RESUMO
Avoidance of harmful substances is survival strategy used cross invertebrates and vertebrates. For example, the nematode Caenorhabditis elegans evolves a sufficient avoidance response to pathogenic bacteria. Despite G protein has been found to exert neural plasticity for avoidance behaviours in C. elegans, the function of Gi/o and Gq subunit signalling in experience-dependent aversive behaviour remains unclear. In this study, we show that EGL-30/Gq coupled with EGL-8/UNC-13 regulates aversive behaviour of C. elegans to pathogenic bacterium Pseudomonas aeruginosa PA01 via acetylcholine and its receptor nAChR. Pyocyanin, a toxin secreted from P. aeruginosa, acts as a signal molecule to trigger aversive behaviour. ODR-3 and ODR-7 in AWA and AWC neurons function as upstream of EGL-30 to induce experience-dependent aversive behaviour to P. aeruginosa, respectively. These results suggested that a novel signalling pathway to regulate a behavioural response.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Pseudomonas aeruginosa/metabolismo , Aprendizagem da Esquiva , Proteínas de Caenorhabditis elegans/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The collision-induced dissociation reaction of O2 (v, j) + N, a fundamental process in nonequilibrium air flows around reentry vehicles, has been studied systematically by applying molecular dynamics simulations on the 2A', 4A' and 6A' potential energy surfaces of NO2 in a wide temperature range. In particular, we have directly investigated the role of the 6A' surface in this process and discussed the applicability of the simplified approximate rate models proposed by Esposito et al. and Andrienko et al. based on the lowest two surfaces. The present work indicates that the state-selected dissociation of O2 + N is dominated by the 6A' surface for all except for the low-lying O2 states. Furthermore, a complete database of rovibrationally detailed cross sections and rate coefficients is a prerequisite for modeling the relevant nonequilibrium air flows in spacecraft reentry. Here, the combination of the quasi-classical trajectory (QCT) and the neural network (NN) has been proposed to predict all state-selected dissociation cross sections and further construct dissociation parameter sets. All NN-based models established in this work accurately reproduce the results calculated from QCT simulations over a wide range of rovibrational quantum numbers with R2 > 0.99. Compared with the explicit QCT simulations, the computational requirement for predicting cross sections and rates based on the NN models significantly reduces. Finally, thermal equilibrium rate coefficients computed from NN models match remarkably well the available theoretical and experimental results in the whole temperature range explored.
RESUMO
This work studies the exhaustive rovibrational state-specific collision-induced dissociation properties of the N2+N system by QCT (quasi-classical trajectory) combined with a neural network method based on the ab initio PES recently published by Varga et al. [Phys. Chem. Chem. Phys. 23, 26273 (2021)]. The QCT combined with a neural network for state-specific dissociation (QCT-NN-SSD) model is developed and used to predict the dissociation cross sections and their energy dependence on the thermal range from a sparsely sampled noisy dataset. It is conservatively estimated that using this method can reduce the cost of the calculation by 96.5%. The rate coefficient of thermal non-equilibrium between different energy modes is obtained by combining the QCT-NN-SSD model with the multi-temperature model. The results show that, for the equilibrium state, dissociation mainly occurs at high vibrational and moderately low rotational levels. When the system is in non-equilibrium, there is no obvious vibrational level preference and highly rotationally excited molecules play a major role in promoting the dissociation by compensating for the lack of vibrational energy. The use of neural network training to generate complete datasets based on limited and discrete data provides an economical and reliable way to obtain a complete kinetic database needed to accurately simulate non-equilibrium flows.
