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SCOPE: Tea is a popular beverage worldwide and has many health functions. Protocatechuic acid (PCA) is an important bioactive component of tea and has benefit to health. In some cases, oocytes after ovulation may miss the optimal fertilization time and enter a postovulatory ageing process. Therefore, to investigate the role of PCA in delaying oocyte ageing is aimed. METHODS AND RESULTS: Metaphase II (MII) oocytes aged in vitro are randomly divided into three groups: control, aged, and aged + PCA. PCA treatment (30 µM) reduces the fragmentation rate and the incidence of abnormal spindle morphology and chromosome misalignment of oocytes aged 24 h in vitro. The mitochondrial dysfunction of aged oocytes, such as decreased mitochondrial membrane potential and excessive accumulation of reactive oxygen (ROS), is also alleviated by PCA. PCA also delays apoptosis of aged oocytes, and improves the sperm binding capacity. Otherwise, aged oocytes treated with PCA have a higher fertilization rate and blastocyst rate compared with untreated aged oocytes in vitro. CONCLUSION: PCA is an important bioactive ingredient of tea that improves aged oocyte quality, suggesting that PCA is available to improve the quality of aged oocytes in vitro.
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Envejecimiento , Semen , Femenino , Masculino , Animales , Ratones , Oocitos/metabolismo , Té/metabolismoRESUMEN
Maternal diabetes mellitus reduces oocyte quality, such as abnormalities of spindle assembly and chromosome segregation, mitochondrial dysfunction, decrease of fertilization rate, increase of ROS, and so on. So, it is important to research how to restore the decreased oocyte quality induced by maternal diabetes mellitus. Polyphenols are the most abundant bioactive components of green tea. It is reported that tea polyphenols have many health functions, for instance anti-oxidation, anti-inflammation, anti-obesity, and anti-diabetes. Thus, we hypothesize that tea polyphenols may play a crucial role in alleviating adverse effects of diabetes on oocyte quality. In the present study, we researched the effects of tea polyphenols on diabetic oocyte maturation in vitro. Compared with the control, oocytes from diabetic mice displayed a lower maturation rate and a higher frequency of spindle defects and chromosome misalignment. However, tea polyphenols significantly increased the oocyte maturation rate, and reduced the incidence of abnormal spindle assembly and chromosome segregation. Tea polyphenols also obviously decreased the reactive oxygen species (ROS) levels in diabetic oocytes, and increased the expression of antioxidant genes (Sod1 and Sod2). Abnormal mitochondrial membrane potential was also alleviated in diabetic oocytes, and the expression of genes regulating mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1) was significantly increased while tea polyphenols were added. Meanwhile, tea polyphenols reduced DNA damage in diabetic oocytes which may be mediated by the increased expression of Rad51, related to DNA damage repair. Our results suggest that tea polyphenols would, at least partially, restore the adverse effects of diabetes mellitus on oocyte quality.
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Diabetes Mellitus Experimental , Polifenoles , Animales , Diabetes Mellitus Experimental/metabolismo , Ratones , Mitocondrias , Oocitos , Polifenoles/metabolismo , Polifenoles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Té/metabolismoRESUMEN
Benzo[ghi]perylene (B[ghi]P) is a polycyclic aromatic hydrocarbon widely found in haze. Long-term exposure to humans or animals can cause serious damage to the respiratory system. Melatonin is an endogenous natural hormone synthesized and released by the pineal gland. In this study, we investigated the effects of melatonin on in vitro cultured B[ghi]P-exposed mouse oocytes and the protective roles of melatonin. Our data indicate that B[ghi]P exposure leads to meiotic maturation arrest and reduced ability of sperm binding and parthenogenetic activation. Also, B[ghi]P exposure disrupts actin filament dynamics, spindle assembly, and kinetochore-microtubule attachment stability, which results in oocyte aneuploidy. Simultaneously, B[ghi]P exposure disturbs the distribution of mitochondria, increases the level of oxidative stress, and induces apoptosis of oocytes. Whereas all of these toxic effects of B[ghi]P can be restored after melatonin supplement. In conclusion, our findings validate that melatonin has a certain protective effect on preventing the reduced oocyte quality caused by B[ghi]P exposure during meiotic maturation in mouse oocytes.
