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Femina ; 49(8): 501-504, 20210831.
Article in Portuguese | LILACS | ID: biblio-1342421


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)

Humans , Male , Female , Urinary Bladder, Overactive , Urinary Incontinence, Urge , Biomarkers , Adenosine Triphosphate , Genomics , Microbiota , Nerve Growth Factors
Frontiers of Medicine ; (4): 372-382, 2021.
Article in English | WPRIM | ID: wpr-888753


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.

Adenosine Triphosphate , Diabetes Mellitus, Type 2 , Humans , Insulin , Insulin Resistance , Obesity
Frontiers of Medicine ; (4): 594-607, 2021.
Article in English | WPRIM | ID: wpr-888746


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.

Adenosine Triphosphate , Animals , Chemical and Drug Induced Liver Injury/etiology , Flavonoids , Humans , Inflammasomes , Mice , NLR Family, Pyrin Domain-Containing 3 Protein , Nigericin
Neuroscience Bulletin ; (6): 1303-1313, 2021.
Article in English | WPRIM | ID: wpr-922625


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

Adenosine Triphosphate , Animals , Antidepressive Agents/therapeutic use , Caloric Restriction , Mice , Mice, Knockout , Prefrontal Cortex
Rev. bras. ortop ; 55(3): 310-316, May-June 2020. tab, graf
Article in English | LILACS | ID: biblio-1138035


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.

Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Osteoarthritis , Aging , Body Mass Index , Adenosine Triphosphate , Family Health , Metabolic Syndrome , Waist Circumference , Health Promotion , Obesity
Acta bioquím. clín. latinoam ; 54(1): 19-28, mar. 2020. graf, tab
Article in Spanish | LILACS | ID: biblio-1130575


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.

Humans , Male , Female , Adult , Middle Aged , Aged , Risk Zone/ethnology , Heart Disease Risk Factors , Primary Health Care , Family , Adenosine Triphosphate , Disease , Causality , Fasting , Diagnosis , Education , Medical History Taking
Acta Physiologica Sinica ; (6): 133-138, 2020.
Article in English | WPRIM | ID: wpr-827075


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.

Adenosine Triphosphate , Metabolism , Apoptosis , Carotenoids , Pharmacology , Cell Cycle , Cells, Cultured , Cytokines , Metabolism , Glucagon-Secreting Cells , Humans , Insulin-Secreting Cells , Lycopene , Pharmacology , Reactive Oxygen Species , Metabolism
Acta Physiologica Sinica ; (6): 532-538, 2020.
Article in Chinese | WPRIM | ID: wpr-827033


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.

AMP-Activated Protein Kinases , Adenosine Triphosphate , Diabetes Mellitus, Type 2 , Energy Metabolism , Humans , Metformin , Obesity
Korean Circulation Journal ; : 395-405, 2020.
Article in English | WPRIM | ID: wpr-816678


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.

Adenosine Triphosphate , Cardiovascular Diseases , Cause of Death , Heart Failure , Heart , Homeostasis , Mitochondria , Mitophagy , Organelles , Quality Control , Spermidine , Unfolded Protein Response
Article in English | WPRIM | ID: wpr-811150


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.

Adenosine Triphosphate , Adiponectin , Autophagy , Diabetes Mellitus , Diabetic Cardiomyopathies , Heart Failure , Mitochondria , Mitochondrial Dynamics , Oxidative Stress , Reactive Oxygen Species , Regeneration , Sirtuins
Bol. latinoam. Caribe plantas med. aromát ; 18(5): 504-517, sept. 2019. ilus, tab, graf
Article in English | LILACS | ID: biblio-1008288


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.

Animals , Male , Mice , Rats , Plant Extracts/therapeutic use , Brain Ischemia/drug therapy , Hypoxia/drug therapy , Enzyme-Linked Immunosorbent Assay , Adenosine Triphosphate/analysis , Rats, Wistar , Lactic Acid/analysis , Pyruvic Acid/analysis , Mice, Inbred BALB C
Rev. SOBECC ; 24(2): 57-61, abr-.jun.2019.
Article in Portuguese | LILACS, BDENF | ID: biblio-1006157


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

Humans , Adenosine Triphosphate , Housekeeping, Hospital , Evaluation Studies as Topic , Disinfectants
Article in English | WPRIM | ID: wpr-719642


Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS (H₂O₂), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.

