Pitaya fruit extract ameliorates the healthspan on copper-induced toxicity of Caenorhabditis elegans.

Copper (Cu) is an essential metal and it is important for metabolism. However, in high concentrations, it becomes toxic. Metal-induced toxicity is the cause of many neurodegenerative diseases. So it is necessary to search mechanisms to find ways of healthy aging. Natural compounds and diets based on fruits are increasingly common and could lead to a healthy life. Pitaya (Hylocereus undatus) is a tropical and Latin American, fruit that is gaining more popularity due to its antioxidant properties. Here, we evaluate the preventive and curative effect of different doses of microencapsulated pulp H. undatus extract on copper-induced toxicity. For this we use the nematode Caenorhabditis elegans, to investigate the effects of pitaya extract on behavior, lipid peroxidation, antioxidant chaperon, and cholinergic nervous system (ColNS). Results showed behavioral changes, decreased cell death biomarkers, and lipid peroxidation caused by copper, and these toxic effects were prevented and reverted by Pitaya's extract. After all, the extract can be used in diet as a supplement and studied to treat or prevent specific diseases, some of them linked to contamination and senility-related conditions. PRACTICAL APPLICATIONS: This research has been aimed to provide the uses of Hylocereus undatus microencapsulated pulp extract for the prevention and treatment of copper-induced toxicity. We have been shown that Pitaya is a good source of antioxidant compounds that can ameliorate the antioxidant system as well as the cholinergic nervous system avoiding behavior changes before and after the metal toxicity of copper. Therefore, the potential applications and common use of this extract can serve as food supplementation to prevent metal oxidative damage as well as to repair clinical cases of copper poisoning.

Fruit extract of red pitaya (Hylocereus undatus) prevents and reverses stress-induced impairments in the cholinergic and antioxidant systems of Caenorhabditis elegans.

The addition of fruit to the diet is very important, and we can use nutraceutical and functional foods for this supplement. A little-known fruit is a red pitaya (Hylocereus undatus) that has been widely reported to have a high antioxidant potential. In this study, we analyzed the in vitro and in vivo antioxidant capacity of microencapsulated pitaya extract on the behavior, antioxidant, and nervous system of the nematode Caenorhabditis elegans. The worms were treated with fruit extract before and after juglone-induced stress, to determine the protective or curative effects of pitaya. We have been evaluated cholinergic, antioxidant, and behavioral biomarkers. We have evidenced that the pulp of pitaya contains antioxidant compounds and can serve as a potential nutraceutical product. In addition, the fruit extract was effective in preventing and/or reverse the stress-induced damages, even at high levels of chemical stress at all evaluated parameters. PRACTICAL APPLICATIONS: The potential applications and uses aimed by this research are related to the supplementation of foods given the antioxidant effect. Our data suggested that the effect of the pitaya fruit microencapsulated pulp extract was effective to prevent and repair the damage caused by oxidative stress. Besides the use of this microencapsulated extract can be an auxiliary in the treatment of diseases related to oxidative damage as well as promoting senescent aging. Another important use is the application of this extract as a dietary supplement to fortify the antioxidant system.

Ilex paraguariensis extract provides increased resistance against oxidative stress and protection against Amyloid beta-induced toxicity compared to caffeine in Caenorhabditis elegans.

Ilex paraguariensis is a plant from South America, used to prepare a tea-like beverage rich in caffeine and polyphenols with antioxidant proprieties. Caffeine consumption is associated with a lower risk of age-associated neuropathologies, besides several extracts that have antioxidant proprieties are known to be neuroprotective, and oxidative stress strongly correlates with Aß-toxicity. This study aims to investigate the neuroprotective effects of the Ilex paraguariensis hydroalcoholic extract (IPHE) and to evaluate if caffeine agent present in IPHE exerts neuroprotective effects in an amyloid beta-peptide (Aß)-induced toxicity in Caenorhabditis elegans. The wild-type and CL2006 worms were treated with IPHE (2 and 4 mg/mL) or caffeine (200 and 400 µM) since larval stage 1 (L1) until they achieved the required age for each assay. IPHE and caffeine increased the lifespan and appeared to act directly by reactive oxygen species (ROS) scavenger in both wild-type and CL2006 worms, also conferred resistance against oxidative stress in wild-type animals. Furthermore, both treatments delayed Aß-induced paralysis and decreased AChE activity in CL2006. The protective effect of IPHE against Aß-induced paralysis was found to be dependent on heat shock factor hsf-1 and FOXO-family transcription factor daf-16, which are respectively involved in aging-related processes and chaperone synthesis, while that of caffeine was dependent only on daf-16. Mechanistically, IPHE and caffeine decreased the levels of Aß mRNA in the CL2006 worms; however, only IPHE induced expression of the heat shock chaperonin hsp-16.2, involved in protein homeostasis. The results were overall better when treated with IPHE than with caffeine.

