Estado redox en pacientes con cáncer de pulmón de células no pequeñas en estadios avanzados tratados con poliquimioterapia / Redox Status in Patients with non-small Cell Lung Cancer in Advanced Stages Treated with Polychemotherapy

RESUMEN Fundamento: en estadios avanzados del cáncer de pulmón de células no pequeñas el tratamiento se basa fundamentalmente en la poliquimioterapia. Estudios previos relacionan el desarrollo de resistencia al cisplatino con el aumento de los niveles del glutatión celular, mientras que, la depleción de este tripéptido se ha asociado con una mayor sensibilidad a este fármaco. Objetivo: evaluar el efecto de la poliquimioterapia con cisplatino y vinblastina en los niveles intracelulares de glutatión y en el estado redox celular en pacientes con cáncer de pulmón de células no pequeñas en estadios avanzados. Métodos: se realizó un estudio de casos y controles en el que se incluyeron 38 pacientes con cáncer de pulmón de células no pequeñas en estadios IIIb-IV, que concluyeron el esquema de tratamiento con cisplatino y vinblastina y 25 individuos aparentemente sanos como grupo control en el período correspondiente al período de mayo del 2016 a mayo del 2018 en el Hospital Neumológico Benéfico Jurídico de la Habana. Las concentraciones intraeritrocitarias del glutatión reducido y oxidado fueron determinadas mediante un método de HPLC-UV. El estado redox celular se calculó mediante la ecuación de Nerst. Los resultados se expresaron como medias y desviación estándar. Se utilizó la prueba no paramétrica U-Mann Whitney para la comparación de las medias aritméticas de las variables de respuesta. Resultados: después del tratamiento se apreció una disminución de las concentraciones de glutatión reducido (920 µM vs. 1252 µM; p=0,036) así como, cambios en el estado redox celular (-338,4 mV vs. -353,2 mV; p=0,029) en contraste con los controles. Conclusiones: la quimioterapia combinada con cisplatino induce una disminución de los niveles glutatión reducido y cambios en el estado redox celular. Estos efectos pueden contribuir a una mayor supervivencia en los pacientes que responden al tratamiento.

ABSTRACT Background: in advanced stages of non-small cell lung cancer, treatment is fundamentally based on polychemotherapy. Previous studies relate the development of resistance to cisplatin with increased levels of cellular glutathione, while depletion of this tripeptide has been associated with greater sensitivity to this drug. Objective: to evaluate the effect of polychemotherapy with cisplatin and vinblastine on intracellular glutathione levels and cellular redox status in patients with non-small cell lung cancer in advanced stages. Methods: a case-control study was carried out that included 38 patients with non-small cell lung cancer in stages IIIb-IV, who completed the treatment scheme with cisplatin and vinblastine, and 25 apparently healthy individuals as a control group from May 2016 to May 2018 at the Benéfico Jurídico Pneumological Hospital in Havana. The intraerythrocyte concentrations of reduced and oxidized glutathione were determined by an HPLC-UV method. The cellular redox state was calculated using the Nerst equation. The results were expressed as means and standard deviation. The non-parametric U-Mann Whitney test was used to compare the arithmetic means of the response variables. Results: after treatment, a decrease in reduced glutathione concentrations (920 µM vs. 1252 µM; p=0.036) was observed, as well as changes in the cellular redox state (-338.4 mV vs.-53.2 mV; p=0.029) in contrast to controls. Conclusions: chemotherapy combined with cisplatin induces a decrease in reduced glutathione levels and changes in the cellular redox state. These effects may contribute to increased survival in patients who respond to treatment.

Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study / 浙江大学学报·医学版

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.

Vitamin D analogues activate vitamin D receptor/glutathione peroxidase 4 pathway to improve ventilator-induced lung injury in mice / 中华危重病急救医学