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Antioxidantes/farmacología , Melatonina/farmacología , Oocitos/efectos de los fármacos , Perileno/análogos & derivados , Animales , Femenino , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Perileno/toxicidadRESUMEN
As the epitome of the modern regenerative medicine, stem cells were proposed in the basic sense no more than 200 years ago. However, the concept of "stem cells" existed long before the modern medical description. The hypothesis that all things, including our sentient body, were generated from a small origin was shared between Western and Chinese people. The ancient Chinese philosophers considered Jing (also known as essence) as the origin of life. In Chinese medicine (CM), Jing is mainly stored in Kidney (Shen) and the so-called Shen-Jing (Kidney essence). Here, we propose that Shen-Jing is the CM term used to express the meaning of "origin and regeneration". This theoretical discovery has at least two applications. First, the actions underlying causing Shen-Jing deficiency, such as excess sexual intercourse, chronic diseases, and aging, might damage the function of stem cells. Second, a large number of Chinese herbs with Shen-Jing-nourishing efficacy had been proven to affect stem cell proliferation and differentiation. Therefore, if Shen-Jing in CM is equivalent with stem cells in regenerative medicine, higher effective modulators for regulating stem-cell behaviors from Kidney-tonifying herbs would be expected.
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Humanos , Medicamentos Herbarios Chinos , Farmacología , Riñón , Medicina Tradicional China , Medicina Regenerativa , Células MadreRESUMEN
Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs-RAGE interaction.
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Nefropatías Diabéticas/tratamiento farmacológico , Espirostanos/farmacología , Anemarrhena/química , Animales , China , Diabetes Mellitus Experimental/complicaciones , Medicamentos Herbarios Chinos/farmacología , Productos Finales de Glicación Avanzada , Interleucina-18/metabolismo , Riñón/efectos de los fármacos , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Ratas Sprague-Dawley , Rizoma/química , Saponinas/farmacología , Ácido Úrico/sangreRESUMEN
The aim of this study is to investigate effects and potential mechanisms of sarsasapogenin (Sar), an active component purified from Rhizoma Anemarrhenae, on high glucose-induced amyloid-beta (Aß) peptide overproduction in HT-22 cells. HT-22 cells were divided into normal glucose; high glucose (HG); HG co-treated with low, middle, and high concentration of Sar (1, 5, 25 µmol/L); and peroxisome proliferator-activated receptor γ (PPARγ) agonist (10 µmol/L pioglitazone). After treatment for 24 h, protein expression of Aß and ß-site Aß precursor protein cleaving enzyme 1 (BACE1) and activated PPARγ level were determined by Western blot; Aß42 levels were also measured by using both immunofluorescence and ELISA methods. BACE1 activity and mRNA level were assessed by fluorospectrophotometry and quantitative PCR, respectively. Cell viability was assayed with a CCK-8 kit. Elevated Aß expression and Aß42 level were found in HG-treated HT-22 cells, accompanied by increased BACE1 protein and mRNA levels as well as enzymatic activity, which was markedly attenuated by three concentrations of Sar and pioglitazone. Moreover, HG reduced nuclear PPARγ levels, which was reversed by middle and high concentrations of Sar as well as pioglitazone. PPARγ antagonist GW9662 (20 µmol/L) pretreatment reversed the effect of Sar on BACE1 protein expression in HG-cultured HT-22 cells. Additionally, Sar suppressed HG-induced decreases in cell viability of HT-22 cells. High glucose can induce an increase in Aß levels and a decrease in cell viability in HT-22 cells, while co-treatment with Sar improves these results, which is mediated likely through activation of PPARγ and subsequent downregulation of BACE1.