Assuntos
Redes Neurais de Computação , Vibração , Cinética , TemperaturaRESUMO
High-fat (HF) diets and low-grade chronic inflammation contribute to the development of insulin resistance and type 2 diabetes (T2D), whereas n-3 polyunsaturated fatty acids (PUFAs), due to their anti-inflammatory effects, protect against insulin resistance. Interleukin (IL)-1ß is implicated in insulin resistance, yet how n-3 PUFAs modulate IL-1ß secretion and attenuate HF diet-induced insulin resistance remains elusive. In this study, a HF diet activated NLRP3 inflammasome via inducing reactive oxygen species (ROS) generation and promoted IL-1ß production primarily from adipose tissue preadipocytes, but not from adipocytes and induced insulin resistance in wild type (WT) mice. Interestingly, endogenous synthesized n-3 polyunsaturated fatty acids (PUFAs) reversed this process in HF diet-fed fat-1 transgenic mice although the HF diet induced higher weight gain in fat-1 mice, compared with the control diet. Mechanistically, palmitic acid (PA), the main saturated fatty acid in an HF diet inactivated AMPK and led to decreased GSK-3ß phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas docosahexaenoic acid (DHA), the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Our GSK-3ß shRNA knockdown study further revealed that GSK-3ß played a pivot role between the upstream AMPK/Akt pathway and downstream Nrf2/Trx1/TXNIP pathway. Given that NLRP3 inflammasome is implicated in the development of most inflammatory diseases, our results suggest the potential of n-3 PUFAs in the prevention or adjuvant treatment of NLRP3 inflammasome-driven diseases.
Assuntos
Diabetes Mellitus Tipo 2 , Ácidos Graxos Ômega-3 , Resistência à Insulina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Proteínas de Transporte , Dieta Hiperlipídica/efeitos adversos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Glicogênio Sintase Quinase 3 beta , Inflamassomos/metabolismo , Resistência à Insulina/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Palmítico/farmacologia , Proteínas Proto-Oncogênicas c-akt , RNA Interferente Pequeno , Espécies Reativas de Oxigênio , TiorredoxinasRESUMO
Currently, research on cardiac injury by aconitine focuses on its effect to directly interfere with the function of cardiac ion channels. Further, abnormal lipid metabolism could cause cardiac injury via inflammatory signaling pathway. In our preliminary study, we discovered that aconitine could alter the metabolism processes of various substances, including palmitic acid. Inspired by these studies, we investigated how elevation of palmitic acid by aconitine causes cardiac injury. Aconitine induced cardiac injury in rats (0.32 mg/kg, d = 7), and the cardiac injury was confirmed by electrocardiogram and serum biochemical study. The proteomic and metabolomic results showed that the palmitic acid level increases in heart tissue, and the NOD-like receptor (NLR) signaling pathway showed a strong effect of cardiac injury. The palmitic acid results in cell viability decline and activates NLR signaling in vitro. The shRNA-mediated knockdown of NLRP3 and NOD1/2 attenuates palmitic acid-induced inhibitory effect on cells and inhibited activation of the NLR signaling pathway. Collectively, this study reveals that aconitine provoked palmitic acid elevation could aggravate cardiac injury via the NLR signaling pathway. This study suggests that drug triggered disorder of the metabolism process could evoke cardiac injury and could propose a new strategy to study drug cardiac injury.
Assuntos
Aconitina/farmacologia , Metabolômica , Miócitos Cardíacos/efeitos dos fármacos , Ácido Palmítico/metabolismo , Proteômica , Aconitina/metabolismo , Animais , Linhagem Celular , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Ratos , Ratos WistarRESUMO
Negative feelings caused by external stress can continually agonize adrenergic receptors via promoting catecholamine secretion, causing cardiovascular disease. This study examines the mechanism by which persistent ß-adrenergic receptor agonism induces myocardial injury. A rat model of cardiac injury was herein established using isoproterenol (5 mg/kg, continuous intraperitoneal injection for 3 days), and multiomics technology combined with metabolomics and proteomics was used to explore the mechanism by which persistent ß-adrenergic receptor agonism induces myocardial injury. The mechanism underlying this phenomenon was further verified at the cellular level. Isoproterenol-induced persistent ß-adrenergic receptor agonism promoted the release of reactive oxygen species, and P53, S100-A9, and complement 3 were shown to be involved in complement system activation pathways. Our data have demonstrated that isoproterenol could trigger ROS/P53/S100-A9 positive feedback to aggravate myocardial damage associated with complement activation.
