Smallanthus sonchifolius (Yacon) leaves: an emerging source of compounds for diabetes management

Diabetes mellitus is a chronic metabolic disease that develops mainly due to insulin deficiency or resistance to insulin action. All forms of diabetes are characterized by chronic hyperglycemia, which has an important role in the pathogenesis of diabetic complications. Leaves of Smallanthus sonchifolius (Poepp.&Endl.) H. Robinson (yacon) have been used since ancient times to prepare medicinal herbal tea with beneficial health properties. This review aims to discuss some key aspects related to the potential use of S. sonchifolius leaves and their natural biomolecules for the prophylaxis and treatment of diabetes as well as the potential mechanisms of action.Fil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Genta, Susana Beatriz de Fátima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Quantizing with a higher time derivative

We review the classical and quantum theory of the Pais-Uhlenbeck oscillator as the toy-model for quantizing f(R) gravity theories.Comment: LaTeX, 28 pages, no figures; published as a chapter in "Advances in Quantum Field Theory", InTech Publishers 2012, p. 49-73; available at http://www.intechopen.com/articles/show/title/quantizing-with-a-higher-time-derivativ

Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy

Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation

An unusual cause of alveolar hemorrhage post hematopoietic stem cell transplantation: A case report

BACKGROUND: Hematopoietic stem cell transplantation is being increasingly used in cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell transplant, results from bacterial, viral and fungal infections, coagulopathy, and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage associated with Strongyloides stercoralis hyperinfection in stem cell transplant patients has been rarely reported. CASE PRESENTATION: We describe an unusual cause of alveolar hemorrhage post hematopoietic stem cell transplant due to Strongyloides hyperinfection. Therapy with parenteral ivermectin and thiabendazole was initiated but the patient deteriorated and died of respiratory failure and septic shock. CONCLUSION: Strongyloides stercoralis hyperinfection is an unusual cause of alveolar hemorrhage early after hematopoietic stem cell transplant with very high mortality

Yacon roots (Smallanthus sonchifolius) improve oxidative stress in diabetic rats

Context: Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae (yacon) roots are a natural product recognized by the traditional medicine to treat diabetes-related problems. There are no reports concerning the potential of yacon roots to reduce oxidative stress and ameliorate diabetes complications in diabetic animals. Objective: This work analyzes the in vivo antioxidant activity and beneficial effects of yacon roots, using a model of streptozotocin-induced diabetes in rats. Materials and methods: Lipid peroxidation and other indicators of oxidative stress were determined in liver and kidney homogenates from non-diabetic rats, untreated diabetic rats, and diabetic rats treated orally with yacon flour (340 mg fructooligosaccharide/kg/d) as a diet supplement for 90 d. Biochemical parameters were determined in liver, kidney, and blood at the end of the experimental period. Results: Yacon supplementation to diabetic rats produced a significant decrease in malondialdehyde levels in both liver (-30.97%) and kidney (-19.15%). Hepatic superoxide dismutase and catalase activities were significantly lower in diabetic-treated rats (-13.46 and-64.33%, respectively) compared with diabetic controls. Similar results were observed in kidney. The treatment of diabetic rats produced an increase of glutathione peroxidase and glutathione levels in liver (172.50 and 35.91%, respectively) and kidney (177.78 and 57.76%, respectively). Plasma cholesterol and triacylglycerol levels and liver fatty acid composition, which were altered in diabetic rats, reverted back to nearly normal with yacon treatment. Conclusions: These results indicate that yacon root flour is a potential diet supplement with high in vivo antioxidant activity.Fil: Habib, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Serra Barcellona, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Genta, Susana Beatriz de Fátima. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Expression pattern of glycoside hydrolase genes in Lutzomyia longipalpis reveals key enzymes involved in larval digestion

The sand fly Lutzomyia longipalpis is the most important vector of American Visceral Leishmaniasis. Adults are phytophagous (males and females) or blood feeders (females only), and larvae feed on solid detritus. Digestion in sand fly larvae has scarcely been studied, but some glycosidase activities putatively involved in microorganism digestion were already described. Nevertheless, the molecular nature of these enzymes, as the corresponding genes and transcripts, were not explored yet. Catabolism of microbial carbohydrates in insects generally involves β-1,3-glucanases, chitinases, and digestive lysozymes. In this work, the transcripts of digestive β-1,3-glucanase and chitinases were identified in the L. longipalpis larvae throughout analysis of sequences and expression patterns of glycoside hydrolases families 16, 18, and 22. The activity of one i-type lysozyme was also registered. Interestingly, this lysozyme seems to play a role in immunity, rather than digestion. This is the first attempt to identify the molecular nature of sand fly larval digestive enzymes