Objective:To investigate the role of vitamin D analogue paricalcitol in activating vitamin D receptor/glutathione peroxidase 4 (VDR/GPX4) pathway in ventilator-induced lung injury (VILI).Methods:Twenty-four male C57BL/6J mice were randomly divided into control group, high tidal volume (HVT) induced VILI model group (HVT group), paricalcitol control group (P group), and paricalcitol pretreatment group (P+HVT group), with 6 mice in each group. The mice were endotracheal intubated and ventilated at 40 mL/kg tidal volume to prepare VILI model, while those in the control group were intubated without ventilation. The mice in the P+HVT group were intraperitoneally injected with paricalcitol 0.2 μg/kg once a day 1 week before modeling, while those in the P group were intraperitoneally injected paricalcitol 0.2 μg/kg once a day for 1 week before the experiment. After ventilation for 4 hours, the mice were sacrificed for lung tissue collection. Lung injury was evaluated by wet/dry (W/D) ratio, hematoxylin-eosin (HE) staining and Masson staining. The expressions of VDR and GPX4 were determined by Western blotting and immunohistochemistry. Malondialdehyde (MDA) and glutathione (GSH) contents were determined by micro method.Results:After HVT for 4 hours, compared with the control group, lung injury score and W/D ratio were significantly higher (lung injury score: 0.430±0.035 vs. 0.097±0.025, lung W/D ratio: 4.860±0.337 vs. 3.653±0.332, both P < 0.05), collagen fiber deposition was significantly increased, the content of MDA in lung tissue was significantly increased (nmol/g: 212.420±8.757 vs. 97.073±5.308, P < 0.05), GSH content and the protein expressions and immunoreactive score (IRS) of VDR and GPX4 were significantly decreased [GSH (μg/g): 44.229±1.690 vs. 70.840±0.781; VDR protein (VDR/GAPDH): 0.518±0.029 vs. 0.762±0.081, GPX4 protein (GPX4/GAPDH): 0.452±0.032 vs. 0.649±0.034; IRS score: VDR was 4.168±0.408 vs. 10.167±0.408, GPX4 was 4.333±1.033 vs. 10.333±0.516; all P < 0.05], which meant that the mice in HVT group showed obvious lung injury. After VDR was activated by paricalcitol, compared with the HVT group, lung injury score and W/D ratio were significantly decreased (lung injury score: 0.220±0.036 vs. 0.430±0.035, lung W/D ratio: 4.015±0.074 vs. 4.860±0.337, both P < 0.05), collagen fiber deposition was reduced, MDA content in lung tissue was decreased (nmol/g: 123.840±8.082 vs. 212.420±8.757, P < 0.05), GSH content and the protein expressions and IRS score of VDR and GPX4 were significantly up-regulated [GSH (μg/g): 63.094±0.992 vs. 44.229±1.690; VDR protein (VDR/GAPDH): 0.713±0.056 vs. 0.518±0.029, GPX4 protein (GPX4/GAPDH): 0.605±0.008 vs. 0.452±0.032; IRS score: VDR was 9.000±0.632 vs. 4.168±0.408, GPX4 was 8.833±0.408 vs. 4.333±1.033; all P < 0.05], which meant that lung injury in P+HVT group was significantly improved. Conclusion:Vitamin D analogue paricalcitol ameliorates pulmonary oxidation-reduction imbalance by activating the VDR/GPX4 pathway, thereby alleviating VILI.

Treino de Força Reduz Stress Oxidativo Cardíaco e Renal em Ratos com Hipertensão Renovascular / Strength Training Reduces Cardiac and Renal Oxidative Stress in Rats with Renovascular Hypertension

Resumo Fundamento O treino de força tem efeitos benéficos em doenças renais, além de ajudar a melhorar a defesa antioxidante em animais saudáveis. Objetivo Verificar se o treino de força reduz o dano oxidativo ao coração e rim contralateral para cirurgia de indução de hipertensão renovascular, bem como avaliar as alterações na atividade das enzimas antioxidantes endógenas superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx). Métodos Dezoito ratos machos foram divididos em três grupos (n=6/grupo): placebo, hipertenso e hipertenso treinado. Os animais foram induzidos a hipertensão renovascular através da ligação da artéria renal esquerda. O treino de força foi iniciado quatro semanas após a indução da hipertensão renovascular, teve 12 semanas de duração e foi realizada a 70% de 1RM. Depois do período de treino, os animais foram submetidos a eutanásia e o rim esquerdo e o coração foram retirados para realizar a quantificação de peróxidos de hidrogênio, malondialdeído e grupos sulfidrílicos, que são marcadores de danos oxidativos. Além disso, foram medidas as atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. O nível de significância adotado foi de 5% (p < 0,05). Resultados Depois do treino de força, houve redução de danos oxidativos a lipídios e proteínas, como pode-se observar pela redução de peróxidos de hidrogênio e níveis sulfidrílicos totais, respectivamente. Além disso, houve um aumento nas atividades das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase. Conclusão O treino de força tem o potencial de reduzir danos oxidativos, aumentando a atividades de enzimas antioxidantes. (Arq Bras Cardiol. 2021; 116(1):4-11)