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Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/biosíntesis , Medicamentos Herbarios Chinos/farmacología , Glucosa/toxicidad , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/biosíntesis , Espirostanos/farmacología , Animales , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , RatonesRESUMEN
Scientifically elucidating the mode of action of Chinese medicine has become an urgent challenge to Chinese medicine researchers.Opinions on the mode of Chinese medicine effect are active.The scientific hypothesis that additive effect is the key mode of action for Chinese medicine,trigger the scholars and experts in pharmacology field of Chinese medicine to think and contend.The opinion of additive effect provides a new interpretation for mode of action and action characteristics of Chinese medicine.It plays a positive role in the development of pharmacology of Chinese medicine.According to current research results of traditional Chinese medicine (TCM) and clinical cases,this paper made further thinking and summary on the key mode of action for Chinese medicine.The summary is as follows.The diversity of Chinese medicine structure and complexity of Chinese medicine targets determine the complicated mode of action of Chinese medicine.Mode of action for Chinese medicine is complex and variable,which is to adapt to changes in the environment.The genetic diversity of the body receptors due to evolution and the diversity of Chinese medicine and biological complex network control system have determined that a single component of Chinese medicine is more likely to act synergistically by targeting on different targets.From the point of view of Monarch,Minister,Assistant and Guide theory of Chinese medicine,additive effect has limitation.Therefore,just using additive effect is unable to fully explain the Chinese medicine compatible regularity of Monarch,Minister,Assistant and Guide theory.Additive effect is one of action types for Chinese medicine.It is worth to consider if there has any other more important action type for Chinese medicine.
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Transgenic pigs failed to accord milk yield curve to lactate rhFIX-a vitamin K (VK) dependent protein even fed with VK enriched to 8 times higher than nutritional requirement. A further higher VK supplementation may be required. Homozygous transgenic sows (n = 4, 200 kg) at their 3rd nursing were divided into control and treatment groups and respectively received VK enriched and further menadione (soluble VK) supplemented diet (220 mg/kg VK enriched diet) for 33 days. At next lactation, control sows than received treatment and previous treated were fed on control diet. Results revealed that menadione treatment increased milk bioactivity of rhFIX from the 7th day of 73 to the 21st day of 153 IU/mL; it gradually decreased to 96 IU/mL on 35th day of lactation. Under control feeding, bioactivity remained relatively unchanged. However, milk rhFIX concentration and ratio of activated rhFIX responded little to the treatment. The menadione-induced bioactivity curve agrees with the known lactation pattern of sow means rhFIX secretion is still galactopoietic but requires high VK intake to show. The ineffectual VK spend on lactational carboxylation might be common in other mammary VK dependent expression system but can be effectively overcome by a high supplementation of menadione with a 5-folds improvement in quality.
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Animales Modificados Genéticamente , Factor IX/genética , Leche/metabolismo , Sus scrofa/genética , Vitamina K/farmacología , Animales , Suplementos Dietéticos , Factor IX/metabolismo , Femenino , Homocigoto , Humanos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Vitamina K 3/farmacologíaRESUMEN
The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This animal breeds normally with no obvious defect in development. The IfitmDel animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months of age and under normal feeding conditions. The increased weight corresponds with elevated fat mass, and in tolerance tests they are hyporesponsive to insulin but respond normally to glucose. Both young (4 mo) and older (12 mo) IfitmDel mice have enhanced levels of serum leptin suggesting a defect in leptin/leptin receptor signaling. Analysis of the gene expression profiles in the hypothalamus of IfitmDel animals, compared to WT, demonstrated an altered ratio of Pomc and Npy neuropeptide expression, which likely impairs the satiation response of the IfitmDel animal leading to an increased eating behavior. Also elevated in hypothalamus of IfitmDel mice were pro-inflammatory cytokine expression and reduced IL-10. Anatomical analysis of the hypothalamus using immunohistochemistry revealed that microglia exhibit an abnormal morphology in IfitmDel animals and respond abnormally to Poly:IC challenge. These abnormalities extend the phenotype of the IfitmDel mouse beyond abnormal responses to viral challenge to include a metabolic phenotype and weight gain. Further, this novel phenotype for the IfitmDel mouse could be related to abnormal neuropeptide production, inflammatory status and microglia status in the hypothalamus.