Adenosine Triphosphate , Apoptosis , Biological Phenomena , Blotting, Western , Cell Line , Cell Survival , Flow Cytometry , G1 Phase Cell Cycle Checkpoints , Membrane Potential, Mitochondrial , Metabolism , Ovarian Neoplasms , Phytochemicals , Reactive Oxygen Species , Superoxides
Article in English | WPRIM | ID: wpr-719421


PURPOSE: The p38 mitogen-activated protein kinase (MAPKs) play a crucial role in the production of pro-inflammatory cytokines and over-expression of it increase cytokines which promote cancer. Among four isoforms, p38α has been well studied in head and neck squamous cell carcinoma (HNSCC) and other cancers as a therapeutic target. p38δ has recently emerged as a potential disease-specific drug target. Elevated serum p38α level in HNSCC was reported earlier from our lab. This study aims to estimate the levels of p38 MAPK-isoforms in the serum of HNSCC and design peptide inhibitor targeting the same. MATERIALS AND METHODS: Levels of p38 MAPK isoforms in the serum of HNSCC and healthy controls were quantified by surface plasmon resonance technology. The peptide inhibitor for p38 MAPK was designed by molecular modeling using Grid-based Ligand Docking with Energetics tools and compared with known specific inhibitors. RESULTS: We have observed highly elevated levels of all four isoforms of p38 MAPK in serum of HNSCC patients compared to the control group. Further, serum p38α, p38β, and p38δ levels were down regulated after therapy in follow-up patients, while p38γ showed no response to the therapy. Present study screened designed peptide WFYH as a specific inhibitor against p38δ. The specific inhibitor of p38δ was found to have no effect on p38α due to great structural difference at ATP binding pocket. CONCLUSION: In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

Adenosine Triphosphate , Carcinoma, Squamous Cell , Cytokines , Epithelial Cells , Follow-Up Studies , Head , Humans , Models, Molecular , Neck , p38 Mitogen-Activated Protein Kinases , Protein Isoforms , Protein Kinases , Surface Plasmon Resonance
Acta Physiologica Sinica ; (6): 388-394, 2019.
Article in Chinese | WPRIM | ID: wpr-777175


The aim of this study was to determine the effects of extremely low frequency electromagnetic field (ELF-EMF) on energy metabolism and oxidative stress in Caenorhabditis elegans (C. elegans). Worms in three adult stages (young adult stage, egg-laying stage and peak egg-laying stage) were investigated under 50 Hz, 3 mT ELF-EMF exposure. ATP levels, ATP synthase activity in vivo, reactive oxygen species (ROS) content, and changes of total antioxidant capacity (TAC) were detected, and worms' oxidative stress responses were also evaluated under ELF-EMF exposure. The results showed that ATP levels were significantly increased under this ELF-EMF exposure, and mitochondrial ATP synthase activity was upregulated simultaneously. In young adult stage, worms' ROS level was significantly elevated, together with upregulated TAC but with a decreased ROS-TAC score indicated by principal component analysis. ROS level and TAC of worms had no significant changes in egg-laying and peak egg-laying stages. Based on these results, we concluded that ELF-EMF can enhance worm energy metabolism and elicit oxidative stress, mainly manifesting as ATP and ROS level elevation together with ATP synthase upregulation and ROS-TAC score decrease in young adult C. elegans.

Adenosine Triphosphate , Metabolism , Animals , Caenorhabditis elegans , Radiation Effects , Electromagnetic Radiation , Energy Metabolism , Mitochondrial Proton-Translocating ATPases , Metabolism , Oxidative Stress , Reactive Oxygen Species
Acta Physiologica Sinica ; (6): 625-636, 2019.
Article in Chinese | WPRIM | ID: wpr-777148


Mitochondrial dynamics, involving mitochondrial fusion, fission and autophagy, plays an important role in maintaining cellular physiological function and homeostasis. Mitochondria are the "energy plant" of human body, so the changes of mitochondrial fusion, division and autophagy are important for cell respiration and energy production. On the other hand, energy metabolism influences mitochondrial dynamics in turn. This paper reviewed the recent advances in studies on the relationship between energy metabolism and the proteins regulating mitochondrial fusion, fission and autophagy. The association of mitochondrial dynamics with electron chain complex expression, oxidative phosphorylation and ATP synthesis upon exercise intervention will provide theoretical references for the further studies in sports training and disease intervention.

