Significado biológico y utilidad clínica del lactato en la sepsis / Biological significance and clinical utility of lactate in sepsis

La sepsis es un problema global de salud y la progresión hacia el shock séptico se asocia con un incremento marcado de la morbimortalidad. En este escenario, el aumento del lactato plasmático demostró ser un indicador de gravedad y un predictor de mortalidad, y suele interpretarse casi exclusivamente como marcador de baja perfusión tisular. Sin embargo, últimamente se produjo un cambio de paradigma en la exégesis del metabolismo y propiedades biológicas del lactato. En efecto, la adaptación metabólica al estrés, aun con adecuado aporte de oxígeno, puede justificar la elevación del lactato circulante. Asimismo, otras consecuencias fisiopatológicas de la sepsis, como la disfunción mitocondrial, se asocian con el desarrollo de hiperlactatemia sin que necesariamente se acompañen de baja perfusión tisular. Interpretar el origen y la función del lactato puede resultar de suma utilidad clínica en la sepsis, especialmente cuando sus niveles circulantes fundamentan las medidas de reanimación.

Sepsis is a global health problem; progression to septic shock is associated with a marked increase in morbidity and mortality. In this setting, increased plasma lactate levels demonstrated to be an indicator of severity and a predictor of mortality, and are usually interpreted almost exclusively as a marker of low tissue perfusion. However, a recent paradigm shift has occurred in the exegesis of lactate metabolism and its biological properties. Indeed, metabolic adaptation to stress, even with an adequate oxygen supply, may account for high circulating lactate levels. Likewise, other pathophysiological consequences of sepsis, such as mitochondrial dysfunction, are associated with the development of hyperlactatemia, which is not necessarily accompanied by low tissue perfusion. Interpreting the origin and function of lactate may be of great clinical utility in sepsis, especially when circulating lactate levels are the basis for resuscitative measures.

Application of Insect Medicines in Treatment of Coronary Microvascular Dysfunction Based on Comorbidity Theory of "Blood-Vessel-Cardiac Collaterals" / 中国实验方剂学杂志

Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

Xihuangwan Inhibits Mitochondrial Energy Metabolism in Ovarian Cancer Cells / 中国实验方剂学杂志

ObjectiveTo study the effect of Xihuangwan extract on mitochondrial energy metabolism in ovarian cancer SKOV3 and HEY cells and to explore the underlying mechanism. MethodSKOV3 and HEY cells were cultured in vitro and treated with different concentrations （0， 5， 10， 15， 20 g·L-1） of Xihuangwan extract. Methyl thiazolyl tetrazolium （MTT） was used to examine the viability of SKOV3 and HEY cells treated with Xihuangwan extract. The adenosine-triphosphate （ATP） levels in SKOV3 and HEY cells were measured by kit. Flow cytometry was employed to measure the content of reactive oxygen species （ROS） in cells. Western blot was employed to determine the protein levels of peroxisome proliferator-activated receptor-γ co-activator 1α （PGC1α）， transcription factor A， mitochondrial （TFAM）， translocase of outer mitochondrial membrane 20 （TOMM20）， and aplasia Ras homologue member Ⅰ （ARHⅠ） in SKOV3 and HEY cells. Mito-Tracker Green staining was used to observe the morphological changes of mitochondria in SKOV3 and HEY cells. ResultCompared with blank group， Xihuangwan extract treatment for 24， 48 h inhibited the viability of SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）. Compared with blank group， Xihuangwan extract （10， 15， 20 g·L-1） groups presented lowered ATP levels （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had lower ATP level than the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with blank group， Xihuangwan extract increased the content of ROS in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had higher ROS content than the 10 g·L-1 Xihuangwan extract group （P<0.05）. Compared with blank group， Xihuangwan extract up-regulated the expression level of ARHⅠ protein in SKOV3 and HEY cells in a concentration-dependent manner （P<0.01）， and the expression levels of ARHⅠ protein was higher in the 20 g·L-1 Xihuangwan extract group than in the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with the blank group， Xihuangwan extract down-regulated the protein levels of PGC1α， TFAM， and TOMM20 in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the protein levels of TFAM and TOMM20 in the HEY cells treated with 20 g·L-1 Xihuangwan extract were lower than those in the HEY cells treated with 10， 15 g·L-1 Xihuangwan extract （P<0.05）. Compared with the blank group， 20 g·L-1 Xihuangwan extract decreased the Mito-Tracker fluorescence intensity of SKOV3 and HEY cells （P<0.05）. ConclusionXihuangwan can compromise the mitochondrial function of ovarian cancer SKOV3 and HEY cells and reduce cell energy metabolism to inhibit the proliferation of SKOV3 and HEY cells by up-regulating ARHⅠ and inhibiting PGC1α/TFAM signaling axis.

Role of sirtuin 5 in cardiovascular diseases / 中国药理学通报

Cardiovascular diseases ( CVDs ) are the leading cause of death worldwide and pose a serious threat to human health. Silent information regulator 5 ( SIRT5 ) , which is widely distributed in cardiac myocytes, vascular smooth muscle cells and endothelial cells,as a novel deacylation-modifying enzyme,plays an important role in CVDs through deacetylation, desuccinylation and demalonylation. This review summarizes the pathophysiolog-ical mechanism of SIRT5 from the aspects of energy metabolism, regulation of inflammatory response and oxidative stress, apart from the role of SIRT5 in CVDs such as myocardial infarction, myocardial hypertrophy, arrhythmia, atherosclerosis and heart failure. This review also figures out the current research progress of SIRT5 -related inhibitors and agonists, so as to provide strategies for targeting SIRT5 to prevent and treat CVDs.

Effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia / 中国药房

OBJECTIVE To investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia. METHODS H9c2 cells were divided into blank group， model group， quercetin high-dose， medium-dose and low-dose groups （40， 20， 10 μmol/L）， and positive control group （cyclosporine A， 1 μmol/L）. Reactive oxygen species （ROS）， mitochondrial membrane potential （MMP）， openness of mitochondrial permeability transition pore （MPTP）， adenosine triphosphate （ATP）， malondialdehyde （MDA）， lactate dehydrogenase （LDH） and creatine kinase （CK） were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group， model group， quercetin high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg）， and positive control group （trimetazidine， 6.3 mg/kg）， with 8 rats in each group. They were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last medication， myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH， MDA， creatine kinase isoenzyme-MB （CK-MB）， superoxide dismutase （SOD）， complex Ⅰ， complex Ⅳ and ATP in serum were all determined. RESULTS Compared with the model group， ROS fluorescence intensity， openness of MPTP， the contents of CK， LDH and MDA were significantly decreased in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of MMP and ATP were all increased significantly （P＜0.01）； the contents of CK-MB， LDH and MDA in serum were all decreased significantly in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of SOD， complex Ⅰ， complex Ⅳ and ATP （except for positive control group） were increased significantly （P＜ 0.05 or P＜0.01）. CONCLUSIONS Quercetin can effectively reduce myocardial hypoxic injury， promote endogenous energy production and improve mitochondrial function after myocardial ischemia.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Research progress on mitochondria regulating anti-tumor immunity / 浙江大学学报·医学版

Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.

Critical speed, thresholds for vo2max and boundaries of the severe exercise intensity domain / Velocidad crítica, vo2máx y límites de el dominio de la intensidad del ejercicio severo / Velocidade crítica, vo2max e limites de o domínio de intensidade de exercício severo

ABSTRACT Introduction: The severe exercise intensity domain can be defined as the range of work rates or speeds over which VO2max can be elicited. Objectives: Our purpose was to determine if critical speed (running analog of critical power) identifies the lower boundary of the severe domain and to identify the upper boundary of the domain. Methods: Twenty-five individuals performed five running tests to exhaustion, each lasting > 2.5 min and < 16 min. The two-parameter speed vs time-to-exhaustion relationship generated values for critical speed and the three-parameter speed vs time-to-reach-VO2max relationship generated values for the threshold speed above which VO2max can be elicited. The relationships were solved to calculate the minimum time needed to elicit VO2max. Results: Critical speed (3.00 ± 0.38 m·s−1) and the threshold speed above which VO2max can be elicited (2.99 ± 0.37 m·s−1) were correlated (r = 0.83, p < 0.01) and did not differ (p = 0.70), confirming critical speed as the lower boundary of the severe domain. The minimum time needed to elicit VO2max (103 ± 7 s) and the associated highest speed at which VO2max can be elicited (4.98 ± 0.52 m·s−1) identified the upper boundary of the severe domain for these participants. Conclusion: The critical power concept, which requires no metabolic measurements, can be used to identify the lowest speed at which VO2max can be elicited. With addition of metabolic measurements, mathematical modeling can also identify the highest speed and shortest exercise duration at which VO2max can be elicited. Evidence Level I; Validating cohort study with good reference standards.

RESUMEN Introducción: El dominio de la intensidad del ejercicio severo se puede definir como el rango de ritmos o velocidades de trabajo sobre las que se puede obtener el VO2max. Objetivos: Nuestro propósito fue determinar si la velocidad crítica (funcionamiento analógico de potencia crítica) identifica el límite inferior del dominio severo e identificar el límite superior del dominio. Métodos: Veinticinco personas realizaron cinco pruebas de carrera hasta el agotamiento, cada una con una duración de > 2,5 min y <16 min. La relación de dos parámetros de velocidad frente a tiempo de agotamiento generó valores para la velocidad crítica y la relación de tres parámetros de velocidad frente a tiempo de alcance de VO2max generó valores para la velocidad umbral por encima del cual se puede obtener el VO2max. Las relaciones se resolvieron para calcular el tiempo mínimo necesario para obtener el VO2max. Resultados: La velocidad crítica (3,00 ± 0,38 m·s−1) y la velocidad umbral por encima de la cual se puede obtener el VO2max (2,99 ± 0,37 m·s−1) se correlacionaron (r = 0,83, p < 0,01) y no difirieron (p = 0,70), lo que confirma la velocidad crítica como el límite inferior del dominio severo. El tiempo mínimo necesario para obtener el VO2max (103 ± 7 s) y la velocidad más alta asociada a la que se puede obtener el VO2max (4,98 ± 0,52 m·s−1) identificaron el límite superior del dominio severo para estos participantes. Conclusión: El concepto de potencia crítica, que no requiere mediciones metabólicas, se puede utilizar para identificar la velocidad más baja a la que se puede obtener el VO2max. Con la adición de mediciones metabólicas, el modelado matemático también puede identificar la velocidad más alta y la duración más corta del ejercicio a la que se puede obtener VO2max. Nivel de Evidencia I; Estudio de cohortes con alto estándar de referencia.

