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1.
J Lipid Res ; 65(2): 100499, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38218337

RESUMO

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.


Assuntos
Aterosclerose , Cicloexilaminas , Ferroptose , Fenilenodiaminas , Animais , Camundongos , Humanos , Fosfolipídeos , Fosforilcolina , Éteres Fosfolipídicos/metabolismo , Éteres Fosfolipídicos/farmacologia , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Proteína 3 Ligante de Ácido Graxo
2.
Zhongguo Zhong Yao Za Zhi ; 49(1): 88-99, 2024 Jan.
Artigo em Zh | MEDLINE | ID: mdl-38403342

RESUMO

Anemarrhena asphodeloides is a common medicinal material used in clinical prescriptions and Chinese patent medicine. In this study, the Illumina platform was used to obtain the chloroplast genome sequences of seven kinds of A. asphodeloides from different areas. The specific DNA barcodes were screened by comparative genomics analysis, and the DNA barcodes were used to identify the germplasm resources and analyze the genetic diversity of A. asphodeloides samples from different areas in China. All the seven chloroplast genomes had a ring structure. The total length was 156 801-156 930 bp, and 113 genes were annotated, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The comparative genomics analysis showed that rps16, trnG-GCC, atpF, rpoB, ycf3, rpl16, ndhF, trnS-GCU_trnG-GCC, petN-psbM, and ndhF-rpl32 were potential candidates for specific DNA barcodes of A. asphodeloides. In this study, the second intron of ycf3 and atpF intron sequences with a sequence length of 700-800 bp and easy amplification were selected for polymerase chain reaction(PCR) amplification and sequencing of 594 samples from 26 areas. The sequence analysis showed that six and eight haplotypes of ycf3 and atpF sequences could be identified, respectively, and 17 haplotypes could be identified by combined analysis of the two sequences, which were named Hap1-Hap17. The haplotype diversity(H_d), nucleotide diversity(P_i), and genetic distance of A. asphodeloides in 26 populations were 0.68, 0.93×10~(-3), and 0-0.003 1, respectively, indicating that the genetic diversity within the species of A. asphodeloides is rich. The intermediary adjacent network analysis showed that Hap5 was the oldest haplotype, which was mainly distributed in Yixian county of Baoding, Hebei province, Hequ county of Xinzhou, Shanxi province, and Xiangfen county of Linfen, Shanxi province. This study has important guiding significance for the identification of A. asphodeloides species, the protection and development of germplasm resources, and the identification of production areas, and it provides a research basis for further revealing the genetic evolution law of A. asphodeloides.


Assuntos
Anemarrhena , Anemarrhena/química , Código de Barras de DNA Taxonômico , Variação Genética , China , Filogenia
3.
Zhongguo Zhong Yao Za Zhi ; 46(1): 171-176, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33645067

RESUMO

The aim of this paper was to study the effect and mechanism of fucoxanthin on insulin resistance of obese mice induced by high-fat diet. Fifty C57 BL/6 J male mice were randomly divided into control group and high-fat diet group. The insulin resistance model was induced with high-fat diet for 12 weeks, and model mice were randomly divided into model group, fucoxanthin-0.2% group, fucoxanthin-0.4% group and metformin group. After dietary treatment for 6 weeks, the body weight and epididymal fat weight in each group were measured. Fasting blood glucose(FBG), fasting insulin(FINS), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) were measured, and insulin resistance index(HOMA-IR) was calcula-ted. The pathological morphology in liver was observed by hematoxylin eosin staining, and the expressions of some key proteins in insulin receptor substrate 1(IRS-1)/posphoinositide 3-kinase(PI3 K)/serine-threonine kinase(Akt) and peroxisome proliferators-activated receptor-γ(PPARγ)/sterol regulatory element binding protein-1(SREBP-1)/fatty acid synthetase(FAS) pathways in liver were detected by Western blot. According to the findings, compared with the model group, levels of body weight, epididymal fat weight, FBG, FINS, TC, TG, LDL-C and HOMA-IR, as well as protein expressions of PPARγ, SREBP-1 and FAS in liver were significantly reduced(P<0.05 or P<0.01), while level of HDL-C and protein expressions of p-IRS-1, IRS-1, PI3 K and p-Akt in liver were signi-ficantly increased after treatment with fucoxanthin(P<0.05 or P<0.01). And the pathological changes of liver tissue in fucoxanthin-treated mice were also improved obviously. The results showed that fucoxanthin could improve obesity, hyperglycemia and hyperlipidemia, and alleviate insulin resistance in obese mice, and its mechanism is possibly related to the regulation of IRS-1/PI3 K/Akt and PPARγ/SREBP-1/FAS pathways.


