Nanoformulations for the Delivery of Dietary Anthocyanins for the Prevention and Treatment of Diabetes Mellitus and Its Complications.

Diabetes mellitus (DM) is a metabolic disease characterized by abnormal blood glucose levels-hyperglycemia, caused by a lack of insulin secretion, impaired insulin action, or a combination of both. The incidence of DM is increasing, resulting in billions of dollars in annual healthcare costs worldwide. Current therapeutics aim to control hyperglycemia and reduce blood glucose levels to normal. However, most modern drugs have numerous side effects, some of which cause severe kidney and liver problems. On the other hand, natural compounds rich in anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin) have also been used for the prevention and treatment of DM. However, lack of standardization, poor stability, unpleasant taste, and decreased absorption leading to low bioavailability have hindered the application of anthocyanins as therapeutics. Therefore, nanotechnology has been used for more successful delivery of these bioactive compounds. This review summarizes the potential of anthocyanins for the prevention and treatment of DM and its complications, as well as the strategies and advances in the delivery of anthocyanins using nanoformulations.

Anti-Inflammatory and Antimicrobial Activities of Portuguese Prunus avium L. (Sweet Cherry) By-Products Extracts.

The bioactivity of natural by-products in food and pharmaceutical applications is the subject of numerous studies. Cherry production and processing generates large amounts of biowaste, most of which is not used. The recovery of these by-products is essential for promoting the circular economy and to improving sustainability in the food industry. In this work, we explored the anti-inflammatory and antimicrobial potential of two different extracts from stems, leaves, and flowers of Portuguese cherries. The anti-inflammatory potential was studied on lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW 264.7) by evaluating the effect of by-products on cellular viability and nitric oxide (NO) production. Disc diffusion and minimum inhibitory concentration (MIC) were used to determine antimicrobial activity. The cherry by-products had no cytotoxic effect on RAW 264.7 cells, and were able to inhibit nitrite production in a dose-dependent manner. Moreover, all aqueous infusions showed good antioxidant activity against NO radicals. Moreover, leaf extracts showed the best activity against most of the strains studied. The results revealed, for the first time, interesting anti-inflammatory and antimicrobial properties of cherry by-products. This could potentially be of interest for their therapeutic use in the treatment of inflammation-related diseases or in controlling the growth of microorganisms.

Cherries and Blueberries-Based Beverages: Functional Foods with Antidiabetic and Immune Booster Properties.

Nowadays, it is largely accepted that the daily intake of fruits, vegetables, herbal products and derivatives is an added value in promoting human health, given their capacity to counteract oxidative stress markers and suppress uncontrolled pro-inflammatory responses. Given that, natural-based products seem to be a promising strategy to attenuate, or even mitigate, the development of chronic diseases, such as diabetes, and to boost the immune system. Among fruits, cherries and blueberries are nutrient-dense fruits that have been a target of many studies and interest given their richness in phenolic compounds and notable biological potential. In fact, research has already demonstrated that these fruits can be considered functional foods, and hence, their use in functional beverages, whose popularity is increasing worldwide, is not surprising and seem to be a promising and useful strategy. Therefore, the present review reinforces the idea that cherries and blueberries can be incorporated into new pharmaceutical products, smart foods, functional beverages, and nutraceuticals and be effective in preventing and/or treating diseases mediated by inflammatory mediators, reactive species, and free radicals.

Mineral Content and Volatile Profiling of Prunus avium L. (Sweet Cherry) By-Products from Fundão Region (Portugal).

Large amounts of Prunus avium L. by-products result from sweet cherry production and processing. This work aimed to evaluate the mineral content and volatile profiling of the cherry stems, leaves, and flowers of the Saco cultivar collected from the Fundão region (Portugal). A total of 18 minerals were determined by ICP-MS, namely 8 essential and 10 non-essential elements. Phosphorus (P) was the most abundant mineral, while lithium (Li) was detected in trace amounts. Three different preparations were used in this work to determine volatiles: hydroethanolic extracts, crude extracts, and aqueous infusions. A total of 117 volatile compounds were identified using HS-SPME/GC-MS, distributed among different chemical classes: 31 aldehydes, 14 alcohols, 16 ketones, 30 esters, 4 acids, 4 monoterpenes, 3 norisoprenoids, 4 hydrocarbons, 7 heterocyclics, 1 lactone, 1 phenol, and 2 phenylpropenes. Benzaldehyde, 4-methyl-benzaldehyde, hexanal, lilac aldehyde, and 6-methyl-5-hepten-2-one were the major volatile compounds. Differences in the types of volatiles and their respective amounts in the different extracts were found. This is the first study that describes the mineral and volatile composition of Portuguese sweet cherry by-products, demonstrating that they could have great potential as nutraceutical ingredients and natural flavoring agents to be used in the pharmaceutical, cosmetic, and food industries.