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Hipotálamo/metabolismo , Redes y Vías Metabólicas/fisiología , Microglía/patología , Obesidad/metabolismo , Edad de Inicio , Animales , Antígenos de Diferenciación/genética , Citocinas/metabolismo , Eliminación de Gen , Perfilación de la Expresión Génica , Inmunohistoquímica , Leptina/sangre , Ratones , Familia de Multigenes/genética , Neuropéptido Y/metabolismo , Obesidad/patología , Proopiomelanocortina/metabolismoRESUMEN
OBJECTIVE: To study the effect of medicines for activating blood and reinforcing Qi on the number of new micro-vessels and the protein expressions of VEGF and bFGF in the infarcted myocardium edge area of acute myocardial infarction (AMI) model in rats. METHOD: The AMI model of rats was established. After the successful model establishment, rats were randomly divided into the sham-operated group, the model group, the Danshen-Huangqi (1 : 2) group, the Danshen-Huangqi (1 : 1) group, the Chuanxiong-Huangqi (1 : 2) group, the Danshen group, the Chuanxiong group, the Chishao group and the Shexiang Baoxin pill group, with five rats in each group. Rats in each medicated group were orally administered with drugs as per 13.5 g x kg(-1) x d(-1) once everyday for three weeks. The immunohistochemical SP method was adopted to detect the expression of vWF in myocardial tissues, and count the number of micro-vessels (MVC). The protein expression of VEGF and bFGF in myocardial tissues were determined by Western blot. RESULT: The new micro-vessels stained by vWF factor could be found in the infarcted myocardium edge area of the sham-operated group, the model group and all of medicated groups. The sham-operated group show unobvious new micro-vessels in myocardial tissues. A small amount of new micro-vessels could be seen in the infarcted myocardium edge area of the model group. Whereas a larger number of micro-vessels could be seen in the infarcted myocardium edge area of all of medicated groups. The differences between the sham-operated group and the model group had statistical significance (P < 0.05). The differences between each medicated group and the model group had statistical significance as well (P < 0.05 or P < 0.01). The lowest protein expression of VEGF and bFGF was found in myocardium of the sham-operated group, with the statistical significance compared with the model group (P < 0.05). Compared with the model group, each medicated group showed significant increase in the protein expression of VEGF and bFGF, with the statistical significance between them (P < 0.05 or P < 0.01). CONCLUSION: The Danshen group, the Chuanxiong group, the Chishao group, the Danshen-Huangqi (1 : 2) group, the Danshen-Huangqi (1 : 1) group and the Chuanxiong-Huangqi (1 : 2) group show the effect in promoting angiogenesis. Their mechanism for promoting angiogenesis may be related to the improvement of the protein expressions of VEGF and bFGF, so as to increase the contents of VEGF and bFGF and promote the angiogenesis of new vessels.
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Medicamentos Herbarios Chinos/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Qi , Animales , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Masculino , Microcirculación/efectos de los fármacos , Microvasos/efectos de los fármacos , Microvasos/fisiopatología , Infarto del Miocardio/fisiopatología , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
<p><b>OBJECTIVE</b>To evaluate the effect of compound bushen recipe (CBR) in improving the survival state of stress and the overall life span in C. elegans by simulating chronic fatigue syndrome (CFS) under various stress states.</p><p><b>METHODS</b>The tolerance and the average survival time of adult larvae against heat stress (35 degrees C), oxidative stress (250 microg/mL juglone), and in vivo Abeta protein toxicity (Abeta(1-42) transgenic mutant CL4176) under the intervention of the high (500 mg/L), middle (250 mg/L), and low (100 mg/L) dose CBR were observed. The effect of CBR on the average live time (at 25 degrees C), movement distance in 20 seconds, the frequency of pharyngeal pump in 30 seconds, and the reproductive capability were assessed.</p><p><b>RESULTS</b>Compared with the control group, the survival time of heat stressed C. elegans could be significantly increased in each CBR group (P < 0.01). The survival time of heat stressed C. elegans could be elongated, the protein toxicity be attenuated, and the live time prolonged in the high and middle dose CBR groups (P < 0.01, P < 0.05).The movement distance and the frequency of pharyngeal pump could also be increased in the high dose CBR group (P < 0.01). There was no statistical difference in the reproductive capability among all groups (P > 0.05).</p><p><b>CONCLUSIONS</b>CBR could significantly enhance the stress capacity of C. elegans against internal and external environment, and prolong their lifespan. It did not interfere their normal production, and also could improve the quality of life, thus laying a foundation for further mechanism studies and pharmacological researches on CBR in preventing and treating CFS.</p>