Assuntos
Calgranulina B/metabolismo , Isoproterenol/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Masculino , Contração Miocárdica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Proteômica , Ratos , Ratos WistarRESUMO
As one of the main air pollutants, nitrogen oxides (NOx) have serious effects on human health and the environment. In our previous study, we found that Mn-MOF-74 shows excellent catalytic performance for the selective catalytic reduction (SCR) reaction with NH3 being the reductant (NH3-SCR) at low temperature. To obtain a further understanding of the NH3-SCR mechanism in Mn-MOF-74, in this paper, we investigated two important parts of the NH3-SCR process in Mn-MOF-74 using the density functional theory (DFT) method. On the one hand, the structural characteristics of two types of oxygen vacancies of Mn-MOF-74, namely carboxyl oxygen vacancies and hydroxyl oxygen vacancies, and their adsorption properties to reaction species were calculated. It was found that the oxygen vacancies not only activate the reaction species, but also promote the desorption of NO2 molecules from metal sites for the subsequent rapid SCR reactions. On the other hand, we studied the effect of H2O on the structural stability and catalytic performance of Mn-MOF-74. It was found that the interaction of Mn-O bonds was weakened by H2O. Therefore, the influence of H2O should be considered for the future design of MOF-based catalysts for the SCR process.
Assuntos
Teoria da Densidade Funcional , Estruturas Metalorgânicas/química , Oxigênio/química , Água/química , Poluentes Atmosféricos/química , Poluentes Atmosféricos/isolamento & purificação , Catálise , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/isolamento & purificação , Substâncias Redutoras/químicaRESUMO
BACKGROUND: The lack of availability of skilled providers in low- and middle- income countries is considered to be an important barrier to achieving reductions in maternal and child mortality. However, there is limited research on programs increasing the availability of skilled birth attendants in developing countries. We study the implementation of the Nigeria Midwives Service Scheme, a government program that recruited and deployed nearly 2,500 midwives to rural primary health care facilities across Nigeria in 2010. An outcome evaluation carried out by this team found only a modest impact on the use of antenatal care and no measurable impact on skilled birth attendance. This paper draws on perspectives of policymakers, program midwives, and community residents to understand why the program failed to have the desired impact. METHODS: We conducted semi-structured interviews with federal, state and local government policy makers and with MSS midwives. We also conducted focus groups with community stakeholders including community leaders and male and female residents. RESULTS: Our data reveal a range of design, implementation and operational challenges ranging from insufficient buy-in by key stakeholders at state and local levels, to irregular and in some cases total non-provision of agreed midwife benefits that likely contributed to the program's lack of impact. These challenges not only created a deep sense of dissatisfaction with the program but also had practical impacts on service delivery likely affecting households' uptake of services. CONCLUSION: This paper highlights the challenge of effectively scaling up maternal and child health interventions. Our findings emphasize the critical importance of program design, particularly when programs are implemented at scale; the need to identify and involve key stakeholders during planning and implementation; the importance of clearly defining lines of authority and responsibility that align with existing structures; and the necessity for multi-faceted interventions that address multiple barriers at the same time.
