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El ambiente obesogénico promueve la obesidad al facilitar el acceso y consumo de una amplia variedad de alimentos palatables altos en calorías. La activación del receptor de GLP1 (GLP1R) reduce la ingesta de alimentos, enlentece el vaciamiento gástrico y promueve un balance energético negativo a través de su acción en distintos órganos como el músculo esquelético, disminuyendo así el peso corporal. La obesidad inducida por dieta alta en grasa disminuye el efecto anorexigénico de la administración sistémica vía intra-peritoneal de EX4 (agonista de GLP1R). Sin embargo, se desconoce si la exposición a un ambiente obesogénico previo a la manifestación de obesidad disminuye los efectos anorexigénicos de EX4 o un posible efecto de EX4 sobre marcadores de oxidación de ácidos grasos y termogénesis en músculo esquelético. El objetivo de esta investigación fue determinar el efecto a corto plazo de la dieta CAF, un modelo del ambiente obesogénico humano, sobre la capacidad de EX4 de reducir la ingesta y modular la expresión de marcadores proteicos de oxidación de ácidos grasos y termogénesis (CPT1 y UCP2) en músculo de ratones. Nuestros datos muestran que una inyección intraperitoneal de EX4 a ratones C57BL/6J alimentados con dieta CAF o dieta control durante 10 días no altera la ingesta calórica total, peso corporal, o la expresión de proteínas marcadoras de los procesos de beta-oxidación y de termogénesis (CPT1 y UCP2). Estos datos sugieren que protocolos alternativos de administración de EX4 son necesarios para observar los efectos fisiológicos de la activación de GLP1R.
The obesogenic environment promotes obesity by facilitating access to and consumption of a wide variety of palatable, high-calorie foods. Activation of the GLP1 receptor (GLP1R) reduces food intake, slows gastric emptying, and promotes a negative energy balance by acting on organs such as skeletal muscle, thus decreasing body weight. Obesity induced by a high-fat diet decreased the anorexigenic effect of intraperitoneal systemic administration of EX4 (GLP1R agonist). However, it is unknown whether exposure to an obesogenic environment before the manifestation of obesity diminishes the anorexigenic effects of EX4 or a possible effect of EX4 on markers of fatty acid oxidation and thermogenesis in skeletal muscle. This investigation aimed to determine the short-term effect of the CAF diet, a model of the human obesogenic environment, on the ability of EX4 to reduce intake and modulate the expression of protein markers of fatty acid oxidation and thermogenesis (CPT1 and UCP2) in mouse muscle. Our data show that intraperitoneal injection of EX4 to C57BL/6J mice fed CAF diet or control diet for ten days does not alter total caloric intake, body weight, or expression of proteins markers of beta-oxidation and thermogenesis processes (CPT1 and UCP2). These data suggest that alternative EX4 administration protocols are necessary to observe the physiological effects of GLP1R activation.
Subject(s)
Animals , Male , Mice , Diet/adverse effects , Exenatide/administration & dosage , Obesity/etiology , Obesity/metabolism , Oxidation-Reduction , Blotting, Western , Muscle, Skeletal/metabolism , Thermogenesis , Fatty Acids/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Uncoupling Protein 2 , Irinotecan , Injections, Intraperitoneal , Mice, Inbred C57BLABSTRACT
bjective To observe the changes of upper extremity sensory function in patients with radicular cervical spondylosis and evaluate the treatment effect, by using the method of suspension exercise therapy (SET) and soft tissue manipulation. Methods A total of 72 patients with cervical spondylosis were divided into observation group (treated by SET combined with manipulation)and control group (treated by purely cervical traction) by simple random method. Both groups received 4-week continuous treatment for 6 times per week. The somatosensory evoked potential(SEP), current perception threshold (CPT) before and after the treatment in two groups were separatedly tested, and changes in visual analogue scale (VAS) pain scores of the affected limbs were examined, so as to determine the effective rate of treatment. Results After treatment, the latency of SEP was shortened mainly in brachial plexus potential N9 and cervical spinal potential N13 in two groups (P<0.05). The CPT levels and the VAS pain scores of the affected limbs were reduced in two groups (P<0.01), and the treatment effect in observation group was better that in control group (P<0.01)．Conclusion SET combined with soft tissue manipulation can effectively promote the repair of nerve sense function of cervical spondylotic radiculopathy.