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Animales , Caenorhabditis elegans , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Usos Terapéuticos , Síndrome de Fatiga Crónica , Quimioterapia , Longevidad , Estrés FisiológicoRESUMEN
The relationship between disease in Western medicine (WM) and pattern in Chinese medicine (CM) is a key scientific issue in integrative medicine (IM). The theory of "different patterns in the same disease" has greatly promoted the development of IM and the modernization of CM. However, this concept is frequently misinterpreted in the clinical practice. The individual difference was overemphasized, while common changes among patients suffering from the same disease were neglected. As a result, the identification and treatment of common changes based patterns were weakened. The theory of "analogous patterns in the same disease" combines the concept of "different patterns in the same disease" and "microcosmic identification of patterns", which reveals the core mechanism of CM from the pathogenesis, and identifies the major pattern by analyses of manifestations and pathologic changes. And under the guidance of the theory of "formula corresponding to pattern", the major formula can be set for the major pattern. For those differences among individuals suffering from the same disease, they can be identified as different analogous patterns (subtypes) within a same major pattern, and can be treated with analogous formulae deriving from modified major formula. The theory of "analogous patterns in the same disease" clarifies the intrinsic relationship between the disease and pattern, perfects and develops the theory of "different patterns in the same disease", and it is an important innovation in thinking ways and research methods of IM.
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Humanos , Medicina Integrativa , Medicina Tradicional China , MétodosRESUMEN
Holistic concept is a characteristic contribution of Chinese medicine to medical science. Based on holistic concept, we investigated the correlation of Shenyang deficiency syndrome with the hypothalamus-pituitary-target gland axis; and revealed by gene chip technique the molecular network regulatory rule of intervention with Chinese drugs on hypothalamus-pituitary-adrenal-thymus axis in aged rats as a model for Shen deficiency syndrome; also the two major gene regulation pathways, namely, the neuro-endocrine-immune pathway and the neuro-endocrine-bone metabolic pathway, in hypothalamus, pituitary, adrenal, lymphocytes, kidney, liver, bone of aged rats, so as to advance the holistic research on Chinese medicine syndromes. Recently, based on the dynamic, intervention and multi-layer integration requirement of systematic biology, the common rule of aging was found at three different levels, the whole genomic transcription level, the metabolic level and the single ageing signaling pathway level. Meanwhile, it was demonstrated that the temporal and spatial association of genes will be weakened gradually along with aging. And Epimedium Flavonoids (EF), an extracts from Epimedium have been proved to be capable of effectively reversing both of these systemic changes. Thus, the transition of study from holistic concept to systematic biologic viewpoint could surely promote the progression of Chinese medicine to modern life science.
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Animales , Ratas , Envejecimiento , Genética , Fisiología , Salud Holística , Enfermedades Renales , Medicina Tradicional China , Métodos , Biología de Sistemas , Métodos , Deficiencia YangRESUMEN
Stem cells are the cells with capacities of self-renovation, multiplication and differentiation. By activating endogenous stem cells to promote regeneration response has provided a new thinking for the treatment of degenerative diseases. The authors found that epimedium flavonoids (EF) can promote the proliferation and migration of adrenocortical stem cells in corticosterone-treated rats (as a model of Shen-yang deficiency); and through gene-chip test it was showed that EF could significantly up-regulate the growth hormone (GH), growth hormone releasing hormone (GHRH) and other growth factors such as insulin-like growth factor binding protein (IGFBP) and nerve growth factor (NGF) in the model rats. In natural aging rats (as model for Shen deficiency), EF could make the gene expression of multiple tissues youthening, and up-regulate the lowered expressions of GH, GHRH, IGFBP and NGF, etc. Further study on the in vitro isolated and cultivated neuro-stem cells proved that EF and its components have direct promoting actions on stem cell proliferation. All the above-mentioned outcomes indicated that the actions of EF and its extracts on stem cells are possibly the cytological basis for their effects on counteracting the suppression of glucocorticoids on hypothalamus-pituitary-adrenal (HPA) axis and retarding aging; also illustrated that TCM could treat diseases by a way of activating endogenous stem cells through mobilizing and elevating hormones and cytokines levels, and bringing the reserved potential of organism into full play.
