Icariin improves renal interstitial fibrosis in a rat model of chronic renal failure by regulating mitochondrial dynamics / 中国中药杂志

This study aims to explore the effect of icariin(ICA) on mitochondrial dynamics in a rat model of chronic renal failure(CRF) and to investigate the molecular mechanism of ICA against renal interstitial fibrosis(RIF). CRF was induced in male Sprague-Dawley(SD) rats with 5/6(ablation and infarction, A/I) surgery(right kidney ablation and 2/3 infarction of the left kidney). Four weeks after surgery, the model rats were randomized into the following groups: 5/6(A/I) group, 5/6(A/I)+low-dose ICA group, and 5/6(A/I)+high-dose ICA group. Another 12 rats that received sham operation were randomly classified into 2 groups: sham group and sham+ICAH group. Eight weeks after treatment, the expression of collagen-Ⅰ(Col-Ⅰ), collagen-Ⅲ(Col-Ⅲ), mitochondrial dynamics-related proteins(p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2), and mitochondrial function-related proteins(TFAM, ATP6) in the remnant kidney tissues was detected by Western blot. The expression of α-smooth muscle actin(α-SMA) was examined by immunohistochemical(IHC) staining. The NRK-52 E cells, a rat proximal renal tubular epithelial cell line, were cultured in vitro and treated with ICA of different concentration. Cell viability was detected by CCK-8 assay. In NRK-52 E cells stimulated with 20 ng·mL~(-1) TGF-β1 for 24 h, the effect of ICA on fibronectin(Fn), connective tissue growth factor(CTGF), p-Drp1 S616, p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 was detected by Western blot, and the ATP content and the mitochondrial morphology were determined. The 20 ng·mL~(-1) TGF-β1-stimulated NRK-52 E cells were treated with or without 5 μmol·L~(-1) ICA+10 μmol·L~(-1) mitochondrial fusion promoter M1(MFP-M1) for 24 h and the expression of fibrosis markers Fn and CTGF was detected by Western blot. Western blot result showed that the levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were increased and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were decreased in 5/6(A/I) group compared with those in the sham group. The levels of Col-Ⅰ, Col-Ⅲ, and p-Drp1 S616 were significantly lower and the levels of p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6 were significantly higher in ICA groups than that in 5/6(A/I) group. IHC staining demonstrated that for the expression of α-SMA in the renal interstitium was higher in the 5/6(A/I) group than in the sham group and that the expression in the ICA groups was significantly lower than that in the 5/6(A/I) group. Furthermore, the improvement in the fibrosis, mitochondrial dynamics, and mitochondrial function were particularly prominent in rats receiving the high dose of ICA. The in vitro experiment revealed that ICA dose-dependently inhibited the increase of Fn, CTGF, and p-Drp1 S616, increased p-Drp1 S637, Mfn1, Mfn2, TFAM, and ATP6, elevated ATP content, and improved mitochondrial morphology of NRK-52 E cells stimulated by TGF-β1. ICA combined with MFP-M1 further down-regulated the expression of Fn and CTGF in NRK-52 E cells stimulated by TGF-β1 compared with ICA alone. In conclusion, ICA attenuated RIF of CRF by improving mitochondrial dynamics.

Effect of Anti-Oxidative of Ethyl Pyruvate and Taurine on the Red Blood Cell Storage at 4 ℃ / 中国实验血液学杂志