Guarana (Paullinia cupana Mart.) protects against amyloid-ß toxicity in Caenorhabditis elegans through heat shock protein response activation.

Alzheimer disease (AD) is a progressive neurodegenerative brain disorder that causes significant disruption in normal brain functioning, representing the most common cause of dementia in the elderly. The main hallmark of AD is the presence of amyloid plaques in the brain formed by the deposition of insoluble amyloid protein (Aß) outside of neurons. Despite intensive investigation of the mechanisms of AD pathogenesis during the past three decades, little has been achieved in terms of effective treatments or ways to prevent the disease. Paullinia cupana, known as guarana, is a plant endemic to the Amazon region in Brazil with several beneficial effects reported, including delayed aging. In this study, we investigated the effects of chronic consumption of guarana ethanolic extract (GEE) on Aß toxicity using a C. elegans model of AD. We analyzed the behavioral phenotype, oxidative damage and Aß protein expression in worms treated with GEE. In addition, we investigated the possible role of the heat shock response on the beneficial effects induced by GEE. Overall, our data demonstrate that chronic GEE treatment decreased the formation of Aß aggregates in C. elegans, preventing the behavioral deficits and the oxidative damage inducible by Aß expression, due to activation of the heat shock protein (HSP) response. This finding provides a new alternative against amyloidogenic neurodegenerative diseases and other diseases caused by protein accumulation during aging.

Guanosine Prevents against Glutamatergic Excitotoxicity in C. elegans.

Glutamatergic neurotransmission is present in most mammalian excitatory synapses and plays a key role in central nervous system homeostasis. When over-activated, it can induce excitotoxicity, which is present in several neuropathologies. The nucleoside guanosine (GUO) is a guanine-based purine known to have neuroprotective effects by modulating glutamatergic system during glutamate excitotoxicity in mammals. However, GUO action in Caenorhabditis elegans, as well as on C. elegans glutamatergic excitotoxicity model, is not known. The GUO effects on behavioral parameters in Wild Type (WT) and knockouts worms for glutamate transporters (GLT-3, GLT-1), glutamate vesicular transporter (EAT-4), and NMDA and non-NMDA receptors were used to evaluate the GUO modulatory effects. The GUO tested concentrations did not alter the animals' development, but GUO reduced pharyngeal pumps in WT animals in a dose-dependent manner. The same effect was observed in pharyngeal pumps, when the animals were treated with 4 mM of GUO in glr-1, nmr-1 and eat-4, but not in glt-3 and glt-3;glt-1 knockouts. The double mutant glt-3; glt-1 for GluTs had decreased body bends and an increased number of reversions. This effect was reverted after treatment with GUO. Furthermore, GUO did not alter the sensory response in worms with altered glutamatergic signaling. Thus, GUO seems to modulate the worm's glutamatergic system in situations of exacerbated glutamatergic signaling, which are represented by knockout strains to glutamate transporters. However, in WT animals, GUO appears to reinforce glutamatergic signaling in specific neurons. Our findings indicate that C. elegans strains are useful models to study new compounds that could be used in glutamate-associated neurodegenerative diseases.

Ilex paraguariensis modulates fat metabolism in Caenorhabditis elegans through purinergic system (ADOR-1) and nuclear hormone receptor (NHR-49) pathways.

