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Metal-organic frameworks (MOFs) are emerging as promising candidates for electrochemical glucose sensing owing to their ordered channels, tunable chemistry, and atom-precision metal sites. Herein, the efficient nonenzymatic electrochemical glucose sensing is achieved by taking advantage of Ni(II)-based metal-organic frameworks (Ni(II)-MOFs) and acquiring the ever-reported fastest response time. Three Ni(II)-MOFs ({[Ni6L2(H2O)26]4H2O}n (CTGU-33), {Ni(bib)1/2(H2L)1/2(H2O)3}n (CTGU-34), {Ni(phen)(H2L)1/2(H2O)2}n (CTGU-35)) have been synthesized for the first time, which use benzene-1,2,3,4,5,6-hexacarboxylic acid (H6L) as an organic ligand and introduce 1,4-bis(1-imidazoly)benzene (bib) or 1,10-phenanthroline (phen) as spatially auxiliary ligands. Bib and phen convert the coordination mode of CTGU-33, affording structural dimensions from 2D of CTGU-33 to 3D of CTGU-34 or 1D of CTGU-35. By tuning the dimension of the skeleton, CTGU-34 with 3D interconnected channels exhibits an ultrafast response of less than 0.4 s, which is superior to the existing nonenzymatic electrochemical sensors. Additionally, a low detection limit of 0.12 µM (S/N = 3) and a high sensitivity of 1705 µA mM-1 cm-2 are simultaneously achieved. CTGU-34 further showcases desirable anti-interference and cycling stability, which demonstrates a promising application prospect in the real-time detection of glucose.
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Berberine, which is a potential antidepressant, exhibits definite efficiency in modulating the gut microbiota. Depressive behaviors in mice induced using chronic unpredictable mild stress (CUMS) stimulation were evaluated by behavioral experiments. The markers of neurons and synapses were measured using immunohistochemical staining. An enzyme-linked immunosorbent assay was adopted to analyze serum inflammatory cytokines levels and neurotransmitters were evaluated by LC-MS/MS. Untargeted metabolomics of tryptophan metabolism was further performed using LC-MS/MS. The target enzymes of berberine involved in tryptophan metabolism were assayed using AutoDock and GRMACS softwares. Then, antibiotics was utilized to induce intestinal flora disturbance. Berberine improved the depressive behaviors of mice in a microbiota-dependent manner. Increased neurons and synaptic plasticity were observed following berberine treatment. Meanwhile, berberine decreased serum levels of TNF-α, IL-1ß, and IL-4 and increased levels of IL-10. Moreover, berberine induced retraction of the abnormal neurotransmitters and metabolomics assays revealed that berberine promoted tryptophan biotransformation into serotonin and inhibited the kynurenine metabolism pathway, which was attributed to the potential agonist of tryptophan 5-hydroxylase 1 (TPH1) and inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). In conclusion, berberine improves depressive symptoms in CUMS-stimulated mice by targeting both TPH1 and IDO1, which are involved in tryptophan metabolism.
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Berberina , Triptofano , Camundongos , Animais , Triptofano/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Berberina/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Neurotransmissores , Estresse Psicológico/tratamento farmacológico , Modelos Animais de Doenças , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Triptofano HidroxilaseRESUMO
Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.
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Berberina , Isquemia Encefálica , Sulfeto de Hidrogênio , Microbiota , Animais , Berberina/farmacologia , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Microglia/metabolismo , Ratos , Esfingolipídeos/metabolismo , Nervo Vago/metabolismoRESUMO
Inspired by the metal active sites of [NiFeSe]-hydrogenases, a dppf-supported nickel(II) selenolate complex (dppf=1,1'-bis(diphenylphosphino)ferrocene) shows high catalytic activity for electrochemical proton reduction with a remarkable enzyme-like H2 evolution turnover frequency (TOF) of 7838â s-1 under an Ar atmosphere, which markedly surpasses the activity of a dppf-supported nickel(II) thiolate analogue with a low TOF of 600â s-1 . A combined study of electrochemical experiments and DFT calculations shed light on the catalytic process, suggesting that selenium atom as a bio-inspired proton relay plays a key role in proton exchange and enhancing catalytic activity of H2 production. For the first time, this type of Ni selenolate-containing electrocatalyst displays a high degree of O2 and H2 tolerance. Our results should encourage the development of the design of highly efficient oxygen-tolerant Ni selenolate molecular catalysts.