Abstract Background Strength training has beneficial effects on kidney disease, in addition to helping improve antioxidant defenses in healthy animals. Objective To verify if strength training reduces oxidative damage to the heart and contralateral kidney caused by the renovascular hypertension induction surgery, as well as to evaluate alterations in the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) endogenous antioxidant enzymes. Methods Eighteen male rats were divided into three groups (n=6/group): sham, hypertensive, and trained hypertensive. The animals were induced to renovascular hypertension through left renal artery ligation. Strength training was initiated four weeks after the induction of renovascular hypertension, continued for a 12-weeks period, and was performed at 70% of 1RM. After the training period, the animals were euthanized and the right kidney and heart were removed for quantitation of hydroperoxides, malondialdehyde and sulfhydryl groups, which are markers of oxidative damage. In addition, the activity of SOD, CAT, and GPx antioxidant enzymes was also measured. The adopted significance level was 5% (p < 0.05). Results After strength training, a reduction in oxidative damage to lipids and proteins was observed, as could be seen by reducing hydroperoxides and total sulfhydryl levels, respectively. Furthermore, an increased activity of superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzymes was observed. Conclusion Strength training is able to potentially reduce oxidative damage by increasing the activity of antioxidant enzymes. (Arq Bras Cardiol. 2021; 116(1):4-11)

Research progress on metabolism and efficacy of small molecular prodrug nanosystems responsive to tumor redox microenvironment / 药学学报

Compared with normal tissues and cells, the tumor microenvironment has significant differences. For example, glutathione-related metabolic enzymes and reactive oxygen species are highly expressed in different subcellular structures, resulting in an unbalanced redox state. Aiming at the specific redox state in tumor tissues and cells, a series of small molecule prodrug self-assembled nanoparticles can be designed and connected by intelligent response linkers including disulfide bonds, sulfide bonds, and selenium bonds, thioketal bonds, etc. The in vitro and in vivo efficiency and metabolic mode of these nanoparticles are related to the type of linker. This review will summarize the tumor redox microenvironment, the design of intelligent responsive small molecule prodrug nanoparticles, and the metabolic pathways of small molecule prodrug nanoparticles with different connecting linkers and their relationship with drug efficacy.

Correlation of oxidation reduction potential and total motile sperm count: Its utility in the evaluation of male fertility potential / 亚洲男科学杂志(英文版)

Oxidative stress (OS) is detrimental to sperm functions, and the oxidation reduction potential (ORP) is a good measure of OS as it considers the balance between oxidants and reductants. Total motile sperm count (TMSC) is viewed as the single most important semen analysis parameter that can predict male infertility severity, and its correlation with ORP has never been undertaken. The objectives of this study were to assess the correlation between ORP and TMSC, to identify the ORP cutoff value based on the TMSC result, and to compare this cutoff value with previously reported ORP cutoff values in literature. One thousand one hundred and sixty-eight infertile patients and 100 fertile controls were enrolled. Demographic and semen data of the participants were retrieved and analyzed. Wilcoxon's rank-sum test compared variables between infertile men and fertile controls; Spearman's correlation assessed the static ORP (sORP)-TMSC relationship for the whole sample and among each group individually. Using a 20×106TMSC threshold, receiver operator characteristic (ROC) analysis determined the sORP cutoff associated with the highest predictive values. TMSC was significantly negatively correlated with sORP across all participants (r = 0.86, P < 0.001), among infertile patients (r = 0.729, P < 0.001), and among fertile controls (r = 0.53, P < 0.001). A 20-million TMSC threshold determined an sORP cutoff value of 2.34 mV/106sperm/ml to be associated with 82.9% sensitivity, 82.8% specificity, 91.5% positive predictive value (PPV), 68.5% negative predictive value (NPV), and 82.9% overall accuracy. Compared with previously reported cutoff values in searched literature, the 2.34 mV/106sperm/ml cutoff value identified in our study yielded the highest overall diagnostic accuracy in the evaluation of infertile men.

