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1.
Meat Sci ; 191: 108847, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35594692

RESUMO

To explore the effects and underlying mechanism of vitamin A on beef marbling fat development, angus steers were injected vitamin A at birth and 1 month of age and in vitro experiments were performed to investigate the effects of retinoic acid (RA) on angiogenesis and adipogenesis of intramuscular stromal vascular (SVF) cells. Results showed that vitamin A administration increased the intramuscular PDGFRα+ adipose progenitors, improved adipogenic potential of intramuscular SVF cells and dramatically upregulated VEGFA. At slaughter, vitamin A increased intramuscular triacylglycerols by 45% without affecting overall fatness. In a 3D culture system, RA promoted capillary sprout development and promoted the subsequent adipogenesis of intramuscular SVF cells by activating VEGFA/VEGFR2 signaling. However, during terminal adipogenesis, RA downregulated PPARγ, C/EBPα and inhibited lipid accumulation. In conclusion, vitamin A/RA upregulate VEGFA and stimulate intramuscular vascular capillary development, which increases intramuscular adipose progenitors and contributes to adipocyte formation. When administrated at neonatal stage, vitamin A promotes beef marbling development without affecting overall fatness.


Assuntos
Músculo Esquelético , Vitamina A , Adipócitos , Adipogenia/fisiologia , Tecido Adiposo , Animais , Bovinos , Tretinoína , Vitamina A/farmacologia
2.
J Org Chem ; 84(14): 9087-9092, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31273973

RESUMO

Sekgranaticin (1), a novel hybrid polyketide with a complex 6/6/6/6/6/6/6 7-ring system, was isolated together with granaticins A (2) and B (3) and methyl granaticinate (4) from the culture broth of Streptomyces sp. 166#. Its structure was elucidated by spectroscopic analysis. The absolute configuration was determined on the basis of the calculated 13C NMR and electronic circular dichroism data. Compounds 1-4 exhibited potent cytotoxicity against cancer cell lines MCF-7, A549, P6C, and HCT-116 with IC50 values of 0.02-6.77 µM. The biosynthetic pathway of sekgranaticin (1) was proposed.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Policetídeos/química , Streptomyces/química , Antibacterianos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Naftoquinonas/química , Streptomyces/classificação
3.
Artigo em Inglês | MEDLINE | ID: mdl-30848195

RESUMO

AIM AND OBJECTIVE: Small molecule targeted drugs can effectively reduce the toxicity and side effects of drugs, and improve the efficacy of drugs by their specific antitumor activity. Hence, the development of small molecular targeted drugs for cancer has important significance. This study was undertaken to design and synthesize novel phenazine-chromene hybrid molecules in order to optimize the structure and improve the efficacy of this kind of hybrids. MATERIALS AND METHODS: O-diaminobenzene was used as starting material to synthesize twentyfour heterocyclic compounds designed as hybrid molecules of phenazine and 4H-chromene pharmacophores by facile methods. The structures of the compound were confirmed by 1H NMR, 13C NMR and HRMS. Furthermore, the synthesized compounds were evaluated for in vitro activity against four human cancer cell lines and two non-cancer cell lines by MTT test. RESULTS: Some compounds showed strong cytotoxic activities against HepG2 and A549 cancer lines (IC50 = 5-10 µM). Comparing 2i with 2l, the introduction of hydrophilic groups on the phenazine core could not improve the antiproliferative activity significantly. Except 2d and 3c, compounds owning chlorine substituent on the 4H-chromene pharmacophore seemingly contribute to enhance the compounds' antiproliferative activity. Specially, compound 3c showed highest cytotoxicity against A549 cells with IC50 values of 3.3±0.4 µM. Furthermore, all compounds showed low or no cytotoxicity against HUVEC and L02 non-cancer cells in vitro. CONCLUSION: Compound 3c may be used as potential lead molecule against A549 cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzopiranos/farmacologia , Produtos Biológicos/farmacologia , Fenazinas/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Benzopiranos/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Fenazinas/química , Relação Estrutura-Atividade
4.
Chin J Nat Med ; 16(5): 358-365, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29860997

