or HSD11B2 gene overexpression associates with improvements in the metabolic profile. In face of these demonstrations, research efforts are now being turned both into the inhibition of 11β-HSD1 as a possible pharmacological target and into the role of dietary habits on the establishment or the prevention of the metabolic syndrome, obesity and T2DM through 11β-HSD1 modulation. We intend to review and discuss 11β-HSD1 and obesity, the metabolic syndrome and T2DM and to highlight the potential of its inhibition for therapeutic or prophylactic approaches in those metabolic diseases.

Nitric oxide‐mediated regulation of oxidative stress in plants under metal stress: a review on molecular and biochemical aspects

Abstract: Given their sessile nature, plants continuously face unfavorable conditions throughout their life cycle, including water scarcity, extreme temperatures and soil pollution. Among all, metal(loid)s are one of the main classes of contaminants worldwide, posing a serious threat to plant growth and development. When in excess, metals which include both essential and non-essential elements, quickly become phytotoxic, inducing the occurrence of oxidative stress. In this way, in order to ensure food production and safety, attempts to enhance plant tolerance to metal(loid)s are urgently needed. Nitric oxide (NO) is recognized as a signaling molecule, highly involved in multiple physiological events, like the response of plants to abiotic stress. Thus, substantial efforts have been made to assess NO potential in alleviating metal-induced oxidative stress in plants. In this review, an updated overview of NO-mediated protection against metal toxicity is provided. After carefully reviewing NO biosynthetic pathways, focus was given to the interaction between NO and the redox homeostasis followed by photosynthetic performance of plants under metal excess.

Oxidative stress in phenylketonuria: future directions.

Abstract: Phenylketonuria represents the most prevalent inborn error of amino acid metabolism. In early diagnosed patients adequate and continued dietary treatment results in a good neurologic outcome. Natural protein and phenylalanine-restricted diet, even if rich in fruits and vegetables, represents a serious risk for nutritional deficiencies, albeit universally accepted. In the last few years, a growing number of reports have been describing oxidative stress as a concern in phenylketonuric patients. The diet itself includes good sources of dietary antioxidants (phytochemicals, some vitamins and minerals) but also a risk factor for some deficiencies (selenium, zinc, ubiquinone-10 and L-carnitine). Additionally, the extreme stringency of the diet may impose a reduced synthesis of endogenous antioxidants (like ubiquinone-10 and glutathione). Furthermore, increased phenylalanine levels, and its metabolites, may enhance the endogenous synthesis of reactive species and free radicals and/or interfere with the endogenous synthesis of enzymatic antioxidants (like glutathione peroxidase). Therefore, oxidative stress will probably increase, mainly in late diagnosed patients or in those with bad metabolic control. Considering the known association between oxidative stress, obesity and cardiovascular disease, it seems advisable to look further to the impact of oxidative stress on body macromolecules and structures (like lipoprotein oxidation), especially in phenylketonuric patients with late diagnosis or bad metabolic control, in order to prevent future increased risks. Recommendations for PKU patient's clinical follow-up improvement and educational goals are included.

Metabolically Healthy Obesity-Heterogeneity in Definitions and Unconventional Factors.

Abstract: The concept of heterogeneity among obese individuals in their risk for developing metabolic dysfunction and associated complications has been recognized for decades. At the origin of the heterogeneity idea is the acknowledgement that individuals with central obesity are more prone to developing type 2 diabetes and cardiovascular disease than those with peripheral obesity. There have been attempts to categorize subjects according to their metabolic health and degree of obesity giving rise to different obese and non-obese phenotypes that include metabolically unhealthy normal-weight (MUHNW), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Individuals belonging to the MHO phenotype are obese according to their body mass index although exhibiting fewer or none metabolic anomalies such as type 2 diabetes, dyslipidemia, hypertension, and/or unfavorable inflammatory and fribinolytic profiles. However, some authors claim that MHO is only transient in nature. Additionally, the phenotype categorization is controversial as it lacks standardized definitions possibly blurring the distinction between obesity phenotypes and confounding the associations with health outcomes. To add to the discussion, the factors underlying the origin or protection from metabolic deterioration and cardiometabolic risk for these subclasses are being intensely investigated and several hypotheses have been put forward. In the present review, we compare the different definitions of obesity phenotypes and present several possible factors underlying them (adipose tissue distribution and cellularity, contaminant accumulation on the adipose tissue, dysbiosis and metabolic endotoxemia imposing on to the endocannabinoid tone and inflammasome, and nutrient intake and dietary patterns) having inflammatory activation at the center.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Induction of autophagy by spermidine promotes longevity

Abstract: Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells In addition, spermidine administration potently inhibited oxidative stress in ageing mice In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity

The role of alkaline phosphatase in mineralization

Abstract: Purpose of reviewAlkaline phosphatase is an important component in hard tissue formation, highly expressed in mineralized tissue cells. It is appropriate to review the current status of this important enzyme.Recent findingsThe mechanism with which this enzyme carries out its function is not complete

Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases

Abstract: The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein homeostasis, as well as the regulation of inflammation. Thus, NRF2 activation provides cytoprotection against numerous pathologies including chronic diseases of the lung and liver; autoimmune, neurodegenerative and metabolic disorders; and cancer initiation. One NRF2 activator has received clinical approval and several electrophilic modifiers of the cysteine-based sensor KEAP1 and inhibitors of its interaction with NRF2 are now in clinical development. However, challenges regarding target specificity, pharmacodynamic properties, efficacy and safety remain.

Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's diseases

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there are few therapeutics that affect the underlying disease mechanism. Recent epidemiological studies, however, suggest that lifestyle changes may slow the onset/progression of AD. Here we have used TgCRND8 mice to examine directly the interaction between exercise and the AD cascade. Five months of voluntary exercise resulted in a decrease in extracellular amyloid-β (Aβ) plaques in the frontal cortex (38%; p = 0.018), the cortex at the level of the hippocampus (53%; p = 0.0003), and the hippocampus (40%; p = 0.06). This was associated with decreased cortical Aβ1-40 (35%; p = 0.005) and Aβ1-42 (22%; p = 0.04) (ELISA). The mechanism appears to be mediated by a change in the processing of the amyloid precursor protein (APP) after short-term exercise, because 1 month of activity decreased the proteolytic fragments of APP [for α-C-terminal fragment (α-CTF), 54% and p = 0.04; for β-CTF, 35% and p = 0.03]. This effect was independent of mRNA/protein changes in neprilysin and insulin-degrading enzyme and, instead, may involve neuronal metabolism changes that are known to affect APP processing and to be regulated by exercise. Long-term exercise also enhanced the rate of learning of TgCRND8 animals in the Morris water maze, with significant (p < 0.02) reductions in escape latencies over the first 3 (of 6) trial days. In support of existing epidemiological studies, this investigation demonstrates that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model.