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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1052-1063, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621912

RESUMO

The mechanism of total polyphenols of Cydonia oblonga Miller(TPCOM) against kidney cancer was elucidated through a combination of network pharmacology, bioinformatics, and experimental verification. The active polyphenolic compounds from C. oblonga were screened by network pharmacological techniques and kidney cancer-related targets were collected through the database. The differential gene expression analysis was performed on RNA sequencing data from tumor tissue and normal tissue of kidney cancer patients obtained from the Gene Expression Omnibus(GEO) database. The results of network pharmacology predictions and differential gene expression analysis were used to identify the core genes targeted by TPCOM in kidney cancer. Survival analysis was conducted to identify key targets that could impact patient survival, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) enrichment analyses. Cell proliferation and activity experiments(cell counting kit-8) were conducted using TPCOM at concentrations ranging from 20 to 640 µg·mL~(-1) on 786-O and Renca cells. Additionally, TPCOM at concentrations of 40, 80, and 160 µg·mL~(-1) was applied to kidney cancer cells to assess its effect on cell migration and its regulation of protein expression levels related to the protein kinase B(Akt), mammalian target of rapamycin(mTOR), and phosphoinositide 3-kinase(PI3K) signaling pathways. Network pharmacology predicted eight active polyphenolic compounds from C. oblonga. Survival analysis revealed 15 significantly differentially expressed genes in kidney cancer that were affected by TPCOM and had a significant impact on patient survival. KEGG and GO analysis results indicated that these 15 targets were primarily associated with the PI3K/Akt signaling pathway, cell migration, and proliferation. The results showed that TPCOM could inhibit the proliferation of 786-O and Renca cells, with IC_(50) values of 121.4 and 137.9 µg·mL~(-1), respectively. TPCOM was also found to inhibit the migration of these cells and suppress the PI3K/Akt/mTOR signaling pathway. TPCOM may exert its anti-kidney cancer effects by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway, thereby restraining the proliferation and migration of kidney cancer cells. This study provides a foundation for the research on the anti-tumor effects of natural product C. oblonga, particularly in Xinjiang, and holds significance for further promoting its development and utilization.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Serina-Treonina Quinases TOR/genética , Proliferação de Células , Simulação de Acoplamento Molecular
2.
Biometals ; 37(1): 131-142, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37682402

RESUMO

The repair and reconstruction of large bone defects after bone tumor resection is still a great clinical challenge. At present, orthopedic implant reconstruction is the mainstream treatment for repairing bone defects. However, according to clinical feedback, local tumor recurrence and nonunion of bone graft are common reasons leading to the failure of bone defect repair and reconstruction after bone tumor resection, which seriously threaten the physical and mental health of patients. On this basis, here the self-developed low modulus Ti-12Mo-10Zr alloy (TMZ) was chosen as substrate material. To improve its biological activity and osteointegration, calcium, oxygen, and phosphorus co-doped microporous coating was prepared on TMZ alloy by microarc oxidation (MAO). Then, black phosphorus (BP) nanosheets were incorporated onto MAO treated TMZ alloy to obtain multifunctional composites. The obtained BP-MAO-TMZ implant exhibited excellent photothermal effects and effective ablation of osteosarcoma cancer cells under the irradiation of 808 nm near infrared laser, while no photothermal or therapeutic effects were observed for TMZ alloy. Meanwhile, the structure/component bionic coating obtained after MAO treatment as well as the P-driven in situ biomineralization performance after incorporation of BP nanosheets endowed BP-MAO-TMZ implant with synergistic promoting effect on MC3T3-E1 osteoblasts' activity, proliferation and differentiation ability. This study is expected to provide effective clinical solutions for problems of difficult bone regeneration and tumor recurrence after tumor resection in patients with bone tumors and to solve a series of medical problems such as poor prognosis and poor postoperative quality of patients life with malignant bone tumors.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Fósforo , Titânio/farmacologia , Recidiva Local de Neoplasia , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico , Terapia Combinada , Ligas/farmacologia
3.
Medicine (Baltimore) ; 102(32): e34629, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37565919