Sweet cherry phenolics revealed to be promising agents in inhibiting P-glycoprotein activity and increasing cellular viability under oxidative stress conditions: in vitro and in silico study.

This study aimed to explore the total phenolic and anthocyanin content (TPC and TAC, respectively), and the biological potential of Portuguese sweet cherry cultivars. The TPC and TAC values ranged between 72.9 and 493.6 gallic acid equivalents per 100 g fresh weight (fw), and from 1.0 to 179.1 cyanidin 3-O-rutinoside equivalents per 100 g fw, respectively. Cristalina total extract was the most effective in capturing DPPH reactive species, whereas the colored fraction and the total extract of Saco cultivar were the most efficient in scavenging ferric and peroxide species. Celeste total extract was the most effective in inhibiting α-glucosidase enzyme. Phenolic-rich extracts and standard phenolics also revealed ability to interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and to increase cellular viability under conditions of oxidative stress. Computational studies were performed to evaluate the interaction between phenolics and the P-gp activity. This study revealed that cherry extracts and their phenolic compounds present notable biological properties, encouraging the development of cherry-based dietary and medicinal supplements. PRACTICAL APPLICATION: The interest in phenolic-rich sources has increased significantly in recent years, given their capacity to prevent the development of chronic disorders, such as cancer. Recent evidence suggests that phenolic compounds can act as P-glycoprotein (P-gp) inhibitors, an important drug efflux transporter, preventing multidrug resistance, and thus, enhancing the therapeutic efficacy of some drugs in certain target cells. Our results indicate that enriched-fractions from sweet cherries can effectively interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and protect against oxidative damage.

Dietary Effects of Anthocyanins in Human Health: A Comprehensive Review.

In recent years, the consumption of natural-based foods, including beans, fruits, legumes, nuts, oils, vegetables, spices, and whole grains, has been encouraged. This fact is essentially due to their content in bioactive phytochemicals, with the phenolic compounds standing out. Among them, anthocyanins have been a target of many studies due to the presence of catechol, pyrogallol, and methoxy groups in their chemical structure, which confer notable scavenging, anti-apoptotic, and anti-inflammatory activities, being already recommended as supplementation to mitigate or even attenuate certain disorders, such as diabetes, cancer, and cardiovascular and neurological pathologies. The most well-known anthocyanins are cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside. They are widespread in nature, being present in considerable amounts in red fruits and red vegetables. Overall, the present review intends to discuss the most recent findings on the potential health benefits from the daily intake of anthocyanin-rich foods, as well as their possible pharmacological mechanisms of action. However, before that, some emphasis regarding their chemical structure, dietary sources, and bioavailability was done.

Valorisation of Prunus avium L. By-Products: Phenolic Composition and Effect on Caco-2 Cells Viability.

Prunus avium L. by-products, such as stems, leaves, and flowers, are used in folk medicine to prevent and treat some diseases. However, their phenolic composition and in vitro bioactivities against tumor cells are poorly known. In this work, we compared the phenolic profile and the biological potential of aqueous infusions and hydroethanolic extracts of P. avium leaves, stems, and flowers from Saco cultivar, collected from the Fundão region (Portugal). Among the fifty-two phenolic compounds tentatively identified by HPLC-DAD-ESI/MSn, the hydroxycinnamic acids were the most abundant. Both extracts of stems revealed a higher activity against DPPH•. Meanwhile, hydroethanolic extracts from stems and flowers and aqueous infusions of flowers were the most effective in inhibiting the growth of the human epithelial colorectal adenocarcinoma (Caco-2) cells at concentrations above 200 µg/mL. More detailed knowledge about the phenolic composition and health-promoting properties of Portuguese P. avium by-products allows for increasing the biological and commercial value of these bio-wastes, which may have a positive impact on food and pharmaceutical industries, as on the valorization of the local economy.