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Objective:To investigate the changes of CPT1A and CPT1B protein expression in rat intestinal epithelial cells (IEC-6) after 60Co γ-ray irradiation, and the mechanism of the influence of carnitine palmitoyltransferase 1 (CPT1) on the proliferation of irradiated IEC-6 cells. Methods:IEC-6 cells were cultured in serum-normal medium or in serum-starved medium overnight, and pretreated with 20 μmol/L palmitic acid (PA) before irradiation with 0, 5, 10, and 15 Gy. At 24 h after irradiation, the cellular protein was collected for the measurement of CPT1A and CPT1B proteins by Western blot. The influences of ETO, an inhibitor of CPT1, on the survival and proliferation of irradiated IEC-6 cells were analyzed by colony formation assay and CCK-8 assay. The protein expressions and phosphorylation levels of the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) in 5 Gy irradiated IEC-6 cells pre-treated with ETO were analyzed by Western blot at 48 h after radiation.Results:When IEC-6 cells were cultured in serum-normal medium together with PA, the protein level of CPT1A was significantly increased after 15 Gy irradiation ( t=-2.82, P<0.05). When IEC-6 cells were cultured in serum-starved medium, the protein level of CPT1A was significantly increased at 5, 10, and 15 Gy ( t=-3.28, -8.72, -8.67, P<0.05). When IEC-6 cells were cultured in serum-starved medium together with PA, the protein levels of CPT1A were significantly increased at 5, 10 and 15 Gy ( t=-10.69, -7.02, -8.23, P<0.05), the protein levels of CPT1B were significantly increased at 10 and 15 Gy ( t=-3.73, -5.05, P<0.05). After irradiation, the survival and proliferation of IEC-6 cells in ETO group were significantly lower than those in control group ( t=5.46, 13.22, P<0.05), and the protein level of ERK1/2 and p-JNK in ETO group were significantly lower than those in control group ( t=4.01, 3.29, 10.68, 14.44, P<0.05). Conclusions:CPT1 promoted radiation-induced IEC-6 injury cells survival and proliferation by enhancing the expression level of ERK1/2 protein and the activity of JNK.
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The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.
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Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.
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ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose （300 mg·kg-1）， medium dose （150 mg·kg-1）， and low dose （75 mg·kg-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.
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ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.
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Objetivo: Comparar la salud periodontal de embaraza- das y no embarazadas mediante la aplicación del Índice de Periodontal Comunitario (IPC). Materiales y métodos: Se realizó un estudio ob- servacional de corte transversal. Se reclutaron 100 mujeres embarazadas (EMB) y 50 no embarazadas (NoEMB) que concurrieron al Hospital Materno Provincial de la Ciudad de Córdoba, Dr. Raúl F. Lucini. En todas se registró el IPC con la sonda periodontal WHO 621 en los 6 sextantes de la boca. Los datos se analizaron con el software Infostat/SP; el nivel de significación establecido fue de P <0,05. Resultados: El 70% de las pacientes presentó edades de entre 18 y 25 años. En las EMB el código 3 del IPC fue el más frecuente presente en 240 sextantes (40,1%) y en las NoEMB el código 2 fue el más frecuente con 39 sextantes (43%). A ambos grupos de estudio les corresponde el trata- miento de instrucción de higiene bucal, instrumentación supra y/o subgingival, y/o regularización de obturaciones. Conclusiones: El código 3 fue el más frecuente entre las EMB, a quienes les corresponde un Código de tratamiento periodontal (CTP) 2; las NoEMB presentaron un IPC de 1 y 2 como los más frecuentes y se vinculan con un CTP 1 y 2. Nos encontramos frente a una situación clínica periodontal posible de resolver con terapia básica que puede ser realizada por odontólogos generalistas (AU)