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Animales , Ratas , Corteza Suprarrenal , Biología Celular , Proliferación Celular , Células Cultivadas , Medicamentos Herbarios Chinos , Farmacología , Epimedium , Química , Flavonoides , Farmacología , Ratas Sprague-Dawley , Células Madre , Biología CelularRESUMEN
Eucommia ulmoides Oliv. (Eucommiaceae), a traditional Chinese medicinal plant, was used to study phloem cell differentiation during bark regeneration after girdling on a large scale. Here it is shown that new sieve elements (SEs) appeared in the regenerated tissues before the formation of wound cambium during bark regeneration after girdling, and they could originate from the transdifferentiation of immature/differentiating axial xylem cells left on the trunk. Assays of water-cultured twigs revealed that girdling blocked sucrose transport until the formation of new SEs, and the regeneration of the functional SEs was not dependent on the substance provided by the axis system outside the girdled areas, while exogenous indole acetic acid (IAA) applied on the wound surface accelerated SE differentiation. The experiments suggest that the immature xylem cells can transdifferentiate into phloem cells under certain conditions, which means xylem and phloem cells might share some identical features at the beginning of their differentiation pathway. This study also showed that the bark regeneration system could provide a novel method for studying xylem and phloem cell differentiation.
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Transdiferenciación Celular , Eucommiaceae/fisiología , Floema/fisiología , Corteza de la Planta/fisiología , Xilema/fisiología , Transdiferenciación Celular/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacología , Floema/citología , Corteza de la Planta/citología , Regeneración , Sacarosa/metabolismo , Xilema/citología , Xilema/ultraestructuraRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect and its mechanism of Epimedium flavanoids (EF) in retarding aging with different systematic viewpoints.</p><p><b>METHODS</b>Hypothalamus, pituitary, adrenal and lymphocytes taken from 4-, 10-, 18-, 24-month old rats and from EF treated 24-month old rats were used to measure whole genome mRNA expression by gene array. Serum samples were used for metabonomic assay with high performance liquid chromatography. Using specific gene chip for NF-kappaB signaling pathway to detect the gene expression of the molecule related to that pathway in lymphocytes. Then, a neural network (NN) model was established upon the data obtained to quantitatively evaluate the degree of aging and the efficacy of drug intervention.</p><p><b>RESULTS</b>Gene expression of 199 genes showedan age-dependent pattern, most of which were reversed by EF, and the output of NN model showed that EF made the transcriptomics of 24-month old rats to 8-13 months. Seventeen metabolites among the 1,885 peaks detected were identified to have significant age-depending changes, and EF intervention reset the level of metabolites to a younger (18-month) level. The integral level of gene expression for NF-kappaB signaling pathway decreased significantly along with the increasing of age, and was significantly elevated by EF, NN model showed it approached to 10.5-month old.</p><p><b>CONCLUSION</b>Phenotype of aging at different levels demonstrates a common age-dependent trend; EF can reverse this age-dependent change at different levels in a synchronous manner.</p>
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Animales , Masculino , Ratas , Glándulas Suprarrenales , Metabolismo , Envejecimiento , Genética , Metabolismo , Cromatografía Líquida de Alta Presión , Epimedium , Química , Flavonoides , Farmacología , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Hipotálamo , Metabolismo , Linfocitos , Biología Celular , Metabolismo , FN-kappa B , Sangre , Genética , Metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Métodos , Hipófisis , Metabolismo , Ratas Sprague-Dawley , Transducción de Señal , Factores de Tiempo , Transcripción GenéticaRESUMEN
