A coffee enriched with guarana, selenium, and l-carnitine (GSC) has nutrigenomic effects on oxi-inflammatory markers of relapsing-remitting multiple sclerosis patients: A pilot study.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1ß, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions.

Physical demands and psychophysiological stress in young athletes team sports / Exigências físicas e estresse psicofisiológico em jovens atletas de esportes coletivos

ABSTRACT Training monitoring is important in the development process of the athlete. The objective of the study was to characterize the psychophysiological response and physical demands of soccer, basketball, handball, and volleyball with young athletes. The sample consisted of 61 young athletes of both genders and members of team sports, 10 training sessions for each modality were monitored. The psychophysiological responses were monitored by the session rating perception of exertion (Session RPE) and training impulse (TRIMP). The physical demands were, distance covered (DC), DC by speed zone (DC_Z1, DC_Z2, DC_Z3, DC_Z4, DC_Z5), number of sprints, and duration of the session. In addition, the recovery status (TQR) was also collected. Differences were noted between duration (p<0.001), DC_Z1 (p<0.017), DC_Z2 (p<0.05), DC_Z3 (p<0.05), DC_Z4 (p<0.003), DC_Z5 (p < 0.05), sprints (p < 0.001), TRIMP (p<0.02), Session RPE (p<0.05) and TQR (p<0.007). In psychophysiological responses, handball showed more time in zones 4 and 5 than other modalities. According to physical demands, basketball, and handball had a higher number of sprints and also higher values ​​in DP_Z5. Therefore, the simultaneous monitoring of physical demands and psychophysiological responses provides supplementary information in monitoring young athletes.

RESUMO O monitoramento do treinamento é importante no processo de desenvolvimento dos atletas. O objetivo do estudo foi comparar as respostas psicofisiológicas e as demandas físicas de jovens atletas de futebol, basquete, handebol e voleibol. A amostra foi constituída por 61 indivíduos de ambos os gêneros que foram acompanhados ao longo de 10 sessões de treino de cada modalidade em questão. As respostas psicofisiológicas foram monitoradas através da percepção subjetiva de esforço da sessão (PSE da sessão) e o impulso de treinamento (TRIMP). As demandas físicas analisadas foram a distância total percorrida (DP), DP por zona de velocidade (DP_Z1, DP_Z2, DP_Z3, DP_Z4, DP_Z5), número de sprints e a duração das sessões. Além disso, o estado de recuperação (TQR) também foi analisado. Foram observadas diferenças significativas entre a duração das sessões (p<0,001), DP_Z1 (p<0,017), DP_Z2 (p<0,05), DP_Z3 (p<0,05), DP_Z4 (p<0,003), DP_Z5 (p <0,05), número de sprints (p < 0,001), TRIMP (p<0,02), PSE da sessão (p<0,05) e TQR (p<0,007). Nas respostas psicofisiológicas, o handebol apresentou mais tempo nas zonas 4 e 5 em comparação demais modalidades. Nas demandas físicas, o basquete e o handebol apresentaram maior número de sprints e também maiores valores na DP_Z5. Dessa forma, o monitoramento em conjunto das demandas físicas e respostas psicofisiológicas fornecem informações complementares no monitoramento de jovens atletas.

Worst spasticity in patients post-stroke associated with MNSOD ALA16VAL polymorphism and interleukin-1ß.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

Toxicity, Anti-Inflammatory, and Antioxidant Activities of Cubiu (Solanum sessiliflorum) and Its Interaction with Magnetic Field in the Skin Wound Healing.