RESUMO

One new sorbicillin derivative, 2-deoxy-sohirnone C (1), one new diketopiperazine alkaloid, 5S-hydroxynorvaline-S-Ile (2), and two naturally occurring diketopiperazines, 3S-hydroxylcyclo(S-Pro-S-Phe) (3) and cyclo(S-Phe-S-Gln) (4), together with three known compounds were isolated from the Chinese mangrove endophytic fungus Penicillium sp. GD6. Their structures were determined on the basis of extensive spectroscopic analyses and by comparison with literature data. The absolute configuration of 3-hydroxyl moiety in 3 was determined by Mosher's method, while the absolute stereochemistry of 2 and 4 was established by comparison with the CD spectra of natural and synthesized diketopiperazines. Compound 1 showed moderate antibacterial activity against Methicillin-resistant Staphylococcus aureus with a MIC value of 80 µg·mL-1.


Assuntos
Antibacterianos/farmacologia , Dicetopiperazinas/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Penicillium/química , Resorcinóis/química , Resorcinóis/farmacologia , Rhizophoraceae/microbiologia , Alcaloides/química , Alcaloides/isolamento & purificação , Antibacterianos/química , Antibacterianos/isolamento & purificação , China , Dicroísmo Circular , Dicetopiperazinas/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Resorcinóis/isolamento & purificação , Áreas Alagadas
5.
PLoS One ; 13(6): e0199572, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29949643

RESUMO

Based on the feature of high-altitude permafrost topography and the diverse microbial ecological communities of the Qinghai-Tibetan Plateau, soil samples from thirteen different collection points around Qinghai lake were collected to screen for extremophilic strains with the ability to degrade phenol, and one bacterial strain recorded as TIBETAN4 that showed effective biodegradation of phenol was isolated and identified. TIBETAN4 was closely related to Kocuria based on its observed morphological, molecular and biochemical characteristics. TIBETAN4 grew well in the LB medium at pH 7-9 and 0-4% NaCl showing alkalophilicity and halophilism. The isolate could also tolerate up to 12.5 mM phenol and could degrade 5 mM phenol within 3 days. It maintained a high phenol degradation rate at pH 7-9 and 0-3% NaCl in MSM with 5 mM phenol added as the sole carbon source. Moreover, TIBETAN4 could maintain efficient phenol degradation activity in MSM supplemented with both phenol and glucose and complex water environments, including co-culture Penicillium strains or selection of non-sterilized natural lake water as a culture. It was found that TIBETAN4 showed enzymatic activity of phenol hydroxylase and catechol 1,2-dioxygenase after induction by phenol and the corresponding genes of the two enzymes were detected in the genome of the isolate, while catechol 2,3-dioxygenase or its gene was not, which means there could be a degradation pathway of phenol through the ortho-pathway. The Q-PCR results showed that the transcripts of both the phenol hydroxylase gene and catechol 1,2-dioxygenase gene were up-regulated under the stimulation of phenol, demonstrating again that the strain degraded phenol via ortho-degradation pathway.


Assuntos
Micrococcaceae/isolamento & purificação , Micrococcaceae/metabolismo , Fenol/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas de Cultura de Células , China , Enzimas/genética , Enzimas/metabolismo , Extremófilos , Concentração de Íons de Hidrogênio , Lagos/microbiologia , Micrococcaceae/crescimento & desenvolvimento , Penicillium , Cloreto de Sódio , Microbiologia do Solo
6.
PLoS One ; 12(5): e0178425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542542