Assuntos
Resistência à Insulina , Animais , Dieta Hiperlipídica/efeitos adversos , Insulina , Fígado , Masculino , Camundongos , Camundongos Obesos , Xantofilas
4.
Am J Nephrol ; 51(11): 907-918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152735

RESUMO

BACKGROUND: Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. METHOD: Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. RESULTS: Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (p < 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (p < 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (r = 0.748, p < 0.001; r = 0.899, p < 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74-0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3-2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. CONCLUSIONS: Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.


Assuntos
Rim/patologia , Proteína-Lisina 6-Oxidase/sangue , Insuficiência Renal Crônica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biópsia , Estudos de Casos e Controles , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Valores de Referência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Índice de Gravidade de Doença , Adulto Jovem
5.
FASEB J ; 33(3): 4404-4417, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30576233

RESUMO

Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting ß-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aß formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aß formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.-Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Hipocampo/metabolismo , MicroRNAs/fisiologia , Regiões 3' não Traduzidas , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/biossíntese , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/biossíntese , Ácido Aspártico Endopeptidases/genética , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Inflamação , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/genética , Transtornos da Memória/prevenção & controle , Camundongos , Camundongos Transgênicos , MicroRNAs/biossíntese , MicroRNAs/genética , NF-kappa B/fisiologia , Plasticidade Neuronal , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Cultura Primária de Células , Proteínas Recombinantes/metabolismo
6.
J Nat Prod ; 83(2): 362-373, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32031812

RESUMO

Eight new dammarane-type triterpenoids (1-8), together with a related known analogue (9), were isolated from the roots of Rhus chinensis, a traditional Chinese medicine for treating coronary artery heart disease, guided by LC-MS analysis. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Notably, compounds 1-7 and 9 possess an unusual 17α-side chain, and 1-4, 6, and 9 contain an uncommon 3-methyl-5,6-dihydro-2H-pyran-2-one moiety in the side chain. Compounds 1-5 and 9 have a 3,19-hemiketal bridge in the A ring. In an in vivo bioassay, 1, 2, and 4-6 exhibited significant preventive effects on zebrafish heart failure at 0.5 µg/mL, improving heart dilatation, venous congestion, cardiac output, blood flow velocity, and heart rate. Compound 5, displaying the most promising heart failure preventive activities, showed even better effects on increasing cardiac output (72%) and blood flow velocity (83%) than six first-line heart failure therapeutic drugs. Moreover, 1, 2, and 6 prevented the formation of thrombosis in zebrafish at 0.5 µg/mL. The present investigation suggests that the new dammarane triterpenoids might be partially responsible for the utility of R. chinensis in treating coronary artery heart disease.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Rhus/química , Trombose/tratamento farmacológico , Triterpenos/química , Animais , Estrutura Molecular , Raízes de Plantas/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Peixe-Zebra/fisiologia , Damaranos
7.
J Adv Nurs ; 76(6): 1416-1424, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32108382

RESUMO

AIMS: To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis. BACKGROUND: In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported. DESIGN: A Randomized, Double-Blind, Active-Controlled Trial. METHODS: The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein. RESULTS: Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment. CONCLUSION: Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate. IMPACT: Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Gotosa/tratamento farmacológico , Diclofenaco/uso terapêutico , Dietilaminas/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Supressores da Gota/uso terapêutico , Administração Cutânea , Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , China , Diclofenaco/administração & dosagem , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Supressores da Gota/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Fitoterapia , Distribuição Aleatória
8.
BMC Med Educ ; 20(1): 323, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962664

