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1.
J Neuroinflammation ; 21(1): 81, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566081

RESUMO

BACKGROUND: Senescent astrocytes play crucial roles in age-associated neurodegenerative diseases, including Parkinson's disease (PD). Metformin, a drug widely used for treating diabetes, exerts longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and 1-methyl-4-phenylpyridinium/α-synuclein aggregate-induced premature senescence model, and a mouse model of PD were used to investigate the effect of metformin on astrocyte senescence in vivo and in vitro. Immunofluorescence staining and flow cytometric analyses were performed to evaluate the mitochondrial function. We stereotactically injected AAV carrying GFAP-promoter-cGAS-shRNA to mouse substantia nigra pars compacta regions to specifically reduce astrocytic cGAS expression to clarify the potential molecular mechanism by which metformin inhibited the astrocyte senescence in PD. RESULTS: We showed that metformin inhibited the astrocyte senescence in vitro and in PD mice. Mechanistically, metformin normalized mitochondrial function to reduce mitochondrial DNA release through mitofusin 2 (Mfn2), leading to inactivation of cGAS-STING, which delayed astrocyte senescence and prevented neurodegeneration. Mfn2 overexpression in astrocytes reversed the inhibitory role of metformin in cGAS-STING activation and astrocyte senescence. More importantly, metformin ameliorated dopamine neuron injury and behavioral deficits in mice by reducing the accumulation of senescent astrocytes via inhibition of astrocytic cGAS activation. Deletion of astrocytic cGAS abolished the suppressive effects of metformin on astrocyte senescence and neurodegeneration. CONCLUSIONS: This work reveals that metformin delays astrocyte senescence via inhibiting astrocytic Mfn2-cGAS activation and suggest that metformin is a promising therapeutic agent for age-associated neurodegenerative diseases.


Assuntos
Metformina , Doença de Parkinson , Camundongos , Animais , Doença de Parkinson/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Astrócitos/metabolismo , Neurônios Dopaminérgicos , Nucleotidiltransferases/metabolismo , Mitocôndrias/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , GTP Fosfo-Hidrolases/farmacologia
2.
Cell Mol Biol (Noisy-le-grand) ; 69(13): 102-105, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38158681

RESUMO

The objective of this study was to analyze the effect of curcumin (Cur) on pulmonary fibrosis (PF), so as to provide new clinical evidence for future PF treatment. To achieve these goals, the researchers set up bought human lung fibroblasts MRC-5 as a control group without treatment, a model group for PF cell modeling, and an intervention group for Cur intervention after PF modeling. Cell proliferation capacity and cellular TGF-ß1, α-SMA, Collagen I, Collagen III, Bax, N-cadherin and E-cadherin protein expression were determined. The results show that markedly enhanced cell proliferation capacity and TGF-ß1, α-SMA, Collagen I and Collagen III protein levels were observed in the model group, while the cell activity and fibrosis degree in the intervention group were significantly decreased compared with the model group (P<0.05). In addition, the intervention group exhibited lower N-cadherin and Bax with higher E-cadherin than the model group (P<0.05). In addition, the team found that the inflammatory response and oxidative stress were also more significantly improved in the intervention group (P<0.05). These experimental results tell us that Cur can ameliorate the fibrotic process of PF by inhibiting the activity of MRC-5.


Assuntos
Curcumina , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/metabolismo , Proteína X Associada a bcl-2/metabolismo , Fibrose , Pulmão/patologia , Colágeno/metabolismo , Fibroblastos/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacologia , Colágeno Tipo I/uso terapêutico , Caderinas/metabolismo
3.
J Environ Manage ; 330: 117178, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621315

RESUMO

Soil nitrification driven by ammonia-oxidizing microorganisms is the most important source of nitrous oxide (N2O) and nitric oxide (NO). Biochar amendment has been proposed as the most promising measure for combating climate warming; both have the potential to regulate the soil nitrification process. However, the comprehensive impacts of different aged biochars and warming combinations on soil nitrification-related N2O and NO production are not well understood. Here, 1-octyne and acetylene were used to investigate the relative contributions of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to potential nitrification-mediated N2O and NO production from the fertilized vegetable soil with different aged biochar amendments and soil temperatures in microcosm incubations. Results demonstrated that AOB dominated nitrification-related N2O and NO production across biochar additions and climate warming. Biochar amendment did not significantly influence the relative contribution of AOB and AOA to N2O and NO production. Field-aged biochar markedly reduced N2O and NO production via inhibiting AOB-amoA gene abundance and AOB-dependent N2O yield while fresh- and lab-aged biochar produced negligible effects on AOB-dependent N2O yield. Climate warming significantly increased N2O production and AOB-dependent N2O yield but less so on NO production. Notably, the relative contribution of AOB to N2O production was enhanced by climate warming, whereas AOB-derived NO showed the opposite tendency. Overall, the results revealed that field-aged biochar contributed to mitigating warming-induced increases in N2O and NO production via inhibiting AOB-amoA gene abundance and AOB-dependent N2O yield. Our findings provided guidance for mitigating nitrogen oxide emissions in intensively managed vegetable production under the context of biochar amendments and climate warming.


