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Exploring the changing process of the geographical distribution pattern of Tetracentron sinense Oliv. and its main influencing factors since the last interglacial period can provide a scientific basis for the effective protection and management of the species. The MaxEnt model was used to construct the potential distribution areas of T. sinense in different periods such as the last interglacial (LIG), the last glacial maximum (LGM), the mid-Holocene (MID), and the current and future (2050s and 2070s). On the premise of discussing the influence of dominant environmental factors on its distribution model, the suitable area changes of T. sinense under different ecological climate situations were quantitatively analyzed. (1) The AUC and TSS values predicted by the optimized model were 0.959 and 0.835, respectively, indicating a good predictive effect by the MaxEnt model; the potential suitable areas for T. sinense in the current period are mainly located in Southwest China, which are wider compared to the actual habitats. (2) Jackknife testing showed that the lowest temperature in the coldest month (Bio6), elevation (Elev), seasonal variation coefficient of temperature (Bio4), and surface calcium carbonate content (T-CACO3) are the dominant environmental factors affecting the distribution of T. sinense. (3) From the last interglacial period to the current period, the total suitable area of T. sinense showed a decreasing trend; the distribution points of T. sinense populations in mid-Holocene period may be the origin of the postglacial population, and Southwest China may be its glacial biological refuge. (4) Compared with the current period, the total suitable area ranges of T. sinense in China in the 2050s and 2070s decreased, and the centroid location of its total fitness area all migrated to the northwest, with the largest migration distance in 2070s under the SSPs 7.0 climate scenario. Temperature was the principal factor influencing the geographical distribution of T. sinense. With global warming, the range of T. sinense suitable areas will show a shrinking trend, with a shift toward higher-latitude regions. Ex situ conservation measures could be taken to preserve its germplasm resources.
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Since its initial discovery in 1994, the adipokine leptin has received extensive interest as an important satiety factor and regulator of energy expenditure. Although produced primarily by white adipocytes, leptin can be synthesized by numerous tissues including those comprising the cardiovascular system. Cardiovascular function can thus be affected by locally produced leptin via an autocrine or paracrine manner but also by circulating leptin. Leptin exerts its effects by binding to and activating specific receptors, termed ObRs or LepRs, belonging to the Class I cytokine family of receptors of which six isoforms have been identified. Although all ObRs have identical intracellular domains, they differ substantially in length in terms of their extracellular domains, which determine their ability to activate cell signalling pathways. The most important of these receptors in terms of biological effects of leptin is the so-called long form (ObRb), which possesses the complete intracellular domain linked to full cell signalling processes. The heart has been shown to express ObRb as well as to produce leptin. Leptin exerts numerous cardiac effects including the development of hypertrophy likely through a number of cell signaling processes as well as mitochondrial dynamics, thus demonstrating substantial complex underlying mechanisms. Here, we discuss mechanisms that potentially mediate leptin-induced cardiac pathological hypertrophy, which may contribute to the development of heart failure.
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Insuficiência Cardíaca , Leptina , Remodelação Vascular , Humanos , Cardiomegalia , Coração , Leptina/fisiologia , Transdução de SinaisRESUMO
Background: Since 2009, a series of ambitious health system reforms have been launched in China, including the zero mark-up drug policy (ZMDP); the policy was intended to reduce substantial medicine expenses for patients by abolishing the 15% mark-up on drugs. This study aims to evaluate the impacts of ZMDP on medical expenditures from the perspective of disease burden disparities in western China. Method: Two typical diseases including Type 2 diabetes mellitus (T2DM) in internal medicine and cholecystolithiasis (CS) in surgery were selected from medical records in a large tertiary level-A hospital in SC Province. The monthly average medical expenses of patients from May 2015 to August 2018 were extracted to construct an interrupted time series (ITS) model to evaluate the impact of policy implementation on the economic burden. Results: A total of 5,764 cases were enrolled in our study. The medicine expenses for T2DM patients maintained a negative trend both before and after the intervention of ZMDP. It had declined by 74.3 CNY (P < 0.001) per month on average in the pre-policy period and subsequently dropped to 704.4 CNY (P = 0.028) immediately after the policy. The level change of hospitalization expenses was insignificant (P = 0.197), with a reduction of 677.7 CNY after the policy, while the post-policy long-term trend was significantly increased by 97.7 CNY (P = 0.035) per month contrasted with the pre-policy period. In addition, the anesthesia expenses of T2DM patients had a significant increase in the level under the impact of the policy. In comparison, the medicine expenses of CS patients significantly decreased by 1,014.2 CNY (P < 0.001) after the policy, while the total hospitalization expenses had no significant change in level and slope under the influence of ZMDP. Furthermore, the expenses of surgery and anesthesia for CS patients significantly increased by 320.9 CNY and 331.4 CNY immediately after the policy intervention. Conclusion: Our study indicated that the ZMDP has been an effective intervention to reduce the excessive medicine expenses for both researched medical and surgical diseases, but failed to show any long-term advantage. Moreover, the policy has no significant impact on relieving the overall hospitalization burden for either condition.
