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1.
Artigo em Inglês | MEDLINE | ID: mdl-32124474

RESUMO

Cancer stem cells have been identified as the major cause of cancer initiation and progression. To investigate the effects of puerarin 6″-O-xyloside (PXY), derived from Pueraria lobata (Willd.) Ohwi, on lung cancer stem cells, we enriched and identified a subpopulation of lung cancer stem-like cells (LCSLCs) derived from lung adenocarcinoma A549 cells with traits including high self-renewal and invasive capability in vitro, elevated tumorigenicity in vivo, and high expression of stem cell markers CD44, CD133 and aldehyde dehydrogenase 1 (ALDH1). We found that PXY could impair cell viability, suppress self-renewal and invasive capability, and decrease CD133, CD44 and ALDH1 mRNA expression in LCSLCs in a dose-dependent manner. Furthermore, we showed that PXY suppressed the self-renewal and invasive capability of LCSLCs at least in part through suppressing the activation of Akt/c-Myc signalling. In conclusion, PXY can block the traits of LCSLCs, indicating that PXY may be a candidate compound for lung adenocarcinoma therapy via eliminating LCSLCs.

2.
ACS Chem Neurosci ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32203651

RESUMO

Prenatal stress (PNS) has a prolonged and adverse effect on offspring, leading to a significantly increased vulnerability to developing depression in their later life. Traditional therapies have delayed onset and limited efficacy; thus, it remains an urgent need to find novel medications with fast-onset and high-efficacy potentials. Crocin, with its structure clearly examined, has shown antidepressant-like effects. However, few studies extensively investigated its effect especially in mice exposed to PNS. Using an established PNS model, we tested whether crocin could have a rapid and persistent antidepressant-like effect in PNS mice. Growth hormone secretagogue receptor (GHSR) and phosphoinositide 3-kinase (PI3K) inhibitors were used to test their effects in antidepressant-like effect of crocin. Hippocampal GHSR-PI3K signaling was examined both in PNS mice treated with a single dose of crocin and in combination of GHSR inhibitor. PNS mice showed depression-like behaviors at juvenile and adulthood, and crocin induced an instant and persistent antidepressant-like response in PNS mice in a dose-dependent manner. Moreover, crocin increased the expression of hippocampal synaptic plasticity-associated proteins through the restoration of GHSR-PI3K signaling. Inhibitions of both GHSR and PI3K abolished the effect of crocin in alleviating depressive-like behaviors. More importantly, GHSR inhibitor JMV2959 blocked the enhanced expression of hippocampal plasticity-related proteins induced by crocin. The present study demonstrated that crocin induced a fast-onset and prolonged antidepressant effect in PNS mice and suggested that GHSR-PI3K signaling may play a key role in crocin's effect at least partially by a restoration of hippocampal synaptic plasticity-associated proteins.

3.
Nat Commun ; 11(1): 938, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071314

RESUMO

It is known that the main-group metals and their related materials show poor catalytic activity due to a broadened single resonance derived from the interaction of valence orbitals of adsorbates with the broad sp-band of main-group metals. However, Mg cofactors existing in enzymes are extremely active in biochemical reactions. Our density function theory calculations reveal that the catalytic activity of the main-group metals (Mg, Al and Ca) in oxygen reduction reaction is severely hampered by the tight-bonding of active centers with hydroxyl group intermediate, while the Mg atom coordinated to two nitrogen atoms has the near-optimal adsorption strength with intermediate oxygen species by the rise of p-band center position compared to other coordination environments. We experimentally demonstrate that the atomically dispersed Mg cofactors incorporated within graphene framework exhibits a strikingly high half-wave potential of 910 mV in alkaline media, turning a s/p-band metal into a highly active electrocatalyst.

4.
J Cell Mol Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990147

RESUMO

The purpose of the present study was to evaluate the anti-cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT-116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin-α. The levels of glutamine, glutamic acid, α-ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V-FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT-qPCR, Western blot and immunofluorescence staining. The expressions of cleaved-caspase-3, caspase-3, cleaved-caspase-7, caspase-7, cleaved-PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT-116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine-related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT-116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin-α promoted the inhibitory effect of Lobetyolin on ASCT2-mediated apoptosis. Lobetyolin also exerted anti-cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2-mediated glutamine metabolism, which was possibly governed by p53.