Meat, fruit, and vegetable consumption in sub-Saharan Africa: a systematic review and meta-regression analysis.

CONTEXT: The dietary choices people make affect personal health and have consequences for the environment, both of which have serious implications for the 2030 Sustainable Development Agenda. In global reviews, the literature on meat, fruit, and vegetable consumption in sub-Saharan Africa (SSA) is limited. OBJECTIVE: This systematic review set out to quantify meat, fruit, and vegetable consumption in SSA populations and to answer the following question: How much meat, fruit, and/or vegetables are being consumed daily by which individuals in SSA over the years? DATA SOURCES: Following the PRISMA guidelines, the authors systematically searched the MEDLINE, EMBASE, ASSIA CINAHL, Web of Science, POPLINE, and Google Scholar databases to identify 47 (out of 5922 search results) studies reporting meat, fruit, and/or vegetable consumption in SSA populations. DATA EXTRACTION: Three independent investigators extracted data on year of data collection, study country, study population and geographical context, and population intake of meat, fruit, and/or vegetables. DATA ANALYSIS: Using STATA SE version 15 software, random-effects meta-regression analyses were used to test the effect of year of data collection and method of data collection on population meat, fruit, and vegetable consumption. The analyses also tested any association between age, sex, rural/urban residence, or a country's economic development and population intake of meat, fruits, and/or vegetables. The review was started in 2017 and completed in 2019. RESULTS: Richer SSA countries were likely to consume more meat (ß = 36.76, P = 0.04) and vegetables (ß =43.49, P = 0.00) than poorer countries. Vegetable intake has increased dramatically over the last 3 decades from ≈10 g to ≈110 g (ß = 4.43, P = 0.00). Vegetable (ß= -25.48, P = 0.00) consumption was higher in rural than in urban residents. Although the trend of meat consumption has risen (≈25 g to ≈75 g), the trend is nonsignificant (ß = 0.63, N.S.). Daily average per capita meat consumption was 98 g - above the 70 g recommendation - while fruit and vegetable intake (268 g) remain below the World Health Organization's recommendation (400 g). CONCLUSIONS: Given the low intake of plant-based foods, it is likely that SSA populations may be deficient in high-quality protein and micronutrients as suggested by the EAT-Lancet Commission. There is a need to promote both an adequate supply and demand of plant-based protein and micronutrients, including fruit, vegetables, nuts, seeds, and legumes, in SSA countries. While dietary changes in SSA may offer large absolute benefits, consideration of the magnitude of dietary change, particularly increasing or reducing meat consumption, will need to occur in a way that ensures that policy and interventions support the reduction of undernutrition and micronutrient deficiencies without worsening the prevalence and environmental impacts of noncommunicable diseases. There is also the need for preventive action that ensures that SSA populations do not increase their meat consumption as disposable incomes increase and countries' economic development rises, as is seen in most countries undergoing economic transformation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42018090497.

Multitarget protection of Pterospartum tridentatum phenolic-rich extracts against a wide range of free radical species, antidiabetic activity and effects on human colon carcinoma (Caco-2) cells.

Pterospartum tridentatum is an edible endemic plant common in Portugal. Its flowers are used in culinary and are part of the popular medicine owing to its therapeutic properties. In this study, P. tridentatum flower infusion and hydroethanolic extracts were characterized concerning their phenolic composition and biological potential. By high-performance liquid chromatography method coupled to a diode array detector analysis were detected 13 phenolics. Genistein was the major one. Concerning the biological potential, the hydroethanolic extract was the most active against 2,2-diphenyl-1-picrylhydrazyl● and also as α-glucosidase inhibitor, while the infusion proved to be a remarkable free radical scavenger. Concerning human epithelial colorectal adenocarcinoma (Caco-2) cells, it was observed that both extracts displayed dose-dependent cytotoxicity on the viability of Caco-2 cells, presenting cytotoxic selectivity for these cancer cells when compared to the NHDF normal cell line. Additionally, they also showed protective effects against oxidative stress induced by tert-butyl hydroperoxide on Caco-2 cells. The obtained results suggest that these extracts may be interesting to enrich nutraceutical, pharmaceutical and food industries; however, more studies need to be done for their inclusion in pharmaceutical preparations and/or food additives. PRACTICAL APPLICATION: Pterospartum tridentatum is an endemic plant commonly used in folk medicine due to its depurative and hypoglycaemic properties. For this reason, we decided to determine the phenolic content of infusion and hydroethanolic extracts of P. tridentatum and their biological potential. The obtained results proved that P. tridentatum extracts are a rich source of bioactive compounds and possess great antioxidant and antidiabetic activities, ability to protect human erythrocytes against oxidative damage, inhibiting hemolysis, hemoglobin oxidation, and lipid peroxidation, and to interfere with Caco-2 cells growth and to protect these cells when subject to tert-butyl hydroperoxide oxidative stress conditions.