Aim: To compare the periodontal health of pregnant and non-pregnant women by applying the Community Periodontal Index (CPI). Materials and methods: In an observational, cross-sec- tional study, 100 pregnant women (PREG) and 50 non-preg- nant women (NonPREG) were recruited at the Dr. Raúl F. Lu- cini Provincial Maternity Hospital in Córdoba City. The CPI was determined in the 6 sextants of the mouth using a WHO 621 periodontal probe. The data were analyzed with Infostat SP software. P <0.05 was considered significant. Results: 70% of the patients were 18 to 25 years old. In the PREG group, CPI Code 3 was the most frequent, present in 240 sextants (40.1%), while in the non-PREG group, CPI Code 2 was the most frequent, with 39 sextants (43%). Treat- ment needs in both study groups are oral hygiene instruction, supra- and/or subgingival instrumentation, and/or correction of plaque retentive margins. Conclusions: Code 3 was the most frequent among preg- nant women, which corresponded to Periodontal Treatment Code (CTP) 2. CPI 1 and 2 were the most frequent in non-pregnant women, corresponding to CTP 1 and 2. This periodontal clinical condition can be treated with initial dental hygiene therapy, which can be performed by general dentists (AU)
Subject(s)
Humans , Female , Pregnancy , Adolescent , Adult , Young Adult , Periodontal Diseases/epidemiology , Pregnancy Complications/epidemiology , Periodontal Index , Oral Health , Health Services Needs and Demand , Oral Hygiene/education , Argentina/epidemiology , Cross-Sectional Studies , Health PromotionABSTRACT
Objective:Considering the efficacy of Gegen Qinliantang （GQT） in releasing exterior and clearing interior to alleviate dampness-heat dysentery， we analyzed the mechanism of the chloroform extract of GQT in alleviating enterotoxicity caused by irinotecan to provide an experimental basis for the development of GQT. Method:Kunming mice （<italic>n</italic>=60） were randomly divided into a blank group， a model group， a loperamide group （positive drug of loperamide hydrochloride capsule， 0.4 mg·kg<sup>-1</sup>）， and high- （2.3 g·kg<sup>-1</sup>） and low-dose （1.16 g·kg<sup>-1</sup>） GQT chloroform extract groups. The mouse model of delayed diarrhea was established by intraperitoneal injection of irinotecan hydrochloride （CPT-11， 55 mg·kg<sup>-1</sup>） for four consecutive days， meanwhile， the mice in the blank group only received the same volume of normal saline. Corresponding drugs were administered by gavage on the fifth day， respectively， while the ones in the blank group and model group were given distilled water for five consecutive days. The general condition of mice in each group was observed， and diarrhea indexes of mice were recorded. Pathological changes in colon tissues of mice were observed by hematoxylin-eosin （HE） staining. The tumor necrosis factor （TNF）-<italic>α</italic>， interleukin （IL）-1<italic>β</italic>， cyclooxygenase （COX）-2， intercellular adhesion molecule （ICAM）-1， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， malondialdehyde （MDA） and nitric oxide （NO） levels in colon tissues were detected with the assay kits. Furthermore， the expression levels of Kelch sample epoxy chloropropane associated protein 1 （Keap1）， nuclear factor E<sub>2</sub> related factor 2 （Nrf2）， tight junction protein-1 （ZO-1）， heme oxygenase-1 （HO-1） and tight junction protein （Occludin） were detected by Western blot. Result:Compared with the blank group， the model group showed declined body weight and reduced contents of GSH-Px and SOD （<italic>P</italic><0.01）， whereas increased diarrhea indexes and TNF-<italic>α</italic>， IL-1<italic>β</italic>， COX-2， ICAM-1， MDA and NO levels （<italic>P</italic><0.01）. Abundant inflammatory cells and colonic mucosa with defects， swelling， bleeding， and inflammatory exudation were revealed by HE staining in the mice of the model group. The expression levels of Keap1， Nrf2， ZO-1， HO-1 and Occludin in colon tissues significantly declined （<italic>P</italic><0.01）. Compared with the model group， the loperamide group and the high- and low-dose GQT chloroform extract groups exhibited improved weight loss， reduced diarrhea indexes， diminished TNF-<italic>α</italic>，<italic> </italic>IL-1<italic>β</italic>， COX-2， ICAM-1， MDA and NO， and elevated GSH-Px and SOD. HE staining indicated that the cells were compactly arranged with clear nuclei in the high- and low-dose GQT chloroform extract groups， and the expression levels of Keap1， Nrf2， HO-1， Occludin， and ZO-1 were up-regulated. Conclusion:GQT chloroform extract may alleviate CPT-11-induced delayed diarrhea by regulating inflammation and oxidative stress for enhancing the intestinal barrier function. These findings are expected to provide a reference for exploring the toxicity-attenuating effect of Chinese medicinals on chemotherapy drugs and for developing famous classical formulas.