RESUMO

BACKGROUND: Anxiety and depression have been increasing among Chinese medical students. The psychological well-being of Chinese medical students has become a critical focus of attention for the medical education community. Increasing evidence shows that positive psychology interventions can be effective in the enhancement of psychological well-being, and may help to prevent depressive symptoms in university students. In the present study, we aimed to explore the potential effect of positive psychology education on improving the mental health of Chinese medical students. METHODS: An 8-week classroom-based positive psychology intervention workshop, which was established as an elective course embedded in the regular school curriculum, was conducted at the School of Medicine, South China University of Technology (SCUT), China. Undergraduate medical students of the institute in year-2 or year-3 of academic study participated in this training course voluntarily. The participants' self-reported data on the hope scale, life satisfaction scale, subjective happiness scale, and depression and anxiety scale were collected and analyzed at pre-course (n = 61) and post-course (n = 49) times. The investigation was also validated with an independent cohort of students who enrolled in the course in the year following the preliminary study. RESULTS: The analyses showed that the psychological well-being of the participants were improved after the intervention. Their mean scores on the hope scale, life satisfaction scale and subjective happiness scale were significantly improved (P < 0.05), while their symptom levels of depression and anxiety were significantly reduced (P < 0.01). A similar trend was observed in the validation cohort. CONCLUSIONS: These preliminary findings suggest that positive psychology education holds promise for improving psychological well-being among Chinese medical students. Further investigations with larger and well-controlled sample cohorts may yield more convincing and reliable results.


Assuntos
Estudantes de Medicina , China , Humanos , Projetos Piloto , Psicologia Positiva , Estresse Psicológico
9.
Hum Mol Genet ; 26(16): 3202-3211, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28575308

RESUMO

The functional architecture of the human brain is greatly determined by the temporal and spatial regulation of the transcription process. However, the spatial and temporal transcriptional landscape of long non-coding RNAs (lncRNAs) during human brain development remains poorly understood. Here, we report the genome-wide lncRNA transcriptional analysis in an extensive series of 1340 post-mortem human brain specimens collected from 16 regions spanning the period from early embryo development to late adulthood. We discovered that lncRNA transcriptome dramatically changed during fetal development, while transited to a surprisingly relatively stable state after birth till the late adulthood. We also discovered that the transcription map of lncRNAs was spatially different, and that this spatial difference was developmentally regulated. Of the 16 brain regions explored (cerebellar cortex, thalamus, striatum, amygdala, hippocampus and 11 neocortex areas), cerebellar cortex showed the most distinct lncRNA expression features from all remaining brain regions throughout the whole developmental period, reflecting its unique developmental and functional features. Furthermore, by characterizing the functional modules and cellular processes of the spatial-temporal dynamic lncRNAs, we found that they were significantly associated with the RNA processing, neuron differentiation and synaptic signal transportation processes. Furthermore, we found that many lncRNAs associated with the neurodegenerative Alzheimer and Parkinson diseases were co-expressed in the fetal development of the human brain, and affected the convergent biological processes. In summary, our study provides a comprehensive map for lncRNA transcription dynamics in human brain development, which might shed light on the understanding of the molecular underpinnings of human brain function and disease.


Assuntos
Encéfalo/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Autopsia , Encéfalo/metabolismo , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica , Genoma Humano , Humanos , Elementos Reguladores de Transcrição , Análise Espaço-Temporal , Transcriptoma
10.
Int J Neuropsychopharmacol ; 22(9): 574-584, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125405

RESUMO

BACKGROUND: The hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In this study, we evaluated the motivation for drug seeking in cocaine self-administering rats exposed to an escalated dosing regimen that endeavored to mimic the characteristic of escalating drug intake in human addicts. Tropisetron is a 5-HT3 receptor antagonist and α7-nicotinic receptor partial agonist. Utilizing rats trained on the escalated-dosing regimen, we examined the effects of tropisetron on control over compulsive drug-seeking behavior that was defined as footshock-resistant lever pressing. METHODS: Rats were trained to self-administer cocaine with incremental-infusion doses (from 0.6 to 2.4 mg/kg/infusion) across training sessions (3 h/session) or with a long-access paradigm (i.e., 0.6 mg/kg/infusion, 6 h/d training session). The drug-seeking motivations of 2 groups were estimated by the patterns of drug intake and progressive-ratio schedule. The compulsivity for drug seeking of the group with an escalated dose was further evaluated using the footshock-associated seeking-taking chain task. RESULTS: The rats trained on the dose-escalated protocol achieved the same levels of motivated drug seeking as those subjected to a long-access paradigm, as indicated by cocaine intake per training session and breakpoints on a progressive ratio schedule. Tropisetron attenuated compulsive behavior of rats when pressing of the seeking lever potentially led to footshock. Intriguingly, tropisetron did not change the motivation to seek cocaine when footshock was absent. Tropisetron had no effect on locomotor activities or saccharin self-administration. CONCLUSIONS: These results demonstrate that tropisetron restored control over compulsive cocaine seeking, and they indicate that 5-HT3/α7-nicotinic receptors may be potential therapeutic targets for relieving compulsive drug seeking.