Authentication of honeys from Caramulo region (Portugal): Pollen spectrum, physicochemical characteristics, mineral content, and phenolic profile.

This study aimed to analyze the botanical origin, quality parameters, phenolic compounds, and minerals of 20 honey samples from Caramulo region (Portugal). Six samples were monofloral from Eucalyptus sp., being this one the predominant pollen in the analyzed samples, followed by Castanea sativa. The average values obtained for the physicochemical parameters were as follows: 4.7 pH; 16.8% moisture; 81.4 Brix; 0.3% ash; 512.8 µS/cm electrical conductivity; 22.6 meq/kg free acidity; 12.4 meq/kg lactonic acidity; 35.1 meq/kg total acidity; 2.1 mg/kg hydroxymethylfurfural; and 16.3 °Gothe for diastase activities. A total of 18 phenolics were determined by high-performance liquid chromatography-diode array detector. Hydroxycinnamic acid derivatives and protocatechuic acid were the major ones. Nine minerals were detected by atomic absorption spectrometry; potassium and phosphorus were the predominant mineral elements. This is the first study about honeys from Caramulo region, which revealed to have a good quality and be a rich source of essential minerals and phenolics. PRACTICAL APPLICATION: The interest in the analysis of honey has increased significantly in recent years, concerning its characterization, safety implications, and health impact. Given these facts, the authentication of honeys, based on the geographical and botanical origins, has been assuming great importance, being mainly associated with high-quality honeys. Therefore, we decided to analyze physicochemical parameters, phenolic composition, and mineral content of 20 Caramulo honey samples. Our results indicate that Caramulo honeys possess high-quality levels, good freshness, maturity, and proper processing, and are also rich in several bioactive substances with health-promoting properties, including phenolic compounds, potassium, and phosphorus.

Degradation of polyethylene microplastics in seawater: Insights into the environmental degradation of polymers.

Microplastic contamination of aquatic environments has become an increasingly alarming problem. These, defined as particles <5 mm, are mostly formed due to the cracking and embrittlement of larger plastic particles. Recent reports show that the increasing presence of microplastics in the environment could have significant deleterious consequences over the health of marine organisms, but also across the food chain. Herein, we have studied the effects of artificial seawater on polyethylene (PE)-based beads by exposing them up to eight weeks to saltwater in stirred batch reactors in the dark and examined the structural and morphological changes these endured. Electron microscopy observations showed that artificial seawater induces severe microcracking of the pellets' surfaces. Additionally, Fourier transform infrared spectroscopy (FTIR) analyses evidenced the formation of oxidized groups whenever these particles were exposed to water and an increase in organic matter content of the waters in which the pellets were kept was evidenced by Raman spectroscopy. There were also noticeable consequences in the thermal stability of the polyethylene pellets, as determined by thermogravimetric studies (TGA). Furthermore, the parallel exposure of polyethylene pellets to UV radiation yielded less pronounced effects, thus underscoring its lower preponderance in the degradation of this material. These results highlight the importance of determining the mechanisms of degradation of microplastics in marine settings and what the implications may be for the environment. Overall, the herein presented results show that a relatively short period of time of accelerated exposure can yield quantifiable chemical and physical impacts on the structural and morphological characteristics of PE pellets.

"My Child has Cerebral Palsy": Parental Involvement and Children's School Engagement.