RESUMO

In this study, we designed a microcosm experiment to explore the composition of the bacterial community in the rhizosphere of maize and bulk soil by sequencing the V3-V4 region of the 16S rRNA gene on the Illumina system. 978-1239 OTUs (cut off level of 3%) were found in rhizosphere and bulk soil samples. Rhizosphere shared features with the bulk soil, such as predominance of Acidobacteria, Proteobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Firmicutes, Gemmatimonadetes and TM7. At genus level, many of the dominant rhizosphere genera (Chitinophaga, Nitrospira, Flavobacterium, etc.) displayed different patterns of temporal changes in the rhizosphere as opposed to the bulk soil, showing rhizosphere has more impact on soil microorganisms. Besides, we found that significant growth-related dynamic changes in bacterial community structure were mainly associated with phylum Bacteroidetes, Proteobacteria and Actinobacteria (mainly genera Burkholderia, Flavisolibacter and Pseudomonas), indicating that different growth stages affected the bacterial community composition in maize soil. Furthermore, some unique genera in especial Plant-Growth Promoting Rhizobacteria (PGPR) such as Nonomuraea, Thiobacillus and Bradyrhizobium etc., which were beneficial for the plant growth appeared to be more abundant in the rhizosphere than bulk soil, indicating that the selectivity of root to rhizosphere microbial is an important mechanism leading to the differences in the bacteria community structure between rhizosphere and bulk soil.


Assuntos
Bactérias/genética , Raízes de Plantas/microbiologia , Zea mays/microbiologia , RNA Ribossômico 16S/genética , Rizosfera , Análise de Sequência de DNA/métodos , Solo , Microbiologia do Solo
7.
J Enzyme Inhib Med Chem ; 32(1): 624-631, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28260395

RESUMO

Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists. A homology model was constructed to predict the 3D structure of AdipoR1. By docking to known active peptides, the putative active site of the model was further explored. A virtual screening study was then carried out with a set of manually designed peptides using molecular docking. Peptides with high docking scores were then evaluated for their anti-fibrotic properties. The data indicated that the novel peptide Pep70 significantly inhibited the proliferation of hepatic stellate cells (HSC) and NIH-3T3 cells (18.33% and 27.80%) and resulted in favouring cell-cycle arrest through increasing the accumulation of cells in the G0/G1 phase by 17.08% and 15.86%, thereby reducing the cell population in the G2/M phase by 11.25% and 15.95%, respectively. Additionally, Pep70 exhibited the most marked suppression on the expression of α-smooth muscle actin (α-SMA), collagen type I alpha1 (COL1A1) and TGF-ß1. Therefore, the peptide Pep70 was ultimately identified as an inhibitor of fibrotic responses and as a potential AdipoR1 agonist.


Assuntos
Oligopeptídeos/química , Peptídeos/farmacologia , Receptores de Adiponectina/agonistas , Sequência de Aminoácidos , Animais , Sítios de Ligação/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Células NIH 3T3 , Oligopeptídeos/genética , Peptídeos/síntese química , Peptídeos/química , Ratos , Homologia de Sequência de Aminoácidos , Fator de Crescimento Transformador beta1/agonistas , Fator de Crescimento Transformador beta1/metabolismo
8.
Eur J Pharm Sci ; 93: 123-31, 2016 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-27516150

