The Role of Specialized Pro-Resolving Lipid Mediators in Inflammation-Induced Carcinogenesis.

Cancer is a process involving cell mutation, increased proliferation, invasion, and metastasis. Over the years, this condition has represented one of the most concerning health problems worldwide due to its significant morbidity and mortality. At present, the incidence of cancer continues to grow exponentially. Thus, it is imperative to open new avenues in cancer research to understand the molecular changes driving DNA transformation, cell-to-cell interaction derangements, and immune system surveillance decay. In this regard, evidence supports the relationship between chronic inflammation and cancer. In light of this, a group of bioactive lipids derived from polyunsaturated fatty acids (PUFAs) may have a position as novel anti-inflammatory molecules known as the specialized pro-resolving mediators (SPMs), a group of pro-resolutive inflammation agents that could improve the anti-tumor immunity. These molecules have the potential role of chemopreventive and therapeutic agents for various cancer types, and their effects have been documented in the scientific literature. Thus, this review objective centers around understanding the effect of SPMs on carcinogenesis and their potential therapeutic effect.

Durvillaea antarctica: A Seaweed for Enhancing Immune and Cardiometabolic Health and Gut Microbiota Composition Modulation.

Durvillaea antarctica is the seaweed that is the most consumed by the Chilean population. It is recognized worldwide for its high nutritional value in protein, vitamins, minerals, and dietary fiber. This is a narrative review in which an extensive search of the literature was performed to establish the immunomodulator, cardiometabolic, and gut microbiota composition modulation effect of Durvillaea antarctica. Several studies have shown the potential of Durvillaea antarctica to function as prebiotics and to positively modulate the gut microbiota, which is related to anti-obesity, anti-inflammatory, anticancer, lipid-lowering, and hypoglycemic effects. The quantity of Bacteroides was negatively correlated with that of inflammatory monocytes and positively correlated with the levels of several gut metabolites. Seaweed-derived polysaccharides modulate the quantity and diversity of beneficial intestinal microbiota, decreasing phenol and p-cresol, which are related to intestinal diseases and the loss of intestinal function. Additionally, a beneficial metabolic effect related to this seaweed was observed, mainly promoting the decrease in the glycemic levels, lower cholesterol levels and cardiovascular risk. Consuming Durvillaea antarctica has a positive impact on the immune system, and its bioactive compounds provide beneficial effects on glycemic control and other metabolic parameters.

New Evidence on BPA's Role in Adipose Tissue Development of Proinflammatory Processes and Its Relationship with Obesity.

Bisphenol A (BPA) is a xenobiotic with endocrine disruptor properties which interacts with various receptors, eliciting a cellular response. In the plastic industry, BPA is widely used in the production of polycarbonate and epoxy-phenolic resins to provide elastic properties. It can be found in the lining of canned foods, certain plastic containers, thermal printing papers, composite dental fillings, and medical devices, among other things. Therefore, it is a compound that, directly or indirectly, is in daily contact with the human organism. BPA is postulated to be a factor responsible for the global epidemic of obesity and non-communicable chronic diseases, belonging to the obesogenic and diabetogenic group of compounds. Hence, this endocrine disruptor may be responsible for the development of metabolic disorders, promoting in fat cells an increase in proinflammatory pathways and upregulating the expression and release of certain cytokines, such as IL6, IL1ß, and TNFα. These, in turn, at a systemic and local level, are associated with a chronic low-grade inflammatory state, which allows the perpetuation of the typical physiological complications of obesity.

Specialized Proresolving Lipid Mediators: A Potential Therapeutic Target for Atherosclerosis.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon's secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans' islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (ß) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to ß cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.

Lipid Accumulation Product Is More Related to Insulin Resistance than the Visceral Adiposity Index in the Maracaibo City Population, Venezuela.

BACKGROUND: Visceral adiposity is related to insulin resistance (IR), a metabolic state considered as a risk factor for other cardiometabolic diseases. In that matter, mathematical indexes such as the visceral adiposity index (VAI) and the lipid accumulation product (LAP) could indirectly assess IR based on visceral adiposity. OBJECTIVE: To evaluate the association and diagnostic accuracy of VAI and LAP to diagnose IR in the adult population of Maracaibo city. METHODS: This is a cross-sectional descriptive study with multistage sampling. Receiver operating characteristic (ROC) curves were built to determine VAI and LAP cutoff points to predict IR. A set of logistic regression models was constructed according to sociodemographic, psychobiologic, and metabolic variables. RESULTS: 1818 subjects were evaluated (51.4% women). The area under the curve (AUC) values for LAP and VAI were 0.689 (0.665-0.714) and 0.645 (0.619-0.670), respectively. Both indexes showed a higher IR risk in the upper tertile in bivariate analysis. However, in the logistic regression analysis for the IR risk, only the 2nd (OR: 1.91; 95% CI: 1.37-2.65; p < 0.01) and 3rd (OR: 5.40; 95% CI: 3.48-8.39; p < 0.01) LAP tertiles showed a significant increase. This behaviour was also observed after adjusting for hs-C-reactive protein (hs-CPR). CONCLUSION: Although both indexes show a low predictive capacity in individuals with IR in the Maracaibo city population, the LAP index was more strongly associated with IR.