Engaged students tend to show school-committed behaviors (e.g., attend classes, get involved with the learning process), high achievement, and sense of belonging. However, students with disabilities are prone to show a lack of engagement with school due to the specific difficulties they have to handle. In fact, children with disabilities are likely to show poor participation in school when compared with children without disabilities. This poor involvement is related to their low autonomy to participate in the school activities, which, in turn, results in low school engagement. Parents play a crucial role in their children's education. Parental involvement in school activities promotes autonomous behaviors and, consequently, school engagement. In fact, extant literature has shown close relationships between parental involvement, school engagement, and academic performance. Yet, parental involvement in school activities of children with Cerebral Palsy (CP) has received little direct attention from researchers. These children tend to display lower participation due to the motor, or cognitive, impairments that compromise their autonomy, and have a high likelihood to develop learning disabilities, with special incidences in reading and arithmetic. Therefore, our aim is twofold, to understand the parental styles; and how the perceived parental involvement in school activities is related to their children school engagement. Hence, 19 interviews were conducted with one of the parents of 19 children with CP. These interviews explored the school routines of children and the perceived involvement of parents in those routines. Additionally, children filled out a questionnaire on school engagement. Results show that the majority of the parents were clustered in the Autonomy Allowance and Acceptance and Support parental style, and the majority of their children were perceived as autonomous. Moreover, about a half of the children reported a high level of school engagement. Finally, neither children's autonomous behaviors reported by parents, nor parental style, seem to be related with the children's level of school engagement. Rehabilitation centers and schools could consider training parents/caregivers focusing on their educational needs, promotion of reflections on the usefulness of applying autonomy promotion strategies with their child, and foster their involvement.

Hippocampal neurogenesis response: What can we expect from two different models of hypertension?

Hypertension is associated with cerebrovascular disease, white matter lesion and cognitive deficit, both in experimental models and clinical observations. Furthermore, in non-clinical models it is shown that hippocampus is affected by hypertension and hypoxia. Herein, two distinct hypertension models were used to study neurogenic response in hippocampus. Dahl salt sensitive (DSS) rat model is a genetic based idiopathic model, while chronic intermittent hypoxia (CIH) mimics the hypertension observed in patients with obstructive sleep apnea (OSA). Both models are chronic and trigger hypertension. No macroscopic alterations based on histological analysis were found in hippocampus derived from DSS and CIH exposure rats. Nevertheless, in hippocampus derived from CIH-induced hypertensive rats, there was a decrease on neuronal population (MAP2 and NeuN positive cells) and an increase on astrocytic marker GFAP. Accordingly, a higher increase on Ki67 expressing cells was found in dentate gyrus (DG) region, suggesting an enhancement of cell proliferation, concomitantly with an increase of Nestin staining, which indicates the presence of immature neurons under differentiation. While, in hippocampus of DSS rats with or without high salt diet, there was no remarkable difference indicating potential neuronal loss, astrocytic activation or neurogenesis. Furthermore, in both models hypertension did not alter the levels of expression of the stress response enzyme heme oxygenase-1 in DG. These data indicate that intermittent hypoxia might be the key factor involved in neurogenesis modulation in hippocampus. Furthermore, two hypotheses can be explored: (i) activation of neurogenesis is a response against neuronal loss induced by hypertension and/or hypoxia or (ii) neurogenesis can be directly stimulated by hypoxia as a neuroprotective mechanism.

Predicting approach to homework in Primary school students.

BACKGROUND: The goal of this research was to study the weight of student variables related to homework (intrinsic homework motivation, perceived homework instrumentality, homework attitude, time spent on homework, and homework time management) and context (teacher feedback on homework and parental homework support) in the prediction of approaches to homework. METHOD: 535 students of the last three courses of primary education participated in the study. Data were analyzed with hierarchical regression models and path analysis. RESULTS: The results obtained suggest that students’ homework engagement (high or low) is related to students´ level of intrinsic motivation and positive attitude towards homework. Furthermore, it was also observed that students who manage their homework time well (and not necessarily those who spend more time) are more likely to show the deepest approach to homework. CONCLUSIONS: Parental support and teacher feedback on homework affect student homework engagement through their effect on the levels of intrinsic homework motivation (directly), and on homework attitude, homework time management, and perceived homework instrumentality (indirectly). Data also indicated a strong and significant relationship between parental and teacher involvement.