RESUMO

BACKGROUND: Compound Xiao-ai-fei honey ointment (CXHO) is an anticancer preparation with a long history in Uyghur folk medicine in China and has been used for the treatment of gastric cancer (GC) in Xinjiang, China. Nevertheless, the mechanism of its anticancer effect remains to be investigated. METHODS: Bioactive ingredients of CXHO were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Target genes of ingredients were acquired via the PubChem and Swiss target prediction database. Gene expression profiling of GC was obtained from GSE54129 in the GEO database and analyzed using the limma package in R. The hub genes associated with CXHO in GC were validated using the TIMER2.0 database, GEPIA2 database and Auto Dock tools. The effect of CXHO on migration of GC cells was detected by Transwell chamber assay and Wound healing assay. The effect of CXHO on expression levels of MMP2/MMP9 and NF-κb, PI3K/AKT signaling pathway was detected by Western blot assay. RESULTS: Forty-five bioactive ingredients and their 819 related genes were found. A total of 462 differentially expressed genes were identified between GC patients and healthy controls. Seventeen common target genes were identified as hub genes CXHO against GC. Among them, MMP2 and MMP9 were significantly associated with tumor immune infiltrates and had good binding affinity with effective ingredients. Moreover, we validated the mRNA and protein expression levels and prognostic value of MMP2 and MMP9 by different databases. In addition, Kyoto encyclopedia of genes and genomes and gene ontology analyses showed that the 17 common target genes were mainly involved in steroid hormone biosynthesis and cancer-related pathways. Experimental results showed that CXHO inhibited migration of GC cells and down regulated the expression levels of MMP2/MMP9, NF-κb. In addition, CXHO can inhibited PI3K/AKT signaling pathway. CONCLUSION: We identified and experimental validated 2 pivotal target genes of CXHO against GC and preliminarily analyzed the potential mechanisms by which CXHO inhibits the development of GC. All these findings support CXHO as a promising drug for the treatment of GC.


Assuntos
Insuficiência da Valva Aórtica , Mel , Neoplasias Gástricas , Humanos , NF-kappa B , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Farmacologia em Rede , Pomadas , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
4.
J Cancer Res Clin Oncol ; 149(11): 8467-8481, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37087696

RESUMO

PURPOSE: Esophageal squamous cell carcinoma (ESCC), is a frequent digestive tract malignant carcinoma with a high fatality rate. Daphne altaica (D. altaica), a medicinal plant that is frequently employed in Kazakh traditional medicine, and which has traditionally been used to cure cancer and respiratory conditions, but research on the mechanism is lacking. Therefore, we examined and verified the hub genes and mechanism of D. altaica treating ESCC. METHODS: Active compounds and targets of D. altaica were screened by databases such as TCMSP, and ESCC targets were screened by databases such as GeneCards and constructed the compound-target network and PPI network. Meantime, data sets between tissues and adjacent non-cancerous tissues from GEO database (GSE100942, GPL570) were analyzed to obtain DEGs using the limma package in R. Hub genes were validated using data from the Kaplan-Meier plotter database, TIMER2.0 and GEPIA2 databases. Finally, AutoDock software was used to predict the binding sites through molecular docking. RESULTS: In total, 830 compound targets were obtained from TCMSP and other databases. In addition, 17,710 disease targets were acquired based on GeneCards and other databases. In addition, we constructed the compound-target network and PPI network. Then, 127 DEGs were observed (82 up-regulated and 45 down-regulated genes). Hub genes were screened including TOP2A, NUF2, CDKN2A, BCHE, and NEK2, and had been validated with the help of several publicly available databases. Finally, molecular docking results showed more stable binding between five hub genes and active compounds. CONCLUSIONS: In the present study, five hub genes were screened and validated, and potential mechanisms of action were predicted, which could provide a theoretical understanding of the treatment of ESCC with D. altaica.