Assuntos
Óxido Nítrico , Verduras , Nitrificação , Amônia , Microbiologia do Solo , Archaea , Óxido Nitroso/análise , Solo , Oxirredução
4.
Biochem Biophys Res Commun ; 557: 69-76, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33862462

RESUMO

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 µg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of ß-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific ß-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a ß-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.


Assuntos
Ciclina D1/metabolismo , Regeneração Hepática , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Remifentanil/farmacologia , Traumatismo por Reperfusão/terapia , beta-Arrestina 2/metabolismo , Analgésicos Opioides/farmacologia , Animais , Proliferação de Células/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Hepatectomia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Regulação para Cima
5.
Bioprocess Biosyst Eng ; 44(11): 2303-2313, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34296328

RESUMO

Agaricus bitorquis (Quél.) Sacc. Chaidam (ABSC) is a wild edible fungus uniquely found in the Tibet Plateau. ABSC is rich in polysaccharides that are considered biologically active. This study aimed to determine the feasibility of enhancing exopolysaccharide (EPS) production by ABSC in shake flask culture by supplementing the fermentation medium with anthocyanin extract. Different concentrations of Lycium ruthenicum Murr. (LRM) anthocyanin crude extract were tested on ABSC fermentation. The activity of phosphoglucose isomerase (PGI), phosphoglucose mutase (PGM), and phosphomannose isomerase (PMI), enzymes presumably involved in EPS synthesis by ABSC, was determined. ABSC transcriptomic profile in response to the presence of anthocyanins during fermentation was also investigated. LRM anthocyanin crude extract (0.06 mg/mL) was most effective in increasing EPS content and mycelial biomass (by 208.10% and 105.30%, respectively, P < 0.01). The activity of PGI, PGM, and PMI was increased in a medium where LRM anthocyanin extract and its main components (proanthocyanidins and petunia anthocyanin) were added. RNA-Seq analysis showed that 349 genes of ABSC were differentially expressed during fermentation in the medium containing anthocyanin extract of LRM; 93 genes were up-regulated and 256 genes down-regulated. From gene ontology enrichment analysis, differentially expressed genes were mostly assigned to carbohydrate metabolism and signal transduction categories. Collectively, LRM anthocyanins extract positively affected EPS production and mycelial biomass during ABSC fermentation. Our study provides a novel strategy for improving EPS production and mycelial growth during ABSC liquid submerged fermentation.


Assuntos
Agaricus/metabolismo , Fermentação , Polissacarídeos Fúngicos/biossíntese , Lycium/metabolismo , Extratos Vegetais/metabolismo , Agaricus/genética , Agaricus/crescimento & desenvolvimento , Meios de Cultura , Microscopia Eletrônica de Varredura , RNA Fúngico/genética , Análise de Sequência de RNA/métodos , Transcriptoma
6.
Dokl Biochem Biophys ; 497(1): 144-150, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33895931

RESUMO

Ovarian cancer is the malignant tumour of the female reproductive organ with highest mortality rate among all the types of gynaecological tumours. This study investigated the effect of Dioscorea deltoidea leaf extract (DDLE) on OV-90 and CAOV4 ovarian cancer cells. The results demonstrated that DDLE suppresses OV-90 and CAOV3 cell viability significantly in dose dependent manner. The OV-90 and CAOV3 cell viability were reduced to 24 and 27% respectively with 20 mg/mL DDLE treatment. Five mg/mL DDLE treatment of OV-90 and CAOV4 cells raised percentage of cells in G2-phase to 55.9 and 51.2%, respectively. In 5 mg/mL DDLE -treated OV-90 and CAOV4 cells a prominent suppression in cyclin-D1 and cyclin B1 proteins was observed in 48 h. The DDLE treatment promoted OV-90 and CAOV3 cell apoptosis to 34.65 and 29.89%, respectively. The Fas, FasL, cleaved caspase-3, and Bax levels were up-regulated markedly in the cells after DDLE treatment. Moreover, DDLE treatment suppressed p-mTOR, p-AKT and p-PI3K expression in OV-90 and CAOV3 cells. Thus, DDLE suppressed ovary cancer cell viability and elevated cell apoptosis. Inhibitory effect of DDLE on ovarian cancer cells is associated with targeting PI3K/AKT/mTOR pathway.