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DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs)as a polymer of DNA-triangles.Circularizing a scaffold strand(84-NT)was the critical step followed by annealing with various staple strands to make stiff DNA-triangles.Atomic force microcopy(AFM),native polyacrylamide gel electrophoresis(PAGE),UV-analysis,MTT-assay,flow cytometry,and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT)loading.The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs,with lengths ranging from 2 to 4 μm and diameters ranging from 150 to 300 nm.One sharp band at the top of the lane(500 bp level)with the loss of electrophoretic mobility during the PAGE(native)gel analysis revealed the successful fabrication of DNA-NWs.The loading efficiency of CPT ranged from 66.85％to 97.35％.MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95％concentration compared with the CPT-loaded DNA-NWs.The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22％)compared to the apoptosis(7％)induced by the blank DNA-NWs.The release of CPT from the DNA-NWs was sustained at＜75％for 6 h in the presence of serum,demonstrating suitability for systemic applications.The IC50 of CPT@DNA-NWs was reduced to 12.8 nM CPT,as compared with the free CPT solution exhibiting an IC50 of 51.2 nM.Confocal imaging revealed the targetability,surface binding,and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2)compared with the control cell line.
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A atenção sustentada é um domínio cognitivo presente em atividades essenciais na rotina de jovens universitários que dispendem muitas horas em sala de aula, concentrando a atenção em aulas expositivas, realização de exercícios e estudos para provas. Este estudo investigou a relação entre a prática regular com videogames e a habilidade de atenção sustentada avaliada através do CPT II. Colaboraram com a pesquisa 122 universitários da região metropolitana de Florianópolis, divididos entre jogadores de videogame de ação e não ação, bem como não jogadores. Os participantes responderam uma bateria de testes, incluindo a avaliação da atenção sustentada, mapeamento de dados sociodemográficos e hábitos com videogames. Os resultados demonstram que, ao controlar o impacto de variáveis intervenientes, não se constatou diferença atencional entre os grupos. A comparação entre sexos apresentou significância com relação ao desempenho atencional, em que os homens tendem a responder mais rápido e mulheres cometem menos erros. Os achados sugerem que a prática regular com videogames não possui relação com desempenho atencional e pesquisas futuras devem investigar impactos de variáveis intervenientes, como a comparação entre sexos.
Sustained attention is a cognitive domain present in essential activities in the routine of young university students who spend many hours in the classroom, focusing attention on lectures, performing exercises and studying for tests. This study investigated the relationship between regular practice with video games and the sustained attention skill assessed through CPT II. 122 university students from the metropolitan region of Florianópolis collaborated with the research, divided between action and non-action video game players, as well as non-players. Participants performed a battery of tests, including the assessment of sustained attention, mapping of sociodemographic data and habits with video games. The results demonstrate that, when controlling the impact of intervening variables, there was no attentional difference between the groups. The comparison between sexes was significant in terms of attentional performance, in which men tend to respond faster and women make fewer mistakes. The findings suggest that regular practice with video games is not related to attentional performance and future research should investigate the impacts of intervening variables, such as such as sex comparison.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Attention , Video GamesABSTRACT
It is an established fact that primary and secondary hypertension and related cardiovascular disorders have a familial predisposition. We also know that essential hypertension is the most common amongst hypertensives. The aim of our study was to find out effect of cold pressor test (CPT) on heart rate and blood pressure amongst individuals with and without family history of hypertension. MethodsPresent study was undertaken using within group design consisting of measurements at basal and CPT and the parameters studied were pulse rate and Blood pressure. ResultsIn our study we found that in males with family history of HT (n=15), the mean basal pulse rate was 78.33 beats/min and following CPT it increased to 85.73. Similarly, in males without family history of HT (n=18) mean basal pulse rate was 77.28 beats/min and following CPT it increased to 86.72 beats/min. In both cases it was statistically significant. But it is observed that in case of females with family history of HT (n= 20) mean basal pulse rate was 80.9 beats/min and following CPT it increased to 89.1. Similarly, in Females without family history of HT (n=26) mean basal pulse rate was 77.15 beats/min and following CPT it increased to 84.73 beats/min and in both these cases, it was statistically significant. In males with family history of HT (n=15), mean basal SBP was 115.13 mmHg and following CPT increased to 123.93 and this was statistically significant and the mean DBP was 74.67 mmHg and following CPT it increased to 79.82 mmHg and it was not statistically significant. In males without family history of HT (n=18) mean basal SBP was 114.67 mmHg and following CPT it was increased to 122.89 mmHg and increase was statistically significant and mean DBP was 74.44 mmHg and following CPT it increased to 76.33 mmHg and this increase was not statistically significant. In females with family with family history of HT (n=20) the mean SBP was 114.2 mmHg and following CPT it increased to 121.9 mmHg and it was statistically significant and the mean DBP was 73.75 mmHg and following CPT it increased to 78.80 mmHg and it was not statistically significant. In females without family history of HT (n= 26) the mean basal SBP was 108.23 mmHg and following CPT it increased to 117.08 mmHg and the mean basal DBP was 69.92 mmHg and following CPT it was increased to 76.69 mmHg this increase in both the cases was statistically significant (table 1,2). In both the groups, none of the subjects was found to be hyperreactive to either systolic or diastolic blood pressure when they were subjected to CPT. ConclusionsIn both the groups, subjects were found to be hyporeactive or normoreactive to either systolic or diastolic blood pressure when they were subjected to CPT. But increase in basal blood pressure response is known to be due to CPT.