Assuntos
Carcinoma , Daphne , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Daphne/genética , Farmacologia em Rede , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Simulação de Acoplamento Molecular , Biologia Computacional , Quinases Relacionadas a NIMA
5.
Front Nutr ; 9: 819722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35284437

RESUMO

Weaned piglets stayed in transitional stages of internal organ development and external environment change. The dual stresses commonly caused intestinal disorders followed by damaged growth performance and severe diarrhea. High dose of zinc oxide could improve production efficiency and alleviate disease status whereas caused serious environmental pollution. This research investigated if coated ZnO (C_ZnO) in low dose could replace the traditional dose of ZnO to improve the growth performance, intestinal function, and gut microbiota structures in the weaned piglets. A total of 126 cross-bred piglets (7.0 ± 0.5 kg body weight) were randomly allocated into three groups and fed a basal diet or a basal diet supplemented with ZnO (2,000 mg Zn/kg) or C_ZnO (500 mg Zn/kg), respectively. The test lasted for 6 weeks. C_ZnO improved average daily gain (ADG) and feed efficiency, alleviated diarrhea, decreased the lactulose/mannitol ratio (L/M) in the urine, increased the ileal villus height, and upregulated the expression of Occludin in the ileal tissue and the effect was even better than a high concentration of ZnO. Importantly, C_ZnO also regulated the intestinal flora, enriching Streptococcus and Lactobacillus and removing Bacillus and intestinal disease-associated pathogens, including Clostridium_sensu_stricto_1 and Cronobacter in the ileal lumen. Although, colonic microbiota remained relatively stable, the marked rise of Blautia, a potential probiotic related to body health, could still be found. In addition, C_ZnO also led to a significant increase of acetate and propionate in both foregut and hindgut. Collectively, a low concentration of C_ZnO could effectively promote growth performance and reduce diarrhea through improving small intestinal morphology and permeability, enhancing the barrier function, adjusting the structure of gut microbiota, and raising the concentration of short-chain fatty acids (SCFAs) in the weaned piglets.

6.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34969844

RESUMO

Deoxypodophyllotoxin contains a core of four fused rings (A to D) with three consecutive chiral centers, the last being created by the attachment of a peripheral trimethoxyphenyl ring (E) to ring C. Previous studies have suggested that the iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenase, deoxypodophyllotoxin synthase (DPS), catalyzes the oxidative coupling of ring B and ring E to form ring C and complete the tetracyclic core. Despite recent efforts to deploy DPS in the preparation of deoxypodophyllotoxin analogs, the mechanism underlying the regio- and stereoselectivity of this cyclization event has not been elucidated. Herein, we report 1) two structures of DPS in complex with 2OG and (±)-yatein, 2) in vitro analysis of enzymatic reactivity with substrate analogs, and 3) model reactions addressing DPS's catalytic mechanism. The results disfavor a prior proposal of on-pathway benzylic hydroxylation. Rather, the DPS-catalyzed cyclization likely proceeds by hydrogen atom abstraction from C7', oxidation of the benzylic radical to a carbocation, Friedel-Crafts-like ring closure, and rearomatization of ring B by C6 deprotonation. This mechanism adds to the known pathways for transformation of the carbon-centered radical in Fe/2OG enzymes and suggests what types of substrate modification are likely tolerable in DPS-catalyzed production of deoxypodophyllotoxin analogs.