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Colecistolitíase , Diabetes Mellitus Tipo 2 , Humanos , Pacientes Internados , Análise de Séries Temporais Interrompida , Hospitalização , Política de Saúde , ChinaRESUMO
Probiotics are considered to represent important modulators of gastrointestinal health through increased colonization of beneficial bacteria thus altering the gut microflora. Although these beneficial effects of probiotics are now widely recognized, emerging evidence suggests that alterations in the gut microflora also affect numerous other organ systems including the heart through a process generally referred to as the gut-heart axis. Moreover, cardiac dysfunction such as that seen in heart failure can produce an imbalance in the gut flora, known as dysbiosis, thereby further contributing to cardiac remodelling and dysfunction. The latter occurs by the production of gut-derived pro-inflammatory and pro-remodelling factors which exacerbate cardiac pathology. One of the key contributors to gut-dependent cardiac pathology is trimethylamine N-oxide (TMAO), a choline and carnitine metabolic by-product first synthesized as trimethylamine which is then converted into TMAO by a hepatic flavin-containing monooxygenase. The production of TMAO is particularly evident with regular western diets containing high amounts of both choline and carnitine. Dietary probiotics have been shown to reduce myocardial remodelling and heart failure in animal models although the precise mechanisms for these effects are not completely understood. A large number of probiotics have been shown to possess a reduced capacity to synthesize gut-derived trimethylamine and therefore TMAO thereby suggesting that inhibition of TMAO is a factor mediating the beneficial cardiac effects of probiotics. However, other potential mechanisms may also be important contributing factors. Here, we discuss the potential benefit of probiotics as effective therapeutic tools for attenuating myocardial remodelling and heart failure.
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Herbal-based medications have been used as therapeutic agents for thousands of years, particularly in Asian cultures. It is now well established that these herbal medications contain potent bioactive phytochemicals which exert a plethora of beneficial effects such as those seen on the cardiovascular system. Among the most widely studied of these herbal agents is ginseng, a member of the genus Panax, which has been shown to produce beneficial effects in terms of reducing cardiac pathology, at least in experimental studies. The beneficial effects of ginseng observed in such studies are likely attributable to their constituent ginsenosides, which are steroid-like saponins of which there are at least 100 and which vary according to ginseng species. Many ginseng species such as Panax ginseng (also known as Asian ginseng) and P quinquefolius (North American ginseng) as well as specific ginsenosides have been shown to attenuate hypertrophy as well as other indices of myocardial remodeling in a wide variety of experimental models. Ginkgo biloba on the other hand has been much less studied although the leaf extract of the ancient ginkgo tree has similarly consistently been shown to produce anti-remodeling effects. Ginkgo's primary bioactive constituents are thought to be terpene trilactones called ginkgolides, of which there are currently seven known types. Ginkgo and ginkgolides have also been shown to produce anti-remodeling effects as have been shown for ginseng in a variety of experimental models, in some cases via similar mechanisms. Although a common single mechanism for the salutary effects of these compounds is unlikely, there are a number of examples of shared effects including antioxidant and antiapoptotic effects as well as inhibition of pro-hypertrophic intracellular signaling such as that involving the calcineurin pathway which results in the upregulation of pro-hypertrophic genes. Robust clinical evidence represented by large scale phase 3 trials is lacking although there is limited supporting evidence from small trials at least with respect to ginseng. Taken together, both ginseng and ginkgo as well as their bioactive components offer potential as adjuvant therapy for the treatment of myocardial remodeling and heart failure.