Assuntos
Cocaína/antagonistas & inibidores , Comportamento de Procura de Droga/efeitos dos fármacos , Tropizetrona/farmacologia , Animais , Cocaína/farmacologia , Relação Dose-Resposta a Droga , Eletrochoque , Masculino , Ratos , Esquema de Reforço , Autoadministração
11.
Soft Matter ; 15(33): 6615-6625, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31406972

RESUMO

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

12.
Med Sci Monit ; 25: 1671-1678, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30830898

RESUMO

BACKGROUND Diabetic nephropathy (DN), which is one of the primary causes of end-stage renal disease (ESRD), is increasingly diagnosed in patients due to the continuous increase in the prevalence of diabetic mellitus (DM). Astragali Radix, a traditional Chinese herb, is widely administrated to ameliorate the symptoms of diabetes and diabetic nephropathy, but its mechanism is still not yet fully defined. Calycosin (C16H12O5) is the major active component of Astragali Radix. In this study, we analyzed the role of calycosin in diabetic nephropathy and explored its underlying mechanism. MATERIAL AND METHODS Cell activation, inflammatory cytokines expression and secretion, and protein levels were analyzed in cultured mouse tubular epithelial cells (mTEC). db/db mice were intraperitoneally injected with 10 mg/(kg·d) calycosin or control saline for 4 weeks, followed by analysis of structure injury, inflammation, and NF-κB signaling activity. RESULTS Our results indicated that TNF-α and IL-1ß were significantly induced by advanced glycation end-products (AGEs), but calycosin remarkably reduced the expression of TNF-α and IL-1ß in the cultured mouse tubular epithelial cells (mTEC). Calycosin effectively alleviated kidney injury in diabetic kidneys of db/db mice during the progression of diabetic renal injury, indicated by the reduction of histological injury and immunohistochemical of inflammatory cytokines. Mechanistically, we identified calycosin inhibited diabetes-induced inflammation in kidneys by suppressing the phosphorylation of IKBa and NF-κB p65 in vitro and in vivo. CONCLUSIONS Calycosin significantly ameliorated diabetes-induced renal inflammation in diabetic renal injury by inhibition of the NF-κB-dependent signaling pathway in vivo and in vitro.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Isoflavonas/farmacologia , Animais , Astragalus propinquus , Técnicas de Cultura de Células , Citocinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Células Epiteliais , Inflamação/tratamento farmacológico , Interleucina-1beta/efeitos dos fármacos , Isoflavonas/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Nefrite/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos
13.
Cell Physiol Biochem ; 40(5): 933-943, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27941340

RESUMO

BACKGROUND/AIMS: Salvianolic acid B (Sal B), a major polyphenolic compound of Salvia miltiorrhiza Bunge, has been shown to possess potential antidiabetic activities. However, the action mechanism of SalB in type 2 diabetes has not been investigated extensively. The present study was designed to investigate the effects of Sal B on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as its potential molecular mechanism. METHODS: Male C57BL/KsJ-db/db mice were orally treated with Sal B (50 and 100 mg/kg) or metformin (positive drug, 300 mg/kg) for 6 weeks. RESULTS: Both doses of Sal B significantly decreased fasting blood glucose, serum insulin, triglyceride and free fatty acid levels, reduced hepatic gluconeogenic gene expression and improved insulin intolerance in db/db mice. High dose Sal B also significantly improved glucose intolerance, increased hepatic glycolytic gene expression and muscle glycogen content, and ameliorated histopathological alterations of pancreas, similar to metformin. Sal B treatment resulted in increased phosphorylated AMP-activated protein kinase (p-AMPK) protein expression in skeletal muscle and liver, increased glucose transporter 4 (GLUT4) and glycogen synthase protein expressions in skeletal muscle, and increased peroxisome proliferator-activated receptor alpha (PPARα) and phosphorylated acetyl CoA carboxylase (p-ACC) protein expressions in liver. CONCLUSION: Our data suggest that Sal B displays beneficial effects in the prevention and treatment of type 2 diabetes at least in part via modulation of the AMPK pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Benzofuranos/uso terapêutico , Dislipidemias/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Transdução de Sinais , Animais , Benzofuranos/química , Benzofuranos/farmacologia , Peso Corporal/efeitos dos fármacos , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Glucose/metabolismo , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/genética , Transportador de Glucose Tipo 4/metabolismo , Glicogênio/metabolismo , Glicogênio Sintase/metabolismo , Glicólise/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/genética , Hiperinsulinismo/sangue , Hiperinsulinismo/complicações , Hiperinsulinismo/tratamento farmacológico , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , PPAR alfa/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(7): 625-9, 2016 Jul.
Artigo em Zh | MEDLINE | ID: mdl-27412546

