2,497 research outputs found
3D-Pharmacophore model studies on MexB efflux pump inhibitor of Pseudomonas aeruginosa : Final Report Scientific Research Project Of Student In 2020
No full text50 p.From the database of 139 substances in 18 scafford collected from 20 scientific papers, 6 3D Pharmacophore models were built based on ligand: 4 models based on MPC8 value and 2 models based on IC50 value. Then validate models based on sensitivity, specificity, accuracy and GH score and choose the 3 best models to virtual
screening on large databases such as DrugBank, Traditional Chinese Medical. In which Model (3) has 4 features: 2 hydrophobic centroids and 2 hydro bonding acceptors HHaa. Model (4) with 4 features: 1 aromatic ring, 1 hydrophobic centroid and 2 hydro bonding acceptors RHAA. Model (5) with 4 feartures: 3 hydrophobic centroids and 1 hydro bonding acceptors HHHa
Short term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure
No full textInitiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults, we conducted a double blind study in which seven GH-deficient patients (aged 24-74 yr) each received in random order daily sc injections of placebo, a physiological dose of GH (0.04 U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose) for 7 days, separated by 21-day washout periods. On the seventh day, measurements were made of serum insulin-like growth factor I, body weight, exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone, atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and blood pressure. GH significantly increased mean insulin-like growth factor I levels from 105 ± 11 to 304 ± 45 μg/L during low dose treatment (P = 0.006) and 400 ± 76 μg/L during high dose treatment (P = 0.004). High dose GH caused a 1.2 ± 0.3 kg increase in body weight (P = 0.01) and a 193 ± 65 mmol increase in exchangeable sodium (P = 0.008). Low dose GH had a lesser effect, with no significant increase in body weight, but an increase in exchangeable sodium of 113 ± 37 mmol (P = 0.02). Plasma volume was not significantly affected by GH treatment. Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine pRA levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were not significantly affected by GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h heart rate was significantly higher during low dose (82 ± 2 beats/min; P = 0.0001) and high dose (88 ± 3 beats/min; P = 0.0001) GH treatment than during placebo (67 ± 3 beats/min). However, no significant change in mean 24-h systolic or diastolic blood pressure was observed. In summary, acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium, but no associated increase in blood pressure. We conclude that 1) sodium retention is a physiological effect of GH, but does not cause an acute rise in blood pressure; and 2) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect
RNAseq analysis of fast skeletal muscle in restriction-fed transgenic coho salmon (Oncorhynchus kisutch) : an experimental model uncoupling the growth hormone and nutritional signals regulating growth
No full textBackground Coho salmon (Oncorhynchus kisutch) transgenic for growth hormone (Gh) express Gh in multiple tissues which results in increased appetite and continuous high growth with satiation feeding. Restricting Gh-transgenics to the same lower ration (TR) as wild-type fish (WT) results in similar growth, but with the recruitment of fewer, larger diameter, muscle skeletal fibres to reach a given body size. In order to better understand the genetic mechanisms behind these different patterns of muscle growth and to investigate how the decoupling of Gh and nutritional signals affects gene regulation we used RNA-seq to compare the fast skeletal muscle transcriptome in TR and WT coho salmon. Results Illumina sequencing of individually barcoded libraries from 6 WT and 6 TR coho salmon yielded 704,550,985 paired end reads which were used to construct 323,115 contigs containing 19,093 unique genes of which >10,000 contained >90 % of the coding sequence. Transcripts coding for 31 genes required for myoblast fusion were identified with 22 significantly downregulated in TR relative to WT fish, including 10 (vaspa, cdh15, graf1, crk, crkl, dock1, trio, plekho1a, cdc42a and dock5) associated with signaling through the cell surface protein cadherin. Nineteen out of 44 (43 %) translation initiation factors and 14 of 47 (30 %) protein chaperones were upregulated in TR relative to WT fish. Conclusions TR coho salmon showed increased growth hormone transcripts and gene expression associated with protein synthesis and folding than WT fish even though net rates of protein accretion were similar. The uncoupling of Gh and amino acid signals likely results in additional costs of transcription associated with protein turnover in TR fish. The predicted reduction in the ionic costs of homeostasis in TR fish associated with increased fibre size were shown to involve multiple pathways regulating myotube fusion, particularly cadherin signaling.Peer reviewe
GH and the cardiovascular system: an update on a topic at heart