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Shavasana or a corpse pose is the final pose of a yoga flow. When practiced regularly it is known to restore the body and mind. Aim of our present study was to investigate the effects of shavasana on handgrip and cold pressor test on heart rate and blood pressure in apparently healthy young adults. In today’s world all of us are under constant stress and majority of individuals with sedentary lifestyle suffer from hypertension and each of us react differently to varied internal and external stimuli.METHODSFor convenience, we took 300 apparently healthy medical students of both sexes in the age group of 18 to 22 years and a comparative study was carried out among them. Their basal pulse and BP were recorded from dominant hand. For Hand Grip Test (HGT) handgrip dynamometer (INCO) was used by left hand, and pulse and BP from right hand was recorded and similarly Cold Pressor Test (CPT) was carried out by immersing left hand up to wrist joint in cold water mixed with ice cubes to maintain temperature at 40C and pulse and BP was recorded from right hand. Shavasana was performed for 15 minutes by lying down on the wooden couch, with eyes closed and lying on back, keeping arms six inches away from the body and legs and feet “drop” open and palms facing upwards and concentrating on their breathing, after which pulse and BP was recorded. This was carried out for a period of 30 days.RESULTSData was collected and analysed using paired ‘t’ test and paired differences were calculated using 95% confidence interval of the difference and p value of < 0.05 was taken as scientifically significant. In our study we found that there is significant decrease in basal pulse rate, when compared with CPT, immediately and after performing shavasana for a period of one month, and there was significant increase in pulse rate following HGT (p< 0.001) (table 1 and graph 1). Compared to basal, SBP and DBP, it was observed that there is significant decrease; immediately and after performing shavasana for one month and significant increase with HGT and CPT was observed (p<0.001) (table 1 and graph 1).CONCLUSIONSThere is a significant decrease in basal pulse rate, when compared with CPT, immediately and after performing shavasana for a period of one month, and there was significant increase in pulse rate following HGT (p< 0.001) (table 1 and graph 1). Compared to basal, SBP and DBP it was observed that there is significant decrease; immediately and after performing shavasana for one month and significant increase with HGT and CPT was observed (p<0.001) (table 1 and graph 1).
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A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent and antitumor potency. Particularly, compound was orally active and possessed excellent antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, .) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.
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Camptotheca acuminata produces camptothecin (CPT), a monoterpene indole alkaloid (MIA) that is widely used in the treatment of lung, colorectal, cervical, and ovarian cancers. Its biosynthesis pathway has attracted significant attention, but the regulation of CPT biosynthesis by the APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors (TFs) remains unclear. In this study, a systematic analysis of the AP2/ERF TFs family in C. acuminata was performed, including phylogeny, gene structure, conserved motifs, and gene expression profiles in different tissues and organs (immature bark, cotyledons, young flower, immature fruit, mature fruit, mature leaf, roots, upper stem, and lower stem) of C. acuminata. A total of 198 AP2/ERF genes were identified and divided into five relatively conserved subfamilies, including AP2 (26 genes), DREB (61 genes), ERF (92 genes), RAV (18 genes), and Soloist (one gene). The combination of gene expression patterns in different C. acuminata tissues and organs, the phylogenetic tree, the co-expression analysis with biosynthetic genes, and the analysis of promoter sequences of key enzymes genes involved in CPT biosynthesis pathways revealed that eight AP2/ERF TFs in C. acuminata might be involved in CPT synthesis regulation, which exhibit relatively high expression levels in the upper stem or immature bark. Among these, four genes (CacAP2/ERF123, CacAP2/ERF125, CacAP2/ERF126, and CacAP2/ERF127) belong to the ERF-B2 subgroup; two genes (CacAP2/ERF149 and CacAP2/ERF152) belong to the ERF-B3 subgroup; and two more genes (CacAP2/ERF095 and CacAP2/ERF096) belong to the DREB-A6 subgroup. These results provide a foundation for future functional characterization of the AP2/ERF genes to enhance the biosynthesis of CPT compounds of C. acuminata.