Cubiu, an Amazonian fruit, is widely used as food and popular treatment for pathologies that present an inflammatory pattern, such as skin wound healing. However, there is still no confirmation in the scientific literature about the safety profile, as well as the anti-inflammatory, antioxidant, and healing actions of cubiu. This study is divided into two experimental protocols using Wistar rats. Thus, the first objective (protocol 1) of this study was to evaluate the toxicity of an oral administration of cubiu extract at different doses for 28 days. The macroscopic and microscopic analyses of the liver and kidney were performed, and the following analysis was determined in plasma: glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, glucose, triglycerides, total cholesterol, urea, creatinine, and uric acid. After, we conducted the second protocol aimed to establish the potential antioxidant and anti-inflammatory capacity of cubiu and its interaction with magnetic field in skin wound healing. On days 3, 7, and 14 of treatment, skin and blood samples were collected and analyzed: the oxidative stress biomarkers (reactive substances to thiobarbituric acid, nonprotein thiols, superoxide dismutase, catalase, and glutathione S-transferase), myeloperoxidase enzymatic activity, and cytokines levels (interleukin 1, interleukin 6, interleukin 10, and tumor necrosis factor-alpha). The cubiu has shown to be safe and nontoxic. Both cubiu and magnetic field promoted decreased levels of proinflammatory and prooxidant biomarkers (interleukin 1, interleukin 6, tumor necrosis factor-alpha, and reactive substances to thiobarbituric acid), as well as increased levels of anti-inflammatory and antioxidant biomarkers (interleukin 10, nonprotein thiols, and superoxide dismutase), with greater potential when treatments are used in association. Thus, cubiu promotes antioxidant and anti-inflammatory action in skin wound healing, while also improving results of the conventional treatment for skin healing (magnetic field) when used in association.

Efeito da distribuição da carga interna de treinamento no desempenho de salto vertical em uma pré-temporada de jogadores de voleibol de elite / Effect of the distribution of the internal load of training in vertical jump performance in a preseason of elite volleyball players

O objetivo deste estudo foi examinar os efeitos da distribuição da carga interna de treinamento no desempenho de salto vertical durante a pré-temporada em jogadores de voleibol. A amostra foi composta por 11 jogadores de voleibol da Superliga Masculina de Voleibol (26,4±5,7 anos; 96,6±9,0 kg; 197,6±7,8 cm; 8,1±2,8% de gordura). A pré-temporada foi composta por 11 semanas de treinamento, dividida em três etapas: Etapa 1, com duração de 6 semanas; Etapa 2, com duração de 3 semanas; Etapa 3, com duração de 2 semanas. A carga interna de treinamento foi avaliada em todas sessões de treinamento através da percepção subjetiva de esforço da sessão, as percepções subjetivas de fadiga foram avaliadas ao final de cada semana, por meio da escala de bem-estar e o salto vertical com contra movimento foi avaliado ao final de cada etapa. Os resultados mostraram maiores valores de carga interna de treinamento em Etapa 1 em comparação a Etapa 2 (p = 0,02) e Etapa 3 (p = 0,01), alterações no estado de bem-estar dos atletas durante as três etapas analisadas, considerando os indicadores fadiga (F = 13,1; p < 0,001), estresse (F = 23,8; p < 0,001), humor (F = 16,7; p < 0,001) e bem-estar total (F = 11,2; p < 0,001) e também alterações significativas no salto vertical com contra movimento nos diferentes momentos de avaliação (F = 7,2; p < 0,01). Conclui-se que a distribuição de carga interna de treinamento, juntamente com as capacidades físicas trabalhadas, contribui para que ocorresse melhoria do desempenho no salto vertical com contra movimento e também redução da percepção de fadiga ao final da pré-temporada. (AU)

The aim of this study was to examine the effects of internal training load distribution on vertical jump performance during preseason in volleyball players. The sample consisted of 11 volleyball players from a Men's Volleyball Superliga (26.4 ± 5.7 years, 96.6 ± 9.0 kg, 197.6 ± 7.8 cm, 8.1 ± 2.8% of fat). The pre-season consisted of 11 weeks of training, divided into three stages: Stage 1, lasting 6 weeks; Stage 2, lasting 3 weeks; Stage 3, lasting 2 weeks. The internal training load was evaluated in all training sessions through the session of rating perception of exertion, the subjective perceptions of fatigue were evaluated at the end of each week, through the well-being scale and the vertical jump with counter movement was evaluated at the end of each stage. The results showed higher internal training load values in Stage 1 compared to Stage 2 (p = 0.02) and Stage 3 (p = 0.01), changes in the athletes' state of well-being during the three stages analyzed, considering the fatigue indicators (F = 13.1; p < 0.001), stress (F = 23.8; p < 0.001), mood (F = 16.7; p < 0.001) and total well-being (F = 11.2; p < 0.001) and also significant changes in vertical jump with counter movement at different moments of assessment (F = 7.2; p < 0.01). It is concluded that the distribution of internal training load contributes to an improvement in performance in the vertical jump with counter movement and also a reduction in the perception of fatigue at the end of the pre-season. (AU)

Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats.