No full textIn this review, the importance of growth hormone (GH) for the maintenance of normal cardiac function in adult life is discussed. Physiological effects of GH and underlying mechanisms for interactions between GH and insulin-like growth factor I (IGF-I) and the cardiovascular system are covered as well as the cardiac dysfunction caused both by GH excess (acromegaly) and by GH deficiency in adult hypopituitary patients. In both acromegaly and adult GH deficiency, there is also increased cardiovascular morbidity and mortality possibly linked to aberrations in GH status. Finally, the status of the GH/IGF-I system in relation to heart failure and the potential of GH as a therapeutic tool in the treatment of heart failure are reviewed in this article. © 2014 The Author(s)
Artificial intelligence (AI) development in the Vietnam's energy and economic systems: A critical review
No full textVietnam plans to develop artificial intelligence (AI) markets but is still at the early development stages of investment, regulation and research development. A critical review of facts from international markets and neighbouring regions is thus highly demanded to identify important trends in emerging regulation, development strategies and research relevant to the inherent competitive advantages of Vietnam. We collect AI-related artifacts from major AI markets and Southeast Asian countries and compare this to Vietnam's existing frameworks vis-à-vis investment, regulatory environment and research orientation. We find Vietnam is well behind other countries in Southeast Asia and that public and private investment is required and requires supporting mechanisms to originate the relevant markets at early stages in order to drive effective resource allocation. Specific areas to be focused include agriculture and renewable energy, given the competitive advantages of Vietnam's rich agricultural land and renewable energy resources. We also find AI-related studies are limited, but can be expected to develop significantly given global trends in decarbonisation and sustainable agricultural supply chains. For Vietnam, Hanoi, Ho Chi Minh city and Danang are the focus of central AI hubs but nearby industrial estates should also be developed.Full Tex
Assessing digital transformation readiness: a comprehensive study of local clinics in Northwest Vietnam
No full textLocal clinics are pivotal in delivering primary healthcare, especially in economically disadvantaged areas like Vietnam’s Northwest. However, these regions face notable deficits in healthcare infrastructure. Digital transformation offers a promising solution. This study assesses the digital transformation readiness of 75 local clinics in Northwest Vietnam and investigates the impact of influential factors on this readiness. The study design involved collecting responses from clinic heads or designated representatives through a web-based survey. The sample size comprised 75 local clinics in Northwest Vietnam. Multiple linear regressions were utilised to examine the impact of influential factors on the clinics’ digital transformation readiness. Findings indicate a significant readiness gap among the surveyed clinics, with observed scores falling below the maximum achievable score of 290. Most clinics scored between 63.5 and 116, highlighting substantial room for improvement in digital preparedness. The study unveiled significant relationships between digital readiness and clinic attributes. Negative correlations included clinic head age and reliance on e-wallets. Positive associations included seniority, social media engagement, and clinic characteristics like education and technology use. The regression results highlight positive associations with clinic head seniority, clinic social accounts, personnel using smart devices, and online patient record integration. Conversely, negative associations were noted with clinic head age and e-wallet usage. The findings stress targeted support for older clinic leaders in digital adaptation, highlight experienced leadership’s role, note distractions from financial technologies, emphasise social media’s digital readiness impact, and stress technological adoption’s importance, plus digital record-keeping benefits for clinics and patient care.No Full Tex
Book Review: Comrades Betrayed: Jewish World War I Veterans Under Hitler
No full textThis is a pre-copyedited, author-produced version of an article accepted for publication in [German History] following peer review. The version of record [Grady, T. (2021). [Review of the book Comrades Betrayed: Jewish World War I Veterans Under Hitler by M. Geheran]. German History, 39(3), 478–479] is available online at: https://academic.oup.com/gh/article/39/3/478/6308748Book review of Comrades Betrayed: Jewish World War I Veterans Under HitlerUnfundedAAM out of embargo 24/06/2023, output uploaded to CR 30/01/202
Espressione genica indotta dall'ormone somatotropo nei monociti di bambini sani e con deficit di GH