RESUMO

Adiponectin is an antidiabetic and antiatherogenic adipokine, which plays distinct roles in the balance of energy homoeostasis. As an insulin sensitizing hormone, adiponectin exerts multiple biological effects by the specific receptors (AdipoR1 and AdipoR2), through activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α pathways. AdipoRon, an orally active synthetic small-molecule AdipoR agonist, shows very similar effects to adiponectin in vitro and in vivo, which could be a promising therapeutic approach for obesity-related disorders. In view of the regulatory effects of adiponectin or AdipoRon on inflammatory response and energy metabolism, they might be endowed a curative potential for tissue damage. Hence, its effects and possible mechanism were investigated. In vitro studies on hepatocytes (L02) and macrophages (RAW264.7) suggested a protective and anti-inflammatory potential of AdipoRon. The effects were verified in acute hepatic injury mice induced by d-galactosamine (D-GalN): hepatic lesions were restored by AdipoRon or bicyclol (positive reference drug) pretreatment, which were characterized by a significant increase in serological and hepatic biomarkers (AST, ALT, MDA and NOSs). Besides, AdipoRon attenuated the inflammation in the liver, characterized by the dwindling proinflammatory macrophage infiltration, as well as the shrinkage of tumor necrosis factor-α (TNF-α), transforming growth factor beta 1 (TGF-ß1), interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6); meanwhile conversely promoted AMPK activation by phosphorylation. Combined with liver histopathology, these results demonstrated the hepatoprotective effects of AdipoRon against D-GalN-induced damage, which might be ascribed to the attenuation of inflammation, inhibition of free radical reactions, as well as enhancement of liver energy metabolism.


Assuntos
Galactosamina/efeitos adversos , Fígado/efeitos dos fármacos , Piperidinas/farmacologia , Animais , Linhagem Celular Transformada , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
Chin J Nat Med ; 14(6): 427-33, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27473960

RESUMO

Cranberry extract (CBE) rich in polyphenols are potent to delay paralysis induced by alleviating ß-amyloid (Aß) toxicity in C. elegans model of Alzheimer's disease (AD). In order to better apply CBE as an anti-AD agent efficiently, we sought to deterrmine whether preventive or therapeutic effect contributes more prominently toward CBE's anti-AD activity. As the level of Aß toxicity and memory health are two major pathological parameters in AD, in the present study, we compared the effects of CBE on Aß toxicity and memory health in the C. elegans AD model treated with preventive and therapeutic protocols. Our results revealed that CBE prominently showed the preventive efficacy, providing a basis for further investigation of these effects in mammals.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Suplementos Nutricionais/análise , Extratos Vegetais/administração & dosagem , Vaccinium macrocarpon/química , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Feminino , Frutas/química , Humanos , Masculino , Memória/efeitos dos fármacos
10.
PLoS One ; 11(7): e0156889, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27388166

RESUMO

The pollution of antibiotic resistance genes (ARGs) in livestock farms is a problem which need to be paid more attention to, due to the severe resistance dissemination and the further human health risk. In this study, all the relevant exposure matrices (manure, soil and water) of sixteen animal farms in Southeastern China were sampled to determine twenty-two ARGs conferring resistance to five major classes of antibiotics including tetracyclines, sulfonamides, quinolones, aminoglycosides, and macrolides. The results showed that the spread property of sul genes was most extensive and strong, followed by tet and erm genes. The abundance of tet genes expressing ribosomal protection proteins (tetM, tetO, tetQ, tetT and tetW) was higher than that expressing efflux pump proteins (tetA, tetC, tetE and tetG) in each type of samples. The high abundance and frequency of ermB gene in the matrices should be paid more attention, because macrolides is a major medicine for human use. For manures, it was found that the similar ARGs distribution rules were existing in poultry manure or porcine manure samples, despite of the different origins of these two types of livestock farms. Meanwhile, it was interesting that the distribution rule of tet genes in animal manure was nearly the same as all the ARGs. For soils, the result of nonmetric multi-dimensional scaling (NMDS) analysis showed that the pollution of ARGs in the soils fertilized by poultry and cattle manures were more substantial in northern Jiangsu, but no significant ARGs diversity was observed among porcine manured soils of five different regions. Furthermore, most ARGs showed significant positive relationships with environmental variables such as concentration of sulfonamides, tetracyclines, Cu, Zn and total organic carbon (TOC). The pollution profile and characteristics of so many ARGs in livestock farms can provide significative foundation for the regulation and legislation of antibiotics in China.