RESUMO

OBJECTIVE: To investigate the presence of Cosmc gene mutation in children with Henoch-Schönlein purpura (HSP) and the association between Cosmc gene mutation and the susceptibility to HSP. MESULTS: Eighty-four children who were diagnosed with HSP between March 2014 and December 2015 were selected as the HSP group. Fifty-eight healthy volunteers matched for age and sex were enrolled as the control group. Fasting venous blood (5 mL) from the two groups was collected in EDTA anticoagulated tubes, followed by the isolation of peripheral blood mononuclear cells (PBMCs) through density gradient centrifugation. Genomic DNA was extracted from PBMCs according to the manufacturer's protocol, and the whole exon region of Cosmc gene was amplified by touch-down polymerase chain reaction (touch-down PCR). The PCR products were identified by 1% agarose gel and sequenced in order to further examine the association between Cosmc gene mutation and the susceptibility to HSP. RESULTS: Sequencing results showed two mutations (c.393T>A and c.72A>G) of Cosmc gene in children with HSP. There were no significant differences in the genotype and allele frequencies at the two loci between the HSP and control groups, and this distribution was not associated with sex. CONCLUSIONS: The mutations c.393T>A and c.72A>G in the exon region of Cosmc gene in children with HSP are not associated with the onset of HSP.


Assuntos
Predisposição Genética para Doença , Vasculite por IgA/genética , Chaperonas Moleculares/genética , Mutação , Criança , Pré-Escolar , Feminino , Humanos , Vasculite por IgA/etiologia , Masculino
15.
J Neurooncol ; 125(2): 253-63, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26337623

RESUMO

Isocitrate dehydrogenase 1 (IDH1) mutation is an important prognostic marker in glioma. However, its downstream effect remains incompletely understood. Long non-coding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis in a number of human malignancies, including glioma. Here, we investigated whether and how lncRNA expression profiles would differ between gliomas with or without IDH1 mutation. By using our previously reported lncRNA mining approach, we performed lncRNA profiling in three public glioma microarray datasets. The differential lncRNA expression analysis was then conducted between mutant-type and wild-type IDH1 glioma samples. Comparison analysis identified 14 and 9 lncRNA probe sets that showed significantly altered expressions in astrocytic and oligodendroglial tumors, respectively (fold change ≥ 1.5, false discovery rate ≤ 0.1). Moreover, the differential expressions of these lncRNAs could be confirmed in the independent testing sets. Functional exploration of the lncRNAs by analyzing the lncRNA-protein interactions revealed that these IDH1 mutation-associated lncRNAs were involved in multiple tumor-associated cellular processes, including metabolism, cell growth and apoptosis. Our data suggest the potential roles of lncRNA in gliomagenesis, and may help to understand the pathogenesis of gliomas associated with IDH1 mutation.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação/genética , RNA Longo não Codificante/genética , Neoplasias Encefálicas/mortalidade , Bases de Dados Genéticas/estatística & dados numéricos , Feminino , Perfilação da Expressão Gênica , Glioma/metabolismo , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Estatísticas não Paramétricas , Análise de Sobrevida
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 46(5): 732-5, 2015 Sep.
Artigo em Zh | MEDLINE | ID: mdl-26619545