Adenosine Triphosphate , Autophagy , Energy Metabolism , Exercise , Humans , Mitochondria , Physiology , Mitochondrial Dynamics , Mitochondrial Proteins , Metabolism
Article in Korean | WPRIM | ID: wpr-764425


PURPOSE: The aims of this study were to evaluate the dentist's awareness and the actual status of infection control of noncritical dental instruments. MATERIALS AND METHODS: 40 dental clinics in Daejeon, South Chungcheong, North Chungcheong and North Jeolla provinces were surveyed. The questionnaire was delivered to the dentists belonging to those clinics, and the awareness and the practice of infection control were examined. The microbial contamination on the surface of five noncritical instruments (impression gun, light curing unit, 3-way syringe, shade guide, and dental floss dispenser) used by them was measured with an ATP luminometer. Correlation analysis between the awareness and the actual state of infection control was conducted. RESULTS: Awareness and frequency of infection control was highest in the 3-way syringe. Surface disinfection using disinfectant was most frequent in all instruments. 3-way syringes and shade guides were less contaminated than impression guns, light curing units, and dental floss dispensers. CONCLUSION: 3-way syringes had a significant correlation between user awareness of infection control and surface contamination, and the higher awareness, the lower the contamination measurement was shown.

Adenosine Triphosphate , Dental Clinics , Dental Devices, Home Care , Dental Instruments , Dentists , Disinfection , Firearms , Humans , Infection Control , Syringes
Article in English | WPRIM | ID: wpr-764302


BACKGROUND: Baicalein is a bioactive flavone that is originally extracted from the root of Scutellaria baicalensis Georgi. This plant has long served as Chinese herbal medicine in the management of multiple diseases including inflammatory bowel diseases. Although it has been revealed that baicalein inhibits experimental colitis in mice, the molecular mechanisms still remain largely unrecognized. METHODS: The experimental colitis was induced in mice by 3% dextran sulfate sodium (DSS) in drinking water. The mice were given baicalein (10 or 25 mg/kg) by gavage for 7 days before and after DSS administration. Expression of COX-2 and inducible nitric oxide synthase (iNOS) and molecules involved in NF-κB signaling, such as inhibitor of κBα (IκBα), pIκBα, p65, and phospho-p65 was examined by Western blot analysis in the tissue of the mouse colon. Activity of IκB kinase β (IKKβ) was assessed by measuring the relative amount of radioactive γ-phosphate of ATP transferred to the IκBα substrate protein. The expression and phosphorylation of STAT3 and its target gene cyclin D1 were also measured. RESULTS: Baicalein prominently mitigated the severity of DSS-induced colitis in mice. It inhibited the expression of COX-2 and iNOS. Moreover, baicalein attenuated activity and phosphorylation of IKKβ and subsequent degradation of IκBα. Baicalein suppressed the phosphorylation and nuclear translocation of p65, resulting in a reduced DNA binding activity of NF-κB. Baicalein also suppressed the phosphorylation of STAT3 and expression of cyclin D1. Baicalein exhibited the synergistic effect on inhibition of COX-2 induced by DSS with curcumin, an ingredient of turmeric. CONCLUSIONS: Protective effects of baicalein on DSS-induced colitis are associated with suppression of NF-κB and STAT3 signaling pathways, which may contribute to its cancer preventive effects on colon carcinogenesis.

Adenosine Triphosphate , Animals , Asian Continental Ancestry Group , Blotting, Western , Carcinogenesis , Colitis , Colon , Curcuma , Curcumin , Cyclin D1 , Cyclooxygenase 2 , Dextran Sulfate , Dextrans , DNA , Drinking Water , Herbal Medicine , Humans , Inflammatory Bowel Diseases , Mice , Nitric Oxide Synthase Type II , Phosphorylation , Phosphotransferases , Plants , Scutellaria baicalensis