Study on component-target-pathway multiple interactive network to reveal mechanism of Salvia miltiorrhiza in treatment of microcirculation disturbance / 中草药

Objective: To explore the mechanism of Salvia miltiorrhiza in treatment of microcirculatory disturbance based on network pharmacology. Methods: The targets of S. miltiorrhiza’s active components for treatment of microcirculatory disturbance were screened and predicted by utilizing TCMSP, PubChem Search, Genecards database and Swiss target prediction online tool. Cytoscape 3.3.0 software was adopted to construct an active component-microcirculatory disturbance target network. The protein-protein interaction (PPI) network was established by using STRING database. DAVID database was used to analyze metabolism pathway in target gene ontology (GO) biological process, Kyoto encyclopedia of genes and gnomes (KEGG). Results: Totally 65 active components of S. miltiorrhiza and nine related targets were screened. GO and KEGG pathway enrichment analysis revealed that active components of S. miltiorrhiza participated in oxidation-reduction process, cellular calcium ion homeostasis and other biological processes, and S. miltiorrhiza may regulate VEGF signaling pathway, cholinergic synapse signal transduction, oxytocin signaling pathway, aldosterone-regulated sodium reabsorption pathway and so on. Conclusion: This study reflects the characteristics of multi-components, multi-targets, and multi-pathways of S. miltiorrhiza in the treatment of microcirculation disturbance, which may provide new ideas and methodology for further research on the treatment of microcirculatory disturbance using S. miltiorrhiza.

Kidney Disease in Diabetes Mellitus: Cross-Linking between Hyperglycemia, Redox Imbalance and Inflammation / Doença Renal do Diabetes: Cross-Linking entre Hiperglicemia, Desequilíbrio Redox e Inflamação

Abstract Chronic hyperglycemia is the key point of macro- and microvascular complications associated with diabetes mellitus. Excess glucose is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease, which is currently the leading cause of dialysis in the world. The pathogenesis of the disease is complex, multifactorial and not fully elucidated; many factors and mechanisms are involved in the development, progression and clinical outcomes of the disease. Despite the disparate mechanisms involved in renal damage related to diabetes mellitus, the metabolic mechanisms involving oxidative/inflammatory pathways are widely accepted. The is clear evidence that a chronic hyperglycemic state triggers oxidative stress and inflammation mediated by altered metabolic pathways in a self-perpetuating cycle, promoting progression of cell injury and of end-stage renal disease. The present study presents an update on metabolic pathways that involve redox imbalance and inflammation induced by chronic exposure to hyperglycemia in the pathogenesis of diabetic kidney disease.

Resumo A hiperglicemia crônica é o ponto-chave das complicações macro e microvasculares associadas ao diabetes mellitus. O excesso de glicose é responsável por induzir desequilíbrio redox e inflamação sistêmica e intra-renal, desempenhando um papel crítico na patogênese da doença renal do diabetes, configurada atualmente como a principal causa de doença renal dialítica em todo o mundo. A patogênese da doença é complexa, multifatorial e, não totalmente elucidada, estando vários fatores e mecanismos associados ao seu desenvolvimento, progressão e desfechos clínicos. Apesar dos mecanismos díspares envolvidos nos danos renais durante o diabetes, os caminhos metabólicos pela via oxidativa/inflamatória são amplamente aceitos e discutidos. As evidências acentuam que o estado hiperglicêmico crônico desencadeia o estresse oxidativo e a inflamação mediada por diversas vias metabólicas alteradas em um ciclo-vicioso de autoperpetuação, promovendo aumento da injúria celular e progressão para a doença renal dialítica. O presente artigo traz, portanto, uma atualização sobre os caminhos metabólicos que envolvem o desequilíbrio redox e a inflamação induzidos pela exposição crônica à hiperglicemia na patogênese da doença renal do diabetes.

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Multi-center evaluation of oxidation-reduction potential by the MiOXSYS in males with abnormal semen / 亚洲男科学杂志(英文版)

According to the World Health Organization (WHO), oxidative stress (OS) is a significant contributor to male infertility. Seminal OS can be measured by a number of assays, all of which are either costly or time sensitive and/or require large semen volume and complex instrumentation. One less expensive alternative is to quantify the oxidation-reduction potential (ORP) with the MiOXSYS. In this international multi-center study, we assessed whether ORP levels measured by the MiOXSYS could distinguish semen samples that fall within the 2010 WHO normal reference values from those that do not. Semen samples were collected from 2092 patients in 9 countries; ORP was normalized to sperm concentration (mV/106 sperm/ml). Only those samples with a concentration >1 × 106 sperm ml-1 were included. The results showed that 199 samples fell within the WHO normal reference range while the remaining 1893 samples did not meet one or more of the criteria. ORP was negatively correlated with all semen parameters (P < 0.01) except volume. The area under the curve for ORP was 0.765. The ORP cut-off value (1.34 mV/106 sperm/ml) was able to differentiate specimens with abnormal semen parameters with 98.1% sensitivity, 40.6% specificity, 94.7% positive predictive value (PPV) and 66.6% negative predictive value (NPV). When used as an adjunct to traditional semen analysis, ORP levels may help identify altered functional status of spermatozoa caused by OS in cases of idiopathic male infertility and in male partners of couples suffering recurrent pregnancy loss, and thereby directing these men to relevant medical therapies and lifestyle modifications.