Assuntos
Berberidaceae/enzimologia , Medicamentos de Ervas Chinesas/química , Ligases/química , Proteínas de Plantas/química , Podofilotoxina/análogos & derivados , Oxirredução , Podofilotoxina/química
7.
Artigo em Inglês | MEDLINE | ID: mdl-33281909

RESUMO

Artemisia rupestris L. is the perennial herb of rupestris belonging to Artemisia (Compositae), which is wildly distributed in Xinjiang (China), middle Asia, and Europe. It is known to have anti-inflammatory, hepatoprotective, immune function regulation, and gastrointestinal function regulation effects. AR is used to treat digestive diseases, but the effects of AR on antifunctional dyspepsia (FD) activity have not yet been reported. In this study, we aimed to investigate the therapeutic effects of Artemisia rupestris L. extract (ARE) on gastrointestinal hormones and brain-gut peptide in functional dyspepsia (FD) rats. Sixty Sprague-Dawley rats were randomly divided into 6 groups. An FD rat model was established by irregular tail clamp stimulation for 14 days except the blank group. After FD rat models, the blank group and model group were given menstruum, and the medicated rats were given corresponding medicine for 14 days. The general observations, bodyweight, and food intake were observed, and the content of serum gastrin (GAS), plasma motilin (MTL), plasma vasoactive intestinal peptide (VIP), and plasma somatostatin (SS) by the enzyme-linked immunosorbent assay was observed. The content of plasma VIP and plasma SS in the ARE group was significantly lower than in the model group, and the content of serum GAS and plasma MTL was increased in the ARE group; the GAS expression of antrum and hypothalamus was increased in the ARE group, and SS expression of antrum and hypothalamus was decreased in the ARE group by immunohistochemical detection; the results of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) indicate that ARE inhibits the mRNA expression of VIP. Our results suggest that ARE can recover gastrointestinal hormone levels and regulation of the peripheral and central nervous system and alter gut peptide levels, which confirm the therapeutic effect of ARE on functional dyspepsia.

8.
Biomed Pharmacother ; 131: 110739, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32932045

RESUMO

AIM: The present study aims to investigate the antihypertensive effect and the underlying mechanism of GAO-ZI-YAO, one of the traditional Chinese medicines, in elderly spontaneous hypertensive rats (SHR). METHODS: 12-month-old male SHRs were randomly divided into five groups on the basis of treatment with different doses of GAO-ZI-YAO or angiotensin II receptor-1 blocker (ARB, Irbesartan) for four weeks. Systolic blood pressure (SBP), and serum levels of nitric oxide (NO), endothelin-1 (ET-1), angiotensin II (Ang II), vascular endothelial growth factor (VEGF), interleukin (IL)-1ß, IL-2, IL-6, and tumor necrotic factor (TNF)-α were measured. The pathological changes of ventricular muscle and thoracic aorta were observed by hematoxylin-eosin staining (H&E). RESULTS: GAO-ZI-YAO treatment reduced SBP in a dose-dependent manner accompanied by the inhibition of the development of cardiovascular remodeling. Although GAO-ZI-YAO treatment markedly increased serum levels of NO and suppressed serum levels of Ang II, this medicine did not affect the serum levels of ET-1 and VEGF. In addition, GAO-ZI-YAO also inhibited inflammatory response parameters (inflammatory cell infiltration in cardiac tissues and serum levels of IL-1ß, IL-2, IL-6, and TNF-α) in a dose-dependent manner. CONCLUSION: GAO-ZI-YAO exerts antihypertensive and anti-cardiovascular-remodeling effects in elderly SHR, which may be through regulation of NO, Ang II production, and inflammation.


Assuntos
Anti-Hipertensivos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Medicina Tradicional Chinesa , Angiotensina II/sangue , Angiotensina II/fisiologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Citocinas/sangue , Medicamentos de Ervas Chinesas/farmacologia , Endotelina-1/sangue , Endotelina-1/fisiologia , Irbesartana/uso terapêutico , Masculino , Óxido Nítrico/sangue , Óxido Nítrico/fisiologia , Ratos , Ratos Endogâmicos SHR , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/fisiologia
9.
J Neuroimmunol ; 345: 577286, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32559555