OBJECTIVE@#To investigate the anti-oxidative effect of ethyl pyruvate (EP) and taurine (TAU) on the quality of red blood cells stored at 4±2 ℃, hemolysis, energy metabolism and lipid peroxidation of the red blood cells in the preservation solution were studied at different intervals.@*METHODS@#At 4±2 ℃, the deleukocyte red blood cells were stored in the citrate-phosphate-dextrosesaline-adenine-1 (CPDA-1) preservation (control group), preservation solution with EP (EP-AS), and TAU (TAU-AS) for long-term preservation. The enzyme-linked immunoassay and automatic blood cell analyzer were used to detect hemolysis and erythrocyte parameters. Adenine nucleoside triphosphate (ATP), glycerol 2,3-diphosphate (2,3-DPG) and malondialdehyde (MDA) kits were used to test the ATP, 2,3-DPG and MDA concentration.@*RESULTS@#During the preservation, the rate of red blood cell hemolysis in EP-AS and TAU-AS groups were significantly lower than that in CPDA-1 group (P<0.01). The MCV of EP-AS group was increased with the preservation time (r=0.71), while the MCV of the TAU-AS group was significantly lower than that in the other two groups (P<0.05). The concentration of ATP and MDA in EP-AS and TAU-AS groups were significantly higher than that in CPDA-1 group at the 14th day (P<0.01). The concentrations of 2,3-DPG in the EP-AS and TAU-AS groups were significantly higher than that in the CPDA-1 group from the 7th day (P<0.01).@*CONCLUSION@#EP and TAU can significantly reduce the red blood cell hemolysis rate, inhibit the lipid peroxidation level of red blood cells, and improve the energy metabolism of red blood cells during storage. The mechanism of EP and TAU may be related to their antioxidation and membrane protection effect, so as to improve the red blood cell quality and extend the preservation time.

Study on the quantitative evaluation parameter system for basic acupuncture manipulations based on 3D motion tracking technology / 中国针灸

OBJECTIVE@#To establish a quantitative evaluation parameter system for basic acupuncture manipulations based on 3D motion tracking technology, and to further analyze the characteristics of acupuncture manipulation.@*METHODS@#The motion tracking system Simi Motion Ver.8.5 was used to collect parameters of acupuncture manipulations, so as to establish a quantitative evaluation system mainly in spatial control parameters, time control parameters and stability parameters. Based on the evaluation parameter system, data of acupuncture manipulations (even reinforcing-reducing manipulation using lifting-thrusting technique and twirling technique) were collected from 19 teachers majored in acupuncture-moxibustion, of which the characteristics were analyzed and were compared with the results tested by traditional ATP-Ⅱ acupuncture manipulation parameter determination apparatus (ATP-Ⅱ).@*RESULTS@#The evaluation parameter system could quantitatively analyze the basic acupuncture manipulations in 3 aspects, i.e. space, time and stability. Acupuncture manipulations were performed by shifting the needle body in a certain range along X, Y and Z axes. The amplitude and speed of thumb movement were greater than those of index finger. The time-history of lifting was similar to thrusting, while the time-history of twirling to left was similar to twirling to right in even reinforcing-reducing manipulation. The coordinate-time curve of finger movement of the evaluation system had consistent wave pattern compared with the voltage-time curve generated by ATP-Ⅱ.@*CONCLUSION@#The quantitative evaluation parameter system based on 3D motion tracking technology can objectively evaluate basic acupuncture manipulations, and show the characteristics of different manipulations and the movement details of finger joints.

Isobavachalcone induces cell death through multiple pathways in human breast cancer MCF-7 cells / 南方医科大学学报