Hydrogen productivity of hydrogen-rich sticks increased by ammonium salt / 军事医学

Objective To measure the catalytic effect of ammonium salt solution on hydrogen production , and analyze the relationships between hydrogen concentration and oxygen concentration , oxidation-reduction potential , and pH in solution . Methods Magnesium and water reacted at different concentrations of NH4Cl, (NH4)2SO4, NH4HCO3,(NH4)2CO3, NaHCO3 and Na2SO3 in 40℃water bath for 0, 2, 4, 6, 8 and 10 hours, and above-mentioned four indicators of ammonium salt solution were measured after these reactions .Results The hydrogen concentration in the solution increased with the reaction time and the concentration of the ammonium salt solution .Oxygen concentration and oxidation-reduction potential decreased .The hydrogen concentration in the solution was significantly negatively correlated with the oxygen concentration (r=-0.984).pH increased with the hydrogen concentration in the ammonium salt solution .Conclusion The ammonium salt solution has a good catalytic effect on magnesium and water reaction .NH4Cl has the strongest catalytic effect under the same reaction conditions,followed by (NH4)2SO4, NH4HCO3 and (NH4)2CO3.Thus, this study can provide detailed data on hydrogen production in different solutions .

The synergistic mechanisms of oxidized phospholipids and lipoprotein-associated phospholipase A2 associated with Lp ( a ) in promoting atherosclerosis / 中华检验医学杂志

Lipoprotein ( a ) [ Lp ( a ) ] is considered a causal risk factor for the formation and development of atherosclerosis ( AS).High plasma levels of Lp ( a) is recognized as a predictor of coronary heart disease. However, the pathogenic mechanisms of Lp ( a ) are still unknown. Recent studies demonstrated that a key role in the proatherogenic effects of Lp ( a ) may be linked to its oxidized phospholipids ( OxPL) content.Lipoprotein-associated phospholipase A 2 ( Lp-PLA2 ) is another important factor in Lp( a) functionality.OxPL are hydrolyzed by Lp-PLA2 into lysophosphatidylcholine ( lyso-PC) and oxidized free fatty acid(OxFFA), which are important inflammatory factors on promoting the occurrence and development of AS.The present review article describes Lp-PLA2 hydrolyzing OxPL associated with Lp (a). The process induces inflammatory factors , which promote development of AS .OxPL and Lp-PLA2 can be used as new targets of cardiovascular diseases , which have clinical application value to predict potential cardiovascular diseases .

Modificaciones en el nivel de anión superóxido en leche materna, según la ingesta de flavonoides y carotenoides / Modifications of the superoxide anion level in breast milk by the intake of flavonoids and carotenoids

Resumen: Objetivo: Asociar la ingesta de flavonoides y carotenoides con el nivel en leche materna del anión superóxido, como marcador de estrés oxidativo. Material y métodos: Durante el periodo 2013-2015 se estudió a 100 mujeres lactantes de Córdoba (Argentina), dentro los primeros seis meses posparto; se evaluaron sus datos sanitarios, ingesta alimentaria y nivel lácteo del anión con regresión logística múltiple. Resultados: La ingesta de flavonoides, carotenoides provitamínicos y carotenoides no provitaminas fue de 72 (61) mg/día, 1 813 (1657) µg/día y 5 427 (3664) µg/día, respectivamente. El anión se asoció con la ingesta de flavanoles (RM=1.081; IC95 1.001-1.167) y flavanonas (RM=1.025; IC95 1.001-1.048). No se observó este efecto con otros flavonoides ni con los carotenoides. Conclusiones: La ingesta de flavanoles y flavanonas aumenta el riesgo de oxidación láctea, lo cual es relevante para realizar recomendaciones dietéticas.