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The palladium-catalyzed decarboxylative reactions of phenols and vinyl ethylene carbonate to produce allylic aryl ethers under mild conditions have been established. Adopting an inexpensive PdCl2(dppf) catalyst promotes the efficient conversion of phenols to the corresponding allylic aryl ethers via the formation of a new C-O bond in good isolated yields with complete regioselectivities, acceptable functional group tolerance and operational simplicity. The robust procedure could be completed smoothly by conducting a scaled-up reaction with comparable efficiency to afford the target product.
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Complete chloroplast genome (cpDNA) sequence of Fagus hayatae Palib. is yet to be reported, and the phylogenetic position of this species is still under debate. In this study, the complete cpDNA sequence of F. hayatae was determined from Illumina NovaSeq pair-end sequencing data. Results revealed that it has a sequence length of 158,360 bp and contains 131 annotated genes, which consist of 83 protein-coding genes, 40 tRNA genes, and eight rRNA genes. The phylogenetic analysis of the complete cpDNA sequence indicates that Fagus represents a monophyletic clade within Fagaceae. The species relatedness between F. hayatae and F. engleriana is relatively close.
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Background: To evaluate the persistence of antibody for 10 years, and investigate the effect of one or two booster doses with Kanghua human diploid cells rabies vaccine (HDCV) in China.Methods: Participants were re-recruited at year 10 post the primary phase 3 clinical study. Some of them in Kanghua HDCV group who had been boosted one dose at year 8, received one more dose at this boosted study. Participants who never boosted were randomly assigned to boost 1 or 2 doses of Kanghua HDCV. Blood samples were collected at day 0, 1, 3, 7, and 14. Safety was evaluated from day 0-14.Results: At year 10 after primary vaccination, the seroconversion rates of neutralizing antibody were 98.28-100% in Kanghua and Pasteur groups.After booster, the seroconversion rate in each group reached to 100% from day 7 to day 14. GMCs were similar in the groups with the same booster doses, and two doses of booster induced higher levels of antibody. The reported rates of solicited local and systemic adverse reaction were low, and no serious adverse events were found through the boosted study.Conclusion: 5 doses of Kanghua HDCV maintained long-term immunity at least 10 years. One or two doses of booster, rapidly triggered 100% protection against rabies virus.Trial registration: ClinicalTrials.gov: NCT03774628.
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Vacina Antirrábica , Raiva , Anticorpos Antivirais , Diploide , Humanos , Imunização Secundária , Raiva/prevenção & controle , VacinaçãoRESUMO
Ginseng is an ancient perennial herb belonging to the family Araliaceae and genus Panax which has been used for medical therapeutics for thousands of years, particularly in China and other Asian cultures although increasing interest in ginseng has recently emerged in western societies. Ginseng is a complex substance containing dozens of bioactive and potentially effective therapeutic compounds. Among the most studied are the ginsenosides, which are triterpene saponins possessing a wide array of potential therapeutic effects for many conditions. The quantity and type of ginsenoside vary greatly depending on ginseng species and their relative quantity in a given ginseng species is greatly affected by extraction processes as well as by subjecting ginseng to various procedures such as heating. Adding to the complexity of ginsenosides is their ability to undergo biotransformation to bioactive metabolites such as compound K by enteric bacteria following ingestion. Many ginsenosides exert vasodilatating effects making them potential candidates for the treatment of hypertension. Their vascular effects are likely dependent on eNOS activation resulting in the increased production of NO. One proposed end-mechanism involves the activation of calcium-activated potassium channels in vascular smooth cells resulting in reduced calcium influx and a vasodilatating effect, although other mechanisms have been proposed as discussed in this review.
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Hipertensão/tratamento farmacológico , Panax/química , Animais , Anti-Hipertensivos , Araliaceae/metabolismo , Biotransformação , Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , China , Fermentação , Ginsenosídeos/metabolismo , Ginsenosídeos/farmacologia , Temperatura Alta , Humanos , Modelos Animais , Músculo Liso Vascular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Raízes de Plantas/química , Polissacarídeos/química , Ratos , Saponinas , TriterpenosRESUMO
We determined whether North American ginseng (Panax quinquefolius L.) mitigates the effect of angiotensin II on hypertrophy and heart failure. Angiotensin II (0.3 mg/kg) was administered to rats for 2 or 4 weeks in the presence or absence of ginseng pretreatment. The effect of ginseng (10 µg/mL) on angiotensin II (100 nM) - induced hypertrophy was also determined in neonatal rat ventricular myocytes. We also determined effects of ginseng on fatty acid and glucose oxidation by measuring gene and protein expression levels of key factors. Angiotensin II treatment for 2 and 4 weeks induced cardiac hypertrophy as evidenced by increased heart weights, as well as the upregulation of the hypertrophy-related fetal gene expression levels, with all effects being abolished by ginseng. Ginseng also reduced abnormalities in left ventricular function as well as the angiotensin II-induced increased blood pressure. In myocytes, ginseng abolished the hypertrophic response to angiotensin II as assessed by surface area and gene expression of molecular markers of hypertrophy. Ginseng modulated angiotensin II-induced abnormalities in gene expression and protein levels of CD36, CPT1M, Glut4, and PDK4 in vivo and in vitro. In conclusion, ginseng suppresses angiotensin II-induced cardiac hypertrophy and dysfunction which is related to normalization of fatty acid and glucose oxidation.