RESUMO Introdução: O domínio de intensidade de exercício severo pode ser definido como a faixa de taxas de trabalho ou velocidades sobre as quais o VO2max pode ser obtido. Objetivos: Nosso propósito foi determinar se a velocidade crítica (execução analógica da potência crítica) identifica o limite inferior do domínio severo e identificar o limite superior do domínio. Métodos: Vinte e cinco indivíduos realizaram cinco testes de corrida até a exaustão, cada um com duração > 2,5 min e < 16 min. A relação velocidade de dois parâmetros contra tempo até a exaustão gerou valores para a velocidade crítica e a relação velocidade de três parâmetros contra tempo para alcançar o VO2max valores gerados para a velocidade limite acima da qual o VO2max pode ser obtido. As relações foram resolvidas para calcular o tempo mínimo necessário para eliciar o VO2max. Resultados: A velocidade crítica (3,00 ± 0,38 m·s−1) e a velocidade limite acima da qual o VO2max pode ser eliciado (2,99 ± 0,37 m·s−1) foram correlacionadas (r = 0,83, p < 0,01) e não diferiram (p = 0,70), confirmando a velocidade crítica como o limite inferior do domínio grave. O tempo mínimo necessário para eliciar o VO2max (103 ± 7 s) e a maior velocidade associada na qual o VO2max pode ser eliciado (4,98 ± 0,52 m·s−1) identificou o limite superior do domínio severo para esses participantes. Conclusão: O conceito de potência crítica, que não requer medidas metabólicas, pode ser usado para identificar a velocidade mais baixa em que o VO2max pode ser eliciado. Com a adição de medidas metabólicas, a modelagem matemática também pode identificar a velocidade mais alta e a duração mais curta do exercício em que o VO2max pode ser obtido. Nível de Evidência I; Estudo de coorte com alto padrão de referência.

Analysis of the effectiveness coefficient in greco-roman fighting athletes at different levels of competition / Análisis del coeficiente de eficacia en atletas de lucha griego-romana en distintos niveles de competición / Análise do coeficiente de efetividade em atletas de luta greco-romana em diferentes níveis de competição

ABSTRACT Introduction: Wrestling is an ancient combat sport, individual and of complex performance, which integrates high technical and tactical complexity, associated with a bioenergetic interaction and a high coordinative pattern. In Brazil, the number of competitors at different levels has increased significantly in the last years, evidencing the need to search for answers that can help coaches in the different situations of the competitive calendar. The prescription of the means and methods of training in Greco-Roman wrestling aims at the development of the technical effectiveness. However, there is no evidence of indicators of technical effectiveness, in Brazilian elite athletes of Greco-Roman wrestling, in national and international competitions. Objectives: The objective of the study was to verify and to compare the technical effectiveness of the wrestlers of Greco-Roman fight of the Brazilian selection, in two competitions: one in the national level and the other international. Methods: Seven athletes of the Brazilian wrestling team participated of the investigation (age: 25±5 years; stature: 175±12 cm; corporal mass: 80± 21kg). Analysis of the effective, not effective and total technique were accomplished. After identifying the normality of the data (SHAPIRO WILKS), the Student's t test was used to compare the variables, according to the moment evaluated, considering the significance level of 5%. Results: The results showed a significant decrease (p = 0.03) in the standing effective technique and in the total effective technique (p = 0.01), comparing the national competition with the international competition. Conclusion: Technical effectiveness of Brazilian wrestlers was found to be below the indices presented in studies with competitors from countries considered to have high world performance. In international competition, it presents a negative impact compared to national events. Level of Evidence IV; Therapeutic Studies - Investigation of Treatment Results.

RESUMEN Introducción: El Wrestling es una modalidad de combate milenaria, individual y de rendimiento complejo, que integra elevada complejidad técnico-táctica, asociada a una interacción bioenergética y un alto patrón coordinativo. En Brasil, el número de competidores en diferentes niveles aumentó significativamente en los últimos años, evidenciando la necesidad en la búsqueda de respuestas que auxilien a los entrenadores en las diferentes situaciones del calendario competitivo. La prescripción de los medios y métodos de entrenamiento en la lucha greco-romana tiene como objetivo el desarrollo de la efectividad técnica. Entre tanto, no hay evidencias de indicadores de efectividad técnica, en atletas de alto rendimiento brasileño en la lucha greco-romana, en competencias nacionales e internacionales. Objetivos: El objetivo de este estudio fue verificar y comparar la efectividad técnica de los atletas de lucha greco-romana de la selección brasileña, en dos competencias: una a nivel nacional y otra internacional. Métodos: Participaron de la investigación siete atletas de la selección brasileña de lucha greco-romana (edad: 25±5 años; estatura: 175±12 cm; masa corporal: 80± 21kg). Fueron realizados análisis de la técnica efectiva, no efectiva y total. Después de identificar la normalidad de los datos (SHAPIRO WILKS), fue utilizado el test de t de Student para la comparación de las variables, según el momento evaluado, considerando el nivel de significación de 5%. Resultados: Los resultados mostraron una disminución significativa (p = 0,03) en la técnica efectiva en pie y en la técnica efectiva total (p = 0,01), comparándose la competencia nacional con la internacional. Conclusión: Se concluyó que la eficacia técnica de los luchadores brasileños está por debajo de los índices presentados en estudios con competidores de países considerados de alto rendimiento mundial. En la competición internacional, presenta un impacto negativo en comparación con los eventos nacionales. Nivel de Evidencia IV; Estudios Terapéuticos - Investigación de Los Resultados Del Tratamiento.