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The metabolic effect of Huanglian-Huangqin herb pairs on cerebral ischemia rats was studied by using metabolomic method. The rat model of ischemia reperfusion injury induced by introduction of transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Ultra high performance liquid chromatography-series four pole time of flight mass spectrometry methodï¼UPLC-Q-TOF/MSï¼, Markerlynx software, and principal component analysis and partial least-squares discriminant analysis were used to analyze the different endogenous metabolites among the urine samples of sham rats, cerebral ischemia model rats, Huanglian groups (HL), Huangqin groups (HQ) and Huanglian-Huangqin herb pairs groups (LQ) was achieved, combined with accurate information about the endogenous metabolites level and secondary fragment ions, retrieval and identification of possible biological markers, metabolic pathway which build in MetPA database. The 20 potential biomarkers were found in the urine of rats with cerebral ischemia, which mainly involved in the neurotransmitter regulation, amino acid metabolism, energy metabolism, lipid metabolism and so on. Those metabolic pathways were disturbed in cerebral ischemia model rats, the principal component analysis showed that the normal and cerebral ischemia model is clearly distinguished, and the compound can be given to the normal state of change after HL, HQ, LQ administration. This study index the interpretation of cerebral ischemia rat metabolism group and mechanism, the embodiment of metabonomics can reflect the physiological and metabolic state, which can better reflect the traditional Chinese medicine as a whole view, system view and the features of multi ingredient synergistic or antagonistic effects.
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Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Animais , Biomarcadores/urina , Ratos , Scutellaria baicalensisRESUMO
A new luminescent terbium-metal-organic framework [Tb3(L)2(HCOO)(H2O)5]·DMF·4H2O (1) (H4L = 4,4'-(pyridine-3,5-diyl)diisophthalic acid) has been successfully assembled by Tb(3+) ions and an undeveloped pyridyl-tetracarboxylate. Compound 1 exhibits a 3D porous (3,8)-connected (4.5(2))2(4(2).5(12).6(6).7(5).8(3)) topological framework with fascinating 1D open hydrophilic channels decorated by uncoordinated Lewis basic pyridyl nitrogen atoms. In particular, the Tb-MOF (1) can detect Cu(2+) ions with high selectivity and sensitivity, and its luminescence is nearly entirely quenched in N,N-dimethylformamide (DMF) solution and biological system. In addition, 1 still has high detection for the trace content of nitromethane with 70 ppm, which suggests that 1 is a promising example of dual functional materials with sensing copper ions and nitromethane.
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Our previous investigation had confirmed the inhibition of platelet aggregation of a novel Corni fructus-derived formula composed of malic acid, succinic acid and citric acid with a ratio of 3:2:2. The present study was to further evaluate the anti-thrombotic effect of the formula in vivo. Mice of acute pulmonary thromboembolism, and rats of arterial thrombosis were used to determine the anti-thrombotic effect of the formula. Histology analysis of endothelium was conducted with hematoxylin and eosin stain. TXB2 , 6-K-PGF1α , cAMP, cGMP and NO in rat plasma were determined. In vitro assay of αIIbß3 and phosphorylation of ERK1/2 were performed in ADP-treated platelet. The formula significantly reduced the recovery time and mortality rate of mice with acute pulmonary thromboembolism. Remarkably extended occlusion time, decreased thrombus weight and more integrated endothelium were observed in rat with the formula. Enhanced 6-K-PGF1α , cGMP and NO, but not TXB2 and cAMP, were demonstrated in rat plasma with treatment of the formula. Finally, the formula was shown to inhibit αIIbß3 expression and activation of ERK1/2 in platelet. The formula shows positive anti-thrombotic effect. The direct interference on ADP activated signaling in platelet and regulation of endothelium function are two primary pathways involved in the action on thrombosis.