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.

Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells.

INTRODUCTION: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress. Additionally, patients also have increased peripheral and neural chronic inflammation. The Brazilian fruit, açaí, has been demonstrated to be a neuroprotective agent through its recovery of mitochondrial complex I activity. This extract has previously shown anti-inflammatory effects in inflammatory cells. However, there is a lack of understanding of potential anti-neuroinflammatory mechanisms, such as cell cycle involvement. OBJECTIVE: The objective of this study is to evaluate the anti-neuroinflammatory potential of an açaí extract in lipopolysaccharide-activated BV-2 microglia cells. METHODS: Açaí extract was produced and characterized through high performance liquid chromatography. Following açaí extraction and characterization, BV-2 microglia cells were activated with LPS and a dose-response curve was generated to select the most effective açaí dose to reduce cellular proliferation. This dose was then used to assess reactive oxygen species (ROS) production, double-strand DNA release, cell cycle modulation, and cytokine and caspase protein expression. RESULTS: Characterization of the açaí extract revealed 10 bioactive molecules. The extract reduced cellular proliferation, ROS production, and reduced pro-inflammatory cytokines and caspase 1 protein expression under 1 µg/mL in LPS-activated BV-2 microglia cells but had no effect on double strand DNA release. Additionally, açaí treatment caused cell cycle arrest, specifically within synthesis and G2/Mitosis phases. CONCLUSION: These results suggest that the freeze-dried hydroalcoholic açaí extract presents high anti-neuroinflammatory potential.

In silico and in vivo protective effect of Morus nigra leaves on oxidative damage induced by iron overload.

Morus nigra L. is a plant popularly known as 'amoreira preta', very used in folk medicine. Iron overload (hemochromatosis) is a clinical condition that causes damage to various tissues due to oxidative stress. Therapy to control iron overload is still unsatisfactory. The protective effect on oxidative stress induced by iron overload was verified. Phytochemical characterization was evaluated by UHPLC-MS/MS. The in silico toxicity predictions of the main phytochemicals were performed via computer simulation. To induce iron overload, the animals received iron dextran (50 mg/kg/day). The test groups received doses of 500 and 1000 mg/kg of M. nigra extract for six weeks. Body weight, organosomatic index, serum iron, hepatic markers, cytokines, interfering factors in iron metabolism, enzymatic and histopathological evaluations were analyzed. Vanillic acid, caffeic acid, 6-hydroxycoumarin, p-coumaric acid, ferulic acid, rutin, quercitrin, resveratrol, apigenin and kaempferol were identified in the extract. In addition, in silico toxic predictions showed that the main compounds presented a low probability of toxic risk. The extract of M. nigra showed to control the mediators of inflammation and to reduce iron overload in several tissues. Our findings illustrate a novel therapeutic action of M. nigra leaves on hemochromatosis caused by iron overload.

Trans fat intake during pregnancy or lactation increases anxiety-like behavior and alters proinflammatory cytokines and glucocorticoid receptor levels in the hippocampus of adult offspring.

Changes in dietary habits, including the increased consumption of processed foods, rich in trans fatty acids (TFA), have profound effects on offspring health in later life. Thus, this study aimed to assess the influence of maternal trans fat intake during pregnancy or lactation on anxiety behavior, as well as markers of inflammation, oxidative stress, and expression of glucocorticoid receptors (GR) of adult male offspring. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0 g/kg body weight) during pregnancy or lactation. After weaning, male offspring received only standard diet. On the postnatal day 60, anxiety-like symptoms were assessed, the plasma was collected for the quantification of cytokines levels and the hippocampus removed for biochemical and molecular analysis. Our findings have evidenced that offspring from HVF-supplemented dams during pregnancy or lactation showed significantly greater levels of anxiety behavior. HVF supplementation increased plasma levels of proinflammatory cytokines and these levels were higher in the lactation period. In contrast, HVF supplementation decreased plasma levels of IL-10 in relation to SO/FO in both periods. Biochemical evaluations showed higher reactive species generation, protein carbonyl levels and catalase activity in offspring from HVF-supplemented dams during lactation. In addition, offspring from HVF-supplemented dams showed decreased GR expression in both supplemented periods. Together, these data indicate that consumption of TFA in different periods of development may increase anxiety-like behavior at least in part via alterations in proinflammatory and anti-inflammatory cytokine levels and GR expression in limbic brain regions.