OBJECTIVE@#To explore the effects of isobavachalcone (IBC) on cell death of human breast cancer MCF-7 cells and explore the possible mechanism.@*METHODS@#MCF-7 cells were treated with different concentrations of IBC, and the changes in cell proliferation were assessed using MTT assay. Apoptosis of MCF-7 cells following treatment with 10, 20, and 40 μmol/L IBC was analyzed using flow cytometry with annexin V-FITC/PI double staining and fluorescence microscopy, and the expressions of apoptosis- and autophagy-related proteins (Bax, Bcl-2, Akt, p-Akt, p62, and LC3) were detected with Western blotting. Electron microscopy was used to observe the changes in submicrostructure of the cells following treatment with 40 μmol/L IBC. JC-1 assay kit, ATP assay kit, and reactive oxygen species (ROS) kit were used to determine the effect of IBC on mitochondrial function of the cells.@*RESULTS@#MTT assay showed that IBC significantly inhibited the proliferation of MCF-7 cells in a concentration- and time-dependent manner, with IC50 values of 38.46, 31.31, and 28.26 μmol/L at 24, 48, and 72 h, respectively. IBC also concentration-dependently induced apoptosis of MCF-7 cells. IBC-induced cell death was inhibited by z-VAD-fmk, a caspase inhibitor (P < 0.05), but not by the necroptosis inhibitor necrostatin-1 (Nec-1). Western blotting showed that IBC-induced MCF-7 cell apoptosis by increasing Bax expression and down-regulating the expressions of Bcl-2, Akt and p-Akt-473 (all P < 0.05). With the increase of IBC concentration, the expression of autophagy-related protein p62 and the LC3-II/I ratio increased progressively. Electron microscopy revealed the presence of autophagic bodies in IBC-treated MCF-7 cells. IBC treatment also resulted in decreased mitochondrial membrane potential and intracellular ATP level and increased ROS accumulation in MCF-7 cells (P < 0.05).@*CONCLUSION@#IBC is capable of inducing both apoptosis and autophagy in MCF-7 cells, suggesting the potential value of IBC as a lead compound in the development of anti-breast cancer agents.

Characteristics of amino acid metabolism in myeloid-derived suppressor cells in septic mice / 北京大学学报(医学版)

OBJECTIVE@#To explore the amino acid metabolomics characteristics of myeloid-derived suppressor cells (MDSCs) in mice with sepsis induced by the cecal ligation and puncture (CLP).@*METHODS@#The sepsis mouse model was prepared by CLP, and the mice were randomly divided into a sham operation group (sham group, n = 10) and a CLP model group (n = 10). On the 7th day after the operation, 5 mice were randomly selected from the surviving mice in each group, and the bone marrow MDSCs of the mice were isolated. Bone marrow MDSCs were separated to measure the oxygen consumption rate (OCR) by using Agilent Seahorse XF technology and to detect the contents of intracellular amino acids and oligopeptides through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technology. Different metabolites and potential biomarkers were analyzed by univariate statistical analysis and multivariate statistical analysis. The major metabolic pathways were enriched using the small molecular pathway database (SMPDB).@*RESULTS@#The proportion of MDSCs in the bone marrow of CLP group mice (75.53% ± 6.02%) was significantly greater than that of the sham group (43.15%± 7.42%, t = 7.582, P < 0.001), and the basal respiratory rate [(50.03±1.20) pmol/min], maximum respiration rate [(78.07±2.57) pmol/min] and adenosine triphosphate (ATP) production [(25.30±1.21) pmol/min] of MDSCs in the bone marrow of CLP group mice were significantly greater than the basal respiration rate [(34.53±0.96) pmol/min, (t = 17.41, P < 0.001)], maximum respiration rate [(42.57±1.87) pmol/min, (t = 19.33, P < 0.001)], and ATP production [(12.63±0.96) pmol/min, (t = 14.18, P < 0.001)] of sham group. Leucine, threonine, glycine, etc. were potential biomarkers of septic MDSCs (all P < 0.05). The increased amino acids were mainly enriched in metabolic pathways, such as malate-aspartate shuttle, ammonia recovery, alanine metabolism, glutathione metabolism, phenylalanine and tyrosine metabolism, urea cycle, glycine and serine metabolism, β-alanine metabolism, glutamate metabolism, arginine and proline metabolism.@*CONCLUSION@#The enhanced mitochondrial oxidative phosphorylation, malate-aspartate shuttle and alanine metabolism in MDSCs of CLP mice may provide raw materials for mitochondrial aerobic respiration, thereby promoting the immunosuppressive function of MDSCs. Blocking the above metabolic pathways may reduce the risk of secondary infection in sepsis and improve the prognosis.

Molluscicidal activity of the secondary metabolites from Streptomyces nigrogriseolus XD 2-7 against Oncomelania hupensis and its preliminary mechanisms of molluscicidal actions / 中国血吸虫病防治杂志

OBJECTIVE@#To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity.@*METHODS@#The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7.@*RESULTS@#After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ2 = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05).@*CONCLUSIONS@#The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.