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Ácido Cítrico/farmacologia , Cornus/química , Malatos/farmacologia , Embolia Pulmonar/tratamento farmacológico , Ácido Succínico/farmacologia , Trombose/tratamento farmacológico , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-Dawley , Trombose/sangueRESUMO
OBJECTIVE: To observe the effect of Tongsaimai (TSM) tablets in treating foot trauma of diabetic foot (DF) model rats, and discuss its potential mechanism. METHOD: Male SD rats were selected to duplicate the diabetic foot ulcer model and randomly divided into the blank control group, the model group, the metformin treatment group, and TSM 12.44, 6.22, 3.11 g x kg(-1) groups (n = 10). The healing of ulcer wounds were observed on day 1, 4, 8, 13 and 18. After 18 days, a histopathologic examination was conducted for ulcer tissues. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by hydroxylamine and TBA methods. The content of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined with the radioimmunoassay. The immunohistochemical method was used to observe the expression of vascular endothelial growth factor (VEGF) in ulcer tissues and the number of capillary vessels. RESULT: TSM could alleviate the pathological changes of diabetic foot rats, accelerate the ulcer healing on 4, 8, 13, 18 d, reduce MDA, IL-6, TNF-alpha, VEGF content in rat serum at 18 d (after the rehabilitation period), and enhance the SOD content. Specifically, the TSM 12.44 g x kg(-1) group showed significant differences compared with the model group (P < 0.05, P < 0.01). At 18 d after the treatment (the late rehabilitation period), the VEGF expression of TSM 12.44, 6.22 g x kg(-1) groups and the number of blood capillaries of the TSM 12.44 g x kg(-1) group were significantly lower than that of the model group (P < 0.05, P < 0.01). CONCLUSION: TSM could promote the foot wound healing of DF model rats, reduce MDA, IL-6 and TNF-alpha levels in serum, increase the SOD content and decrease the VEGF expression and the number of blood capillaries in the late rehabilitation period. Its action mechanism may be related to the inhibition of oxidative stress injury and the inflammatory cell infiltration.
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Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Pé Diabético/genética , Pé Diabético/metabolismo , Pé Diabético/fisiopatologia , Modelos Animais de Doenças , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Comprimidos/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
The present study investigated the antiplatelet activity of a novel formula composed by malic acid, succinic acid and citric acid with a ratio of 3:2:2. The IC50 and inhibition of platelet aggregation induced by various agonists as well as platelet adhesion were evaluated in vitro. Of note, the IC50 for the formula inhibiting adenosine diphosphate (ADP)-induced platelet aggregation was 0.185 mg/mL. Meanwhile, the formula showed more potent inhibitory effect on platelet aggregation induced by ADP and thrombin than the single component at same concentration (0.37 mg/mL). Moreover, the formula could prevent platelet adhesion significantly without influence on platelet viability.
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Plaquetas/efeitos dos fármacos , Ácido Cítrico/farmacologia , Cornus/química , Malatos/farmacologia , Ácido Succínico/farmacologia , Difosfato de Adenosina/farmacologia , Animais , Frutas/química , Concentração Inibidora 50 , Masculino , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Coelhos , Trombina/farmacologiaRESUMO
In the principle of "correspondence of prescription and syndrome", this article focuses on key technical issues of traditional Chinese medicine (TCM) biopharmaceutis by using the integrated pharmacokinetic and pharmacodynamic model: (1) As the prescription formulation and compatibility of TCM compounds could be influential to the in vivo pharmacokinetics of chemical components of TCMs, and closely related to therapeutic and adverse effects, how to describe these actions in a biopharmaceutics model? (2) As there are differences between pharmacokinetic processes in the normal and pathological states, how to express characteristic "syndromes" in an animal model? (3) As prescriptions work to reduce and transform syndromes, how o confirm the type and amount of effective substances in case of physiological and pathological indicators and drug distribution in a dynamic corresponding state. In response to the above key issues, we proposed the TCM biopharmaceutic study model based on PK/PD. (1) The integrity of TCMs was better expressed with the effect at the core, supplemented with the component pharmacokinetics; (2) An integrated pharmacokinetic and pharmacodynamic system was established on the basis of pharmacokinetics and pharmacodynamics of many major effective components; (3) AK/PD mathematical function with the three-phase synchronous characterization of "time-concentration-effect" was established by using the data mining techniques, to explore the biopharmaceutic principle of "correspondence of prescriptions and syndromes", in which prescriptions are only required for syndromes, whereas no prescription is required in case of no syndrome.