Assuntos
Dioscorea/química , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Folhas de Planta/química , Regulação para Cima/efeitos dos fármacos
7.
Artigo em Inglês | MEDLINE | ID: mdl-32087972

RESUMO

In both normal turnover of the hepatic tissue and acute hepatic injury, the liver predominantly activates terminally differentiated hepatocytes to proliferate and repair. However, in chronic and severe chronic injury, this capacity fails, and liver progenitor cells (LPCs) can give rise to hepatocytes to restore both hepatic architecture and liver metabolic function. Although the promotion of LPC-to-hepatocyte differentiation to acquire a considerable number of functional hepatocytes could serve as a potentially new therapeutic option for patients with end-stage liver disease, its development first requires the identification of the molecular mechanisms driving this process. Here, we found that the epithelial cell adhesion molecule (EpCAM), a progenitor cell marker, regulates the differentiation of LPCs into hepatocytes through Notch1 signaling pathway. Western blotting (WB) revealed a consistent expression pattern of EpCAM and Notch1 during LPC-to-hepatocyte differentiation in vitro. Additionally, overexpression of EpCAM blocked LPC-to-hepatocyte differentiation, which was in consistent with the repressive role of Notch signaling during hepatic differentiation. WB and immunofluorescence data also showed that the upregulation of EpCAM expression increased the generation of Notch intracellular domain (N1ICD), indicating the promotion of Notch1 activity. Our results established the EpCAM-Notch1 signaling axis as an inhibitory mechanism preventing LPC-to-hepatocyte differentiation in vitro.

8.
Mol Carcinog ; 59(11): 1292-1301, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32924161

RESUMO

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.


Assuntos
Dano ao DNA , Reparo do DNA , Histona Desacetilases/metabolismo , Melanoma Experimental/prevenção & controle , Substâncias Protetoras , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos , Animais , Histona Desacetilases/genética , Melanoma Experimental/etiologia , Melanoma Experimental/patologia , Camundongos , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Células Tumorais Cultivadas
9.
Zhongguo Zhong Yao Za Zhi ; 44(5): 962-967, 2019 Mar.
Artigo em Zh | MEDLINE | ID: mdl-30989856

RESUMO

The phenolic constituents of Wikstroemia chamaedaphne were investigated by various column chromatographic methods including silica gel,Sephadex LH-20,ODS and preparative HPLC,and their chemical structures were identified by physico-chemical properties and spectral analyses. Thirteen phenolic compounds were isolated and elucidated,including five flavonoids: luteolin 7-O-ß-D-glucopyranoside(1),luteolin 4'-O-ß-D-glucopyranoside(2),kaempferol 3-O-ß-D-glucopyranoside(3),chrysoeriol 4'-O-ß-D-glucopyranoside(4),chrysoeriol(5); and eight lignans:(-)-secoisolariciresinol(6),acanthosessilin A(7),(-)-nortrachelogenin(8),(+)-isolariciresinol(9),sesamin(10),syringaresinol(11),(+)-epipinoresinol(12),and [3,3',4,4'-tetrahydro-6,6'-dimethoxy-3,3'-bi-2 H-benzopyran]-4,4'-diol(13). Compounds 1, 3, 5-8, 10, 11 and 13 were obtained from the plants of W. chamaedaphne for the first time,and compounds 1,5,7,10 and 13 were obtained from the Wikstroemia genus for the first time.