Biomarcadores na bexiga hiperativa: artigo de revisão / Biomarkers in overactive bladder: review article

A bexiga hiperativa caracteriza-se pela urgência miccional, geralmente acompa- nhada de noctúria e aumento da frequência urinária. Trata-se de afecção preva- lente, com enorme comprometimento da qualidade de vida, em todos os seus as- pectos. Diversos biomarcadores vêm sendo estudados para melhor caracterização dos diferentes fenótipos da afecção, entre eles as neurotrofinas urinárias, o ATP, a genômica e a microbiota urinária. Acredita-se que tal caracterização poderá ter implicações para prevenção, fisiopatologia e individualização do tratamento.(AU)

The overactive bladder is characterized by urinary urgency, usually accompanied by nocturia and increased urinary frequency. It is a prevalent condition, with enormous impairment of quality of life, in all its aspects. Several biomarkers have been studied to better characterize the different phenotypes of the condition, including urinary neurotrophins, ATP, genomics and urinary microbiota. It is believed that such charac- terization may have implications for prevention, pathophysiology and individualiza- tion of treatment.(AU)

Mechanism of insulin resistance in obesity: a role of ATP / 医学前沿

Obesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named "mitochondrial overheating." Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.

Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity / 医学前沿

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.

The ATP Level in the mPFC Mediates the Antidepressant Effect of Calorie Restriction / 神经科学通报·英文版

Food deprivation can rescue obesity and overweight-induced mood disorders, and promote mood performance in normal subjects. Animal studies and clinical research have revealed the antidepressant-like effect of calorie restriction, but little is known about the mechanism of calorie restriction-induced mood modification. Previous studies have found that astrocytes modulate depressive-like behaviors. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant isoform in mediating astrocyte Ca

Association between Knee Osteoarthritis and Metabolic Syndrome in Non-Institutionalized Elderly Patients / Associação entre osteoartrite de joelho e síndrome metabólica em pacientes idosos não institucionalizados

Abstract Objective This study aimed to analyze the association between knee osteoarthritis (OA) and metabolic syndrome (MS) in non-institutionalized elderly patients. Methods A cross-sectional, randomized study, drawn from a probabilistic cluster study conducted with 416 elderly people from a Family Health Unit (USF, in the Portuguese acronym) of our municipality. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), and OA according to the KellgrLawrence (KL) scale (≥ 2). Results For the statistical analysis, we performed an exploratory data analysis, Mann-Whitney or Chi-Squared tests and univariate and multivariate logistic regressions, with significance level of p < 0.05; the concordance between the evaluators was verified through the Kappa coefficient. There was an association between OA and body mass index (BMI) (p = 0.0021) and between OA and waist circumference (WC) (p < 0.001; odds ratio [OR] = 3.524). There was no significant association between OA and the number of metabolic components nor with SM itself. Conclusion We conclude that knee OA is associated with WC, regardless of weight, and that the increase in its measure reflects a greater chance of MS in non-institutionalized elderly patients.

Resumo Objetivo Este estudo teve o objetivo de analisar a associação entre a osteoartrite (OA) de joelho e a síndrome metabólica (SM) em pacientes idosos não institucionalizados. Métodos Pesquisa transversal, aleatorizada, extraída de um estudo probabilístico por conglomerado realizado com 416 idosos de uma Unidade de Saúde da Família do nosso município. A SM foi definida de acordo com o National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), e a OA de acordo com a escala KellgrLawrence (KL) (≥ 2). Resultados Para a análise estatística, foi realizada uma análise exploratória de dados, testes de Mann-Whitney ou Qui-quadrado e regressões logísticas uni e multivariadas, com nível de significância de p < 0,05; a concordância entre os avaliadores foi verificada através do coeficiente de Kappa. Verificou-se associação entre OA e índice de massa corpórea (IMC) (p = 0,0021) e entre OA e circunferência de cintura (CC) (p < 0,001; razão de chances [RC] = 3,524). Não foi encontrada associação significativa entre a OA e o número de componentes metabólicos nem com a SM em si. Conclusão Conclui-se que a OA de joelho associa-se à CC, independente do peso, e que o aumento em sua medida reflete em uma maior chance de SM em idosos não institucionalizados.