No full text2018 - 2019Somatotropic hormone (GH) has transcriptional effects on the cells of many organs, directly by activating its receptor (GHR) or indirectly through induction of IGF-1 or other mediators. The presence of GHR in almost all cellular tissues makes GH action systemic even if, to date, still not well characterized. The immune system is among the districts where the effect of the somatotropic hormone is documented by mechanisms that are still poorly understood.The primary objective of this study is to determine the transcriptional effect of GH on peripheral blood monocytes. These cells were chosen for the significant expression of GHR on their surface and because they are easily accessible. Although the transcriptional response to somatotropic hormone is specific tissue, the study of the effects of GH on monocytes can serve as a model for other cell types and highlight differences between healthy subjects and those with GH deficiency (GHD).The diagnosis of GHD, during the developmental age, is classically based on the clinical evaluation associated with radiological and laboratory investigations (GH-IGF-1 axis stimulus test). Although provocation tests represent diagnostic gold standard, they have poor reproducibility and accuracy and are characterized by a considerable number of false positives and sometimes negatives.The secondary objective of this study is to identify differential transcriptional profiles between healthy subjects and with GHD.For this purpose, the gene expression of monocytes from healthy children and with GHD was compared in culture, under basal conditions and after stimulation with recombinant GH (rh-GH).Two groups of 12 subjects were selected, group S: healthy male children with normal height and growth rate and group D: children of the same sex and age and suffering from GHD, not yet in replacement therapy. Peripheral blood monocytes were purified by subtraction with monoclonal antibodies and the purity level was determined by laminar flow cytofluorimetry with monoclonal antibodies. Monocytes were grown for 24 hours with and without rh-GH. Total RNA was extracted and frozen until the analysis was performed simultaneously for all the experimental points using the Next Generation Sequencing methodology on Illumina platform. Differential expression of mRNA was analyzed by comparing the monocytes of healthy children and with GHD, stimulated in culture with rh-GH or not stimulated: GHD not stimulated (D-CNTR) vs healthy not stimulated (S-CNTR); healthy non-stimulated (S-CNTR) vs healthy stimulated (S-GH); non-stimulated GHD (D-CNTR) vs stimulated GHD (D-GH); GHD stimulated (D-GH) vs healthy stimulated (S-GH).The analysis between D-CNTR vs S-CNTR groups identified 58 genes with differential expression. Furthermore, 23 genes were modulated by GH in healthy children and 4 genes in children with GHD. Differential analysis between D-GH vs S-GH groups, on the other hand, identified 150 genes with differential expression.Finally, analysis performed by Ingenuity Pathway Analysis software showed a significant increase in NFAT immune pathways and dendritic cell maturation and a consistent increase in the expression of dendritic markers (HLA-A, HLA-C, CCR7) in monocytes of children with GHD compared to healthy children, after stimulation in culture with recombinant GH.In conclusion, the results of this study have demonstrated a clear transcriptional effect of GH on monocytes, direct and indirect through intermediate mediators, suggesting to evaluate the pro-inflammatory status of children with growth hormone deficiency more in depth.Furthermore, this study identified a gene expression profile of monocytes in children with GHD which, once verified in a larger number of patients, could represent an alternative to stimulus tests and guide the diagnosis of GH deficiency.Finally, our study opens future perspectives in order to identify a transcriptional profile or specific genes specific to GHD condition. [edited by Author]XXXII cicl
Avaliação da expressão imuno-histoquímica das células retais produtoras de grelina em ratos Wistar submetidos à dieta de cafeteria
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Médicas, Florianópolis, 2012Introdução: Na atualidade o sobrepeso e a obesidade, induzidos pela dieta e pelo sedentarismo, são doenças muito prevalentes em vários países. Considerados uma epidemia mundial pela Organização Mundial da Saúde (OMS), são importantes fatores de risco para inúmeras afecções, entre elas as neoplasias colorretais. Estudos prévios sugerem que em portadores de obesidade ou sobrepeso há aumento da incidência desse tipo de neoplasia e a piora do prognóstico. Com a descoberta da grelina, em 1999, que é um hormônio orexígeno com potente ação sobre a liberação do hormônio do crescimento (GH) e atuação em diversos sistemas orgânicos, fisiológicos e na carcinogênese, desenvolveram-se diversas pesquisas para elucidar o seu papel e sua importância em todas essas funções. Recentemente, evidenciou-se aumento da expressão de grelina em amostras teciduais de neoplasias colorretais quando comparadas à tecidos colônicos normais. Objetivos: Investigar o impacto da dieta de cafeteria na expressão imuno-histoquímica retal da grelina e avaliar o tipo morfológico das células identificadas. Desenho do Estudo: Estudo analítico experimental do tipo corte transversal com intervenção. Método: Vinte e quatro ratos Wistar machos foram distribuídos em 4 subgrupos de 6 animais cada denominados: SGR1 (ração e água) e SGC1 (dieta de cafeteria, ração e água) por um período de 30 dias; SGR2 (ração e água) e SGC2 (dieta de cafeteria, ração e água) por um período