Abstract: Objective: To associate the intake of flavonoids and carotenoids with the breast milk level of superoxide anion, as an oxidative stress marker. Materials and methods: 100 women from Cordoba (Argentina), who breastfed within the first postpartum 6 months, were studied during the 2013-2015 period, by evaluating their sanitary data, food intake and anion level in milk with multiple logistic regression. Results: The intake of flavonoids, provitamin A carotenoids and non-provitamin carotenoids was 72 (61) mg/d, 1813 (1 657) µg/d y 5427 (3 664) µg/d, respectively. The anion was associated with the intake of flavanols (OR=1.081; CI95 1.001-1.167) y flavanones (OR=1.025; CI95 1.001-1.048). This effect was not seen with other flavonoids and carotenoids. Conclusions: Intake of flavanols and flavanones increases milk oxidation risk, which is relevant to develop diet recommendations.

Rabdomiólise como manifestação de uma doença metabólica: relato de caso / Rhabdomyolysis as a manifestation of a metabolic disease: a case report

RESUMO A rabdomiólise é um processo de destruição muscular com manifestações clínicas variáveis. Em pacientes pediátricos, tem como principal etiologia as doenças infecciosas. Apresentamos o caso de uma adolescente previamente saudável, que foi admitida ao nosso pronto-socorro com histórico de 4 dias com mialgia, fraqueza muscular e urina escura. Na avaliação inicial, apresentava-se desidratada. Os exames de sangue revelaram insuficiência renal aguda e aumento de enzimas musculares. A paciente foi transferida para nossa unidade de terapia intensiva pediátrica. Foi realizado tratamento clínico para correção da desidratação e das consequências iônicas e metabólicas da insuficiência renal. Em razão da oligúria, deu-se início à terapia de substituição renal. A investigação etiológica revelou um defeito da betaoxidação. Sabe-se que doenças metabólicas podem provocar rabdomiólise. A destruição muscular deve ser identificada precocemente, para evitar suas potenciais consequências. Em geral, o tratamento da rabdomiólise é conservador, embora em algumas situações seja necessária uma abordagem mais invasiva.

ABSTRACT Rhabdomyolysis is a process of muscle destruction that can present with varying clinical manifestations. In pediatric patients, its main etiology is infectious diseases. We present a previously healthy adolescent who was admitted to our emergency department with a four-day history of myalgia, muscle weakness and dark urine. At presentation, she was dehydrated. Blood analysis revealed acute renal failure and increased muscular enzymes. She was transferred to our pediatric intensive care unit. Medical therapies for correction of dehydration and the ionic and metabolic consequences of renal failure were performed. Due to oliguria, renal replacement therapy was initiated. An etiological investigation revealed a beta-oxidation defect. Metabolic diseases are a known cause of rhabdomyolysis. Muscular destruction should be diagnosed early in order to avoid its potential consequences. Generally, the treatment of rhabdomyolysis is conservative, although in some situations, a more invasive approach is needed.

Role of oxidation reaction in decrease in activity of acetylcholinesterase in diaphragm of rats with sepsis / 中华麻醉学杂志

Objective To evaluate the role of oxidation reaction in the decrease in the activity of acetylcholinesterase (AChE) in the diaphragm of rats with sepsis.Methods Thirty pathogen-free healthy adult male Sprague-Dawley rats,weighing 220-260 g,were divided into 3 groups using a random number table:sham operation group (group S,n=8),sepsis group (group Sep,n =12) and antioxidant group (group Ant,n=10).Sepsis was induced by cecal ligation and puncture.Group S underwent simple laparotomy.N-acetylcystein 20 mg/kg was injected subcutaneously at 3,6,12 and 18 h after operation,and deferoxamine 20 mg/kg was injected subcutaneously at 3 h after operation in group Ant,while the equal volume of normal saline was given instead in S and Sep groups.At 24 h after operation,the surviving rats were sacrificed,and the diaphragm was removed for determination of the malondialdehyde (MDA) content and activities of AChE,myeloperoxidase (MPO),superoxide dismutase (SOD) and catalase (CAT).SOD/CAT ratio was calculated.Results Compared with group S,the AChE activity was significantly decreased,and MPO and SOD activities were increased in Sep and Ant groups,the MDA content and SOD/CAT ratio were significantly increased,and the CAT activity was decreased in group Sep,and the CAT activity was significantly increased in group Ant (P＜0.05).Compared with group Sep,the AChE and CAT activities were significantly increased,and the MDA content,MPO and SOD activities and SOD/CAT ratio were decreased in group Ant (P＜0.05).Conclusion Oxidation reaction is partially involved in the decrease in the activity of AChE in the diaphragm of rats with sepsis.