Metabolic Syndrome: Is It Time to Add the Central Nervous System?

Metabolic syndrome (MS) is a set of cardio-metabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias. The syndrome affects 25% of adults worldwide. The definition of MS has evolved over the last 80 years, with various classification systems and criteria, whose limitations and benefits are currently the subject of some controversy. Likewise, hypotheses regarding the etiology of MS add more confusion from clinical and epidemiological points of view. The leading suggestion for the pathophysiology of MS is insulin resistance (IR). IR can affect multiple tissues and organs, from the classic "triumvirate" (myocyte, adipocyte, and hepatocyte) to possible effects on organs considered more recently, such as the central nervous system (CNS). Mild cognitive impairment (MCI) and Alzheimer's disease (AD) may be clinical expressions of CNS involvement. However, the association between MCI and MS is not understood. The bidirectional relationship that seems to exist between these factors raises the questions of which phenomenon occurs first and whether MCI can be a precursor of MS. This review explores shared pathophysiological mechanisms between MCI and MS and establishes a hypothesis of a possible MCI role in the development of IR and the appearance of MS.

Advanced Glycation End Products: New Clinical and Molecular Perspectives.

Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.

Microbiota and Diabetes Mellitus: Role of Lipid Mediators.

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.

Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes?

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Stevia rebaudiana Bertoni and Its Effects in Human Disease: Emphasizing Its Role in Inflammation, Atherosclerosis and Metabolic Syndrome.

PURPOSE OF REVIEW: Stevia rebaudiana Bertoni is a perennial shrub with zero calorie content that has been increasing in popularity for its potential use as an adjuvant in the treatment of obesity. The level of evidence supporting general benefits to human health is insufficient. We conducted a review of the literature summarizing the current knowledge and role in human disease. RECENT FINDINGS: Despite stevia's minimal systemic absorption, studies have been promising regarding its potential benefits against inflammation, carcinogenesis, atherosclerosis glucose control, and hypertension. On the other hand, the growing popularity of artificial sweeteners does not correlate with improved trends in obesity. An increased intake of artificial non-caloric sweeteners may not be associated with decreased intake of traditional sugar-sweetened beverages and foods. The effects of Stevia on weight change have been linked to bacteria in the intestinal microbiome, mainly by affecting Clostridium and Bacteroides sp. POPULATIONS: A growing body of evidence indicates that Stevia rebaudiana Bertoni is protective against malignant conversion by inhibition of DNA replication in human cancer cell growth in vitro. Consumption of Stevia has demonstrated to be generally safe in most reports. Further clinical studies are warranted to determine if regular consumption brings sustained benefits for human health.

Rol de la estevia y L-carnitina sobre el impacto glicémico de un suplemento nutricional en adultos / Role of the stevia and L-carnitine of a nutritional supplement on glycemic impact in adults

Actualmente la industria alimentaria ha generado interés en edulcorantes no nutritivos, por ejemplo la estevia y en componentes especiales como la L-carnitina, utilizados en formulaciones de suplementos nutricionales para el control glicémico específicos para diabéticos. El presente estudio evaluó el efecto de la estevia y la L-carnitina sobre el índice glicémico (IG) y la carga glicémica (CG) de un suplemento nutricional en 19 sujetos sanos (9 hombres y 10 mujeres), quienes completaron aleatoriamente 3 pruebas de consumo, 1 para el suplemento y 1 para cada producto de referencia: solución glucosada (SG) y pan blanco (PB), obteniendo muestras de sangre a los tiempos 0, 15, 30, 45, 60, 90 y 120 min; para medición de glicemias, e insulina basal y postprandial. El área de incremento bajo la curva de glucosa (IAUC) fue menor para el suplemento 11.778,73 que para los productos de referencia (SG) 13.724,06; (PB) 13.153,56 α = p 0,005. El IG = (62) y la CG = (16) resultaron intermedios y más bajos que el del pan blanco IG = (69) y la CG = (18), sin diferencias en la insulina postprandial. Esto demuestra que este suplemento nutricional formulado con estevia y L-carnitina es capaz de prolongar la respuesta glicémica sin aumentar los requerimientos insulínicos en sujetos sanos. Se requieren estudios específicos en diabéticos para validar si el impacto glicémico es menor que el producto patrón. La presencia de otros nutrientes en la fórmula, influyentes en estos indicadores, no permite inferir que los resultados se deban únicamente al tipo de endulzante utilizado y a la L-carnitina (AU)