RESUMO

We investigated the effects of matairesinol (MAT) in the experimental autoimmune uveitis (EAU), a classical animal model of uveitis. We found that treatment with MAT could alleviate intraocular inflammation of EAU. Notably, Th17 cells in eyes of EAU mice could be predominantly restrained by MAT. Furthermore, MAT could inhibit Th17 differentiation in vitro. In addition, MAT inhibited the signaling of MAPK and ROR-γt, a pivotal transcription factor for Th17 cell differentiation in vitro and in vivo. Taken together, these results suggested that MAT had immune-suppressive effects on autoimmune inflammation through Th17 cells.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Proteínas do Olho/antagonistas & inibidores , Furanos/uso terapêutico , Lignanas/uso terapêutico , Proteínas de Ligação ao Retinol/antagonistas & inibidores , Células Th17/efeitos dos fármacos , Uveíte/tratamento farmacológico , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Proteínas do Olho/imunologia , Proteínas do Olho/metabolismo , Feminino , Adjuvante de Freund/toxicidade , Furanos/farmacologia , Lignanas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Ligação ao Retinol/imunologia , Proteínas de Ligação ao Retinol/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Uveíte/imunologia , Uveíte/metabolismo
10.
Chemosphere ; 251: 126358, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32155493

RESUMO

Acidic substances, which produced during chlorinated volatile organic compounds, will corrode the commonly used packing materials, and then affect the removal performance of biofiltration. In this study, three biofilters with different filter bed structure were established to treat gaseous chlorobenzene. CaCO3 and 3D matrix material was added in filter bed as pH buffering material and filter bed supporting material, respectively. A comprehensive investigation of removal performance, biomass accumulation, microbial community, filter bed height, voidage, pressure drops, and specific surface area of the three biofilters was compared. The biofilter with CaCO3 and 3D matrix material addition presented stable removal performance and microbial community, and greater biomass density (209.9 kg biomass/m3 filter bed) and growth rate (0.033 d-1) were obtained by using logistic equation. After 200 days operation, the height, voidage, pressure drop, specific surface area of the filter bed consisted of perlite was 27.4 cm, 0.39, 32.8 Pa/m, 974,89 m2/m3, while those of the filter bed with CaCO3 addition was 28.2 cm, 0.43, 21.3 Pa/m, and 1021.03 m2/m3, and those of the filter bed with CaCO3 and 3D matrix material addition was 28.7 cm, 0.55, 17.4 Pa/m, and 1041.60 m2/m3. All the results verified the biofilter with CaCO3 and 3D matrix material addition is capable of sustaining the long-term performance of biofilters. CaCO3 could limit the changes of removal efficiency, microbial community and filter bed structure by buffering the pH variation. And 3D matrix material could maintain the filter bed structure by supporting the filter bed, regardless of the buffering effect.


Assuntos
Clorobenzenos/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Óxido de Alumínio , Biomassa , Filtração/métodos , Gases , Concentração de Íons de Hidrogênio , Dióxido de Silício , Compostos Orgânicos Voláteis/química
11.
Sci Total Environ ; 640-641: 1447-1454, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30021311

RESUMO

The traditional one-liquid phase biofilter (OLPB), with water as the selected liquid phase, demonstrated low performance to volatile hydrophobic organic compounds. In this study, a novel two-liquid phase biofilter (TLPB) using silicone oil and water was established to treat gaseous dichloromethane (DCM). A comprehensive investigation of removal performance, kinetic analysis, biomass accumulations, pressure drops, CO2 productions, and microbial communities of the two biofilters was compared. Results showed that TLPB presented an average removal efficiency of 85% during 200 days of operation, which was higher than that of OLPB (63%). Owing to the buffering effects caused by silicone oil, TLPB demonstrated a superior fluctuation resistance capability than OLPB. TLPB was determined at a higher actual mass distribution coefficient of 6.00 than that of the OLPB (3.99), thereby suggesting a significantly more effective mass transfer process inside TLPB compared with that in OLPB. Furthermore, a rapid biomass accumulation process was observed in TLPB. The specific growth rates of biomass in OLPB and TLPB were calculated as 0.035 and 0.026 g of dry biomass/g of dry filter per day, respectively. The carbon balances were analyzed in the two biofilters. The yield coefficients (Y) were determined at 1.449 and 1.143 g of dry biomass/g of removed VOC for OLPB and TLPB, respectively. However, the corresponding CO2 production fraction was 0.263 g and 0.316 g per 1 g of DCM for OLPB and TLPB, respectively. The variations in fraction of carbon in DCM transformation to biomass and to CO2 suggested distinct microbial transformation pathways of utilizing DCM in the two biofilters, which were mainly caused by the different microbial communities and metabolic activities.