5.
Epilepsy Behav ; 102: 106589, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726317

RESUMO

Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with depression. But, up to date, the association of BR alterations in TCS with depression in patients with epilepsy has never been reported. This study was to investigate the possible role of BR examination via TCS in patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression. Forty-six patients with IGE-TCS and 45 healthy controls were recruited. Echogenicity of the caudate nuclei (CN), lentiform nuclei (LN), substantia nigra (SN), and BR and widths of the lateral ventricle (LV) frontal horns and the third ventricle (TV) were assessed via TCS. The determination of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), and depression severity measured by Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II). The width of TV in patients with epilepsy was found significantly larger than that in healthy controls (p = 0.001), but there was no significant difference in TV width between patients with IGE-TCS with and without depression. There were no significant differences between patients with IGE-TCS and healthy controls in LV frontal horn width, as well as in SN, CN, LN, and BR echogenicity. Here, it seems that patients with IGE-TCS were detected with smaller SN echogenic area compared with controls though they had no statistical significance. Patients with IGE-TCS with hypoechogenic BR had significantly higher C-NDDI-E and BDI-II scores than those with normal BR signal, and most patients with IGE-TCS with depression exhibited hypoechogenic BR, but few patients with IGE-TCS without depression exhibited hypoechogenic BR. In conclusion, BR echogenic signal alterations in TCS can be a biomarker for depression in epilepsy, but it might not be associated with epilepsy itself. The alterations of SN echogenic area and TV width in TCS may reflect a potential role of SN and diencephalon structure in the pathogenesis of epilepsy, which needs to be further elucidated.

6.
Sci Transl Med ; 11(504)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391321

RESUMO

Glioblastoma stem cells (GSCs) reprogram glucose metabolism by hijacking high-affinity glucose uptake to survive in a nutritionally dynamic microenvironment. Here, we trace metabolic aberrations in GSCs to link core genetic mutations in glioblastoma to dependency on de novo pyrimidine synthesis. Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) or the critical downstream enzyme dihydroorotate dehydrogenase (DHODH) inhibited GSC survival, self-renewal, and in vivo tumor initiation through the depletion of the pyrimidine nucleotide supply in rodent models. Mutations in EGFR or PTEN generated distinct CAD phosphorylation patterns to activate carbon influx through pyrimidine synthesis. Simultaneous abrogation of tumor-specific driver mutations and DHODH activity with clinically approved inhibitors demonstrated sustained inhibition of metabolic activity of pyrimidine synthesis and GSC tumorigenic capacity in vitro. Higher expression of pyrimidine synthesis genes portends poor prognosis of patients with glioblastoma. Collectively, our results demonstrate a therapeutic approach of precision medicine through targeting the nexus between driver mutations and metabolic reprogramming in cancer stem cells.

7.
Medicine (Baltimore) ; 98(26): e15917, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261498

RESUMO

Acute onset neurological symptoms evoked by traumatic, surgical, or emotional events in Wilson disease (WD) have never been reported and its clinical characteristics are unclear.We aimed to summarize the clinical characteristics of a special WD whose neurological symptoms acutely developed after traumatic, surgical, or emotional events.Retrospective pilot study.Thirty-one patients who had acute onset neurological symptom as an initial presentation of WD or a new presentation of hepatic WD after mild trauma, surgery, or emotional events were retrospectively studied. All patients were followed for half to 1 year after regular anti-copper treatment.The averaged latency for neurological symptom presentation was 2.79 ±â€Š1.21 hours. The most frequent neurological symptoms were tremor (74%) and basal ganglia (BG) lesions were detected on magnetic resonance imaging in all patients. Lesions in other regions were much less frequently detected. Neurological symptom score and its recovery after treatment were correlated with lesion location: BG area and BG plus other brain areas. Neurological symptoms improved in 21 patients who received timely anti-copper treatment but continued to deteriorate in 6 patients who did not accept regular anti-copper treatment for delayed diagnosis.A diagnosis of WD should be considered when adolescents or adults experience acute presentation of extrapyramidal systems after traumatic, surgical, or emotional stimulation. Timely anti-copper therapy usually gives rise to an excellent prognosis.