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Medicina Tradicional Chinesa , Modelos Biológicos , Farmacocinética , Humanos , SíndromeRESUMO
Despite the accumulated evidence that pair housing could attenuate post-stroke depression (PSD), but less attention has been paid to the healthy cohabitors, and the underlying mechanisms remain unclear. This study aimed to determine whether there is depressive contagion between PSD mice and their healthy cohabitors. PSD was induced by middle cerebral artery occlusion (MCAO) plus restraint stress for four weeks. Three days after MCAO, the mice were restrained two hours per day and isosexually pair-housed for four weeks. The results showed that, compared with the partners pair housed with normal control mice (Ctrl group), the partners pair housed with PSD mice (CH group) displayed depressive-like behaviors, including decreased sucrose preference rate, significantly shorter duration in the center arena and reduced total distance in the open-field test, and extended immobile time in forced swimming test and tail-suspension test without sex differences. Regarding the change in the body weight, only the males showed a significant reduction on days 17 and 24 after treatment. Furthermore, the CH group showed significantly increased corticosterone and decreased oxytocin (OXT) levels in serum, while the mRNA levels of OXT, vasopressin and oxytocin receptor were remarkably upregulated in the hypothalamus of the CH group. However, there was no significant change in the vasopressin receptor V1a. Interestingly, compared with the Ctrl group, there was a significant decrease in butyrate in serum of the CH group. Consistently, they had mild liver dysfunction with increased alanine transaminase, extended hepatic sinus surrounded by enhanced SLC22A9, and significantly increased Iba1-positive macrophages. Moreover, the expression of tight junction protein (Occludin and ZO-1) obviously decreased in the colon with increasing Iba1-positive cells. These results suggest that isosexual pair-housing with PSD mice causes the healthy partners to develop depressive-like behaviors with disturbances in the gut and liver.
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Depressão , Hipotálamo , Camundongos , Feminino , Animais , Masculino , Depressão/etiologia , Depressão/metabolismo , Fígado , Natação , Sacarose , Modelos Animais de DoençasRESUMO
Background: Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer's disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose: To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods: The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of ß-amyloid (Aß)25-35-induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and Aß as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, real-time quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in Aß25-35-stimulated BV2 microglia. Results: Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and Aß25-35-stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in Aß25-35-stimulated BV2 cells. In AD mice, more microglia were clustered in the Aß-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in Aß25-35-stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion: HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD.
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Doença de Alzheimer , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ceramidas/metabolismo , Ceramidas/uso terapêutico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Fosfatos/uso terapêutico , EsfingolipídeosRESUMO
OBJECTIVE: To study the differences between the effects of five Chinese patent medicines on focal cerebral ischemia. Tongsaimai Tablet (TSM), Tongxinluo Capsule (TXL), Buchangnaoxintong (BCNXT), Fufangxueshuantong Capsule (FFXST) and Xuesaitong Capsule. METHODS: The focal cerebral ischemia rats were modeled by electric coagulation. The water content of brain, cerebral index, cerebral infarction rate, superoxide dismutase (SOD), malondialdehyde (MDA), testosterone (T), estradiol (E2) in serum and expression of estrogen receptor (ER) in brain were detected after adminstration. RESULTS: Compared with the sham group, the water content of brain, cerebral index, cerebral infarction rate the content of MDA and E2 in serum and the ER expression of focal cerebral ischemia rats increased, the activity of SOD and the content of T were decreased. All these five Chinese patent medicines could reduce encephaledema (except TXL) and the infarct range, decrease the content of MDA and the expression of ER. BCNXT and TSM could increase the activify of SOD; FFXST, XST and TSM could increase the content of T; BCNXT, FFXST and XST could decrease the content of E2. CONCLUSION: The five Chinese patent medicines have the protection effect on cerebral ischemia, but their mechanisms are not exactly the same.