12.
Oncotarget ; 8(39): 64878-64891, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029398

RESUMO

The present study was carried out to determine whether low dose of zinc oxide nanoparticles (Nano-ZnO) could serve as a potential substitute of pharmacological dose of traditional ZnO in weaned piglets. 180 crossbred weaning piglets were randomly assigned to 3 treatments. Experimental animals were fed basal diet supplemented with 0 mg Zn/kg (Control), 600 mg Zn/kg (Nano-ZnO) and 2000 mg Zn/kg (ZnO) for 14 days. On day 14 after weaning, the piglets fed Nano-ZnO did not differ from those fed traditional ZnO in growth performance and jejunal morphology, while Nano-ZnO treatment could significantly alleviate the incidence of diarrhea (P < 0.05). In jejunum, the mRNA expressions of intestinal antioxidant enzymes and tight junction proteins were increased (P < 0.05) in Nano-ZnO treatment. In ileum, the expression levels of IFN-γ, IL-1ß, TNF-α and NF-κB were decreased (P < 0.05). Gene sequencing analysis of 16S rRNA revealed that dietary Nano-ZnO increased the bacterial richness and diversity in ileum, while decreased both of them in cecum and colon. Specifically, the relative abundances of Streptococcus in ileum, Lactobacillus in colon were increased, while the relative abundances of Lactobacillus in ileum, Oscillospira and Prevotella in colon were decreased (P < 0.05). In conclusion, our data reveal that low dose of Nano-ZnO (600 mg Zn/kg) can effectively reduce piglet diarrhea incidence, similar to high dose of traditional ZnO (2000 mg Zn/kg), which may be mediated by improving intestinal microbiota and inflammation response in piglets, and help to reduce zinc environmental pollution.

13.
Amino Acids ; 49(5): 957-964, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28260165

RESUMO

L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 µmol L-arginine/L for 24-96 h. Cell proliferation, protein turnover, the mammalian target of rapamycin (mTOR) signaling pathway and pre-adipocyte differentiation markers were determined. L-arginine treatment enhanced (P < 0.05) BAPC growth and protein synthesis, while inhibiting proteolysis in a dose-dependent manner. Compared with 50 and 100 µmol/L (the concentrations of arginine in the maternal plasma of obese ewes), 200 µmol L-arginine/L (the concentrations of arginine in the maternal plasma of obese ewes receiving arginine supplementation) increased (P < 0.05) the abundances of phosphorylated mTOR, P70S6K and 4EBP1, as well as the abundances of PGC1α, UCP1, BMP7 and PRDM16. These novel findings indicate that increasing extra-cellular arginine concentration from 50 to 200 µmol/L activates mTOR cell signaling in BAPCs and enhances their growth and development in a dose-dependent manner. Our results provide a mechanism for arginine supplementation to enhance the development of brown adipose tissue in fetal lambs.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Arginina/farmacologia , Regulação da Expressão Gênica no Desenvolvimento , Obesidade/genética , Serina-Treonina Quinases TOR/genética , Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Animais , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/metabolismo , Diferenciação Celular , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fatores de Iniciação em Eucariotos/genética , Fatores de Iniciação em Eucariotos/metabolismo , Feminino , Feto , Obesidade/metabolismo , Obesidade/patologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Carneiro Doméstico , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Dedos de Zinco/genética
14.
Curr Protein Pept Sci ; 18(6): 599-608, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27356939