Assuntos
Emoções , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Criança , Estudos Transversais , Feminino , Seguimentos , Degeneração Hepatolenticular/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudo de Prova de Conceito , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
8.
FEBS Lett ; 593(21): 3054-3063, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31309546

RESUMO

During the development of type 2 diabetes mellitus (T2DM), hyperinsulinemia is the earliest symptom. It is believed that long-term high insulin stimulation might facilitate insulin resistance in the liver, but the underlying mechanism remains unknown. Herein, we report that hyperinsulinemia could induce persistent early growth response gene-1 (Egr-1) activation in hepatocytes, which provides negative feedback inhibition of insulin sensitivity by inducing the expression of protein tyrosine phosphatase-1B (PTP1B). Deletion of Egr-1 in the liver remarkably decreases glucose production, thus improving systemic glucose tolerance and insulin sensitivity. Mechanistic analysis indicates that Egr-1 inhibits insulin receptor phosphorylation by directly activating PTP1B transcription in the liver. Our results reveal the molecular mechanism by which hyperinsulinemia accelerates insulin resistance in hepatocytes during the progression of T2DM.

9.
Curr Drug Targets ; 20(15): 1572-1586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215388

RESUMO

Quinolizidine alkaloids, a main form of alkaloids found in the genus Sophora, have been shown to have many pharmacological effects. This review aims to summarize the photochemical reports and biological activities of quinolizidine alkaloids in Sophora. The collected information suggested that a total of 99 quinolizidine alkaloids were isolated and detected from different parts of Sophora plants, represented by lupinine-type, cytisine-type, sparteine-type, and matrine-type. However, quality control needs to be monitored because it could provide basic information for the reasonable and efficient use of quinolizidine alkaloids as medicines and raw materials. The nonmedicinal parts may be promising to be used as a source of quinolizidine alkaloid raw materials and to reduce the waste of resources and environmental pollution. In addition, the diversity of chemical compounds based on the alkaloid scaffold to make a biological compound library needs to be extended, which may reduce toxicity and find new bioactivities of quinolizidine alkaloids. The bioactivities most reported are in the fields of antitumor activity along with the effects on the cardiovascular system. However, those studies rely on theoretical research, and novel drugs based on quinolizidine alkaloids are expected.

10.
Eur J Pharmacol ; 857: 172424, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31150648

RESUMO

Crocin, an active compound found in Gardenia jasminoides Ellis, has been shown to possess neuron-protective properties, but its potential mechanisms of action still remain poorly understood. In this study, the anti-ischemic effect and underlying mechanism of action of crocin were investigated in male rats with right middle cerebral artery occlusion/reperfusion. Computed tomography and magnetic resonance imaging were used to evaluate the area of infarction 24 h after reperfusion. Neurological scores were employed to evaluate nerve injury. Direct 2,3,5-triphenyltetrazolium chloride staining was used to calculate the infarct ratio 120 h after reperfusion. Finally, HT22 cells and Western blot were used to study the underlying mechanisms. Crocin showed a decreased infarct volume and neurological score in vivo, while the expression of LC3-II/I and AMP-activated protein kinase was remarkably down-regulated with increased levels of p62 and mammalian target of rapamycin (mTOR) expression. However, rapamycin significantly inhibited mTOR, which can impact the anti-ischemic effect of crocin in vitro. These results suggest that crocin may elicit an anti-ischemic effect probably through the mTOR pathway.