RESUMO Introdução: O Wrestling é uma modalidade de combate milenar, individual e de rendimento complexo, que integra elevada complexidade técnico-táctica, associada a uma interação bioenergética e um alto padrão coordenativo. No Brasil, o número de competidores em diferentes níveis aumentou significativamente nos últimos anos, evidenciando a necessidade da busca de respostas que auxiliem os treinadores nas diferentes situações do calendário competitivo. A prescrição dos meios e métodos de treinamento na luta greco-romana visa o desenvolvimento da efetividade técnica. Entretanto, não há evidências de indicadores de efetividade técnica, em atletas de elite brasileira de luta greco-romana, em competições nacionais e internacionais. Objetivo: o objetivo do estudo foi verificar e comparar a efetividade técnica dos lutadores de luta greco-romana da seleção brasileira, em duas competições: uma no nível nacional e a outra internacional. Métodos: Participaram da investigação sete atletas da seleção brasileira de luta greco-romana (idade: 25±5 anos; estatura: 175±12 cm; massa corporal: 80± 21kg). Foram realizadas análises da técnica efetiva, não efetiva e total. Após identificar a normalidade dos dados (SHAPIRO WILKS), foi utilizado o teste t de Student para a comparação das variáveis, segundo o momento avaliado, considerando nível de significância de 5%. Resultados: Os resultados mostraram uma diminuição significativa (p = 0,03) na técnica efetiva em pé e na técnica efetiva total (p = 0,01), comparando-se a competição nacional com a internacional. Conclusão: Concluiu-se que a efetividade técnica dos lutadores brasileiros está abaixo dos índices apresentados em estudos com competidores de países considerados de alto desempenho mundial. Em competição internacional, apresenta um impacto negativo comparativamente a eventos nacionais. Nível de Evidência IV; Estudos Terapêuticos - Investigação dos Resultados do Tratamento.

Calidad y cronotipo del sueño y su relación con la obesidad en población adulta. Revisión bibliográfica narrativa

Introducción: Debido a la alta prevalencia de obesidad a nivel mundial y nacional, y de la incidencia de esta enfermedad en el desarrollo de comorbilidades, estudiar los factores que contribuyan a su desarrollo resulta pertinente. La falta de sueño o el sueño interrumpido pueden estar asociados a la epidemia mundial de la obesidad, y resulta un factor modificable a incluir en su terapéutica. Objetivo: Conocer la evidencia reciente acerca de los mecanismos subyacentes que conforman una posible relación entre la cantidad y/o calidad de sueño con el desarrollo de obesidad en personas adultas Metodología: Revisión bibliográfica de artículos científicos en plataformas virtuales de bases de datos. Se aplicaron distintos filtros: edad (18 a 64 años), estudios realizados en humanos, texto completo, idioma inglés y español, y publicaciones no mayores a 5 años. Los estudios de evaluación de la calidad de sueño debían haber aplicado el Índice de Calidad de Sueño de Pittsburgh, y los de evaluación del cronotipo el Horne and Ostberg's Morningness - Eveningness Questionnaire o el Munich Chronotype Questionnaire . Resultados: Individuos con una insuficiente cantidad y/o calidad de sueño fueron asociados con una mayor probabilidad de desarrollar obesidad. Los principales mecanismos subyacentes encontrados fueron: alteraciones hormonales, metabólicas y un aumento de la ingesta de alimentos principalmente en la noche biológica. Conclusiones: Según la bibliografía seleccionada se concluye que existe evidencia que relaciona la cantidad y/o calidad de sueño con el posible desarrollo de obesidad en población adulta.

Introdução: Devido à alta prevalência da obesidade no mundo e no país e à incidência dessa doença no desenvolvimento de comorbidades, é relevante estudar os fatores que contribuem para o seu desenvolvimento. A falta de sono ou o sono interrompido pode estar associado à epidemia global de obesidade e é um fator modificável a ser incluído em sua terapia. Objetivo: Verificar as evidências recentes sobre os mecanismos subjacentes que compõem uma possível relação entre a quantidade e/ou a qualidade do sono e o desenvolvimento da obesidade em adultos . Metodologia: Revisão bibliográfica de artigos científicos em plataformas de bancos de dados virtuais. Foram aplicados diferentes filtros: idade (18 a 64 anos), estudos em humanos, texto completo, idioma inglês e espanhol e publicações com no máximo 5 anos. Os estudos que avaliaram a qualidade do sono deveriam ter aplicado o Índice de Qualidade do Sono de Pittsburgh, e os que avaliaram o cronotipo deveriam ter aplicado o Horne and Ostberg's Morningness - Eveningness Questionnaire ou o Munich Chronotype Questionnaire . Resultados: Os indivíduos com quantidade e/ou qualidade de sono insuficiente foram associados a uma maior probabilidade de desenvolver obesidade. Os principais mecanismos subjacentes encontrados foram: distúrbios hormonais, metabólicos e aumento da ingestão de alimentos, principalmente na noite biológica. Conclusões: Segundo a bibliografia selecionada, há evidências que relacionam a quantidade e/ou a qualidade do sono com o possível desenvolvimento de obesidade na população adulta