Effect of different solute solutions on hydrogen producing rate of hydrogen rods / 军事医学

Objective To investigate the hydrogen production rate of hydrogen rods in different solute solutions ,and to study the correlations between hydrogen and oxygen concentrations in the solution and the relationships between hydrogen and oxidation-reduction potential .Methods The hydrogen rich solution was produced using metal magnesium to react with water.The experiment was divided into NaCl , Na2SO3, Na2SO4, CH3COOH, and CH3COONa solution groups, respectively, with 0％, 0.2％, 0.9％and 3％in different concentration solutions .The hydrogen content of the corresponding solution was determined at 0, 2, 4, 6, 8, and 10 h.Moreover, the oxygen content in the solution , redox potential and pH value were simultaneously determined .Results Within the same reaction time , the higher concentration of NaCl , the higher the hydrogen production rate .The amount of hydrogen in the solution was negatively correlated with that of oxygen ( R2 =0.9306).The higher the hydrogen content, the lower the oxygen content.With the amount of hydrogen in the solution increasing, oxidation was reduced while pH was increased.The hydrogen-producing rate of hydrogen rods in different solute solutions was the highest with Na2SO3,followed by NaCl and Na2SO4(P<0.05 or P<0.01).In the acetic acid solution, the hydrogen-producing rate of rods was significantly higher than in the sodium salt solution (P<0.05).The hydrogen content increased gradually with time .The oxygen concentration was significantly lower than in the sodium salt solution ( P <0.05), and the oxygen content decreased over time .Conclusion The type and concentration of solutes in solutions and the oxygen content and acidity of a solution have significant influence on the hydrogen -producing rate of hydrogen rods. Therefore, by adjusting the type and concentration of solutes in the solution, we can prepare different types of hydrogen concentration solutions , which can provide detailed reference parameters for hydrogen production of hydrogen rods in clini -cal and practical applications.

Effects of age and gender on anti-inflammatory, anti-oxidative and anti-apoptosis functions of high-density lipoprotein / 中华老年医学杂志

Objective To investigate the effects of age and gender on anti-oxidative,antiinflammatory and anti-apoptosis functions of high-density lipoprotein (HDL).Methods Totally 120 healthy subjects aged from 20 to 60 years were randomly divided into young and middle-aged male (n=60) group and female (n =60) group,and the 120 healthy elderly aged from 60 to 78 years divided into elderly male (n =60) and elderly female (n =60) groups.Serum levels of high-and low-density lipoprotein cholesterol (HDL-C,LDL-C),total cholesterol (TC),and triacylglycerol (TG) were detected.Content of malonaldehyde (MDA) was detected to determine anti-oxidative function of HDL.Adhesion assay of endothelial cells and monocytes (THP1) was adopted to test the protective effects of HDL on endothelial cells.The expressions of endothelial cell adhesion molecules,VCAM-1 and ICAM-1,were analyzed by Western blot.MTT and flow cytometry assays were used to detect the viability and apoptosis of the cells to test anti-apoptosis function of HDL.Results The levels of low-density lipoprotein,triglycerides and total cholesterol were higher in elder female group than in other three groups (all P＜0.05).The level of HDL-C was higher in young and middle-aged females than in other three groups(all P＜0.05).The level of MDA was higher in elder female group than in other three groups(all P＜0.05).The level of MDA was higher in elder male group than in the young and middle-aged male and female groups(all P＜0.05).After protection of HDL,the number of monocytes adhesion and expression levels of VCAM-1 and ICAM-1 were higher in elder groups than in young and middle-aged male and female groups(all P＜ 0.05).Relative survival and viability rates of endothelial cells were higher in young and middle-aged groups than in elder groups (all P＜0.05).Conclusions Ageing in both male and female induces impairments of anti-oxidative,anti-inflammatory and anti-apoptosis functions of HDL,with more evident decrease in anti-oxidative function in females.