Assuntos
Autofagia/efeitos dos fármacos , Carotenoides/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Carotenoides/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
11.
Neuroscience ; 411: 105-118, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31158436

RESUMO

The ventrolateral periaqueductal gray matter (vlPAG) plays a critical role in the pathogenesis of migraine and few studies have shown that vlPAG might be involved in the pathophysiology of epilepsy. But its roles in epileptogenesis and comorbid relationship between migraine and epilepsy have never been reported. In this study, the impairments of vlPAG neuronal network during spontaneous recurrent seizure (SRS) development after status epilepticus (SE) were investigated, and the pain sensitivity as well as the SRS investigated after neurochemical lesion to vlPAG to determine the role of vlPAG in epileptogenesis and in migraine comorbidity with epilepsy. Neuronal loss and alterations of excitatory and inhibitory neural transmission within vlPAG accompanied the development of epileptogenesis induced by SE. On the other hand, neurochemical lesion to vlPAG enhanced frequency and duration of spontaneous seizure event and frequency of epileptiform inter-ictal spike discharges in electroencephalography (EEG), but decreased pain threshold in epileptic rats. This indicates an involvement of the pain regulating structure, vlPAG, in the pathogenesis of epilepsy. This may imply that vlPAG network alterations could be a possible underlying mechanism of the interactive comorbid relationship between epilepsy and migraine.


Assuntos
Epilepsia/fisiopatologia , Limiar da Dor/fisiologia , Dor/fisiopatologia , Substância Cinzenta Periaquedutal/fisiopatologia , Convulsões/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley
12.
J Headache Pain ; 20(1): 53, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092190

RESUMO

BACKGROUND: Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with major depression (MD) and in depressed patients with different neurodegenerative diseases. But, up to date, the association of BR alterations in TCS with depression in migraineurs has never been reported. This study was to investigate the possible role of BR examination via TCS in migraineurs with depression. METHODS: Forty two migraine without aura (MwoA) patients and 40 healthy controls were recruited. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and brainstem raphe (BR) and width of the frontal horns of the lateral ventricles and the third ventricle were assessed with TCS. The diagnosis of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM -IV), and the severity of depression was measured by Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D). RESULTS: There were no significant differences between migraineurs and controls in the width of frontal horn of the lateral ventricle (p = 0.955), width of third ventricle (p = 0.129) as well as in the echogenicity of SN (p = 0.942), CN (p = 0.053), LN (p = 0.052) and BR (p = 0.677). Here, it seems that more migraineurs were detected with increased echogenecity of CN and LN compared with controls (33.3% versus 15.0% for CN, 19.0% versus 5.0% for LN) though they had no statistical significance. Patients with hypoechogenic BR had significantly higher HAM-D and HADS-D scores than those with normal BR signal (p = 0.000 for both HAM-D and HADS-D), and most (83.33%) migraineurs with depression exhibited hypoechogenic raphe but none (0.00%) of the migraineurs without depression exhibited hypoechogenic raphe (p = 0.000). CONLUSIONS: TCS signal alteration of BR can be a biomarker for depression in migraine but it is not associated with migraine headache itself. LN and CN alterations in TCS may reflect a potential role of them in the pathogenesis of migraine, which needs to be further elucidated.


Assuntos
Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/patologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/patologia , Núcleos da Rafe/diagnóstico por imagem , Núcleos da Rafe/patologia , Adulto , Estudos de Casos e Controles , Depressão/diagnóstico por imagem , Depressão/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Ultrassonografia Doppler Transcraniana , Adulto Jovem
13.
Phytomedicine ; 62: 152931, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31085375

RESUMO

BACKGROUND: Euphorbia factor L2 has potent effects on ascites, hydropsy and cancers. PURPOSE: We investigated the pharmacological effects of Euphorbia factor L2 (EFL2) on hepatocellular carcinoma (HCC). METHODS: MTT assay was conducted to determine the proliferative activity of EFL2 on Hep G2 and SMMC-7721 cells. Wound-healing assay, colony formation assay, western blotting and quantitative PCR were carried out to examine the cell migration, p-AKT and p-STAT3 signaling. Moreover, we used human tumor xenograft BALB/c nude mice to detect the effect of EFL2 on HCC in vivo. RESULTS: EFL2 inhibited the proliferation of SMMC-7721 and Hep G2 cells in concentration- and time-dependent manners. EFL2 also suppressed the cell migration and colony formation of hepatocellular carcinoma cells. Using a transforming growth factor-ß (TGF-ß)-induced epithelial-mesenchymal transition (EMT) model, we provided evidences that EFL2 could also inhibit TGF-ß induced cell growth, vimentin, N-cadherin expressions, activation of p-AKT and p-STAT3, whereas up-regulate E-cadherin expression. Furthermore, EFL2 inhibited tumor growth and STAT3 phosphorylation in vivo. CONCLUSION: In conclusion, EFL2 has the potential to be explored as a candidate treatment agent for HCC by inhibiting cell growth and migration both in vitro and in vivo.