Assuntos
Flavonoides/análise , Fenóis/análise , Wikstroemia/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Compostos Fitoquímicos/análise
10.
Lab Invest ; 98(8): 1025-1038, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29789685

RESUMO

As a member from S100 calcium-binding protein family, S100A4 is ubiquitous and elevated in tumor progression and metastasis, but its role in regulating obesity has not been well characterized. In this study, we showed that S100A4 was mainly expressed by stromal cells in adipose tissue and the S100A4 level in adipose tissue was decreased after high-fat diet (HFD). S100A4 deficient mice exhibited aggravated symptoms of obesity and suppressed insulin signaling after 12 weeks of HFD. Aggravated obesity in S100A4 deficient mice were found to be positively correlated with higher inflammatory status of the liver. Then, we found that extracellular S100A4 or overexpressed S100A4 inhibited adipogenesis and decreased mRNA levels of inflammation gene in 3T3-L1 adipocytes in vitro; whereas small interfering RNA (siRNA)-mediated suppression of S100A4 displayed the opposite results. Additionally, the protective effect induced by S100A4 during HFD-induced obesity was tightly related with activation of Akt signaling in adipose tissues, as well as livers and muscles. Taken together, we demonstrate that S100A4 is an inhibitory factor for obesity and attenuates the inflammatory reaction, while activating the Akt signaling, which suggest that S100A4 is a potential candidate for the treatment of diet-induced obesity and its complications.


Assuntos
Inflamação/genética , Obesidade/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Transdução de Sinais/genética , Células 3T3-L1 , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Inflamação/etiologia , Inflamação/metabolismo , Resistência à Insulina/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Obesidade/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Proteína A4 de Ligação a Cálcio da Família S100/deficiência
11.
Zhonghua Nan Ke Xue ; 24(8): 695-699, 2018 Aug.
Artigo em Zh | MEDLINE | ID: mdl-30173427

RESUMO

OBJECTIVE: To investigate the influence of insulin resistance on male reproductive hormones and semen quality. METHODS: Using the electrochemiluminescence method, we measured the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2) and testosterone (T) in the serum of 83 infertile males. We detected the levels of fasting plasma glucose (FPG) and fasting insulin (FINS) and calculated the insulin resistance index presented as homeostasis model assessment of insulin resistance (HOMA-IR). Based on HOMA-IR, we divided the patients into three tertile groups, T1 (HOMA-IR 0.36-0.55, n = 27), T2 (HOMA-IR 0.56-0.80, n = 28) and T3 (HOMA-IR 0.81-1.97, n = 28), obtained their semen parameters by computer-assisted semen analysis (CASA) and analyzed the correlation of HOMA-IR with male reproductive hormone levels and semen parameters. RESULTS: With the elevation of HOMA-IR, the patients of the T1, T2 and T3 groups showed significant decreases in the serum T level (ï¼»14,26 ± 4.27ï¼½ vs ï¼»14.75 ± 5.00ï¼½ vs ï¼»11.62 ± 3.68ï¼½ nmol/L, P <0.05) and the percentage of progressively motile sperm (PMS) (ï¼»51.04 ± 15.10ï¼½% vs ï¼»48.04 ± 16.24ï¼½% vs ï¼»37.84 ± 18.23ï¼½%, P <0.05). HOMA-IR was correlated negatively with the serum T level (r = -0.333, P = 0.002), semen volume (r = -0.23, P = 0.029) and PMS (r = -0.27, P = 0.015), and so was FINS with the serum T level (r = -0.327, P = 0.003) and PMS (r = -0.315, P = 0.004), while the semen volume was correlated positively with the levels of serum T (r = 0.221, P = 0.048) and FSH (r = 0.222, P = 0.047). Multivariate linear regression analysis showed that HOMA-IR was an independent influencing factor for PMS and the body mass index (BMI) was that for the semen volume and total sperm count. CONCLUSIONS: Insulin resistance may reduce semen quality by changing the levels of male reproductive hormones.


Assuntos
Infertilidade Masculina/sangue , Resistência à Insulina , Análise do Sêmen , Adulto , Glicemia/análise , Índice de Massa Corporal , Estradiol/sangue , Jejum/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Masculino , Prolactina/sangue , Reprodução , Sêmen , Contagem de Espermatozoides , Testosterona/sangue
13.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 37(4): 485-489, 2017 04.
Artigo em Zh | MEDLINE | ID: mdl-30650511