Efficacy of carvedilol in reversing hypertension induced by chronic intermittent hypoxia in rats.

Animal models of chronic intermittent hypoxia (CIH) mimic the hypertension observed in patients with obstructive sleep apnoea. Antihypertensive drugs were applied to these animal models to address the physiological mechanism but not to revert established hypertension. We aimed to investigate the efficacy of carvedilol (CVDL), an unselective beta-blocker that exhibits intrinsic anti-α1-adrenergic and antioxidant activities in a rat model of CIH-induced hypertension. The variability of CVDL enantiomers in plasma concentrations was also evaluated. Wistar rats with indwelling blood pressure telemeters were exposed during their sleep period to 5.6 CIH cycles/h, 10.5 h/day, for 60 days. CVDL was administered by gavage beginning on Day 36 of the CIH period and was continued for 25 days. R-(+)-CVDL and S-(-)-CVDL plasma concentrations were monitored by HPLC. CIH significantly increased diastolic and systolic blood pressure by 25.7 and 21.6 mm Hg respectively, while no effect was observed on the heart rate (HR). CVDL administration at 10, 30 and 50 mg/kg/day promoted a significant reduction in HR but did not affect arterial pressure. The S/(R+S) ratio of CVDL enantiomers was lower in rats exposed to CIH. The blockade of the sympathetic nervous system together with the putative pleiotropic effects of CVDL did not alter the CIH-induced hypertension. Although CIH induced pharmacokinetic changes in the R/(R+S) ratio, these effects do not appear to be responsible for the inability of CVDL to reverse this particular type of hypertension.

The progression from a lower to a higher invasive stage of bladder cancer is associated with severe alterations in glucose and pyruvate metabolism.

Cancer cells present a particular metabolic behavior. We hypothesized that the progression of bladder cancer could be accompanied by changes in cells glycolytic profile. We studied two human bladder cancer cells, RT4 and TCCSUP, in which the latter represents a more invasive stage. The levels of glucose, pyruvate, alanine and lactate in the extracellular media were measured by Proton Nuclear Magnetic Resonance. The protein expression levels of glucose transporters 1 (GLUT1) and 3 (GLUT3), monocarboxylate transporter 4 (MCT4), phosphofructokinase-1 (PFK1), glutamic-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) were determined. Our data showed that glucose consumption and GLUT3 levels were similar in both cell lines, but TCCSUP cells displayed lower levels of GLUT1 and PFK expression. An increase in pyruvate consumption, concordant with the higher levels of lactate and alanine production, was also detected in TCCSUP cells. Moreover, TCCSUP cells presented lower protein expression levels of GPT and LDH. These results illustrate that bladder cancer progression is associated with alterations in cells glycolytic profile, namely the switch from glucose to pyruvate consumption in the more aggressive stage. This may be useful to develop new therapies and to identify biomarkers for cancer progression.

Daily consumption of white tea (Camellia sinensis (L.)) improves the cerebral cortex metabolic and oxidative profile in prediabetic Wistar rats.

Diabetes mellitus (DM) is a major public health problem and its incidence is rising dramatically. The brain, particularly the cerebral cortex, is very susceptible to glucose fluctuations and hyperglycaemia-induced oxidative stress. Tea (Camellia sinensis (L.)) is widely consumed; however, the antidiabetic properties of white tea remain largely unexplored. In the present study, we investigated the effects of daily consumption of white tea on the cerebral cortex of prediabetic rats. The cerebral cortex metabolic profile was evaluated, and the expression levels of GLUT, phosphofructokinase-1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were assessed. LDH activity was also determined. The cerebral cortex oxidative profile was determined by evaluating its antioxidant power, lipid peroxidation and protein oxidation levels. Catalase, glutathione, glutamate, N-acetylaspartate, aspartate, choline, γ-aminobutyric acid, taurine and valine contents were determined. Daily consumption of white tea ameliorated glucose tolerance and insulin sensitivity. Moreover, white tea altered the cortex glycolytic profile, modulating GLUT expression and lactate and alanine contents. Finally, white tea consumption restored protein oxidation and lipid peroxidation levels and catalase expression, and improved antioxidant capacity. In conclusion, daily consumption of white tea improved the cerebral cortex metabolic and oxidative profile in prediabetic rats, suggesting it as a good, safe and inexpensive strategy to prevent DM-related effects in the cerebral cortex.