DNA damage and inflammatory response in workers exposed to fuels and paints.

Workers exposed to fuels and paints may present alterations in several parameters. Thus, we assessed potential biomarkers, with the aim of detecting early changes in gasoline station attendants and painters. Blood samples were collected for the analysis of inflammatory and DNA damage markers, besides biochemical, haematological and oxidative stress parameters. Biochemical and haematological parameters, which are assessed with routine exams, showed few changes. However, these findings could mask the workers' real health status. Besides, markers of oxidative damage were not modified. Levels of inflammatory parameters (cytokines and nitric oxide levels) and the DNA damage marker 8-hydroxydeoxyguanosine were significantly changed in the workers. Our results suggest that inflammatory and DNA damage parameters can be potential biomarkers for the biological monitoring of workers exposed to fuels and paints and may contribute to the development of occupational protection standards.

Intra-octahedral distortion on lamellar potassium niobate K4Nb6O17: a periodic DFT study of structural, electronic and vibrational properties.

Structural, electronic and spectroscopic properties of the anhydrous K4Nb6O17 niobate were investigated in the bulk phase using periodic density functional theory (DFT) calculations with global hybrid (B3LYP) and also including dispersion corrections (B3LYP-D3). The degree of native distortion of different niobium octahedra (here named [NbO6-x], or [NbO6]d) were quantified in terms of the effective coordination number (ECoN) and of other classical descriptors of local deformation and were correlated with the electronic structure. The effect of intrinsic deformation was also examined using the quantum theory of atoms in molecules and crystals (QTAIMC), density of states and charge analyses. The nature of the atom-atom interactions was classified by the ratio of the potential to the kinetic energy density at the bcp (3,-1): |V(rbcp)|/|G(rbcp)|, demonstrating that intraoctahedral Nb-O interactions are well characterized as "transit bond" (between the pure covalent and ionic chemical bonds). The vibrational spectra (infrared and Raman intensities) were fully characterized and discussed, correlating the frequencies with the intraoctahedral distortion.

Probing the Site-Selective Doping in SrSnO3:Eu Oxides and Its Impact on the Crystal and Electronic Structures Using Synchrotron Radiation and DFT Simulations.

The impact of Eu3+ doping at the Sr2+ and Sn4+ sites in SrSnO3 on its structural and electronic properties was studied and correlated with the photocatalytic efficiency. The compounds were synthesized using a modified Pechini method. Refinement of the synchrotron X-ray diffraction (S-XRD) data showed that the samples had an orthorhombic Pbnm symmetry. The incorporation of Eu into the lattice led to increased short- and long-range disorder, inducing additional distortion in the SnO6. XANES measurements revealed that mixed Eu valences (Eu3+ and Eu2+) were present in Eu-doped samples, and DFT calculations confirmed the presence of these ions at Sr2+/Sr4+ sites in the SrSnO3, resulting in changes in the electronic behavior. The catalytic performance toward Remazol yellow dye photodegradation and the catalysts' surface properties were also evaluated. The catalytic efficiency followed the order of Sr(Sn0.99Eu0.01)SnO3 > (Sr0.99Eu0.01)SnO3 > SrSnO3. The order was clearly related to selected-site doping that changed the degree of the inter- and intraoctahedral distortion and the introduction of different Eu midgap states, which apparently favor charge separation upon photoexcitation during photocatalysis. The results shown here are of great importance to the functionalization of SrSnO3 and other perovskite materials by lanthanoid ions, especially Eu3+, for effective applications as photocatalysts.

Superoxide imbalance triggered by Val16Ala-SOD2 polymorphism increases the risk of depression and self-reported psychological stress in free-living elderly people.