Proteínas relacionadas con el metabolismo del hierro corporal / Proteins associated with the metabolism of total body iron

RESUMEN Antecedentes: el hierro es uno de los minerales más estudiados; existe amplia información en cuanto a su metabolismo, función, interacciones y regulación; sin embargo, los estudios y análisis realizados se basan en proteínas específicas y pocos integran, en un solo texto, las características de estas moléculas relacionadas con el metabolismo del hierro corporal. Objetivo: profundizar en los aspectos moleculares, metabólicos y de modulación de las proteínas que participan en la homeostasis del hierro y en sus interacciones. Materiales y métodos se hizo una búsqueda sistemática de información en bases de datos científicas de artículos sobre el tema, publicados entre 2006 y 2016. Resultados: la homeostasis del hierro corporal, es un proceso complejo y altamente regulado por diferentes moléculas que participan de manera integrada en su metabolismo; en los últimos años han surgido nuevas proteínas, algunas de ellas participan en el transporte de otros nutrientes y se les ha encontrado relación con el control humoral y celular del hierro; además, involucran la participación de varios órganos, tejidos y sistemas. Esta revisión incluye proteínas encargadas de facilitar el aprovechamiento biológico del nutriente, así como aquellas que protegen a las células de toxicidad por exceso de este mineral.

ABSTRACT Background: Iron is an essential nutrient well studied for its role in human health, and much evidence exists regarding its metabolism, functions, interactions, and regulations. However, studies and analyses that have been done are often based on specific proteins and few integrate into a single text the characteristics of multiple proteins related to total body iron metabolism. Objective: Explore in-depth the molecular, metabolic, and modulation aspects of proteins that participate in iron homeostasis and related interactions. Materials and methods: A literature review was completed using scientific databases in conjunction with a search for related scientific articles published between 2006 and 2016. Results: Homeostasis of total body iron stores is a complex process that is highly regulated by various molecules that participate in an integrated manner in iron metabolism. In recent years, new proteins have been discovered regarding the humoral and cellular control of iron, some of which are also involved in the transport of other nutrients. Additionally, these proteins involve participation from various organs, tissues, and systems. This review includes proteins responsible for facilitating biological utilization of the nutrient, as well as those that protect cells from toxicity of this mineral.

Hydrogen-rich water prepared by hydrogen rods:an experimental study / 军事医学

Objective To verify the efficiency and stability of hydrogen-rich water preparation with hydrogen-rich rods. Methods ①Seven firenew hydrogen-rich rods were separately placed in seven plastic bottles, each filled with distilled water and soaked for 6 h, before the hydrogen concentration of the water was measured.This process was repeated 10 times.②After the hydrogen-rich rods with the strongest and weakest hydrogen product capacity were removed, the remaining 5 hydrogen-rich rods were placed separately into 5 plastic bottles filled with distilled water,put in a water bath pot at 20,40 and 60℃, respectively, and kept for 2, 4, 6, 8 and 10 h, respectively.Then, the hydrogen concentration, oxidation-reduction potential(ORP),and dissolved oxygen concentration(DO) were measured at various time points.③In order to determine the hydrogen emission rate from the hydrogen-rich water, the hydrogen-rich rods were constantly kept in some samples and the others were removed.All the sample bottle caps were kept open during the experimental process, and the hydrogen concentration was measured at such time points as 0, 10 and 30 min, 1, 2, 5, 12, 24, 30, 48 and 72 h, respectively.Results ①The hydrogen-rich rods used in this study could well meet the requirements.②When the environment temperature was kept constant, the hydrogen concentration of the water was increased with the soaking time of the hydrogen-rich rods, and the ORP of the water was reduced.However, the DO of the water was decreased with the rise of the environment temperature.③When the hydrogen-rich water was kept in opened plastic bottles with a 25 mm oral diameter, the hydrogen concentration of the samples with the hydrogen-rich rods reserved was almost about 0.50 ppm until 72 h, and that of the others was reduced to almost 0 ppm.Conclusion Our results demonstrate that the hydrogen-rich rods test is a simple and effective method for preparing hydrogen-rich water, which will be an valuable and useful method for using hydrogen-rich water in health promotion and prevention of chronic diseases.

Advances in IDH mutation in glioma / 肿瘤

Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylic acid cycle, catalyzing the conversion of isocitric acid to α-ketoglutaric acid (α-KG), using nicotinamide adenine dinucleotide (NAD+)/ nicotinamide adenine dinucleotide phosphate (NADP+) as its cofactor to produce NADH/NADPH. It has been recognized that more than 75% of low grade gliomas (WHO grade II and III) and 90% of secondary glioblastoma multiforme carry IDH gene mutation, with R132H mutation being predominant. IDH mutation may modulate epigenetic characteristics, reprogram cell metabolism, and perturb redox homeostasis of gliomas. Targeted inhibition of mutant IDH in glioma can suppress tumor progression and give birth to the novel anticancer medicines.