Introduction: As a result of the high prevalence of obesity worldwide and nationally, and because of the incidence of this disease in the development of comorbidities, studying the factors that contribute to its development is necessary. The lack or disrupted sleep that is affecting our civilization, has been associated with the worldwide epidemic of obesity, being a modifiable factor to include in its therapy. Objective: To find recent evidence about the underlying mechanisms that build a possible relationship between sleep duration and/or quality with the development of obesity in adults. Methods: The search of articles was carried out by using virtual platforms of bibliographic databases, which were filtered by: age (18 to 64 years), human studies, full text, English and Spanish language and publications no longer than 5 years. Studies that evaluated sleep quality had to apply the Pittsburgh Sleep Quality Index (PSQI) and those that evaluated chronotype had to use the Horne and Ostberg's Morningness - Eveningness Questionnaire or the Munich Chronotype Questionnaire Results: Individuals with insufficient sleep duration and/or quality were more likely to become obese. Underlying mechanisms found were hormonal and metabolic alterations and an increase in food intake, mainly during the biological night Conclusions: According to the selected bibliography, there is scientific evidence linking sleep duration and/or quality with the possible development of obesity in adults

Rutin forestalls dysregulated cardiac bioenergetics in bisphenol A and dibutyl phthalate-exposed rats through PPAR? and AMPK modulation

Objectives: Proper cardiac function is greatly dependent on adequate supply and metabolism of energy substrates. Environmental pollutants exposure including plasticizers can trigger adverse cardiac metabolic events. This study was designed to investigate the ameliorative effect of rutin (Rt) on dysregulated cardiac energy metabolism in plasticizer-exposed rats. Materials and Methods: Forty-two rats were randomised into seven groups (n = 6): Control (0.1% dimethyl sulfoxide), bisphenol A (BPA, 25 mg/kg, p.o), dibutyl phthalate (DBP, 25 mg/kg, p.o), BPA + Rt 25 mg/kg, Rt 50 mg/kg, DBP + Rt (25 mg/kg, Rt 50 mg/kg), BPA + DBP and BPA + DBP + Rt, daily for 21 days. Results: BPA and DBP exposure increased plasma glucose, reduced insulin, and increased plasma and cardiac free fatty-acid. Cardiac glucose-6-phosphate level, hexokinase and pyruvate dehydrogenase activities increased in DBP while BPA reduced these variables. Cardiac glucose transporter-4 expression was reduced in BPA group, while cardiac peroxisome proliferator-activated receptor-alpha (PPAR?) and AMP-activated protein kinase (AMPK) expression increased in BPA and DBP-treated rats. However, Rt administration prevents impaired cardiac bioenergetics and glucometabolic regulation. Conclusion: Summarily, Rt improves BPA and DBP-impaired cardiac bioenergetics through PPAR? and AMPK modulation.

Progress of the mechanism of energy metabolism reprogramming regulated by long non-coding RNA in cancer / 肿瘤研究与临床

Although it is widely believed that abnormal energy metabolism exists in cancer cells and affects the biological behavior of cancers, the exact mechanism of energy metabolic reprogramming and specific mechanism of its effect on proliferation, invasion and metastasis of cancer cells have not been clarified. In recent years, studies have shown that long non-coding RNA (lncRNA) can affect energy metabolism, development and progression of cancer cells through binding to specific nucleic acids and proteins at the transcriptional and post-transcriptional stages, and specifically through transcriptional interference, epigenetic regulation of genes, changes in protein activity, competitive binding to microRNA (miRNA) and other related mechanisms. The further study on the mechanism of lncRNA regulating energy metabolism reprogramming of cancer cells is expected to find new markers and targets for diagnosis and treatment of cancer. This paper reviews the current research progress of the mechanism of lncRNA regulating metabolic reprogramming of glucose, fatty acid, protein and nucleotide in cancer, and provides a new idea of lncRNA's regulation of energy metabolism pathways for targeted anticancer therapy.