Caracterización de factores de riesgo cardiovascular en adultos de una zona suburbana de Posadas-Misiones / Characterization of cardiovascular risk factors in adults of a sub-urban area of the city of Posadas-Misiones / Caracterização de fatores de risco cardiovasculares em adultos de uma zona suburbana de Posadas-Misiones

Las enfermedades cardiovasculares son una importante causa de morbimortalidad. Se propuso determinar la frecuencia de los principales factores de riesgo cardiovascular en individuos adultos que asistieron a un centro de atención primaria de una zona suburbana de la ciudad de Posadas-Misiones. Se evaluaron 300 individuos; 203 mujeres y 97 varones, entre 20 y 75 años. Se registraron datos personales, antropométricos y se extrajo sangre con 12 horas de ayuno para las determinaciones bioquímicas. El diagnóstico de síndrome metabólico se basó en los criterios del ATP III. La frecuencia de factores de riesgo fue: hipertensión 21,3%, prehipertensión 36,7%, síndrome metabólico 35,0%, glucemia alterada en ayunas 28,0%, tabaquismo 23,0%, exceso de peso 68,6%, obesidad abdominal 65,0%, índice de filtración glomerular disminuido 12,0%, antecedentes familiares de enfermedad cardiovascular 33,7% e hipercolesterolemia 22,0%. Según nivel de instrucción, los individuos con bajo nivel educativo presentaron mayor frecuencia de factores de riesgo respecto a los individuos con nivel medio y alto. Los resultados de este estudio alertan sobre la necesidad de la búsqueda activa de factores de riesgo para la enfermedad cardiovascular en toda la población.

Cardiovascular diseases are an important cause of morbidity and mortality. The aim of this study was to determine the frequency of the main cardiovascular risk factors in adult individuals who attend a primary care center in a sub-urban area of the city of Posadas-Misiones. The population was composed of 300 individuals: 203 women and 97 men, age range between 20 and 75 years. Personal, anthropometric data were recorded and blood was extracted with 12 hours of fasting for biochemical determinations. The diagnosis of metabolic syndrome was based on ATP III criteria. The frequency of risk factors was: hypertension 21.3%, pre-hypertension 36.7%, metabolic syndrome 35%, altered fasting glycemia 28%, smoking 23%, over weight 68.6%, abdominal obesity 65%, decreased glomerular filtration rate 12%, family history of cardiovascular disease 33.7% and hypercholesterolemia 22%. According to the level of education, a low educational level had a higher cardiovascular risk factor frequency than medium and high-level. The results of this study warn about the need for an active search for risk factors for cardiovascular disease in the entire population.

As doenças cardiovasculares são uma causa importante não só de morbimortalidade. O objetivo foi determinar a frequência dos principais fatores de risco cardiovascular em indivíduos adultos que frequentaram um centro de atenção primária em uma área suburbana da cidade de Posadas-Misiones. 300 indivíduos foram avaliados; 203 mulheres e 97 homens, entre 20 e 75 anos de idade. Dados pessoais, antropométricos foram registrados e foi extraído sangue com 12 horas de jejum para determinações bioquímicas. O diagnóstico de síndrome metabólica foi baseado nos critérios do ATP III. A frequência dos fatores de risco foi: hipertensão 21,3%, pré-hipertensão 36,7%, síndrome metabólica 35,0%, glicemia alterada em jejum 28,0%, tabagismo 23,0%, excesso de peso 68,6%, obesidade abdominal 65,0%, taxa de filtração glomerular diminuída 12,0%, histórico familiar de doença cardiovascular 33,7% e hipercolesterolemia 22,0%. De acordo com o nível de escolaridade, indivíduos com baixo nível educacional apresentaram maior frequência dos factores de risco quando comparados com indivíduos de nível médio e alto. Os resultados deste estudo alertam para a necessidade de busca ativa de fatores de risco para a doença cardiovascular em toda a população.