RESUMO

Type 2 diabetes has become a global public health problem affecting approximately 380 million people throughout the world. It can cause many complications and lead to greater mortality. At present, there is no available medicine for effectively preventing diabetes. L-arginine, a functional amino acid, the precursor of nitric oxide, plays a crucial role in maintenance, reproduction, growth, anti-aging and immunity for animals. Growing clinical evidence indicates that dietary L-arginine supplementation can reduce obesity, decrease arterial blood pressure, resist oxidation and normalize endothelial dysfunction to bring about remission of type 2 diabetes. The potential molecular mechanism may play a role in modulating glucose homeostasis, promoting lipolysis, maintaining hormone levels, ameliorating insulin resistance, and fetal programing in early stages. The possible signaling pathway of the beneficial effects of L-arginine likely involves L-arginine-nitric oxide pathway through which cell signal protein can be activated. Accumulating studies have indicated that L-arginine may have potential to prevent and/or relieve type 2 diabetes via restoring insulin sensitivity in vivo.


Assuntos
Arginina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Metabolismo dos Lipídeos , Obesidade/metabolismo , Animais , Humanos , Resistência à Insulina , Óxido Nítrico/metabolismo , Transdução de Sinais
15.
Oncotarget ; 7(49): 80313-80326, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27880936

RESUMO

Proanthocyanidins have been suggested as an effective antibiotic alternative, however their mechanisms are still unknown. The present study investigated the effects of grape seed proanthocyanidins on gut microbiota and mucosal barrier using a weaned piglet model in comparison with colistin. Piglets weaned at 28 day were randomly assigned to four groups treated with a control ration, or supplemented with 250 mg/kg proanthocyanidins, kitasamycin/colistin, or 250 mg/kg proanthocyanidins and half-dose antibiotics, respectively. On day 28, the gut chyme and tissue samples were collected to test intestinal microbiota and barrier function, respectively. Proanthocyanidins treated piglets had better growth performance and reduced diarrhea incidence (P < 0.05), accompanied with decreased intestinal permeability and improved mucosal morphology. Gene sequencing analysis of 16S rRNA revealed that dietary proanthocyanidins improved the microbial diversity in ileal and colonic digesta, and the most abundant OTUs belong to Firmicutes and Bacteroidetes spp.. Proanthocyanidins treatment decreased the abundance of Lactobacillaceae, and increased the abundance of Clostridiaceae in both ileal and colonic lumen, which suggests that proanthocyanidins treatment changed the bacterial composition and distribution. Administration of proanthocyanidins increased the concentration of propionic acid and butyric acid in the ileum and colon, which may activate the expression of GPR41. In addition, dietary proanthocyanidins improved the antioxidant indices in serum and intestinal mucosa, accompanied with increasing expression of barrier occludin. Our findings indicated that proanthocyanidins with half-dose colistin was equivalent to the antibiotic treatment and assisted weaned animals in resisting intestinal oxidative stress by increasing diversity and improving balance of gut microbes.


Assuntos
Bactérias/efeitos dos fármacos , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Extrato de Sementes de Uva/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Proantocianidinas/farmacologia , Ração Animal , Animais , Animais Recém-Nascidos , Antibacterianos/farmacologia , Antioxidantes/metabolismo , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Ácido Butírico/metabolismo , Colistina/farmacologia , Diarreia/microbiologia , Diarreia/prevenção & controle , Feminino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Permeabilidade , Propionatos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ribotipagem , Sus scrofa , Fatores de Tempo , Desmame , Aumento de Peso/efeitos dos fármacos
16.
Curr Protein Pept Sci ; 17(8): 785-796, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27226197

RESUMO

Antibiotics are one of the most important discoveries in the 20th century and have been widely used for treating animal diseases in the 21st century. However, antibiotic resistance among bacterial pathogens and widespread concerns regarding their use in animals has received great attention all over the world. Great attention has focused on scientific breakthroughs of the alternatives to antibiotics. Various materials such as enzymes, prebiotics, probiotics, minerals, antimicrobial peptides, acidifiers, plants and plant extracts have been tested as possible antibiotics alternatives. Owing to their effects on intestinal microbiota and immune function, research efforts have been conducted on the application of these feed supplements. This review highlights promising research results about the alternatives to antibiotics in animal husbandry that are expected to beneficially limit the adverse effects of antibiotics and ensure the safety of animal-derived foods and the environment.