RESUMO

OBJECTIVE: To test the validity of Caprini risk assessment scale in identifying hospitalized critically ill patients with high venous thromboepbolism (VTE) risks. METHODS: A case-control study was conducted, with 78 VTE patients who were admitted to the ICU of Sichuan Provincial People's Hospital from February 2008 to June 2014 in the case group, and a randomly selected group of 156 non-VTE patients who were-admitted during the same period serving as controls. The medical history, laboratory tests and other related clinical data of the participants. were retrieved. Their VTE risks were assessed using the Caprini risk assessment scale. Multivariate logistic regression analysis was performed to establish the association between Caprini VTE risk classification and the presence of VTE. RESULTS: VTE patients had a Caprini score of 8. 7±3. 5, higher than that of the controls (4. 2 ± 2. 6). More than 88. 4% of VTE ill patients were rated as having "high or very high" risk of VTE by Caprini rating scale, significantly higher than the percentage in the controls (P<0. 001). The logistic regression model identified eight risk factors in the Caprini scale as predictors of VTE: bed-bound in internal medicine wards, severe lung disease (<1 month), sepsis (<1 month), large operation (<1 month), malignant tumor (past or prevalence), deep venous thrombosis (DVT)/pulmonary thromboembolism (PTE) history, family history, and thrombosis'of multiple trauma (<1 month). The odds ratio of VTE in patients with a high and very high risk as identified by Caprini scale was 2. 042 and 11. 681, respectively, compared with those with a low risk. Conclusion Caprini risk assessment scale can predict the risk of VTE in hospitalized critically ill patients.


Assuntos
Estado Terminal , Medição de Risco , Tromboembolia Venosa/diagnóstico , Estudos de Casos e Controles , Hospitalização , Humanos , Estudos Retrospectivos , Fatores de Risco
17.
Biol Pharm Bull ; 37(7): 1253-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24805208

RESUMO

Wild or cultivated Glycyrrhiza uralensis FISCHER (G. uralensis) are the main source of licorice, and they contain the similar compounds, such as the triterpenoid saponins and flavonoids, but above two kinds of the components contents are low level in the cultivated licorice. To produce the high quality cultivated licorices, researchers studied the affecting factors about the compounds producing in the plant of licorice, and then found that the growth years, genetic differences and water deficit are all the important factors. In this paper, we found that there were different distribution patterns of the main five active components (FAC) including glycyrrhizin, liquiritin, isoliquiritin, liquiritigenin and isoliquiritigenin in the taproot and stolon of G. uralensis and maybe they are also important influence factors to the FAC contents of the licorices. In wild G. uralensis, the contents of FAC tended to be lower in the younger parts of the stolon, and in the cultivated G. uralensis taproot, the contents of glycyrrhizin, liquiritin and isoliquiritin tended to increase from top to end, contrary to the contents of liquiritigenin and isoliquiritigenin, which increased first and then decreased. Our results will contribute to the analyses of factors which influence the quality of licorice, and provide some reference for cultivating high quality licorices for herbal medicine.


Assuntos
Flavanonas/isolamento & purificação , Glucosídeos/isolamento & purificação , Glycyrrhiza uralensis/química , Ácido Glicirrízico/isolamento & purificação , Raízes de Plantas/química , Brotos de Planta/química , Cromatografia Líquida de Alta Pressão , Flavanonas/química , Glucosídeos/química , Glycyrrhiza uralensis/genética , Glycyrrhiza uralensis/crescimento & desenvolvimento , Ácido Glicirrízico/química , Isomerismo , Limite de Detecção , Estrutura Molecular , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Especificidade da Espécie
18.
Brain Inj ; 28(12): 1594-601, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25093611