RESUMO

Objective To observe the effect of Bushen Huoxue Recipe (BHR) on paracrine gene expression profiling of uterine natural killer cells (uNK cells) and uterine stromal cells. Methods Human stromal cells were extracted from proliferative phase endometrium of child-bearing age females, which were then divided into the blank group, the control group, and the BHR group. DMEM/F12 was added in cells of the BHR group to dilute into final concentration of 2 mg/mL herbal liquor. Equal volume of DMEM/ F12 was added to cells in the normal group and the control group. Cells in the control group and the BHR group were cultured for 24 h, with 20% serum-free DMEM plus 80% uNK cell secretion extracting solution added. Then they were cultured in 5% CΟ2 at 37 °C for 6 h. Total RNAs were extracted after culture. The gene expression profile of stromal cells was detected using gene chip technology. At the same time mR- NA and protein expressions of chemokine (C-X-C motif) ligand 1 (CXCL1), intercellular cell adhesion molecule-1 (ICAM-1) , IL-8, and leukocyte inhibitor factor (LIF) were screened and detected using qRT- PCR and ELISA. Results Compared with the blank group, profiles of differentiated genes with 4-fold in- crease (a total of 63 genes) were basically agreeable in the control group and the BHR group. Compared with the control group, IL-15 receptor alpha (IL-15RA) was up-regulated by 1. 27 times, vascular endotheli- ai growth factor (VEGF) up-regulated by 1. 55 times, LIF up-regulated by 1. 45 times, IL-8 up-regulated by 1. 10 times, IL-11 up-regulated by 1. 23 times, transforming growth factor-ß (TGF-ß) up-regulated by 1. 40 times, epidermal growth factor (EGF) up-regulated by 1. 10 times, chemokine (C-C motif) ligand 8 (CCL8) up-regulated by 1.13 times, transporter 1 (TAP1 ) up-regulated by 1. 02 times, chemokine (C-X-C motif) receptor 2 (CXCR2) up-regulated by 1. 22 times, ICAM-1 up-regulated by 1. 15 times (P <0. 05) in the BHR group. Conclusion uNK paracrine played an important role in elevating endometrial receptivity and embry- o implantation, and BHR could improve and elevate the function of this paracrine system.


Assuntos
Medicamentos de Ervas Chinesas , Expressão Gênica , Células Matadoras Naturais , Criança , Medicamentos de Ervas Chinesas/farmacologia , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo
14.
Zhonghua Nan Ke Xue ; 23(8): 745-750, 2017 Aug.
Artigo em Zh | MEDLINE | ID: mdl-29726652

RESUMO

Metabonomics is an emerging branch of science for the study of endogenous small molecule metabolites in organisms, which plays an important role in evaluatingthediagnosis and treatment of male infertility by exploring the metabolites of body fluids, cells and tissues. With its advantages ofmass information, noninvasiveness, and celerity, metabonomics will be widely applied to clinical researches in the future. This review introducesmetabonomics and its analytical techniques and data processing procedures,its latest application in the studies of the etiology, diagnosis and the treatment of male infertility, and the prospect of its future application in the researches of male reproduction.


Assuntos
Infertilidade Masculina , Metabolômica , Líquidos Corporais/metabolismo , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/etiologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/terapia , Masculino
15.
Zhonghua Nan Ke Xue ; 23(10): 894-898, 2017 Oct.
Artigo em Zh | MEDLINE | ID: mdl-29727538