Ilex paraguariensis is a well-known plant that is widely consumed in South America, primarily as a drink called mate. Mate is described to have stimulant and medicinal properties. Considering the potential anti-lipid effects of I. paraguariensis infusion, we used an extract of this plant as a possible modulator of fat storage to control lipid metabolism in worms. Herein, the I. paraguariensis-dependent modulation of fat metabolism in Caenorhabditis elegans was investigated. C. elegans were treated with I. paraguariensis aqueous extract (1 mg/ml) from L1 larvae stage until adulthood, to simulate the primary form of consumption. Expression of adipocyte triglyceride lipase 1 (ATGL-1) and heat shock protein 16.2, lipid accumulation through C1-BODIPY-C12 (BODIPY) lipid staining, behavioral parameters, body length, total body energy expenditure and overall survival were analyzed. Total body energy expenditure was determined by the oxygen consumption rate in N2, nuclear hormone receptor knockout, nhr-49(nr2041), and adenosine receptor knockout, ador-1(ox489) strains. Ilex paraguariensis extract increased ATGL-1 expression 20.06% and decreased intestinal BODIPY fat staining 63.36%, compared with the respective control group, without affecting bacterial growth and energetic balance, while nhr-49(nr2041) and ador-1(ox489) strains blocked the worm fat loss. In addition, I. paraguariensis increased the oxygen consumption in N2 worms, but not in mutant strains, increased N2 worm survival following juglone exposure, and did not alter hsp-16.2 expression. We demonstrate for the first time that I. paraguariensis can decrease fat storage and increase body energy expenditure in worms. These effects depend on the purinergic system (ADOR-1) and NHR-49 pathways. Ilex paraguariensis upregulated the expression of ATGL-1 to modulate fat metabolism. Furthermore, our data corroborates with other studies that demonstrate that C. elegans is a useful tool for studies of fat metabolism and energy consumption.

Perfil de inaptidão na triagem clínica e sorológica de candidatos à doação de sangue / Profile of inability in the clinic and serological screening of candidates for blood donation

Objetivo: Caracterizar os candidatos quanto ao gênero e analisar a prevalência dos critérios de inaptidão adotados às doações de sangue, realizadas no Banco de Sangue Santa Maria, em Santa Maria, RS. Métodos: Dados retrospectivos arquivados foram avaliados, analisando-se os critérios de exclusão na triagem clínica e sorológica, no período de janeiro de 2005 até dezembro de 2010. Foram analisados 20.264 doadores. O estudo foi aprovado pelo Comitê de Ética e Pesquisa da Universidade Federal do Rio Grande do Sul-UFRGS, sob número de protocolo 18147. Resultados: Novecentos e setenta e seis (5%) candidatos foram considerados inaptos pela triagem clínica e 19.288 (95%) foram considerados aptos para prosseguirem com os testes laboratoriais. Dos doadores aptos, 941 (5%) foram excluídos na triagem sorológica, totalizando 18.347 bolsas de sangue disponíveis para uso. Predominaram os doadores do sexo masculino (62%) e a principal causa de exclusão, na triagem clínica, foi hipertensão (0,7%). Para a triagem sorológica, a principal causa de exclusão foi a Doença de Chagas (1,5%). Conclusão: Ressaltou-se a importância da triagem clínica, tendo em vista que ela excluiu 5% dos candidatos à doação e a relevância da triagem sorológica ser feita corretamente, evitando que resultados falso-negativos sejam liberados.

Objective: Characterize donors by gender and analyze theprevalence of the inability criteria of donations made at the SantaMaria Blood Bank, located at Santa Maria, Brazil. Methods: First,we searched historical data for exclusion criteria used in clinicaland serological screenings during the period from January, 2005 toJuly, 2010. We evaluated 20,264 blood donors' data for this study.The Ethical Committee of Rio Grande do Sul Federal UniversityUFRGSapproved this study under the protocol number 18147.Results: Nine hundred and seventy-six (5%) candidates wereconsidered unfit by the clinical screening and 19,288 (95%) wereconsidered fit. From the resulting fit population of the clinicalscreening, 941 (5%) were excluded from donating by the serologicalscreening, totaling 18.347 blood donations fit for use. The resultsshows that majority of the donors were male (62%) and the leadingcause of exclusion from donating in the clinical screening washypertension (0.7%). As for the serological screening, the leadingcause for exclusion was Chagas disease (1.5%). Conclusion: Thestudy stress the importance of the clinical screening process, giventhat it excluded 5% of blood donations, which were unfit for use. Wealso notice the relevance of a correctly done serological screening,thus avoiding that false-negative results are released.