RESUMO

BACKGROUND: Dexamethasone (DEXA) is commonly used to reduce brain swelling during neurosurgical procedures. DEXA, however, has many side-effects that can increase the risks of post-operative complications. In contrast, progesterone (PRO) has fewer side-effects and has been found to be neuroprotective on traumatic brain injury (TBI). Whether PRO may be used as an alternative to DEXA during routine procedures has not been fully explored. OBJECT: To compare the effects of DEXA and PRO on surgical brain injury (SBI). METHODS: Seventy-five adult male Sprague Dawley rats were randomized into five groups: (1) SBI + drug vehicle (peanut oil, 1 ml kg(-1)); (2) SBI + DEXA (1 mg kg(-1)); (3) SBI + low-dose PRO (10 mg kg(-1)); (4) SBI + high-dose PRO (20 mg kg(-1)); and (5) sham SBI + drug vehicle. Magnetic resonance imaging study and assessments of brain water content (BWC), blood-brain barrier (BBB) permeability, cellular inflammatory responses and matrix metalloproteinase 9 (MMP-9) expression were conducted. RESULTS: This model consistently resulted in increased BWC and BBB disruption. PRO reduced astrocyte and microglia responses and attenuated brain oedema with preservation of BBB. A significant down-regulation of MMP-9 expression occurred in the PRO 20 group. CONCLUSIONS: PRO is as effective as DEXA in reducing brain oedema and inflammation following SBI; 10 mg kg(-1) of PRO was demonstrated to be more effective in relieving acute cellular inflammatory responses.


Assuntos
Edema Encefálico/metabolismo , Lesões Encefálicas/metabolismo , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Inflamação/metabolismo , Procedimentos Neurocirúrgicos/efeitos adversos , Progesterona/farmacologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Western Blotting , Edema Encefálico/tratamento farmacológico , Edema Encefálico/imunologia , Lesões Encefálicas/imunologia , Lesões Encefálicas/cirurgia , Modelos Animais de Doenças , Regulação para Baixo , Inflamação/tratamento farmacológico , Masculino , Inibidores de Metaloproteinases de Matriz , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(5): 541-5, 2014 09.
Artigo em Zh | MEDLINE | ID: mdl-25372638

RESUMO

OBJECTIVE: To investigate the changes of plasma gelsolin level in patients with critical illness and its application in prognostic evaluation. METHODS: Ninety six critically ill patients admitted in ICU of Sichuan Provincial People's Hospital from February 2012 to December 2013 were enrolled in the prospective cohort study. Plasma gelsolin levels were detected with enzyme linked immunosorbent assay (ELISA) at admission (d1), d2, d4 and d8 after admission, and also detected in blood samples of 186 healthy subjects as controls. Logistic regression model was used to analyze the relationship between the level of plasma gelsolin and prognosis of patients. RESULTS: The average levels of plasma gelsolin were significantly lower in critically ill patients than those in control subjects (F=1986.37, P<0.01). There was significant difference in overall level of gelsolin between survival patients and fatal patients (F=16.691, P<0.01). APACHE Ⅱ score was associated with survival outcomes (r=0.489, P=0.009); the APACHE Ⅱ score was significantly higher in fatal patients than that in survival patients (29.5±7.7 vs 22.1±5.7, t=5.375, P<0.01). There was a negative correlation between plasma gelsolin levels and fatal outcomes (r=-0.512, P<0.01). Logistic regression analysis showed that the overall plasma gelsolin levels and the last measured level was a prognostic factor for critically ill patients (P<0.05). CONCLUSION: Plasma gelsolin levels are correlated with the severity of critically ill patients, and plasma gelsolin can be used as indicator of prognosis.


Assuntos
Estado Terminal , Gelsolina/sangue , APACHE , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Modelos Logísticos , Plasma , Prognóstico , Estudos Prospectivos
20.
Zhongguo Zhong Yao Za Zhi ; 39(7): 1326-8, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25011278

RESUMO

The acquisition and storage of the image data are important in the Chinese medicine resources survey, and it is important data and evidence for the process and the results. The image data of the Chinese medicinal materials' habitat, original plant or animal, processing in habitat, commodity form, the relative contents and workshop scenarios in the investigation are important for the compiling of the Color Atlas of National Chinese Medicine Resources, mapping the digital scattergram of the Chinese medicine resources, establishing the digital Chinese medicine plant herbarium and acquiring the documentary of the Chinese medicine resource survey. The content, procedures and methods of the video data collecting have been related and analyzed in this article to provide reference for the Chinese medicine resources survey.


Assuntos
Conservação dos Recursos Naturais , Medicamentos de Ervas Chinesas/análise , Armazenamento e Recuperação da Informação/métodos , Plantas Medicinais/química , Bases de Dados Factuais , Ecossistema , Fotografação , Plantas Medicinais/crescimento & desenvolvimento
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