Assuntos
Pessoal Técnico de Saúde/provisão & distribuição , Acessibilidade aos Serviços de Saúde , Tocologia , Serviços de Saúde Rural , Países em Desenvolvimento , Grupos Focais , Humanos , Serviços de Saúde Materna , Tocologia/economia , Nigéria , Equipe de Assistência ao Paciente , Participação dos Interessados , Recursos HumanosRESUMO
BACKGROUND: The Nigerian Midwives Service Scheme (MSS) is an ambitious human resources project created in 2009 to address supply side barriers to accessing care. Key features include the recruitment and deployment of newly qualified, unemployed and retired midwives to rural primary healthcare centres (PHCs) to ensure improved access to skilled care. This study aimed to understand, from multiple perspectives, the views and experiences of childbearing women living in areas where it has been implemented. METHODS: A qualitative study was undertaken as part of an impact evaluation of the MSS in three states from three geo-political regions of Nigeria. Semi-structured interviews were conducted around nine MSS PHCs with women who had given birth in the past six months, midwives working in the PHCs and policy makers. Focus group discussions were held with wider community members. Coding and analysis of the data was performed in NVivo10 based on the constant comparative approach. RESULTS: The majority of participants reported that there had been positive improvements in maternity care as a result of an increasing number of midwives. However, despite improvements in the perceived quality of care and an apparent willingness to give birth in a PHC, more women gave birth at home than intended. There were some notable differences between states, with a majority of women in one northern state favouring home birth, which midwives and community members commented stemmed from low levels of awareness. The principle reason cited by women for home birth was the sudden onset of labour. Financial barriers, the lack of essential drugs and equipment, lack of transportation and the absence of staff, particularly at night, were also identified as barriers to accessing care. CONCLUSIONS: Our research highlights a number of barriers to accessing care exist, which are likely to have limited the potential for the MSS to have an impact. It suggests that in addition to scaling up the workforce through the MSS, efforts are also needed to address the determinants of care seeking. For the MSS this means that the while the supply side, through the provision of skilled attendance, still needs to be strengthened, this should not be in isolation of addressing demand-side factors.
Assuntos
Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Serviços de Saúde Materna/estatística & dados numéricos , Tocologia/métodos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Atenção Primária à Saúde/métodos , Adolescente , Adulto , Parto Obstétrico/psicologia , Parto Obstétrico/estatística & dados numéricos , Feminino , Grupos Focais , Parto Domiciliar/psicologia , Parto Domiciliar/estatística & dados numéricos , Humanos , Nigéria , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Gravidez , Pesquisa Qualitativa , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Limited availability of skilled health providers in developing countries is thought to be an important barrier to achieving maternal and child health-related MDG goals. Little is known, however, about the extent to which scaling-up supply of health providers will lead to improved pregnancy and birth outcomes. We study the effects of the Midwives Service Scheme (MSS), a public sector program in Nigeria that increased the supply of skilled midwives in rural communities on pregnancy and birth outcomes. METHODS: We surveyed 7,104 women with a birth within the preceding five years across 12 states in Nigeria and compared changes in birth outcomes in MSS communities to changes in non-MSS communities over the same period. RESULTS: The main measured effect of the scheme was a 7.3-percentage point increase in antenatal care use in program clinics and a 5-percentage point increase in overall use of antenatal care, both within the first year of the program. We found no statistically significant effect of the scheme on skilled birth attendance or on maternal delivery complications. CONCLUSION: This study highlights the complexity of improving maternal and child health outcomes in developing countries, and shows that scaling up supply of midwives may not be sufficient on its own.
Assuntos
Serviços de Saúde Materna , Tocologia , Resultado da Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Países em Desenvolvimento , Feminino , Humanos , Masculino , Serviços de Saúde Materna/estatística & dados numéricos , Nigéria , Gravidez , Serviços de Saúde Rural , Inquéritos e Questionários , Recursos HumanosRESUMO
In recent years, the incidence of coronary heart disease and rheumatoid arthritis has been increasing, which has become a common public health problem worldwide. YiYiFuZi (YYFZ ) powder is a classical traditional Chinese prescription, which is commonly used to treat metabolic diseases such as rheumatoid arthritis, with an ideal curative effect, but the therapeutic mechanism is still unclear. In this study, from the perspective of clinical metabolomics, combined with network pharmacology, we sought the comorbidity mechanism and key targets of coronary heart disease and rheumatoid arthritis and the mechanism by which YYFZ powder exerts therapeutic effects, combined with molecular docking and atomic force microscopy to determine the effective components, and found that the higenamine and steroid components in YYFZ powder can bind acid sphingomyelinase enzymes to affect the sphingolipid pathway to produce therapeutic effects, which can bind to sugars existing as a glycoside.