<p><b>OBJECTIVE</b>To establish a quantitative mathematical model of Shen-deficiency syndrome of TCM by utilizing whole-genome transcriptional profiles.</p><p><b>METHODS</b>The 4, 10, 18, 24 months old SD rats were used, 24-months aged rats intervened by Epimedium Flavonoids (EF) were adopted in the experiment. Rats' hypothalamus, pituitary, adrenal, lymphocytes, bone, liver, and kidney, and spleen were taken for determining whole-genome mRNA expression with gene chip, and a quantitative nerve network model was established by utilizing the gene expression profile of different aged rats, then the model was used to evaluate the effects of EF on Shen-deficiency syndrome.</p><p><b>RESULTS</b>Totally 199 genes showing age-dependent characteristics were screened out from the 7 kinds of tissue, most of them were neuro-endocrine immune related genes. Evaluation based on the mathematical model showed the age of hypothalamus, pituitary, adrenal, liver, kidney, bone, and spleen in the 24-months rats after EF intervention was 12.64, 10.87, 8.10, 12.70, 11.93, 13.14, and 10.13 months, respectively.</p><p><b>CONCLUSION</b>A quantitative mathematical model can be established based on the gene expression profile, it is suitable for estimating the efficacy of Shen-tonifying drugs. EF can make the gene expression of elder close to the young state, suggesting that EF has action in improving Shen-deficiency syndrome and delaying senescence.</p>
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Animales , Masculino , Ratas , Diagnóstico Diferencial , Medicamentos Herbarios Chinos , Farmacología , Epimedium , Química , Perfilación de la Expresión Génica , Enfermedades Renales , Diagnóstico , Genética , Medicina Tradicional China , Modelos Teóricos , Ratas Sprague-Dawley , Síndrome , Deficiencia Yang , Diagnóstico , GenéticaRESUMEN
It has been found that the hypofunction status of hypothalamus-pituitary-adrenal (HPA) axis exists in patients with Shen-yang deficiency syndrome of TCM, also presents in most asthma patients. Seasonal attack of asthma can be prevented with Shen-tonifying drugs by improving adrenocortical function. Since patients subject to long-term glucocorticoids display hypofunction condition of HPA axis, Shen-tonifying drugs should be helpful to gluocorticoid withdrawal for getting higher success rate. Basic researches also indicated that the activating of adrenocortical stem cells and promoting regeneration of adrenal cortex is one of the mechanisms underlying improvement of adrenocortical function. Series of research showed that hypofunction of adrenocortex is the general pathological change in some diseases, so, Shen-tonifying drugs act a part in unitarily modulating the adrenocortical function, to get the therapeutic effect of both regulating the whole and improving the local.
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Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Asma , Terapéutica , Sistema Hipotálamo-Hipofisario , Fisiología , Medicina Tradicional China , Métodos , Síndrome Nefrótico , Terapéutica , Sistema Hipófiso-Suprarrenal , Fisiología , Deficiencia YangRESUMEN
<p><b>OBJECTIVE</b>To explore similarity and difference of connotation between Shen deficiency syndrome (SDS) and Shen-yang deficiency syndrome (SYDS) on the molecular level.</p><p><b>METHODS</b>The senescent SD rats and corticosterone-treated rats were adopted for models of SDS and SYDS respectively, their syndrome was differentiated according to the therapeutic efficacy of treatment with epimedium flavonoids (EF). The gene expression profiles of hypothalamas, pituitary, adrenal gland and lymphocytes (HPAT axis) were detected before and after EF treatment using gene chip provided by Affymetrix company.</p><p><b>RESULTS</b>As compared with the young rats, the ageing rats and corticosterone-treated rats showed a significant down-regulation in highly consistent pattern, of various neurotransmitters of HPAT axis firstly, followed with that of growth and sex hormone related genes. EF could reverse the above genes expression in both models, and for SYDS model rats, it could also significantly up-regulate the gene expressions of heat shock protein, cytochrome P450 and thyroid stimulating hormone (TSH).</p><p><b>CONCLUSION</b>Both SDS and SYDS model rats show connotation of Shen deficiency, and the substantial base of Shen-yang deficiency syndrome resides in the process of oxidative phosphorylation of energy metabolism accelerated by thyroid hormone.</p>