BACKGROUND: Oxidative stress and chronic inflammatory states triggered by a single-nucleotide polymorphism (SNP) in superoxide dismutase manganese-dependent gene (Val16Ala-SOD2) have been associated with the risk of developing several chronic, nontransmissible diseases. However, it is still not clear whether the VV-SOD2 genotype that causes higher basal superoxide anion levels has any impact on the risk for depression and self-reported psychological stress in elderly people. METHODS: In the present study, we tested this hypothesis using a case-control study where depression was detected using the Geriatric Depression Scale-15 (GDS-15). A total of 612 Brazilian free-living elderly subjects with a mean age of 67.1 ± 7.1 years old (number of controls, C = 497, and depressive individuals, D = 115) were included in this study. All participants had similar social, health, and lifestyle variables, with the exception of polypharmacy (≥5 medicines daily intake), which was higher in the D group, compared to C subjects. RESULTS: Our results showed that the VV-SOD2 genotype significantly increased the risk for depression and psychological stress in the elderly subjects, independently of sex/gender, age, and other prior diseases and health indicators (depression risk = 1.842, 1.109-3.061 95% CI, p = .018). VV-subjects also had a higher daily intake of antidepressants, anxiolytics, and anti-inflammatory drugs than A-allele subjects. CONCLUSION: Our findings support the hypothesis that genetically induced oxidative superoxide-hydrogen peroxide imbalance may be involved in an increased risk for developing depression and psychological stress in free-living elderly people without other chronic nontransmissible diseases.

Interaction between low-level laser therapy and Guarana (Paullinia cupana) extract induces antioxidant, anti-inflammatory, and anti-apoptotic effects and promotes proliferation in dermal fibroblasts.

BACKGROUND: Low-level laser therapy (LLLT) has several clinical applications; however, its benefits are not universal. Therefore, combination therapy with LLLT and extracts from the guarana (Paullinia cupana) plant may improve its effectiveness as guarana extracts exhibit anti-aging properties. OBJECTIVES: To evaluate the antioxidant, anti-inflammatory, anti-apoptotic, and proliferative effects of combined LLLT and guarana extract therapy on human dermal fibroblasts. METHODS: Human dermal fibroblasts (HFF-1) were cultured and initially exposed to several concentrations (1, 3, 5, 10, 30 µg/mL) of guarana extract. The experimental concentration of guarana extract was selected by analyzing cytokine levels, DNA oxidation, and apoptotic markers in LLLT-exposed (4 J/cm2 ) and LLLT-unexposed fibroblast cultures. After 72 hours, the cells were analyzed using spectrophotometric, fluorimetric, immunological, and gene expression (qRT-PCR) assays. Flow cytometry was used to evaluate the effect of each treatment on cell cycle. RESULTS: Fibroblasts treated with guarana (5 µg/mL) exhibited anti-inflammatory and anti-apoptotic properties been used in complementary protocols. Combined guarana and LLLT treatment significantly decreased protein carbonylation, lipoperoxidation, and DNA oxidation, downregulated the mRNA and protein expression of pro-inflammatory molecules, and upregulated IL-10 gene and protein expression. Guarana plus LLLT also decreased the levels of caspases 1, 3, and 8, increased the percentage of S-phase cells, and decreased FGF-1 and KGF-1 levels. Some of these changes were also observed after treatment with guarana or LLLT alone. CONCLUSIONS: Our results suggest that concomitant treatment with guarana and LLLT may promote fibroblast biostimulation and thus is clinically relevant.

Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes.

BACKGROUND: The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers. METHODS: A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron. RESULTS: The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile. CONCLUSIONS: Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.

Gamma-hexalactone flavoring causes DNA lesion and modulates cytokines secretion at non-cytotoxic concentrations.