Mitochondrial Mechanisms in Diabetic Cardiomyopathy

Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca²⁺ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.

Divergent effects of lycopene on pancreatic alpha and beta cells / 生理学报

Lycopene is an antioxidant which has potential anti-diabetic activity, but the cellular mechanisms have not been clarified. In this study, different concentrations of lycopene were used to treat pancreatic alpha and beta cell lines, and the changes of cell growth, cell apoptosis, cell cycle, reactive oxygen species (ROS), ATP levels and expression of related cytokines were determined. The results exhibited that lycopene did not affect cell growth, cell apoptosis, cell cycle, ROS and ATP levels of alpha cells, while it promoted the growth of beta cells, increased the ratio of S phase, reduced the ROS levels and increased the ATP levels of beta cells. At the same time, lycopene treatment elevated the mRNA expression levels of tnfα, tgfβ and hif1α in beta cells. These findings suggest that lycopene plays cell-specific role and activates pancreatic beta cells, supporting its application in diabetes therapy.

Novel role of intracellular ATP in obesity pathology / 生理学报

ATP is an important energy source for cells. Traditionally, intracellular ATP levels are believed to be relatively stable and will not rise consistently in the physiological conditions. However, new studies suggest that ATP levels may rise in multiple tissues under the condition of energy surplus contributing to the metabolic disorders in obesity. However, the molecular mechanism of ATP elevation remains unknown in obesity except the increase in energy supply. Based on our experimental results and the findings reported in the literature, we discuss the cellular and molecular mechanisms by which ATP levels are regulated in cells by multiple factors, including superoxide ions, mitochondrial flash, antioxidants, anti-apoptotic molecule Bcl-xL, AMP-activated protein kinase (AMPK) and metformin. Contribution of these factors to the alteration of ATP set-point will be discussed together with their impact on insulin resistance in type 2 diabetes mellitus. With a focus on the energy surplus in obesity, we explore the mechanism of insulin resistance induced by ATP elevation and provide an answer to the contradiction between the new experimental results and the traditional viewpoint of intracellular ATP. We propose that elevation of intracellular ATP may lead to metabolic disorder in obesity through activation of a feedback mechanism that inhibits mitochondrial function.

Mitochondrial Quality Control in the Heart: New Drug Targets for Cardiovascular Disease

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.

Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease

Antihypoxic and anti-ischemic properties of the North Caucasus flora plant extracts / Propiedades antihipóxicas y antiisquémicas de los extractos de plantas de la flora del norte del Cáucaso

Nowdays it is established that ischemic brain damage like ischemic stroke is one of the leading cause of death and disability in the population that assumes relevance development of anti-ischemic drugs. The work studied the anti-hypoxic and anti-ischemic effect of 7 plant extracts. Antihypoxic activity was assessed on models of hypobaric, hypercapnic, histotoxic, hematotoxic hypoxia. Anti-ischemic activity of test-extracts was studied on the focal cerebral ischemia model. Administration of Tagetes patula, Gaillardia pulchella, Sorbaria sorbifolia, Grossularia reclinata, Ribes nigrum, Rubus caesius and Lysimachia punctata extracts contributed to the necrosis zone reduction by 56.6% (p<0.05); 37.3% (p<0.05); 73.2% (p<0.05); 49.4% (p<0.05); 42.5% (p<0.05); 85.5% (p<0.05); 44.2% (p<0.05) and also restored aerobic metabolism in brain tissue. Test - objects increased of the animal lifespan under hypoxia conditions. Based on the data obtained, it is assumed that further studies of North Caucasus flora plant extracts as cerebro-protective agents are promising.