RESUMO
As a generally edible plant, Ixeris denticulata (Houtt.) Stebb is widely distributed in China. Its medicinal value has attracted much attention in recent years. However, the chemical markers that cause quality and taste differences in I. denticulata from different regions are currently unclear. In this study, samples from 8 different origins were collected and analysed by UPLC-Q-TOF/MS. A metabolomics data processing strategy and machine learning method were established to explore the reasons for the difference in quality and taste of different origins from the perspective of chemical composition. With the established strategy, 10 characteristic chemical markers were identified that could be used to distinguish the origins of I. denticulata. The strategy proposed in this study could provide a certain basis for quality control and reasonable consumption of I. denticulata and additional food and medicinal homologous species.
Assuntos
Asteraceae/química , Aprendizado de Máquina , Asteraceae/metabolismo , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão , MetabolômicaRESUMO
In this study, a novel stepwise rapid tracking strategy was reported to identify the active molecules from Ixeris sonchifolia Hance (IsH) in the treatment of coronary heart disease (CHD) based on "affinity mass spectrometry (MS)-atomic force microscopy (AFM) imaging" technology. First, vascular endothelial growth factor receptor 2 (VEGFR2) of the vascular endothelial growth factor (VEGF) signal transduction pathway located on the cell membrane was revealed to be the core target protein in CHD treatment through network pharmacology and bioinformatics. In addition, affinity MS screening based on VEGFR2 identified isochlorogenic acid A and luteolin-7-O-glucuronide as having stronger affinity with VEGFR2. Then, the active molecule was elucidated based on the observation that its actions accompanied the molecular morphological changes by AFM imaging and it could act on the binding pocket of VEGFR2 through molecular docking which further demonstrated the analysis and inference of AFM imaging. The methyl thiazolyl tetrazolium (MTT) assay finally confirmed that the active molecules specifically combined with the potential core target protein to protect the viability of cardiomyocytes, which identified the main potential active molecules in IsH for the treatment of CHD and provided a possible mechanism for the protective role of the drug. The technology established in this study could facilitate the rapid tracing of potential active molecules in traditional Chinese medicine (TCM), which would provide further a reference for research on quality, molecular mechanisms and new drugs.
Assuntos
Asteraceae/química , Medicamentos de Ervas Chinesas/farmacologia , Imagem Óptica , Inibidores de Proteínas Quinases/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas , Medicina Tradicional Chinesa , Microscopia de Força Atômica , Simulação de Acoplamento Molecular , Miócitos Cardíacos/efeitos dos fármacos , Inibidores de Proteínas Quinases/química , Ratos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Surface plasmon resonance (SPR) analysis of the main components of liquorice was performed and a novel strong mineralocorticoid receptor (MR) agonist, namely liquiritinapioside (LA), whose the binding constant was 1.093â¯×â¯10-5â¯M, was reported. As a supplement, LA has been further demonstrated to have a strong MR binding capacity through competitive binding experiments (the enrichment factor of LA was 10.22%). This study also validated the activity of LA on H9c2 cells. The expression of collagen I and the results of Masson staining were used to determine the ability of this substance to cause H9c2 cell fibrosis. Moreover, western blotting was used to verify the mechanism of compound-induced myocardial fibrosis. Overall, the attained results showed that LA could induce the activation of the TGF-ß1/p38 MAPK signalling pathway through the MR to induce H9c2 cell fibrosis.