RESUMO

OBJECTIVE: To investigate the influence of inflammatory factors on semen parameters in the seminal plasma of obese men. METHODS: Based on the body mass index (BMI), 171 males were divided into a normal group (BMI < 24 kg/m2, n = 59), an overweight group (24 ≤ BMI < 28 kg/m2, n = 54), and an obesity group (BMI =≥ 28 kg/m2, n = 58). The routine semen parameters of the subjects were obtained by computer-assisted semen analysis, the levels of TNF-α, IL-6 and VEGF in the seminal plasma were measured by ELISA, and the correlation of BMI with the above indexes was analyzed. RESULTS: Sperm concentration was significantly decreased in the obesity group in comparison with the normal and overweight groups (ï¼»40.19 ± 24.05ï¼½ vs ï¼»66.54 ± 34.81ï¼½ and ï¼»57.73 ± 24.61ï¼½ ×106/ml, P <0.01), and so was the total number of sperm (ï¼»110.22 ± 75.44ï¼½ vs ï¼»200.75 ± 102.66ï¼½ and ï¼»157.46 ± 112.89ï¼½ ×106, P <0.01) and the percentage of progressively motile sperm (PMS) (ï¼»30.80 ± 15.56ï¼½ vs ï¼»50.75 ± 10.17ï¼½ and ï¼»39.71 ± 9.73ï¼½%, P <0.01). The levels of TNF-α and IL-6 in the seminal plasma were markedly elevated in the obesity group as compared with the normal and overweight groups (ï¼»76.90 ± 14.64ï¼½ vs ï¼»64.47 ± 11.92ï¼½ and ï¼»69.74 ± 12.32ï¼½ pg/ml, P <0.05; ï¼»54.17 ± 17.81ï¼½ vs ï¼»39.26 ± 9.09ï¼½ and ï¼»46.25 ± 13.66ï¼½ pg/ml, P <0.01), while that of VEGF remarkably reduced in the former group in comparison with the latter two (ï¼»154.24 ± 30.23ï¼½ vs ï¼»199.23 ± 36.28ï¼½ and ï¼»181.57 ± 34.41ï¼½ pg/ml, P <0.01). The levels of TNF-α, IL-6, and VEGF were significantly correlated with BMI (r = 0.254, 0.321 and -0.407, P <0.01), those of TNF-α and IL-6 negatively with the percentage of PMS (r =-0.163, P <0.05; r = -0.333, P <0.01). There was a positive correlation between TNF-α and IL-6 (r = 0.468, P <0.01), a negative correlation between IL-6 and VEGF (r = 0.177, P <0.05), but no correlation between TNF-α and VEGF (r = 0.058, P >0.05). CONCLUSIONS: The levels of TNF-α and IL-6 are increased and that of VEGF decreased in the seminal plasma of obese males, which may affect the semen quality.


Assuntos
Índice de Massa Corporal , Interleucina-6/análise , Obesidade , Sêmen/química , Fator de Necrose Tumoral alfa/análise , Fator A de Crescimento do Endotélio Vascular/análise , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Sobrepeso , Análise do Sêmen/métodos , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides
16.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3747-3754, 2017 Oct.
Artigo em Zh | MEDLINE | ID: mdl-29235290

RESUMO

In this report, a heat and high-pressure homogenization method was used to prepare dioscin nanostructured lipid carriers, and the formulation of dioscin nanostructured lipid carriers was optimized by central composite design-response surface methodology. In vitro evaluation data showed that the preparation of dioscin nanostructured lipid carriers under optimal process by central composite design-response surface methodology had a spherical shape and homogeneous size distribution, with a particle size of (90.9±0.6) nm, a polydispersity index of (0.253±0.07), Zeta potential of (-45.7±0.5) mV, encapsulation efficiency of (90.2±0.5)%, and the drug loading of (23.30±0.10)%. These results clearly indicate that the preparation of dioscin nanostructured lipid carriers made with the heat and high-pressure homogenization method have very good physical and chemical properties, suitable for therapeutic applications.


Assuntos
Diosgenina/análogos & derivados , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Diosgenina/administração & dosagem , Tamanho da Partícula
17.
Phytother Res ; 30(2): 323-30, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26646778

RESUMO

Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to investigate the anticancer effects of total flavonoids in D. genkwa (TFDG) in vitro and in vivo. HT-29 and SW-480 human colorectal cancer cells were cultured to investigate the anticancer activity of TFDG. In addition, the Apc(Min/+) mouse model was applied in the in vivo experiment. Results of the cell experiment revealed that TFDG possessed significant inhibitory effects on HT-29 and SW-480 human colorectal cancer cells (both p < 0.01). Furthermore, our in vivo data showed that after treatment with TFDG, there was a significant increase in life span (both p < 0.01) and tumor numbers were reduced in the colon (both p < 0.01), which was supported by the data of tumor distribution, body weight changes and organ index. Our results also indicated that expressions of interleukin (IL)-1α, IL-1ß, IL-6, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in gut tissue were downregulated by treatments of TFDG, and immunity cytokine secretions in the serum were regulated after oral administration of TFDG. Taken together, these findings suggested that TFDG has a potential clinical utility in colorectal cancer therapeutics, and TFDG's action is likely linked to its ability to regulate immune function and inhibit the production of inflammatory cytokines.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Daphne/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Animais , Linhagem Celular Tumoral/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plantas Medicinais/química
18.
Int J Med Sci ; 12(7): 559-65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26180512