14.
Zhongguo Zhong Yao Za Zhi ; 44(3): 518-525, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-30989917

RESUMO

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae_ukn. The relative abundance of Desulfovibrio and Streptococcaceae_ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.


Assuntos
Croton/química , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glycyrrhiza/química , Animais , Diuréticos , Interações de Medicamentos , Intestinos , Camundongos , Raízes de Plantas/química , Sementes/química
15.
J Ethnopharmacol ; 236: 136-146, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-30851368

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice and Yuanhua are both famous herbs in Traditional Chinese Medicine (TCM), and their combination is used by some TCM doctors to treat renal and gastrointestinal diseases as well as tumors. On the other hand, the compatibility theory of TCM warns that toxic effects might be triggered by Licorice-Yuanhua combination. The usability of Licorice-Yuanhua combination has long been controversial due to lack of evidence and mechanism illustration. Colonic hydrogen sulfide (H2S) metabolism imbalance is closely related with colonic inflammation, tumor promotion and many other diseases. AIM OF THE STUDY: This study was carried out to investigate if licorice-Yuanhua combination could induce potential toxic effects in the aspect of colonic H2S metabolism. MATERIALS AND METHODS: Normal mice were treated with high or low doses of Licorice, Yuanhua and Licorice-Yuanhua combination. Fecal H2S concentration was measured by colorimetric method, colon sulfomucin production was compared through tissue staining, fecal microbiota and microbial metagenomes were analyzed by 16S rDNA sequencing and data mining. RESULTS: Data shows that although licorice cannot change colonic H2S concentration, it can exacerbate Yuanhua induced H2S rising. Licorice or Yuanhua increases colon sulfomucin production, and their combination further enhances this effect. 16S rDNA sequencing analysis revealed that licorice or Yuanhua has little influence on gut microbiota, however, licorice-Yuanhua combination can impact gut microbiota structural balance and increase the abundance of Desulfovibrio genus and other related genera. Moreover, the combination extensively changes microbial metagenomes, influencing 1172 genes that cannot be changed by individual licorice or Yuanhua. By searching in KEGG database, ten genes are annotated with H2S producing gene, and these genes are remarkably increased by licorice-Yuanhua combination, more significantly than licorice or Yuanhua. CONCLUSIONS: This study provides evidences and mechanisms for licorice induced risks, which is related with colonic H2S metabolism disturbance, gut microbiota and microbial metagenomes. More risk assessment should be evaluated when licorice was used in combination with foods, herbs or drugs. The study provides an example where healthy risks can be induced by combination of food additive, herbs or drugs, through regulating gut microbiota and its metagenomes.


Assuntos
Colo/efeitos dos fármacos , Daphne/química , Medicamentos de Ervas Chinesas/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Glycyrrhiza/química , Sulfeto de Hidrogênio/metabolismo , Animais , Colo/metabolismo , Colo/microbiologia , Desulfovibrio/efeitos dos fármacos , Desulfovibrio/genética , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/isolamento & purificação , Fezes/química , Flores/química , Microbioma Gastrointestinal/genética , Sulfeto de Hidrogênio/análise , Masculino , Medicina Tradicional Chinesa , Metagenoma/genética , Camundongos Endogâmicos ICR , Raízes de Plantas/química
16.
J Ethnopharmacol ; 229: 222-232, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30339979