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Isquemia Encefálica/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Edema Encefálico/prevenção & controle , Isquemia Encefálica/sangue , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Malondialdeído/sangue , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/uso terapêutico , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue , Testosterona/sangue , Água/metabolismoRESUMO
BACKGROUND: S. baicalensis, a traditional herb, has great potential in treating diseases associated with aberrant lipid metabolism, such as inflammation, hyperlipidemia, atherosclerosis and Alzheimer's disease. AIM OF THE STUDY: To elucidate the mechanism by which S. baicalensis modulates lipid metabolism and explore the medicinal effects of S. baicalensis at a holistic level. MATERIALS AND METHODS: The potential active ingredients of S. baicalensis and targets involved in regulating lipid metabolism were identified using a network pharmacology approach. Metabolomics was utilized to compare lipids that were altered after S. baicalensis treatment in order to identify significantly altered metabolites, and crucial targets and compounds were validated by molecular docking. RESULTS: Steroid biosynthesis, sphingolipid metabolism, the PPAR signaling pathway and glycerolipid metabolism were enriched and predicted to be potential pathways upon which S. baicalensis acts. Further metabolomics assays revealed 14 significantly different metabolites were identified as lipid metabolism-associated elements. After the pathway enrichment analysis of the metabolites, cholesterol metabolism and sphingolipid metabolism were identified as the most relevant pathways. Based on the results of the pathway analysis, sphingolipid and cholesterol biosynthesis and glycerophospholipid metabolism were regarded as key pathways in which S. baicalensis is involved to regulate lipid metabolism. CONCLUSION: According to our metabolomics results, S. baicalensis may exert its therapeutic effects by regulating the cholesterol biosynthesis and sphingolipid metabolism pathways. Upon further analysis of the altered metabolites in certain pathways, agents downstream of squalene were significantly upregulated; however, the substrate of SQLE was surprisingly increased. By combining evidence from molecular docking, we speculated that baicalin, a major ingredient of S. baicalensis, may suppress cholesterol biosynthesis by inhibiting SQLE and LSS, which are important enzymes in the cholesterol biosynthesis pathway. In summary, this study provides new insights into the therapeutic effects of S. baicalensis on lipid metabolism using network pharmacology and lipidomics.
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Medicamentos de Ervas Chinesas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipidômica , Medicamentos de Ervas Chinesas/metabolismo , Humanos , Medicina Tradicional Chinesa , MetabolômicaRESUMO
Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.
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The development of efficient MOF-based electrocatalysts with good stability to produce hydrogen is a great challenge in the field of sustainable energy conversion. Herein, we introduced a controlled in-situ sulfurization strategy to generate a highly active and stable hybrid catalyst containing good conductive Fe3S4 ultrasmall nanosheets attached on the surface of 3D MIL-53(Fe) for the hydrogen evolution reaction in acidic solutions.
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Alzheimer's disease (AD) is a progressive neurodegenerative disease with neither definitive pathogenesis nor effective treatment method so far. Huang-Lian-Jie-Du-Tang (HLJDT) is a classic formula of traditional Chinese medicine (TCM) proven to have ameliorative effects on learning and memory deficits of dementia. Morris water maze (MWM) test and pathology analysis have demonstrated that HLJDT could ameliorate learning and memory deficits in AD mouse model, which may act via its anti-neuroinflammation properties. According to our previous studies, an UPLC-QTOF/MS-based metabolomics approach was performed to explore the potential mechanisms of HLJDT on preventing AD. As a result, a total of 23 potential metabolites (VIP >1, |Pcorr| >0.58, CUFjk excludes 0, Pâ¯<â¯0.05) contributing to AD progress were identified. The metabolic pathway analysis with MetPA revealed that glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism and tryptophan metabolism were disturbed in mouse model of AD. After HLJDT treatment, 14 metabolites were restored back to the control-like levels.