Intermittent hypoxia can improve myocardial energy metabolism / 中华物理医学与康复杂志

Objective:To explore any effect of intermittent hypoxia (IH) on myocardial energy metabolism and its mechanism.Methods:Twenty-one male Sprague-Dawley rats were randomly divided into a sham operation group, a myocardial infarction group and an observation group. The latter two groups received occlusion of the left anterior descending coronary artery. The observation group then lived in an hypoxic environment intermittently for 4 hours/day, 5 days/week for four weeks, while the other 2 groups were exposed to a normal level of oxygen. The ejection fraction of the left ventricle (LVEF) was measured at 1 week after the modeling and 4 weeks after the start of the intervention. Also at that point myocardial fibrosis, mitochondrial structure, ATP content, and the protein expressions of adenosine monophosphate-activated protein kinase alpha1 (AMPKα1) and sirtuins protein family member 3 (SIRT3) were assessed in all three groups.Results:A significant decrease in the LVEF, the number of mitochondria, ATP content, AMPKα1 and SIRT3 protein were observed in the infarction group compared with the sham group. There was also a significant increase in the myocardial fibrosis index. Moreover, the LVEF decreased significantly and the myocardial fibrosis index had increased significantly in the observation group compared with the sham operation group, though the two groups exhibited no significant differences the number of mitochondria, ATP content, or the expression of AMPKα1 or SIRT3. Compared with the myocardial infarction group, in the observation group there was a significant increase in the LVEF, the number of mitochondria, ATP content, and the expression of AMPKα1 and SIRT3 protein, with a significant decrease in the fibrosis index. AMPKα1 and SIRT3 level were positively inter-correlated and positively correlated with LVEF and ATP content.Conclusions:IH intervention can promote ATP synthesis and improve mitochondrial structure by regulating the AMPKα1/SIRT3 pathway, reducing myocardial fibrosis and enhancing cardiac function.

Changes in metabolic capacity and gene expression of brown adipose tissue in the first and third trimester of pregnancy / 中华内分泌代谢杂志

Objective:To explore gene expression and metabolic capacity changes of brown adipose tissue(BAT)during different gestation periods.Methods:A normal pregnancy model was established using C57BL/6J mice, while infertile mice of the same age were served as the control group. The morphological alteration of BAT during pregnancy as well as the gene expression of uncoupling protein 1(UCP1) and other fat browning and mitochondrial marker genes were detected. Moreover, BATs from early and late gestation were selected to screen differentially expressed genes in relation to pregnancy progressing by RNA sequencing(RNA-seq), and gene ontology(GO) and Kyoto gene and gene sequencing(KEGG)were performed.Results:With pregnancy progressing, the size of BAT lipid droplets was substantially enlarged, UCP1 protein expression was decreased( P<0.01), and the fat browning marker genes(Ucp1, Dio2, and Pgc1α)and the mitochondrial marker gene CytC were downregulated( P<0.001). Additionally, a total of 1 298 distinct genes were identified by RNA-seq, 906 of which were upregulated and 392 were downregulated at later stage of pregnancy. GO and KEGG analyses revealed that the differentially expressed genes were mainly enriched in bioregulatory functional pathways such as lipid metabolism, sex steroid hormones, and inflammatory factors. Conclusion:BAT in mice showed larger lipid droplets and reduced thermogenic and metabolic capacity during late gestation, and BAT gene expression was significantly different in different periods of gestation, so reduced metabolic capacity of BAT may contribute to metabolic abnormality during pregnancy.

Influence of protein energy wasting on frailty in elderly patients on maintenance hemodialysis / 中华老年医学杂志

Objective:To explore the correlation between protein energy wasting(PEW)and frailty in elderly patients on maintenance hemodialysis(MHD)and influencing factors of frailty.Methods:Clinical data of patients over 60 who had received regular hemodialysis treatment at Beijing Huairou Hospital between September to December 2021 were collected.According to Fried's evaluation criteria, patients were divided into a frailty group and a non-frailty group, and differences between the two groups were compared.Spearman correlation analysis was conducted to assess the correlation between protein energy wasting and frailty.Logistic regression was used to analyze the influencing factors of frailty in elderly patients on MHD.Results:A total of 81 MHD patients enrolled in this study, with 36 in the frailty group.The frailty group was older, had a higher proportion of patients with PEW, and underwent more months of dialysis, with a higher proportion of patients with diabetic nephropathy as the primary disease, having high levels of C-reactive protein(CRP), and having low KT/V, hemoglobin, albumin, body mass index(BMI), mid-arm circumference(MAC)and mid-arm muscle circumference(MAMC), and the differences with the control group were statistically significant(all P<0.05). The Fried frailty phenotype was positively correlated with age( r=0.021, P=0.047), but negatively associated with HGB( r=-0.329, P=0.003), albumin( r=0.021, P=0.047), BMI( r=0.021, P=0.047), TSF( r=-0.274, P=0.013), MAC( r=-0.554, P<0.001)and MAMC( r=-0.293, P=0.008). A Logistic regression equation was constructed using frailty as the dependent variable.The results showed that age, months of dialysis, KT/V, serum albumin and CRP were independent factors influencing the development of frailty in elderly patients with MHD. Conclusions:PEW and frailty coexist and interact with each other in elderly patients with MHD.Clinicians should place emphasis on the assessment of frailty and protein energy wasting in elderly dialysis patients and achieve early detection and intervention to avoid adverse clinical outcomes.