de 60 dias. O peso dos animais e do reto amputado, o número e o tipo de células imunorreativas à grelina foram registrados e comparados entre os subgrupos. Na análise estatística foram utilizados os testes ANOVA com correção de Bonferroni, qui quadrado, teste t pareado e teste t de Student. Resultados: Houve aumento significativo do peso corporal em todos os subgrupos (P 0,001). O peso no dia da cirurgia foi significativamente maior na comparação do SGC2 com os demais subgrupos: SGR1 (P=0,003), SGC1 (P= 0,010) e SGR2 (P= 0,001). Não houve diferença na comparação da média do número absoluto de células imunorreativas (P= 0,685) e na comparação entre expressão e não expressão (P=0,330) entre os subgrupos, nem entre o peso final (P=0,993) e o peso retal (P= 0,230) com a imunoexpressão. Todas as células imunorreativas identificadas foram do tipo "fechado". Conclusão: Os resultados do presente estudo não demonstraram influência da dieta de cafeteria sobre o número de células retais imunorreativas à grelina quando comparado aos controles nem aos dois períodos de ingesta e apenas células imunorreatoras do tipo "fechado" foram identificadas no reto de ratos Wistar.Abstract : Introduction: Obesity and overweight induced by diet and lifestyle are considered a global epidemic by the World Health Organization (WHO), especially in western countries. They are important risk factors for several conditions, including colorectal cancer. Obese and overweight patients have already demonstrated an increased incidence and worse prognosis associated with colorectal cancer. Since discovery of ghrelin in 1999, which is a potent orexigenic hormone and releaser of the growth hormone (GH) that has many physiologic functions, several studies began to elucidate its role and importance in several areas including carcinogenesis. Recently it was demonstrated an increase on tissue ghrelin expression in colorectal cancers samples. Objectives: To investigate the impact of cafeteria diet on ghrelin expression in rectal tissue and identify the morphologic cell type. Study Design: Analytical and experimental transversal study with intervention. Methods: Twenty-four male Wistar rats were divided into 4 subgroups of 6 animals each: RCG1 (rat chow and water) and CAFG1 (cafeteria diet, rat chow and water) for a period of 30 days; RCG2 (rat chow and water) and CAFG2 (cafeteria diet, rat chow and water) for a period of 60 days. The animal and rectal weight, the number and the type of immunoreactive ghrelin cells were recorded and compared between the subgroups. ANOVA with Bonferroni correction, chi square, t student and paired t tests were applied. Results: There was a significant increase in body weight in all subgroups (P=0,001). The weight on the operation day was significantly higher in the CAFG2 in comparison with others subgroups: RCG1 (P=0,003), CAFG1 (P=0,010) and RCG2 (P=0,001). There was no difference in the total of immunoreactive cells (P=0,685), presence or absence of ghrelin expression between the subgroups (P=0, 330), nor in the final weight (P= 0,993) and rectal weight (P=0,230) in comparison with imunoexpression. All the immunoreactive cells identified were closed-type. Conclusion: The present study showed no influence of cafeteria diet on the amount of immunoreactive rectal cells of ghrelin when compared to controls and with two periods of exposure. Only one type (closed-type) of immunoreactive cells was expressed in the rectum
Comparison of Two Methods for In Vivo Estimation of the Glenohumeral Joint Rotation Center (GH-JRC) of the Patients with Shoulder Hemiarthroplasty
No full textDetermination of an accurate glenohumeral-joint rotation center (GH-JRC) from marker data is essential for kinematic and dynamic analysis of shoulder motions. Previous studies have focused on the evaluation of the different functional methods for the estimation of the GH-JRC for healthy subjects. The goal of this paper is to compare two widely used functional methods, namely the instantaneous helical axis (IHA) and symmetrical center of rotation (SCoRE) methods, for estimating the GH-JRC in vivo for patients with implanted shoulder hemiarthroplasty. The motion data of five patients were recorded while performing three different dynamic motions (circumduction, abduction, and forward flexion). The GH-JRC was determined using the CT-images of the subjects (geometric GH-JRC) and was also estimated using the two IHA and SCoRE methods. The rotation centers determined using the IHA and SCoRE methods were on average 1.4760.62 cm and 2.0760.55 cm away from geometric GH-JRC, respectively. The two methods differed significantly (two-tailed p-value from paired t-Test ,0.02, post-hoc power ,0.30). The SCoRE method showed a significant lower (two-tailed p-value from paired t-Test ,0.03, post-hoc power ,0.68) repeatability error calculated between the different trials of each motion and each subject and averaged across all measured subjects (0.6260.10 cm for IHA vs. 0.4360.12 cm for SCoRE). It is concluded that the SCoRE appeared to be a more repeatable method whereas the IHA method resulted in a more accurate estimation of the GH-JRC for patients with endoprostheses.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin
- …