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Doença de Alzheimer/sangue , Medicamentos de Ervas Chinesas/metabolismo , Metabolômica/métodos , Espectrometria de Massas em Tandem/métodos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Transgênicos , Distribuição Aleatória , Resultado do TratamentoRESUMO
Potential growth of two widely-grown hybrid rice varieties in the Jinhua district of Zhejiang Province, Shanyou63 for mid-rice and Xieyou46 for late rice, was simulated using a crop growth model of WOFOST. Parameters of the rice growth in WOFOST were calibrated through field experiments from 1999 to 2002 in Jinhua. The potential yield simulated with WOFOST was about 12 t/ha for Shanyou63 and 10 t/ha for Xieyou46, which are in good agreement with the highest recorded yield obtained in this area. Under farmers practice, current yield is about 7.5 t/ha for Shanyou63 and 6.5 t/ha for Xieyou46. There is a gap between the actual rice yield and the potential yield for these two hybrid rice varieties grown in this area. The attainable target yields were set to 70% to 75% of their potential yields for the two varieties. A recently developed software "Nutrient Decision Support System (NuDSS)" for irrigated rice was used to optimize nutrient management for these two rice varieties. According to NuDSS, the optimal fertilizer N requirement for the target yields was about 150 kg/ha for Shanyou63 and about 120 kg/ha for Xieyou46, which were only about 70% of the fertilizer N application under current farmers' practice. Comparing with farmers' practice, there is great potential to increase actual rice yields and to reduce fertilizer N use rates by improving rice crop management practice in Jinhua.
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Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Agricultura , China , Fertilizantes , Solo/análiseRESUMO
Field experiments were conducted in farmers' rice fields in 2001 and 2002 to study the effects of nitrogen (N) management strategies on N use efficiency in recovery (RE), agronomy (AE) and physiology (PE) and redistribution of dry matter accumulation (DMA) and nitrogen accumulation (NA) in two typical rice cultivars in Jinhua, Zhejiang Province. This study aimed mainly at identifying the possible causes of poor fertilizer N use efficiency (NUE) of rice in Zhejiang by comparing farmers' fertilizer practice (FFP) with advanced site-specific nutrient management (SSNM) and real-time N management (RTNM). The results showed that compared to FFP, SSNM and RTNM reduced DMA and NA before panicle initiation and increased DMA and NA at post-flowering. There is no significant difference between SSNM and FFP in post-flowering dry matter redistribution (post-DMR) and post-flowering nitrogen redistribution (post-NR). These results suggest that high input rate of fertilizer N and improper fertilizer N timing are the main factors causing low NUE of irrigated rice in the farmer's routine practice of Zhejiang. With SSNM, about 15% of the current total N input in direct-seeding early rice and 45% in single rice could be reduced without yield loss in Zhejiang, China.
Assuntos
Produtos Agrícolas/metabolismo , Nitrogênio/metabolismo , Oryza/metabolismo , FertilizantesRESUMO
The microbial communities under irrigated rice cropping with different fertilizer treatments, including control (CK), PK, NK, NP, NPK fertilization, were investigated using phospholipid fatty acid (PLFA) profile method. The results of this study revealed that the fertilizer practice had an impact on the community structure of specific microbial groups. The principal components analysis (PCA) showed that proportion of the actinomycete PLFAs (10Me 18:0 and 10Me 16:0) were the lowest in the PK treatment and the highest in the NPK treatment, which means that soil nitrogen status affected the diversity of actinomycetes, whereas nitrogen cycling was related to the actinomycets. Under CK treatment, the ratio of Gram-positive to Gram-negative bacteria was lower compared with that in fertilizer addition treatments, indicating that fertilizer application stimulated Gram-positive bacterial population in paddy soil. The fatty acid 18:2omega6,9, which is considered to be predominantly of fungal origin, was at low level in all the treatments. The ratio of cyl9:0 to 18: 1omega7, which has been proposed as an indicator of stress conditions, decreased in PK treatment. Changes of soil microbial community under different fertilizer treatments of paddy soil were detected in this study; however, the causes that lead to changes in the microbial community still needs further study.