Assuntos
Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos/genética , Fazendas , Genes Bacterianos , Esterco/microbiologia , Criação de Animais Domésticos/métodos , Animais , Antibacterianos/farmacologia , Carbono/análise , Bovinos , Galinhas , China , Fertilizantes , Concentração de Íons de Hidrogênio , Gado , Macrolídeos/uso terapêutico , Esterco/análise , Solo , Suínos , Medicina Veterinária
11.
Arthritis Rheumatol ; 68(8): 1989-2002, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26946325

RESUMO

OBJECTIVE: Although transforming growth factor ß (TGFß) is recognized as being a key trigger of fibroblast activation in systemic sclerosis (SSc), prominent innate immunity suggests that additional pathways contribute to disease persistence. Toll-like receptor 9 (TLR9) is implicated in autoimmunity and fibrosis; however, the expression, mechanism of action, and pathogenic role of TLR9 signaling in SSc remain uncharacterized. The aim of this study was to explore the expression, activity, and potential pathogenic role of TLR9 in the context of skin fibrosis in SSc and in mouse models of experimental fibrosis. METHODS: Expression and localization of TLR9 were evaluated in SSc skin biopsy specimens and explanted skin fibroblasts. Fibrotic responses elicited by type A CpG oligonucleotide and mitochondrial DNA (mtDNA) were examined in human skin fibroblasts by a combination of real-time quantitative polymerase chain reaction, Western blot analysis, transient transfection, immunofluorescence microscopy, and functional assays. Expression of TLR9 was examined in 2 distinct mouse models of experimental fibrosis. RESULTS: Skin biopsy specimens obtained from 2 independent cohorts of SSc patients showed up-regulation of TLR9, and myofibroblasts were the major cellular source. Moreover, SSc skin biopsy specimens showed evidence of TLR9 pathway activation. CpG induced robust TLR9-dependent fibrotic responses in explanted normal fibroblasts that could be blocked by bortezomib and were mediated through the action of endogenous TGFß. Mice with experimental fibrosis showed a time-dependent increase in TLR9 localized primarily to myofibroblasts in the dermis. CONCLUSION: In isolated fibroblasts, TLR9 elicits fibrotic responses mediated via endogenous TGFß. In patients with SSc, mtDNA and other damage-associated TLR9 ligands in the skin might trigger localized activation of TLR9 signaling, TGFß production, and consequent fibroblast activation. Disrupting this fibrotic process with inhibitors targeting TLR9 or its downstream signaling pathways might therefore represent a novel approach to SSc therapy.


Assuntos
Fibroblastos/fisiologia , Escleroderma Sistêmico/imunologia , Receptor Toll-Like 9/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Animais , Células Cultivadas , Feminino , Fibrose/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Escleroderma Sistêmico/complicações , Transdução de Sinais , Pele/patologia
12.
Cell Signal ; 28(5): 460-468, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26876613

RESUMO

Ultraviolet B (UVB) radiation is the major environmental risk factor for developing skin cancer, the most common cancer worldwide, which is characterized by aberrant activation of Akt/mTOR (mammalian target of rapamycin). Importantly, the link between UV irradiation and mTOR signaling has not been fully established. Apigenin is a naturally occurring flavonoid that has been shown to inhibit UV-induced skin cancer. Previously, we have demonstrated that apigenin activates AMP-activated protein kinase (AMPK), which leads to suppression of basal mTOR activity in cultured keratinocytes. Here, we demonstrated that apigenin inhibited UVB-induced mTOR activation, cell proliferation and cell cycle progression in mouse skin and in mouse epidermal keratinocytes. Interestingly, UVB induced mTOR signaling via PI3K/Akt pathway, however, the inhibition of UVB-induced mTOR signaling by apigenin was not Akt-dependent. Instead, it was driven by AMPK activation. In addition, mTOR inhibition by apigenin in keratinocytes enhanced autophagy, which was responsible, at least in part, for the decreased proliferation in keratinocytes. In contrast, apigenin did not alter UVB-induced apoptosis. Taken together, our results indicate the important role of mTOR inhibition in UVB protection by apigenin, and provide a new target and strategy for better prevention of UV-induced skin cancer.