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Angiotensina II , Panax , Animais , Cardiomegalia , Insuficiência Cardíaca , Miócitos Cardíacos , RatosRESUMO
Depression is a common aspect of the modern lifestyle, and most patients are recalcitrant to the current antidepressants. Fingolimod (FTY720), a sphingosine analogue approved for the treatment of multiple sclerosis, has a significant neuroprotective effect on the central nervous system. The aim of this study was to determine the potential therapeutic effect of FTY720 on the behavior and cognitive function of rats exposed daily to chronic unpredictable mild stress (CUMS), and elucidate the underlying mechanisms. The 42-day CUMS modeling induced depression-like behavior as indicated by the scores of sugar water preference, forced swimming, open field and Morris water maze tests. Mechanistically, CUMS caused significant damage to the hippocampal neurons, increased inflammation and oxidative stress, activated the NF-κB/NLRP3 axis, and skewed microglial polarization to the M1 phenotype. FTY720 not only alleviated neuronal damage and oxidative stress, but also improved the depression-like behavior and cognitive function of the rats. It also inhibited NF-κB activation and blocked NLRP3 inflammasome assembly by down-regulating NLRP3, ACS and caspase-1. Furthermore, FTY720 inhibited the microglial M1 polarization markers iNOS and CD16, and promoted the M2 markers Arg-1 and CD206. This in turn reduced the levels of TNF-α, IL-6 and IL-1ß, and increased that of IL-10 in the hippocampus. In conclusion, FTY720 protects hippocampal neurons from stress-induced damage and alleviates depressive symptoms by inhibiting neuroinflammation. Our study provides a theoretical basis for S1P receptor modulation in treating depression.
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Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Cloridrato de Fingolimode/farmacologia , Estresse Psicológico/tratamento farmacológico , Animais , Depressão/fisiopatologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Moduladores do Receptor de Esfingosina 1 Fosfato/farmacologia , Estresse Psicológico/fisiopatologiaRESUMO
To understand the defense mechanism of Arundinaria spanostachya clonal populations in response to grazing by giant pandas, dynamic variations in A. spanostachya clonal population structure and biomass allocation in a wild giant panda habitat at the Liziping Nature Reserve were evaluated, as well as whether the clonal populations would be continuously used by the wild giant pandas. The population density of each age-class in the grazed and control plots after grazing (2014a and 2015a) was similar to that before grazing (2013a). The effects of grazing on the size-class and height-class structures were relatively lower. Before and after grazing, the perennial individuals showed the highest total biomass, followed by the biennial and annual individuals, and the maximum dry matter content in each module was found in the culm, followed by the branch and leaf. The dry matter content of A. spanostachya individuals increased as the age class increased, whereas the total water content decreased. The maximum water content allocation in the modules was observed in the culm, and no significant differences were found between the shoot and leaf. Thus, foraging by the wild giant pandas had no impact on the size-class and height-class structures and biomass allocation of A. spanostachya clonal populations, and the clonal populations have established an adaptive mechanism against grazing by giant pandas. After grazing, the A. spanostachya clonal populations showed greater self-adjustment ability to restore the status to that before grazing and, thus, continuously supply food for the giant pandas. Further management intervention of A. spanostachya clonal populations after the foraging of wild giant pandas is not needed, which has implications for understanding the impact of co-evolutionary mechanisms between giant panda and its staple bamboo species.