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: As recorded in traditional Chinese medicine (TCM) theory, Genkwa Flos (YH) and Glycyrrhizae Radix et Rhizoma (GC) compose one herbal pair of the so-called "eighteen incompatible medicaments", which indicate pairs of herbs that are mutually incompatible and that theoretically should not be applied simultaneously. However, the theory has been called into question due to a lack of evidence. AIMS OF STUDY: In this study, the incompatibility of YH and GC was investigated based on an assessment of the toxic effects of their combination by traditional safety methods and a modern metabonomic approach. MATERIALS AND METHODS: Sprague-Dawley rats were used to evaluate the subacute toxicity of YH and YH-GC. The serum, urine, and several tissues were collected for biochemical analysis, histopathological examination, and metabonomic analysis. RESULTS: Rats exposed to a dose of 1.0 g/kg YH (3 times of the Chinese Pharmacopoeia maximum dose) exhibited toxicity of the heart, liver, kidney and testes, and rats exposed to a YH-GC combination (1.0 g/kg YH + 1.0 g/kg GC) exhibited similar hepatotoxicity, which aggravated renal and reproductive toxicity. Following this, a metabonomic study tentatively identified 14 potential biomarkers in the YH group and 10 potential biomarkers in the YH-GC group, and metabolic pathways were then constructed. YH disturbed the pathways of glycerophospholipid metabolism, primary bile acid biosynthesis, and sphingolipid metabolism, while YH-GC combination induced disruptions in phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and glycerophospholipid metabolism. CONCLUSION: The toxicities of YH and YH-GC combination above the Chinese Pharmacopoeia dose were obvious but different. Metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of the YH-GC combination that caused liver, kidney and reproductive injuries in rats.


Assuntos
Daphne , Glycyrrhiza , Extratos Vegetais/farmacologia , Animais , Flores , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metabolômica , Miocárdio/patologia , Ratos Sprague-Dawley , Rizoma , Testículo/efeitos dos fármacos , Testículo/patologia
17.
BMC Ophthalmol ; 18(1): 286, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390645

RESUMO

BACKGROUND: To investigate thickness changes in the corneal epithelium and Bowman's layer after overnight silicone hydrogel contact lens (CL) wear by using ultra-high resolution optical coherence tomography (UHROCT). METHODS: Eleven subjects without CL wearing history were recruited for this study. An UHROCT was used to measure the thickness of the epithelium (ET), Bowman's layer (BT), stroma (ST), and total cornea (CCT) at the center of both eyes. A silicone hydrogel CL was inserted in the right eye of each subject, and the fellow non-CL wearing left eye served as the control. The lens was inserted at 9:30 pm and removed at 8:00 am the next morning. The subjects were evaluated at 9:00 pm (baseline), 9:30 pm (lens insertion), 10:00 pm (before sleep), 7:00 am (waking), 7:30 am, and 8:00 am (lens removal). RESULTS: Compared to the lens insertion level, the ET of the lens-wearing eye increased by 5.73% at eye opening (P = 0.001). The ET of the non-CL wearing eye and the BT in both eyes did not change after overnight CL wear. Compared to baseline, the CCT of the lens-wearing eye increased by 2.87% upon waking (P = 0.003) and recovered 30 min later (P = 0.555). In contrast, compared to baseline, the CCT of the non-CL wearing eye did not increase upon waking (P = 0.105). CONCLUSIONS: By using UHROCT, we found that overnight CL wear induced different swelling responses in the various sublayers of the cornea. TRIAL REGISTRATION: Retrospectively registered. Registration number: ChiCTR1800015115 . Registered 07 March 2018.


Assuntos
Lâmina Limitante Anterior/patologia , Lentes de Contato Hidrofílicas , Edema da Córnea/diagnóstico , Epitélio Anterior/patologia , Silicones , Adulto , Edema da Córnea/etiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica
18.
Front Pharmacol ; 9: 1047, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319404