Assuntos
Anticarcinógenos/farmacologia , Apigenina/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Serina-Treonina Quinases TOR/antagonistas & inibidores , Raios Ultravioleta , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Queratinócitos/citologia , Queratinócitos/enzimologia , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos da radiação , Neoplasias Cutâneas/prevenção & controle , Serina-Treonina Quinases TOR/metabolismo
13.
J Gerontol A Biol Sci Med Sci ; 71(12): 1564-1573, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26405062

RESUMO

A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans In this article, we report that supplementation of this cranberry extract delayed Aß toxicity-triggered body paralysis in the C elegans AD model. Genetic analyses indicated that the cranberry-mediated Aß toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C elegans against Aß toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated Aß toxicity in C elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.


Assuntos
Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/imunologia , Peptídeos beta-Amiloides/toxicidade , Proteínas de Caenorhabditis elegans/biossíntese , Caenorhabditis elegans/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Vaccinium macrocarpon , Animais , Animais Geneticamente Modificados , Proteínas de Ligação a DNA/efeitos dos fármacos , Modelos Animais de Doenças , Fatores de Transcrição Forkhead , Fatores de Transcrição de Choque Térmico , Imunidade Inata , Extratos Vegetais/química , Proantocianidinas/química , Substâncias Protetoras/química , Transdução de Sinais , Fatores de Transcrição/efeitos dos fármacos
14.
Mar Drugs ; 13(8): 5201-18, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26295240

RESUMO

Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hence, in this article, the antifibrotic effects and possible mechanisms of r-sHSA, a recombinant protein with hepatoprotection potential, were investigated. Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type I collagen (Col1A1) and α-smooth muscle actin (α-SMA). It turned out those fibrosis indicators were typically inhibited by r-sHSA, suggesting its capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further investigated in vivo on CCl4-induced hepatic fibrosis, in view of significant improvement of the biochemical and histological indicators. More specifically, CCl4-intoxication induced a significant increase in serological biomarkers, e.g., transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed hepatic antioxidative status; most of the parameters were spontaneously ameliorated to a large extent by withdrawal of CCl4, although the fibrotic lesion was observed histologically. In contrast, r-sHSA treatment markedly eliminated fibrous deposits and restored architecture of the liver in a dose dependent manner, concomitantly with the phenomena of inflammation relief and HSCs deactivation. To sum up, these findings suggest a therapeutic potential for r-sHSA in hepatic fibrosis, though further studies are required.


Assuntos
Fibrose/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Tubarões/metabolismo , Actinas/metabolismo , Animais , Biomarcadores/metabolismo , Linhagem Celular , Colágeno Tipo I/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibrose/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Fígado/metabolismo , Cirrose Hepática/metabolismo , Camundongos , Células NIH 3T3 , Ratos
15.
Environ Sci Pollut Res Int ; 22(18): 13950-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25948386