Assuntos
Glycyrrhiza/efeitos adversos , Glycyrrhiza/química , Mineralocorticoides , Receptores de Mineralocorticoides/agonistas , Animais , Linhagem Celular , China , Colágeno Tipo I/metabolismo , Fibrose , Flavanonas/efeitos adversos , Flavanonas/análise , Flavanonas/metabolismo , Glucosídeos/efeitos adversos , Glucosídeos/análise , Glucosídeos/metabolismo , Glycyrrhiza/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miocárdio/patologia , Extratos Vegetais/química , Receptores de Mineralocorticoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Terpenos , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVE: To study the chemical constituents from the leaves of Acer truncatum. METHOD: Various chromatographic techniques were used to isolate and purify the constituents. The structures of these compounds were elucidated on the basis of spectral analysis. RESULT: Seven compounds were isolated and identified as p-sitosterol (1), beta-amyrin (2), beta-amyrin acetate (3), 3, 5-dihydroxy-4-methoxybenzoic acid (4), astragalin (5), quercetin-3-O-beta-D-galactoside (6), and quercetin-3-O-alpha-L-rhamnoside (7). CONCLUSION: All of compounds were isolated from this plant for the first time.
Assuntos
Acer/química , Ácido Gálico/análogos & derivados , Quempferóis/isolamento & purificação , Ácido Oleanólico/análogos & derivados , Plantas Medicinais/química , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Quempferóis/química , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Folhas de Planta/químicaRESUMO
OBJECTIVE: There is growing evidence indicating that reactions of inflammatory system play an important role in stroke and development of carotid plaques. It is purposed to understand the relationship between serum level of c-reactive protein (CPR) and size of cerebral infarction, carotid plaques and prognosis of ischemic stroke. METHODS: A total of 121 patients with ischemic stroke were included in the study. Serum level of CRP was measured within 72 hours after onset of index stroke. All patients were scored by CNDF based on deficit in their clinical neurological function, and examined with CT/MRI and carotid duplex ultrasound scanning. RESULTS: Leukocyte count and blood glucose level at admission were significantly higher in the group with abnormal serum level of CRP than those with normal one (P = 0.045 and P = 0.021, respectively). Incidence of territory infarction (42 cases, 61.76%) was also significantly higher than that of lacunar infarction (23 cases, 43.4%), with P = 0.044. Occurrence of carotid plaques was higher in the former (32 cases, 65.30%) than that in the latter (17 cases, 34.69%), with P = 0.035. CNFD scores were higher in the former (ranging 6 - 35, with a median of 18) than those in the latter (ranging 6 - 28, with a median of 11), with Mann-Whitney U test, P = 0.0001. And, more severe prognosis was also found in the former than in the latter, with P = 0.0001. CONCLUSION: Serum level of CRP was an important prognostic marker for carotid plaque and stroke.
Assuntos
Proteína C-Reativa/metabolismo , Acidente Vascular Cerebral/diagnóstico , Idoso , Arteriosclerose/complicações , Biomarcadores/sangue , Artérias Carótidas/patologia , Estenose das Carótidas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Acidente Vascular Cerebral/patologiaRESUMO
After having successfully expanded health insurance coverage, China now faces the challenge of building an effective and efficient delivery system to serve its large and aging population. The country finds itself at a crossroads-it can emulate the models of Western countries with their well-known limitations, or embark on an ambitious endeavor to create an innovative and sustainable model. We recommend that China choose the second option and design and implement a health care system based on population health management principles and sophisticated health information technology. Taking this path could yield a triple dividend for China: Health care will contribute to the growth of service sector employment, stimulate domestic demand by unlocking savings, and enable China to export its health system development capabilities to other emerging economies, mirroring its success in building other critical infrastructure. These forces can help turn the Chinese Dream into a reality.
RESUMO
The discovery of a pyrrolopyrimidine class of LIM-kinase 2 (LIMK2) inhibitors is reported. These LIMK2 inhibitors show good potency in enzymatic and cellular assays and good selectivity against ROCK. After topical dosing to the eye in a steroid induced mouse model of ocular hypertension, the compounds reduce intraocular pressure to baseline levels. The compounds also increase outflow facility in a pig eye perfusion assay. These results suggest LIMK2 may be an effective target for treating ocular hypertension and associated glaucoma.