RESUMO

BACKGROUND: Propofol may result in hypotension and respiratory depression, while etomidate is considered to be a safe induction agent for haemodynamically unstable patients because of its low risk of hypotension. We hypothesized that etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol. The primary endpoint was to compare the haemodynamic effects of etomidate vs. propofol in ERCP cases. The secondary endpoint was overall survival. METHODS: A total of 80 patients undergoing ERCP were randomly assigned to an etomidate or propofol group. Patients in the etomidate group received etomidate induction and maintenance during ERCP, and patients in the propofol group received propofol induction and maintenance. Cardiovascular parameters and procedure-related time were measured and recorded during ERCP. RESULTS: The average percent change to baseline in MBP was -8.4±7.8 and -14.4±9.4 with P = 0.002, and in HR was 1.8±16.6 and 2.4±16.3 with P = 0.874 in the etomidate group and the propofol group, respectively. MBP values in the etomidate group decreased significantly less than those in the propofol group (P<0.05). The ERCP duration and recovery time in both groups was similar. There was no significant difference in the survival rates between groups ( p = 0.942). CONCLUSIONS: Etomidate anesthesia during ERCP caused more stable haemodynamic responses compared with propofol.


Assuntos
Anestesia/efeitos adversos , Etomidato/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Propofol/administração & dosagem , Adolescente , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Colangiopancreatografia Retrógrada Endoscópica , Etomidato/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propofol/efeitos adversos
19.
Planta Med ; 81(10): 784-90, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26039267

RESUMO

The present study investigated the flavonoids from Abrus cantoniensis against ethanol-induced gastric ulcers in mice. The flavonoids from A. cantoniensis were extracted with ethanol and purified by macroporous resin and polyamide. The 2,2-diphenyl-1-picrylhydrazyl assay was used to measure the antioxidative activities in vitro. The ethanol-induced ulcer mouse model was used to evaluate the gastroprotective activities of the flavonoids from A. cantoniensis. In addition, a method was established to ensure accuracy for animal ulcer evaluation. The flavonoids from A. cantoniensis showed a strong free radical scavenging capacity with an IC50 of 43.83 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl assay. At doses between 28.16-112.67 mg/kg, the flavonoids conspicuously reduced the ulcer index in ethanol-induced mice (p<0.001). Significant differences were found in the levels of superoxide dismutase, catalase, glutathione, and myeloperoxidase in the stomach tissues between the flavonoids from the A. cantoniensis groups and the ethanol control group. The gastroprotective effect of the flavonoids from A. cantoniensis could be due to its antioxidative activity of the defensive mechanism. The data revealed that the flavonoids from A. cantoniensis could be a potential therapeutic agent for gastric ulcer prevention and treatment.


Assuntos
Abrus/química , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/química , Antioxidantes/química , Catalase/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Etanol/efeitos adversos , Flavonoides/química , Glutationa/metabolismo , Masculino , Camundongos Endogâmicos ICR , Estrutura Molecular , Peroxidase/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Superóxido Dismutase/metabolismo
20.
Phytother Res ; 29(1): 22-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25175534

RESUMO

Different members of Lagochilus genus have been used in folkloric medicine to treat hemorrhages and inflammation. However, only a few species of them have received scientific attention supporting their efficacy. Here, the hemostatic and antiinflammatory activities of five Lagochilus species were determined and compared by using in vivo assays. The results showed that the extracts of Lagochilus lanatonodus and Lagochilus diacanthophyllus showed better hemostatic activities among five species. The high doses of L. lanatonodus extracts were able to shorten the values of thrombin time, activated partial thromboplastin time and prothrombin time in a rat model. Moreover, the extracts of L. lanatonodus and L. diacanthophyllus showed strong inhibitory effects on the acute phase of inflammation in both xylene-induced ear edema mouse model and carrageenan-induced paw edema rat model. In parallel, the treatment of these extracts modulated the expressions of those inflammatory parameters, that is, nitric oxide, prostaglandin E2 , inducible nitric oxide synthase, malondialdehyde and superoxide dismutase. L. lanatonodus and L. diacanthophyllus showed better hemostatic and antiinflammatory activities in several test models: these results therefore supported the folkloric utilization. L. lanatonodus was found to be the most active Lagochilus species.


Assuntos
Anti-Inflamatórios/farmacologia , Hemostáticos/uso terapêutico , Inflamação/tratamento farmacológico , Lamiaceae/química , Extratos Vegetais/farmacologia , Animais , Carragenina/efeitos adversos , Dinoprostona/metabolismo , Edema/tratamento farmacológico , Lamiaceae/classificação , Masculino , Malondialdeído/metabolismo , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Testes de Toxicidade Aguda
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