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@#[Abstract] Objective: To investigate the mechanisms of carnitine palmitoyltransferase 1c (CPT1c) expression to affect the proliferation and apoptosis of human thyroid papillary cancer B-CPAP cells through the AMP-dependent/activated protein kinase (AMPK) pathway in the low glucose and hypoxic conditions. Methods: Firstly,humanthyroidpapillarycarcinomaB-CPAP cells were cultured under normal condition or low glucose and hypoxic condition respectively, followed with the treatment of AMPK inhibitor compound C. Western blotting was used to detect the expressions of AMPK, p-AMPK, peroxisome proliferator-activated receptor α (PPARα) and CPT1c; the proliferation and apoptosis were detected by CCK-8 and Flow cytometry, respectively. Then PPARα-siRNA was synthesized and transfected into B-CPAP cells to knock down PPARα, and then the cells were cultured under normal or low glucose and hypoxic condition respectively.Above indicators were also detected to verify the regulation of PPARα on CPT1c. Finally, the human luciferase reporter plasmid containing CPT1c gene promoter was constructed, and the effect of PPARα on the activity of CPT1c promoter luciferase activity was observed by immunofluorescence. Results: The expressions ofAMPK, p-AMPK, PPARα and CPT1c were significantly increased in B-CPAP cells under low glucose and hypoxia condition (P<0.05 or P<0.01), while cell proliferation and apoptosis rate did not change significantly (P>0.05). After the treatment of AMPK inhibitor compound C, the expressions of p-AMPK, PPARα and CPT1c in low glucose and hypoxia group were significantly decreased (P<0.05 or P<0.01), the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). However, the change range was smaller than that in the normal culture + compound C group (P<0.05).After PPARα knockdown, the expressions ofAMPK, p-AMPK, PPARα and CPT1c in cancer cells cultured under normal conditions were significantly decreased (P<0.05 or P<0.01), and the inhibitory rate on cell proliferation and apoptosis rate were significantly increased (P<0.05). While under low glucose and hypoxia condition, the expression of CPT1c in cells after transfection was significantly decreased (P<0.05), and the inhibition rate on cell proliferation and the apoptosis rate were significantly increased (P<0.05); However, the change range was still lower than that of normal condition group after transfection (P<0.05).After PPARα overexpression, the ratio of fluorescence in the empty vector group was not significantly different from that of the blank group (P>0.05), and the ratio of fluorescence was significantly increased in PPARα over-expression group (P<0.05). Conclusions: AMPK can increase the expression of PPARα to promote the expression of CPT1c in thyroid cancer B-CPAP cells under low glucose and hypoxia conditions, thereby inhibiting cell apoptosis and maintaining cell proliferation ability.
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Introduction: Autonomic nervous system (ANS) is involvedin energy metabolism and regulation of the cardiovascularsystem. Autonomic dysfunction has been suggested tooccur in obese individuals in both adults and children but acomprehensive study of the autonomic status in young adultsis scant. So aim of the study was to evaluate and comparecardiovascular autonomic functions in young adults on thebasis of BMI.Material and methods: 150 healthy young students of MMUaged 18–25 years, divided into four groups based on BMI asper Asian criteria (underweight, normal weight, overweightand obese). Various autonomic function tests done were Lyingto Standing test, Valsalva manoeuvre, Hand grip test (HGT)and Cold pressor test (CPT).Results: The mean baseline SBP and DBP were significantlyhigher in obese subjects followed by overweight, normalweight and under weight. No parasympathetic alterationbetween different BMI groups was seen. Mean values ofresting SBP and DBP were significantly higher and bloodpressure response to HGT and CPT was significantly lower inobese as compared to normal weight subjects.Conclusion: Our study revealed an altered autonomicfunction in the form of impaired sympathetic activity withno parasympathetic modulation in obese young adults. Soweight reduction and moderate intensity aerobic exerciseprogrammes should be incorporated into daily living, whichmay delay or prevent the onset of hypertension.