RESUMO

Chelerythrine (CH), is a kind of benzo[c] phenanthridine alkaloid isolated from plants such as Chelidonium, with pharmacological activities as antitumor, antibiosis and anti-inflammation. However, few studies have demonstrated whether CH could protect against lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the underlying mechanism is also uncertain. The purpose of the present study was to investigate the anti-inflammatory effects of CH on LPS-induced ALI in mice and in RAW264.7 cells. In this study, we demonstrated that treatment with CH significantly ameliorated LPS-induced pathological changes in the lung. CH also attenuated LPS-induced W/D ratio, inflammatory cell infiltration. Meanwhile, LPS-induced Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß) production and oxidative stress were markedly suppressed by CH. Furthermore, western blot showed that CH suppressed LPS-stimulated inflammation of RAW264.7 cells through activation of nuclear factor kappa-B (NF-κB) pathway. Knocking down of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the reduction of nuclear translocation of the NF-κB p65, which triggered inflammation. These experimental results provided evidence that CH could be a potential therapeutic candidate for the intervention of ALI caused by LPS.

19.
J Ophthalmol ; 2018: 2401213, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30225139

RESUMO

Purpose: To investigate the psychometric properties of three commonly used dry eye questionnaires including McMonnies Questionnaire (MQ), the Ocular Surface Disease Index (OSDI), and the Salisbury Eye Evaluation Questionnaire (SEEQ) in Chinese. Methods: This prospective cross-sectional study was conducted at the Eye Hospital of Wenzhou Medical University. Ninety-eight participants completed three questionnaires in a random order. Ophthalmic examinations including tear break-up time, corneal fluorescein staining score, and Schirmer I test were performed. Reliability, validity, and accuracy were assessed for three questionnaires. Results: There were 35 mild-to-moderate dry eye patients, 14 severe dry eye patients, and 49 non-dry eye patients. The Cronbach α of MQ, OSDI, and SEEQ was 0.54, 0.74, and 0.76, respectively, and the intraclass correlation coefficients were 0.91, 0.90, and 0.94, respectively. There were significant differences (P < 0.05) in MQ and OSDI scores among different groups, but there were no statistically significant differences between the mild-to-moderate group and the severe group in terms of SEEQ scores. With cutoff values for abnormal MQ of 15, OSDI of 27.2, and SEED of 1, respectively, good dry eye diagnostic accuracies were obtained. Conclusions: The three questionnaires showed fair accuracy in the diagnosis of dry eye. The cutoff values of OSDI changed when applied to Chinese people.

20.
Biomed Res Int ; 2018: 6762146, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30069475

RESUMO

Glucocorticoids intake is the most common cause of secondary osteoporosis. Clinical studies have shown that 50% patients develop glucocorticoids-induced osteoporosis (GCIOP) after taking glucocorticoids for more than 6 months. Hydroxysafflor yellow A (HYA) is one main active ingredient in Carthamus tinctorius L. Previous studies have shown that HYA promoted bone marrow mesenchymal stem cells to differentiate into osteoblasts which promoted bone formation. Therefore, we speculated that HYA has a therapeutic effect on GCIOP. However, there is no in vivo evidence about the anti-GCIOP effect of HYA. In this paper, the effect of HYA (0.1, 1.0, and 10.0 µM) on bone formation in normal zebrafish was investigated firstly. Secondly, the reversal effect of HYA on GCIOP was also evaluated by zebrafish model. It is demonstrated that HYA not only promoted bone formation in normal zebrafish (compared to Control group), but also reversed glucocorticoid induced bone loss (compared to Prednisolone group) according to the intervention of HYA in upregulating the area of mineralized bones (p < 0.01), increasing cumulative optical density (p < 0.01), promoting bone formation related gene expression (AKP, Type I, Runx2, OPG, and OCN, p < 0.01), inhibiting bone resorption related gene expression (TRACP, p < 0.01), and elevating whole-body trace mineral elements (Ca, P, K, Mg, Zn, and Fe) levels (p < 0.01). In conclusion, HYA had the potential to prevent and heal GCIOP by promoting bone mineralization, osteoblasts viability, and bone collagen expression and inhibiting bone resorption.


Assuntos
Reabsorção Óssea/tratamento farmacológico , Chalcona/análogos & derivados , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Quinonas/farmacologia , Animais , Densidade Óssea , Osso e Ossos , Calcificação Fisiológica/efeitos dos fármacos , Chalcona/farmacologia , Humanos , Osteoblastos/fisiologia , Peixe-Zebra
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