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Adaptação Fisiológica , Herbivoria , Poaceae , Ursidae , Animais , Biomassa , Ecossistema , Densidade DemográficaRESUMO
Diabetes mellitus (DM) is a chronic metabolic disorder associated with elevated blood glucose levels due either to insufficient insulin production (type 1 DM) or to insulin resistance (type 2 DM). The incidence of DM around the world continues to rise dramatically with more than 400 million cases reported today. Among the most serious consequences of chronic DM are cardiovascular complications that can have deleterious effects. Although numerous treatment options are available, including both pharmacological and nonpharmacological, there is substantial emerging interest in the use of traditional medicines for the treatment of this condition and its complications. Among these is ginseng, a medicinal herb that belongs to the genus Panax and has been used for thousands of years as a medicinal agent especially in Asian cultures. There is emerging evidence from both animal and clinical studies that ginseng, ginseng constituents including ginsenosides, and ginseng-containing formulations can produce beneficial effects in terms of normalization of blood glucose levels and attenuation of cardiovascular complications through a multiplicity of mechanisms. Although more research is required, ginseng may offer a useful therapy for the treatment of diabetes as well as its complications.
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Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Panax/química , Animais , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêuticoRESUMO
Protection of the ischemic and reperfused myocardium represents a major therapeutic challenge. Translating results from animal studies to the clinical setting has been disappointing, yet the need for effective intervention, particularly to limit heart damage following infarction or surgical procedures such as coronary artery bypass grafting, is substantial. Among the many compounds touted as cardioprotective agents is ginseng, a medicinal herb belonging to the genus Panax, which has been used as a medicinal agent for thousands of years, particularly in Asian societies. The biological actions of ginseng are very complex and reflect composition of many bioactive components, although many of the biological and therapeutic effects of ginseng have been attributed to the presence of steroid-like saponins termed ginsenosides. Both ginseng and many ginsenosides have been shown to exert cardioprotective properties in experimental models. There is also clinical evidence that traditional Chinese medications containing ginseng exert cardioprotective properties, although such clinical evidence is less robust primarily owing to the paucity of large-scale clinical trials. Here, we discuss the experimental and clinical evidence for ginseng, ginsenosides, and ginseng-containing formulations as cardioprotective agents against ischemic and reperfusion injury. We further discuss potential mechanisms, particularly as these relate to antioxidant properties.
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Cardiotônicos/farmacologia , Panax/química , Animais , Ginsenosídeos/farmacologia , HumanosRESUMO
PURPOSE: This study aimed to identify potential epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer that went undetected by amplification refractory mutation system-Scorpion real-time PCR (ARMS-PCR). MATERIALS AND METHODS: A total of 200 specimens were obtained from the First Affiliated Hospital of Guangzhou Medical University from August 2014 to August 2015. In total, 100 ARMS-negative and 100 ARMS-positive specimens were evaluated for EGFR gene mutations by Sanger sequencing. The methodology and sensitivity of each method and the outcomes of EGFR-tyrosine kinase inhibitor (TKI) therapy were analyzed. RESULTS: Among the 100 ARMS-PCR-positive samples, 90 were positive by Sanger sequencing, while 10 cases were considered negative, because the mutation abundance was less than 10%. Among the 100 negative cases, three were positive for a rare EGFR mutation by Sanger sequencing. In the curative effect analysis of EGFR-TKIs, the progression-free survival (PFS) analysis based on ARMS and Sanger sequencing results showed no difference. However, the PFS of patients with a high abundance of EGFR mutation was 12.4 months [95% confidence interval (CI), 11.6-12.4 months], which was significantly higher than that of patients with a low abundance of mutations detected by Sanger sequencing (95% CI, 10.7-11.3 months) (p<0.001). CONCLUSION: The ARMS method demonstrated higher sensitivity than Sanger sequencing, but was prone to missing mutations due to primer design. Sanger sequencing was able to detect rare EGFR mutations and deemed applicable for confirming EGFR status. A clinical trial evaluating the efficacy of EGFR-TKIs in patients with rare EGFR mutations is needed.