Currently the food industry has generated interest in non-nutritive sweeteners, for example Stevia and in special components such as L-carnitine, used in formulations of nutritional supplements for glycemic control specific for diabetics. The present study evaluated the effect of stevia and L-carnitine on the glycemic index (GI) and glycemic load (CG) of a nutritional supplement in 19 healthy subjects (9 men and 10 women), who randomly completed 3 consumption tests, 1 for the supplement and 1 for each reference product: Glucose solution (SG) and white bread (PB), obtaining blood samples at the 0, 15, 30, 45, 60, 90 and 120 min times; for measurement of blood glucose, basal and postprandial insulin. The increase area under the glucose curve (IAUC) was lower for supplement 11,778.73 than for reference products (SG) 13,724.06; (PB) 13,153.56 α = p 0.005. IG = (62) and CG = (16) were intermediate and lower than white bread IG = (69) and CG = (18), with no difference in postprandial insulin. This demonstrates that this nutritional supplement formulated with stevia and L-carnitine is able to prolong the glycemic response without increasing the insulin requirements in healthy subjects. Specific studies are required in diabetics to validate whether the glycemic impact is lower than the standard product. The presence of other nutrients in the formula, influential in these indicators, does not allow to infer that the results are due only to the type of sweetener used and the L-carnitine (AU)

Efecto del consumo de una fórmula con carbohidratos de liberación prolongada sobre la respuesta glicémica e insulina post-prandial en individuos sanos / Consumption effect of a formula with extended release carbohydrates on the glycemic response and post prandial insulin in healthy individuals

Existen fórmulas enterales específicas para mejorar el control glicémico en diabéticos; con carbohidratos cuya respuesta glicémica sería de interés indagar. Se determinó el efecto del consumo de una fórmula con carbohidratos de liberación prolongada sobre la respuesta glicémica e insulina post-prandial en 21 sujetos sanos; (11 hombres y 10 mujeres) entre (17 y 25 años), quienes consumieron en 2 ocasiones la fórmula enteral polimérica para diabéticos y el alimento de referencia (pan blanco), en una cantidad de 50 g de carbohidratos disponibles. La glicemia fue medida a los 0, 15, 30,45, 60, 75, 90, 105 y 120 min y las concentraciones de insulina en ayuno y a los 120 min. El área bajo la curva de glicemia fue calculada resultando más baja para la fórmula 11718,20. ± 1112,38 que para el pan blanco 13269,18 ± 1351,05, (p<0,001). El índice glicémico (IG) resultó intermedio (63,33±5,22), y más bajo al compararlo con los rangos de IG publicados para el alimento de referencia(80-96). Se produjo una menor concentración de glicemia posterior al consumo de la fórmula; sin incrementos en los requerimientos de insulina, presumiendo un uso adecuado en diabéticos y una respuesta de saciedad más prolongada. Este efecto y la hemoglobina glicosilada deberían estudiarse tras el consumo en períodos prolongados en sujetos con diabetes(AU)

There are specific formulas of enteral nutrition to improve glycemic control in diabetic patients containing different types of carbohydrates which glycemic response should be investigated. The consumption effect of a formula with carbohydrates with extended release was determined on the glycemic response and postprandial insulin in 21 healthy individuals (11 men and 10 women) from 17 to 25 years old, who consumed in two different time the polymeric enteral formula for diabetics and the reference food (white bread) in a quantity of 50 g of available carbohydrates. The glycemia was measured at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min and the insulin concentrations in fasting and within 120 min. The area in the glycemic curve was measured being the lowest the formula 11718.20. ± 1112.38 than in white bread 13269.18 ± 1351.05 (P<0.001). The glycemic index (GI) resulted to be intermediate (63.33±5.22) and lower when compared to the GI ranks published for the reference food (80-96). A lower concentration of glycemia occurred after the consumption of the formula, without increments in the insulin requirements; thus, assuming an adequate use in diabetic and a more extended feeling of fullness. This effect and the glycated hemoglobin should be studied after the extended consumption in people with diabetes(AU)