Revisiting cAMP signaling in the carotid body.

Chronic carotid body (CB) activation is now recognized as being essential in the development of hypertension and promoting insulin resistance; thus, it is imperative to characterize the chemotransduction mechanisms of this organ in order to modulate its activity and improve patient outcomes. For several years, and although controversial, cyclic adenosine monophosphate (cAMP) was considered an important player in initiating the activation of the CB. However, its relevance was partially displaced in the 90s by the emerging role of the mitochondria and molecules such as AMP-activated protein kinase and O2-sensitive K(+) channels. Neurotransmitters/neuromodulators binding to metabotropic receptors are essential to chemotransmission in the CB, and cAMP is central to this process. cAMP also contributes to raise intracellular Ca(2+) levels, and is intimately related to the cellular energetic status (AMP/ATP ratio). Furthermore, cAMP signaling is a target of multiple current pharmacological agents used in clinical practice. This review (1) provides an outline on the classical view of the cAMP-signaling pathway in the CB that originally supported its role in the O2/CO2 sensing mechanism, (2) presents recent evidence on CB cAMP neuromodulation and (3) discusses how CB activity is affected by current clinical therapies that modify cAMP-signaling, namely dopaminergic drugs, caffeine (modulation of A2A/A2B receptors) and roflumilast (PDE4 inhibitors). cAMP is key to any process that involves metabotropic receptors and the intracellular pathways involved in CB disease states are likely to involve this classical second messenger. Research examining the potential modification of cAMP levels and/or interactions with molecules associated with CB hyperactivity is currently in its beginning and this review will open doors for future explorations.

Can Tea Consumption be a Safe and Effective Therapy Against Diabetes Mellitus-Induced Neurodegeneration?

Diabetes mellitus (DM) is a metabolic disease that is rapidly increasing and has become a major public health problem. Type 2 DM (T2DM) is the most common type, accounting for up to 90-95% of the new diagnosed DM cases. The brain is very susceptible to glucose fluctuations and hyperglycemia-induced oxidative stress (OS). It is well known that DM and the risk of developing neurodegenerative diseases are associated. Tea, Camellia sinensis L., is one of the most consumed beverages. It contains several phytochemicals, such as polyphenols, methylxanthines (mainly caffeine) and L-theanine that are often reported to be responsible for tea's health benefits, including in brain. Tea phytochemicals have been reported to be responsible for tea's significant antidiabetic and neuroprotective properties and antioxidant potential. Epidemiological studies have shown that regular consumption of tea has positive effects on DM-caused complications and protects the brain against oxidative damage, contributing to an improvement of the cognitive function. Among the several reported benefits of tea consumption, those related with neurodegenerative diseases are of great interest. Herein, we discuss the potential beneficial effects of tea consumption and tea phytochemicals on DM and how their action can counteract the severe brain damage induced by this disease.

Bicarbonate-sensitive soluble and transmembrane adenylyl cyclases in peripheral chemoreceptors.

Stimulation of the carotid body (CB) chemoreceptors by hypercapnia triggers a reflex ventilatory response via a cascade of cellular events, which includes generation of cAMP. However, it is not known if molecular CO2/HCO3(-) and/or H(+) mediate this effect and how these molecules contribute to cAMP production. We previously reported that the CB highly expresses HCO3(-)-sensitive soluble adenylyl cyclase (sAC). In the present study we systematically characterize the role of sAC in the CB, comparing the effect of isohydric hypercapnia (IH) in cAMP generation through activation of sAC or transmembrane-adenylyl cyclase (tmAC). Pharmacological deactivation of sAC and tmAC decreased the CB cAMP content in normocapnia and IH with no differences between these two conditions. Changes from normocapnia to IH did not effect the degree of PKA activation and the carotid sinus nerve discharge frequency. sAC and tmAC are functional in CB but intracellular elevations in CO2/HCO3(-) in IH conditions on their own are insufficient to further activate these enzymes, suggesting that the hypercapnic response is dependent on secondary acidosis.