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Adenocarcinoma/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Análise de Sequência de DNA/métodos , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Idoso de 80 Anos ou mais , Animais , Sequência de Bases , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Mutação , Resultado do TratamentoRESUMO
Heart failure is a major medical and economic burden throughout the world. Although various treatment options are available to treat heart failure, death rates in both men and women remain high. Potential adjunctive therapies may lie with use of herbal medications, many of which possess potent pharmacological properties. Among the most widely studied is ginseng, a member of the genus Panax that is grown in many parts of the world and that has been used as a medical treatment for a variety of conditions for thousands of years, particularly in Asian societies. There are a number of ginseng species, each possessing distinct pharmacological effects due primarily to differences in their bioactive components including saponin ginsenosides and polysaccharides. While experimental evidence for salutary effects of ginseng on heart failure is robust, clinical evidence is less so, primarily due to a paucity of large-scale well-controlled clinical trials. However, there is evidence from small trials that ginseng-containing Chinese medications such as Shenmai can offer benefit when administered as adjunctive therapy to heart failure patients. Substantial additional studies are required, particularly in the clinical arena, to provide evidence for a favourable effect of ginseng in heart failure patients.
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Cardiomegalia/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Ginsenosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Panax/química , Extratos Vegetais/uso terapêutico , Animais , Cardiomegalia/diagnóstico , Cardiomegalia/fisiopatologia , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/isolamento & purificação , Células Cultivadas , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Ginsenosídeos/efeitos adversos , Ginsenosídeos/isolamento & purificação , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Resultado do TratamentoRESUMO
There is increasing evidence for a beneficial effect of ginseng on cardiac pathology. Here, we determined whether North American ginseng can modulate the deleterious effects of the ß-adrenoceptor agonist isoproterenol on cardiac hypertrophy and function using in vitro and in vivo approaches. Isoproterenol was administered for 2 weeks at either 25 mg/kg per day or 50 mg/kg per day (ISO25 or ISO50) via a subcutaneously implanted osmotic mini-pump to either control rats or those receiving ginseng (0.9 g/L in the drinking water ad libitum). Isoproterenol produced time- and dose-dependent left ventricular dysfunction, although these effects were attenuated by ginseng. Improved cardiac functions were associated with reduced heart masses, as well as prevention in the upregulation of the hypertrophy-related fetal gene expression. Lung masses were similarly attenuated, suggesting reduced pulmonary congestion. In in vitro studies, ginseng (10 µg/mL) completely suppressed the hypertrophic response to 1 µmol/L isoproterenol in terms of myocyte surface area, as well as reduction in the upregulation of fetal gene expression. These effects were associated with attenuation in both protein kinase A and cAMP response element-binding protein phosphorylation. Ginseng attenuates adverse cardiac adrenergic responses and, therefore, may be an effective therapy to reduce hypertrophy and heart failure associated with excessive catecholamine production.
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Agonistas Adrenérgicos beta/toxicidade , Cardiomegalia/prevenção & controle , Extratos Vegetais/uso terapêutico , Saponinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Disfunção Ventricular Esquerda/prevenção & controle , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/diagnóstico por imagem , Relação Dose-Resposta a Droga , Isoproterenol/toxicidade , Masculino , Panax , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Transdução de Sinais/fisiologia , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin-dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.
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Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Cardiomegalia/metabolismo , Meios de Cultivo Condicionados/metabolismo , Endotelina-1/metabolismo , Leptina/metabolismo , Miócitos Cardíacos/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Cardiomegalia/patologia , Células Cultivadas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Ratos Sprague-DawleyRESUMO
The Janus kinase (JAK) system is involved in numerous cell signaling processes and is highly expressed in cardiac tissue. The JAK isoform JAK2 is activated by numerous factors known to influence cardiac function and pathologic conditions. However, although abundant, the role of JAK2 in the regulation or maintenance of cardiac homeostasis remains poorly understood. Using the Cre-loxP system, we generated a cardiac-specific deletion of Jak2 in the mouse to assess the effect on cardiac function with animals followed up for a 4-month period after birth. These animals had marked mortality during this period, although at 4 months mortality in male mice (47%) was substantially higher compared with female mice (30%). Both male and female cardiac Jak2-deleted mice had hypertrophy, dilated cardiomyopathy, and severe left ventricular dysfunction, including a marked reduction in ejection fractions as assessed by serial echocardiography, although the responses in females were somewhat less severe. Defective cardiac function was associated with altered protein levels of sarcoplasmic reticulum calcium-regulatory proteins particularly in hearts from male mice that had depressed levels of SERCA2 and phosphorylated phospholamban. In contrast, SERCA2 was unchanged in hearts of female mice, whereas phosphorylated phospholamban was increased. Our findings suggest that cardiac JAK2 is critical for maintaining normal heart function, and its ablation produces a severe pathologic phenotype composed of myocardial remodeling, heart failure, and pronounced mortality.