BACKGROUND: The γ-hexalactone is a flavoring agent for alcoholic beverages, teas, breads, dairy products, coffees, buttery products among others. It presents low molecular weight and exhibits sweet fruity aroma with nuances of nuts. As far as we know, both literature and government regulations have gaps regarding the safe use of the γ-hexalactone. In this context, the main objective of this work was to evaluate the effects of γ-hexalactone through in silico and in vitro approaches. METHODS: The in silico analysis was performed through four free online platforms (admetSAR, Osiris Property Explorer®, pkCSM platform and PreADMET) and consisted of comparative structural analysis with substances present in databases. The computational prediction was performed in the sense of complement and guide the in vitro tests. Regarding in vitro investigations, screening of cytotoxicity (assessed by cell proliferation and viability parameters) in lymphocytes exposed to γ-hexalactone for 72 h were carried out previously to determine non-cytotoxic concentrations. Following this screening, concentrations of 5.15, 0.515, and 0.0515 µM were selected for the study of the respective potentials: genotoxic (assessed by DNA comet assay), chromosomal mutation (analysis of micronucleus frequency) and immunomodulatory (cytokine quantification using ELISA immunoassay). The results of in vitro assays were compared by one-way analysis of variance (ANOVA), followed by Bonferroni's post hoc test, conducted by statistic software. RESULTS: The platform PreADMET pointed out that γ-hexalactone is potentially mutagenic and carcinogenic. The comet assay data corroborate with these results demonstrating that γ-hexalactone at 5.15 µM caused lymphocytes DNA damage. In relation to cytokine secretion, the results indicate that lymphocytes were activated by γ-hexalactone at non-cytotoxic concentrations, involving an increase in the IL-1 levels in all tested concentrations, ranging from approximately 56 to 93%. The γ-hexalactone only at 5.15 µM induced increase in the levels of IL-6 (~ 60%), TNF-α (~ 68%) and IFN-γ (~ 29%), but decreased IL-10 (~ 46%) in comparison with the negative control (p < 0.05). No change was observed in total lymphocytes or in cell viability at the concentrations tested. CONCLUSIONS: In summary, the γ-hexalactone demonstrated immunomodulatory and genotoxic effects at non-cytotoxic concentrations in healthy lymphocytes.

Association between Urinary Levels of Interleukin-6, Interleukin-10 and Tumor Necrosis Factor-Alpha with Glomerular and Tubular Damage Indicators in Patients with Type 2 Diabetes.

BACKGROUND: This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D. RESULTS: Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile. CONCLUSIONS: Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.

Caffeinated beverages contribute to a more efficient inflammatory response: Evidence from human and earthworm immune cells.

The role of caffeinated beverages on efficiency of acute inflammatory responses is not yet fully understood. This study analyzed the effect of five hot water extracts, coffee (CO), black/green tea (BT/GT), yerba mate (YM), and guarana (GU) on inflammatory modulation of non-activated human peripheral blood mononuclear cells (PBMCs), yeast-activated human neutrophils, and granulocytic coelomocytes from Eisenia fetida earthworm. Based on preliminary tests, a concentration of 10 µg/mL was chosen for subsequent assays, as at this concentration, the extracts exhibited antioxidant, genoprotective, and non-cytotoxic properties. Immunoassays using 24-h PBMC supernatant showed that all extracts decreased levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IFN-γ), and increased levels of the anti-inflammatory cytokine, IL-10. Further, these extracts induced overexpression of cytokine genes in 24-h cultures. These results suggest that an increase in the levels of mRNAs and/or inactive cytokines in the cytoplasm improves the "immune cytokine response. Analysis of the yeast encapsulation processes, and production of human neutrophils and coelomocyte extracellular DNA traps suggests that extracts also improve the immune response in humans and earthworms. However, for E. fetida, the intensity of these results varied from extract. Overall, our results suggest that caffeinated beverages may improve an organism's efficiency against acute inflammatory processes.

The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells.

Pyridostigmine bromide (PB), an acetylcholinesterase (AChE) enzyme inhibitor. Experimental evidence showed that when combined with other drugs or exercise, PB caused extensive neural and/or systemic oxidative stress. However, no studies have been conducted on the genetic influence associated with basal oxidative superoxide-hydrogen peroxide (S-HP) imbalance, such as that triggered by Val16Ala-SOD2 single nucleotide polymorphism (SNP, rs4880). This SNP, (homozygous genotypes) has been associated with several chronic degenerative disorders. Therefore, we evaluated whether the SOD-SNP could alter cyto-genotoxic effects triggered by different PB-concentrations in peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from volunteers carrying different SOD2-genotypes and were cultured with various concentrations of PB. PB effects in quantity of enzyme AChE, mortality rate, oxidative stress markers, and DNA damage were assessed. Protein and gene expression of antioxidant enzymes, apoptotic markers and DNA repair enzyme, were evaluated in 24 h cultures. In general, PB up-regulated expression of antioxidant enzymes, and did not trigger apoptotic events. However, AA-PBMCs seemed more sensitive to PB exposure, in a protein decrease of the enzyme AChE by 10%, cell-mortality at concentrations of 20 and 40 ng/mL, protein carbonylation, and DNA damage, as analyzed by the Comet assay. Contrarily, PB demonstrated cyto-genoprotective effects on V-allele cells. These results indicated that genetic factors that increase HP-release may affect PB efficiency and safety.