Effect of Shenqi Pills （肾气丸） on Cognitive Function and Hippocampal Glucose Energy Metabolism in Type 2 Diabetes Mellitus Model Mice / 中医杂志

ObjectiveTo explore the effect and possible mechanism of Shenqi Pills （肾气丸） on cognitive impairment and hippocampal glucose energy metabolism in type 2 diabetes mellitus （T2DM）. MethodsSixty C57BL/6 mice were randomly divided into control group， model group， rosiglitazone group and Shenqi Pills low-， medium- and high-dose groups， with 10 mice in each group. T2DM model was induced by a high-fat diet combined with intraperitoneal injection of streptozotocin in all the groups except for the control group. After successful modeling， the high-， medium-， and low-dose Shenqi Pills groups were given 2.08， 1.04， and 0.52 g/（kg·d） of Shenqi Pills granules by gavage respectively， while the rosiglitazone group was given 3 mg/（kg·d） of rosiglitazone tablets by gavage， and the control group and model group were gavaged with 10 ml/（kg·d） of distilled water， all for 8 consecutive weeks. The body weight and fasting blood glucose （FBG） level were recorded every two weeks. The Morris water maze test was performed on the 8th week of medication. After 8-week medication， oral glucose tolerance test （OGTT） and fasting insulin level were measured， hippocampal glucose energy metabolism-related products were quantitatively detected by liquid chromatography tandem mass spectrometry， and KEGG annotation analysis was performed. ResultsCompared to those measured at the same timepoints in the control group， the body mass on week 6 and 8， as well as the FBG level on week 2， 4， 6 and 8 in the model group increased； the blood glucose level at 0， 30， 60 and 120 minutes of the OGTT test increased， while fasting insulin level after 8-week medication decreased. The escape latency of the model group was significantly prolonged on the 3rd and 4th days， and the escape latency time increased， while the total swimming distance， platform quadrant residence time and the number of platform crossings decreased （P＜0.05 or P＜0.01）. Compared to those measured at the same timepoints in the model group， the body mass on week 6 in the low-dose Shenqi Pills group， on week 6 and 8 in the medium- and high-dose groups， and on week 8 in the rosiglitazone group were significantly reduced； the FBG levels in all the Shenqi Pills groups and rosiglitazone group on week 6 and 8 decreased， while fasting insulin levels increased. In the OGTT test， blood glucose in the medium-dose group of Shenqi Pills at all timepoints decreased； in the Morris water maze test， the escape latency period of the medium- and high-dose Shenqi Pills groups was shortened on the 3rd and 4th days， while the escape latency time was reduced， and the total swimming distance， platform quadrant residence time， and number of platform crossings increased in the medium-dose Shenqi Pills group （P＜0.05 or P＜0.01）.The medium-dose Shenqi Pills showed best effect， therefore it was selected for the targeted quantitative detection of metabolites. The medium-dose Shenqi Pills group could regulate the disorder of glucose metabolism in the hippocampus of T2DM mice， and 13 differential metabolites were found，up-regulating α-ketoglutarate and 3-phosphoglyceric acid， and down-regulating fumaric acid， glutamatic acid， lactatic acid， inosine， malic acid， adenine， fructose 1,6-diphosphate and others. KEGG annotation of differential metabolites suggested that Shenqi Pills was closely related to the regulation of glucose metabolism disorder and insulin resistance in the hippocampus region of T2DM model mice， as well as neurodegenerative diseases and ABC transport， hypoxia-inducible factor 1 （HIF）， forkhead transcription factor （FoXO） and cyclic adenosine monophosphate （cAMP） signaling pathways. ConclusionShenqi Pills can improve learning and memory abilities and cognitive impairment in T2DM mice， and may act its role by regulating glucose energy metabolism in the hippocampus of T2DM.

Effects of manipulating lactate dehydrogenase gene on metabolism of HEK-293 and production of human adenovirus / 生物工程学报

Reducing lactate accumulation has always been a goal of the mammalian cell biotechnology industry. When animal cells are cultured in vitro, the accumulation of lactate is mainly the combined result of two metabolic pathways. On one hand, glucose generates lactate under the function of lactate dehydrogenase A (LDHA); on the other hand, lactate can be oxidized to pyruvate by LDHB or LDHC and re-enter the TCA cycle. This study comprehensively evaluated the effects of LDH manipulation on the growth, metabolism and human adenovirus (HAdV) production of human embryonic kidney 293 (HEK-293) cells, providing a theoretical basis for engineering the lactate metabolism in mammalian cells. By knocking out ldha gene and overexpression of ldhb and ldhc genes, the metabolic efficiency of HEK-293 cells was effectively improved, and HAdV production was significantly increased. Compared with the control cell, LDH manipulation promoted cell growth, reduced the accumulation of lactate and ammonia, significantly enhanced the efficiency of substrate and energy metabolism of cells, and significantly increased the HAdV production capacity of HEK-293 cells. Among these LDH manipulation measures, ldhc gene overexpression performed the best, with the maximum cell density increased by about 38.7%. The yield of lactate to glucose and ammonia to glutamine decreased by 33.8% and 63.3%, respectively; and HAdV titer increased by at least 16 times. In addition, the ATP production rate, ATP/O2 ratio, ATP/ADP ratio and NADH content of the modified cell lines were increased to varying degrees, and the energy metabolic efficiency was significantly improved.