Hoy en día, se ha establecido que el daño cerebral isquémico, como el accidente cerebrovascular isquémico, es una de las principales causas de muerte y discapacidad en la población lo cual hace relevante el desarrollo fármacos antiisquémicos. En este trabajo se estudió el efecto antihipóxico y antiisquémico de siete extractos de plantas. La actividad antihipóxica se evaluó en modelos de hipoxia hipocrática, hipercápnica, histotóxica y hematotóxica. La actividad antiisquémica de los extractos de prueba se estudió en el modelo de isquemia cerebral focal. La administración de los extractos de Tagetes patula; Gaillardia pulchella; Sorbaria sorbifolia; Grossularia reclinata; Ribes nigrum; Rubus caesius y Lysimachia punctata contribuyeron a la reducción de la zona de necrosis en un 56,6% (p<0,05); 37,3% (p<0,05); 73,2% (p<0,05); 49,4% (p<0,05); 42,5% (p<0,05); 85,5% (p<0,05); 44.2% (p<0.05), respectivamente, además, de restaurar el metabolismo aeróbico en el tejido cerebral. Comparado con el control, se observó un aumento en el tiempo de sobrevida del animal en condiciones de hipoxia. Sobre la base de los interesantes datos obtenidos, se sugiere estudios adicionales de extractos de plantas de la flora del Cáucaso Norte como agentes protectores del cerebro.

Monitoramento da limpeza de produtos para saúde com teste adenosina trifosfato / Monitoring of health products cleaning with adenosine triphosphate testing / Monitoreo de la limpieza de productos para la salud con test adenosín trifosfato

Objetivo: Avaliar a qualidade da limpeza dos produtos para saúde utilizando o teste de superfície adenosina trifosfato (ATP) em um Centro de Materiais e Esterilização. Método: Trata-se de um estudo transversal, descritivo, de natureza quantitativa, realizado em uma clínica particular de Belo Horizonte, Minas Gerais. Foram avaliados 26 formulários com 102 testes de ATP entre maio de 2017 e maio de 2018. Resultados: Os valores dos testes de ATP nos canulados variaram de 55 a 206 unidades relativas de luz (RLU), com média de 124±46. Para instrumentais, os resultados alternaram entre 14 e 82 RLU, com média de 54±28. Conclusão: Os testes de ATP não são específicos, mas sugerem ausência de resíduos em todos os instrumentais. Conclui-se que uma estrutura física adequada, protocolos de limpeza baseados em evidências e o gerenciamento de recursos materiais e humanos contribuem para a garantia da qualidade do processo de limpeza.

Purpose: Evaluating the cleaning quality of health products by using the surface adenosine triphosphate (ATP) test in a Central Sterile Services Department. Method: It is a descriptive, cross-sectional study with a quantitative approach, conducted in a private clinic in Belo Horizonte, Minas Gerais. Twenty-six survey forms with 102 ATP tests were evaluated between May 2017 and May 2018. Results: The numbers in ATP tests in the lumened instruments vary from 55 to 206 relative luminescence units (RLU), with a mean of 124±46. In surgical instruments, results alternated between 14 and 82 RLU, with a mean of 54±28. Conclusion: ATP tests are not specific, but they suggest absence of residues in all the instruments. The conclusion is that a proper physical structure, evidence-based cleaning protocols and human and material resource management contribute to ensure the cleaning process quality

Objetivo: Evaluar la calidad de la limpieza de los productos para la salud utilizando el test de superficie adenosín trifosfato (ATP) en un Centro de Materiales y Esterilización. Método: Se trata de un estudio transversal, descriptivo, de naturaleza cuantitativa, realizado en una clínica particular de Belo Horizonte, Minas Gerais. Fueron evaluados 26 formularios con 102 test de ATP entre mayo de 2017 y mayo de 2018. Resultados: Los valores de los test de ATP en las cánulas variaron de 55 a 206 unidades relativas de luz (RLU), con promedio de 124±46. Para instrumentales, los resultados alternaron entre 14 y 82 RLU, con promedio de 54±28. Conclusión: Los test de ATP no son específicos, pero sugieren ausencia de residuos en todos los instrumentales. Se concluye que una estructura física adecuada, protocolos de limpieza basados en evidencias y la gestión de recursos materiales y humanos contribuyen para la garantía de la calidad del proceso de limpieza