Assuntos
Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Ração Animal , Criação de Animais Domésticos/métodos , Animais , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Transdução de Sinais/imunologia , Transdução de Sinais/fisiologia , Medicina Veterinária/métodos
17.
J Biomed Nanotechnol ; 11(2): 351-61, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26349311

RESUMO

In this study, solid lipid nanoparticles were formulated for transdermal delivery of aconitine to improve its safety and permeability. Aconitine-loaded solid lipid nanoparticles were formulated as an oil-in-water microemulsion. Drug encapsulation efficiencies for these formulations were higher than 85%, and correlated positively with levels of surfactant and oil matrix. The size of the solid lipid nanoparticles was increased with an increase of the oil matrix, and reduction of the surfactant levels. Compared with an ethanol tincture, all the tested solid lipid nanoparticle formulations achieved improved transdermal fluxes and drug deposition in skin in vitro. Real-time monitoring of drug distribution in rat dermis using in vivo microdialysis showed that aconitine concentration was markedly higher following application of solid lipid nanoparticles, compared to tincture, throughout the experimental period. A regional comparison of rat skin found that application of solid lipid nanoparticles to the scapular region resulted in higher AUC(0-t) and C(max), compared to those achieved with application to the abdomen or chest (p < 0.05). In contrast, the application to the chest resulted in the lowest AUC(0-t) and C(max). Together with findings of a structural study of the skin, these results indicated that the drug accumulated more readily in thicker skin regions, and to a lesser extent in well-perfused skin, because of drug transfer to capillaries. The superior transdermal permeability of aconitine-loaded solid lipid nanoparticles contributed to stronger anti-inflammatory and analgesic effects on mouse in vivo models of pain than the tincture (p < 0.05). In vitro and in vivo studies indicated that smaller particle sizes of solid lipid nanoparticles enhanced the transdermal permeability of aconitine, which can promote drug efficacy, reduce administration time, and improve medication safety.


Assuntos
Aconitina/administração & dosagem , Portadores de Fármacos/síntese química , Lipídeos/química , Nanopartículas/química , Aconitina/farmacocinética , Administração Cutânea , Analgésicos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Células Cultivadas , Química Farmacêutica , Portadores de Fármacos/química , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Permeabilidade , Ratos , Ratos Sprague-Dawley , Pele/metabolismo , Absorção Cutânea
18.
Huan Jing Ke Xue ; 36(10): 3603-10, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26841591

RESUMO

Xining, Ningbo and Beijing were closen as the representative cities about biochemical treatment of kichen waste. The treatment facilities of these cities were investigated and set as the sampling points. The main compositions and the material contents were analyzed by GC/MS, the odor concertration was obtained by the Triangle odor bag method. The results showed that oxygenated hydrocarbons including alcohol, aldehyde, ketone, ester were higher than others in the odor gases, however, the largest contribution to odor pollution were sulfocompounds and the 2nd materials were terpenes; According to the research of the three enterprises, ethyl alcohol, limonene, sulfuretted hydrogen, methyl mercaptan, dimethyl sulfide, dimethyl disulfide, acetaldehyde and ethyl acetate were likely to be considered as the typical odorants from the biochemical treatment facilities of kichen waste.


Assuntos
Resíduos de Alimentos , Gases/análise , Odorantes/análise , Eliminação de Resíduos/métodos , Acetaldeído , Pequim , China , Cidades , Etanol , Hidrocarbonetos , Sulfeto de Hidrogênio , Compostos de Sulfidrila , Sulfetos
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