Effect of aerobic pedal exercise on sleep quality and energy metabolism of female college students with mild sleep disorder / 中国学校卫生

Objective@#To explore the intervention effect of aerobic step exercise on sleep quality of female college students, so as to provide a new perspective to improve the sleep quality of female college students.@*Methods@#In the 2020 fall semester, a total of 41 female college students with mild or more severe sleep disorders were selected from Beijing Normal University through a questionnaire and were randomly divided into experimental group ( n =29) and control group ( n =12). The experimental group received 55 minutes/time step aerobic exercise intervention for 8 weeks, three times a week, while the control group received no exercise intervention from October to December. The two groups maintained the original learning and living habits, without additional physical activity. The Pittsburgh Sleep Quality Index Scale and portable sleep monitor were used to assess the subjects sleep quality from both subjective and objective aspects. Changes in energy metabolism were observed by triaxial accelerometer and standing body composition analyzer.@*Results@#After exercise intervention, subjective sleep quality factor (1.24±0.43, 0.86±0.58), sleep efficiency factor (0.66±0.67, 0.07±0.25), sleep disorder factor (1.24± 0.51 , 1.03±0.18), daytime dysfunction factor (1.90±0.86, 1.48± 0.82 ) and PSQI score (7.21±1.85, 5.66±2.09) significantly improved ( t=3.64, 4.63, 2.27, 2.36, 3.29, P <0.05). The ratio of sleep to wakefulness decreased (25.54±7.86, 20.85± 5.13), the ratio of deep sleep (31.79±12.20, 38.32±10.19) and sleep efficiency (73.99±7.91, 78.68±5.12) increased significantly ( t=-2.12, -2.39, -2.21, P <0.05). Lean body mass [(38.55±2.95, 39.07±2.94)g] and basal metabolic rate [(1 257.45±41.14, 1 262.66 ±42.22)kcal] of the experimental group significantly increased after the intervention of medium high intensity aerobic pedal exercise ( F=5.95, 3.49, P <0.05). Total energy expenditure was positively correlated with subjective sleep quality and sleep efficiency ( r=-0.26, -0.44, P <0.05).@*Conclusions@#The 8 week aerobic step exercise intervention can increase the daytime energy consumption and basic metabolism of female college students. Improve the sleep depth and efficiency of female college students, reduce sleep disorders, and then effectively improve sleep quality.

Morphological Characteristics and the Role of Mitochondria in Ferroptosis / 中国生物化学与分子生物学报

Ferroptosis is a unique mode of iron-dependent cell death driven by lipid peroxidation. It is characterized by morphological changes in mitochondria, including densification of mitochondrial membranes and associated reduction in the volume, rupture of outer membranes and reduction or disappearance of the mitochondrial crest, which is different from that of apoptosis, autophagy and pyroptosis. Mitochondria, as the core of cell metabolism, are important organelles for iron metabolism, lipid metabolism and energy metabolism. However, it remains controversial debates as how mitochondria participate in ferroptosis and the underlying mechanisms during its progression. This review summaries the current understanding of the occurrence and defense mechanisms of ferroptosis, and the role of mitochondria in promoting and inhibiting ferroptosis, which includes the tricarboxylic acid cycle and glycolysis, reactive oxygen species, and lipid metabolism in mitochondria and their roles in driving ferroptosis. Moreover, we also summarize the defense mechanisms against ferroptosis through detoxification of mitochondrial lipid peroxidation by mitochondrial dihydroorotate dehydrogenase, as well as mitochondrial ferritin. Other mitochondrial molecules and their regulation of ferroptosis is stated at the end. This paper reviews the latest research progress of mitochondria in the process of ferroptosis, which aims to further understand the function of mitochondria in ferroptosis and its mechanism in the occurrence and development of ferroptosis, and therefore provides a theoretical foundation for the basic research of cell biology and strategies for investigation of clinical diseases.

Astragaloside IV inhibits Ang H-induced cell proliferation and collagen expression in cardiac fibroblasts by activating short-chain acyl-CoA dehydrogenase / 中国药理学通报

Aim To explore the effect of astragaloside IV (AS-IV) on cell proliferation and collagen expression in cardiac fibroblasts (CFs) of rats induced with angiotensin II (Ang II) and its mechanism. Methods CFs were pretreated with short-chain acyl-CoA dehydrogenase (SCAD) siRNA1186 for 12 h and then co-treated with Ang TJ and AS-IV for 36 h. The expressions of SCAD, α-SMA, collagen I and collagen III in CFs were detected by Western blot. mRNA expression levels of SCAD, a-SMA, collagen I and collagen III in CFs were detected by quantitative real-time PCR. The SCAD enzymatic activity, the content of ATP, hydroxyproline and free fatty acid were measured by detection kits. Results The expression of α-SMA, collagen I and collagen III were up-regulated (all P < 0. 01) in CFs induced by Ang II compared with the control cells, and the expression and enzymatic activity of SCAD significantly decreased (P < 0. 01, P< 0. 05). The content of ATP decreased (P < 0.01), and the content of hydroxyproline and free fatty acids increased (all P < 0.01). Compared with Ang II group, SCAD expression and enzymatic activity, and ATP content were significantly increased (all P < 0.01) in Ang II + AS-TV group, but the content of hydroxyproline and free fatty acids, and the expression of α-SMA, collagen I and collagen III significantly decreased (all P < 0.01). However, compared with the Ang II + NC group, there was no significant difference in all indices in the Ang II + SiRNA1186 + AS-TV group. The protective effect of AS-TV on Ang II -induced cell proliferation and collagen expression in CFs was eliminated by the interference of SCAD SiRNA1186. Conclusions AS-IV may inhibit Ang II-induced cell proliferation and collagen expression in CFs by activating SCAD.