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OBJECTIVES: This study intended to identify the deficits of cognitive control among patients with bipolar I disorder and their first-degree relatives, and identify the possibility of cognitive control as an endophenotype of bipolar disorder. METHODS: The study included three groups: euthymic states patients with bipolar I disorder (n = 55), unaffected first-degree relatives of probands with bipolar I disorder (n = 30), and a healthy control group (n = 51), that was matched on age, sex, and years of education. The AX version of the continuous performance test (CPT) was used to examine cognitive control. Error rate, correct response times of each subsets (AX, BX, AY, BY), and d' as an indication of accuracy sensitivity index were calculated. Psychopathology, intelligence, and psychomotor speed were also assessed. RESULTS: Patients with bipolar I disorder showed significantly worse error rates in the AX (p = 0.01) and BX (p = 0.02) subsets and d' (p = 0.05) than the others. They also showed more delayed correct response times than the healthy control group and first-degree relatives in all subsets (p < 0.01). But first-degree relatives showed neither high error rates nor delayed correct response times than healthy control group. CONCLUSIONS: These findings suggest that cognitive control is impaired in bipolar I disorder but less likely to be an endophynotype of bipolar I disorder.
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Humans , Bipolar Disorder , Education , Endophenotypes , Intelligence , Psychopathology , Reaction TimeABSTRACT
Objective To explore the effect of the combination of carnitine palmityl transferase 1( CPT1) inhibitor etomoxir and chemotherapy drug cisplatin on lung cancer cell line A549 proliferation and migration of lung cancer. Methods CCK8 was applied to investigate the effect of the combination of etomoxir and cisplatin on A549 survival. Transwell test was used to detect migration of lung cancer cell line A549 treated with the combination of etomoxir and cisplatin. Apoptosis of A549 was detected by annexin V/PI. A549 transplanted mice were used to test therapeu-tic effect of etomoxir combined with cisplatin. Results Tumor cells proliferation and migration were inhibited by the combination of etomoxir and cisplatin. Apoptosis of tumor cells was enhanced by the combination of etomoxir. After the treatment of the combination of etomoxir and cisplatin, tumor growth of mouse was inhibited. Conclusions The combination of etomoxir and cisplatin can decrease tumor cells survival and induce tumor cells apoptosis, and then inhibit tumor growth in mouse lung cancer model.
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Aim To investigate the role and mecha-nism of exchange protein directly activated by cAMP (Epac) protein in the paraventricular nucleus(PVN) of the hypothalamus in the development of inflammatory pain in rats. Methods Adult SD male rats were cho-sen to establish the model of inflammatory pain through subcutaneous injection of complete Freund's adjuvant(CFA) on the center of left hind foot. Western blot was used to detect the changes of the expression of Ep-ac protein. Thermal withdrawal latency(TWL) was ob-served after the PVN injecting 8p-CPT-2′-O-Me-cAMP (8p-CPT),the agonist of Epac. Then activated down-stream MEK1/2 protein of Epac in PVN was detected using Western blot when the potency was the strongest.Results ① Compared with normal saline(control group),TWL decreased significantly on d 1, d 3, d 5, d 7,d 9 on the ipsilateral foot of CFA group rats(P<0.01),whereas it returned to normal level in d 13;the paw mechanical withdrawal threshold(PMWT) de-creased significantly on d 6,d 8,d 10,d 12 and d 14 (P<0.05);②Compared with the control,the Epac1 protein in CFA group rats began to decrease from d 3, and significantly decreased on d 3 and d 9(P<0.05), however the expression of Epac2 had no significant change, meanwhile p-MEK1/2 protein decreased sig-nificantly on d 3(P<0.05);③Compared with micro-injection of saline into the PVN(Saline group), the heat hyperalgesia of 20 min and 1h decreased signifi-cantly and TWL increased significantly after PVN ad-ministration of 8p-CPT(8p-CPT group)(P <0.05);paraventricular nucleus p-MEK1/2 protein expression increased significantly in 30 min(P <0.05) and re-covered to normal level 2 h after administration. Con-clusion The Epac1-MEK1/2 signaling pathway in the paraventricular nucleus of the hypothalamus may be in-volved in the development of chronic inflammatory pain induced by CFA.