Smallanthus macroscyphus: a new source of antidiabetic compounds

The aim of the present study was to analyze the in vivo hypoglycaemic effects of both decoction of Smallanthus macroscyphus leaves and pure crystalline polymatin A isolated from its leaves. Phytochemical analysis of the leaf decoction showed that its major constituents were caffeic, chlorogenic and three dicaffeoilquinic acids, together with the sesquiterpene lactone polymatin A. Oral glucose tolerance test in normal rats was performed to evaluate the hypoglycemic activity and to choose the minimum effective dose of the decoction and polymatin A. They have effective hypoglycemic activity at the minimum dose of 140 mg dry extract and 14 mg crystalline powder/kg body weight, respectively, and were selected for the following experiments. Oral administration of a single-dose of decoction produced a moderate lowering effect in fasting glycemia of normal rats, whereas polymatin A had no significant effect. We also assessed the effect of a single-dose on post-prandial blood glucose, resulting in an inhibition of the hyperglycemic peak after sucrose overload. Daily administration of decoction or polymatin A for 4 weeks produced an effective glycemic control in diabetic animals, with a decrease in urinary glucose excretion and a significant reduction in the HbA1c levels. Although there were no significant increases in plasma insulin levels, both treatments improved the fasting blood glucose/insulin ratio. In vivo acute toxicity studies were performed in adult Wistar rats. There were no deaths or signs of toxicity observed after oral administration of decoction or polymatin A at any dose level up to the highest dose tested (14.0 g /kg and 2.8 g /kg, respectively). The results presented here strongly support the notion that S. macroscyphus represents a new source of antidiabetic compounds that could help to manage diabetes more efficiently and safely.Fil: Serra Barcellona, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Coll Araoz, Maria Victoria. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; ArgentinaFil: Cabrera, Wilfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Habib, Natalia Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Catalan, Cesar Atilio Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto de Quimica del Noroeste; ArgentinaFil: Grau, Alfredo. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Ecología Regional; ArgentinaFil: Genta, Susana B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Colonisation resistance in the sand fly gut:Leishmania protects Lutzomyia longipalpis from bacterial infection

BACKGROUND: Phlebotomine sand flies transmit the haemoflagellate Leishmania, the causative agent of human leishmaniasis. The Leishmania promastigotes are confined to the gut lumen and are exposed to the gut microbiota within female sand flies. Here we study the colonisation resistance of yeast and bacteria in preventing the establishment of a Leishmania population in sand flies and the ability of Leishmania to provide colonisation resistance towards the insect bacterial pathogen Serratia marcescens that is also pathogenic towards Leishmania. METHODS: We isolated microorganisms from wild-caught and laboratory-reared female Lutzomyia longipalpis, identified as Pseudozyma sp. Asaia sp. and Ochrobactrum intermedium. We fed the females with a sugar meal containing the microorganisms and then subsequently fed them with a bloodmeal containing Leishmania mexicana and recorded the development of the Leishmania population. Further experiments examined the effect of first colonising the sand fly gut with L. mexicana followed by feeding with, Serratia marcescens, an insect bacterial pathogen. The mortality of the flies due to S. marcescens was recorded in the presence and absence of Leishmania. RESULTS: There was a reduction in the number of flies harbouring a Leishmania population that had been pre-fed with Pseudozyma sp. and Asaia sp. or O. intermedium. Experiments in which L. mexicana colonised the sand fly gut prior to being fed an insect bacterial pathogen, Serratia marcescens, showed that the survival of flies with a Leishmania infection was significantly higher compared to flies without Leishmania infection. CONCLUSIONS: The yeast and bacterial colonisation experiments show that the presence of sand fly gut microorganisms reduce the potential for Leishmania to establish within the sand fly vector. Sand flies infected with Leishmania were able to survive an attack by the bacterial pathogen that would have killed the insect and we concluded that Leishmania may benefit its insect host whilst increasing the potential to establish itself in the sand fly vector. We suggest that the increased ability of the sand fly to withstand a bacterial entomopathogen, due to the presence of the Leishmania, may provide an evolutionary pressure for the maintenance of the Leishmania-vector association