RESUMO

The overuse of antibiotics in livestock farms is general, leading to a wide distribution of antibiotic resistance genes (ARGs) in aquatic environment adjacent to livestock farms. However, researches of the distribution and types of ARGs in aquatic environment of China are still in the initial stage. In this study, wastewater and surface water samples were collected from 12 livestock farms (four pig farms, four cattle farms, and four chicken farms) in Jiangsu Province of China. The prevalence, abundance, and distribution of 22 ARGs were investigated, which were categorized into six groups, including nine tetracyclin resistance genes, three sulfonamides resistance genes, three quinolone resistance genes, two macrolide resistance genes, three aminoglycoside resistance genes, and two multidrug resistance genes, employing quantitative real-time PCR (qPCR). The results suggested that all of the 22 ARGs were detected in samples. Sul1, sul2, and tetM were the most abundant with the average concentration of 3.84 × 10(1) copies/16S recombinant RNA (rRNA) gene copies, 1.62 × 10(1) copies/16S rRNA gene copies, 2.33 × 10(1) copies/16S rRNA gene copies, respectively. Principle component analysis revealed that the comprehensive pollution of ARGs in northern Jiangsu was more serious. ARGs in wastewater were more abundant when compared to that in surface water. A preliminary study regarding the fate of ARGs after an aerobiotic process showed that tetA, tetC, sul1, sul2, oqxB, and qnrS were significantly increased. And, among the tetracycline resistance genes, the efflux pump genes were enriched while the ribosomal protection protein encoding genes were decreased in the aerobiotic process. The prevalance of ARGs in water environment is of concern; more surveillance is required to determine the pollution level and pattern of antibiotic resistance genes.


Assuntos
Resistência Microbiana a Medicamentos/genética , Microbiologia da Água , Agricultura , Aminoglicosídeos/farmacologia , Animais , Antibacterianos/farmacologia , Bovinos , Galinhas , China , Resistência a Múltiplos Medicamentos/genética , Genes Bacterianos , Macrolídeos/farmacologia , Tipagem Molecular , Quinolonas/farmacologia , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , Sulfonamidas/farmacologia , Suínos , Águas Residuárias/microbiologia
16.
Eur J Med Chem ; 90: 695-706, 2015 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-25506809

RESUMO

A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCT116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.22 and 1.24 µM against MCF7, HCT116 and DU145 respectively. Preliminary anti-cancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 6l against HCT116 using flow cytometry, and the results suggested that compound 6l inhibited tumor proliferation through inducing early and late cellular apoptosis in a concentration-dependent manner and causing cell cycle arrest in the S-phase.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Diterpenos/farmacologia , Desenho de Fármacos , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Diterpenos/síntese química , Diterpenos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
17.
PLoS One ; 9(11): e112626, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25405870

RESUMO

Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of antibiotic resistance genes (ARGs) increasingly in the soil. The frequency of sulfonamide resistance genes was sul1 > sul2 > sul3 in pig-manured soil DNA and sul2 > sul1 > sul3 in chicken-manured soil DNA. Further analysis suggested that the frequency distribution of the sul genes in the genomic DNA and plasmids of the SR isolates from manured soil was sul2 > sul1 > sul3 overall (p<0.05). The combination of sul1 and sul2 was the most frequent, and the co-existence of sul1 and sul3 was not found either in the genomic DNA or plasmids. The sample type, animal type and sampling time can influence the prevalence and distribution pattern of sulfonamide resistance genes. The present study also indicated that Bacillus, Pseudomonas and Shigella were the most prevalent sul-positive genera in the soil, suggesting a potential human health risk. The above results could be important in the evaluation of antibiotic-resistant bacteria and genes from manure as sources of agricultural soil pollution; the results also demonstrate the necessity and urgency of the regulation and supervision of veterinary antibiotics in China.


Assuntos
Farmacorresistência Bacteriana/genética , Genes Bacterianos , Esterco/microbiologia , Microbiota/genética , Microbiologia do Solo , Sulfonamidas/farmacologia , Bacillus/efeitos dos fármacos , Bacillus/genética , Bacillus/isolamento & purificação , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , China , Fertilizantes/microbiologia , Microbiota/efeitos dos fármacos , Pseudomonas/efeitos dos fármacos , Pseudomonas/genética , Pseudomonas/isolamento & purificação , Shigella/efeitos dos fármacos , Shigella/genética , Shigella/isolamento & purificação , Solo/química
18.
Fish Shellfish Immunol ; 40(2): 414-23, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25108086

RESUMO

Complement factor I (FI) is a plasma serine proteinase that plays an essential role in the modulation of the complement cascade. In the presence of substrate modulating cofactors (Factor H, C4bp, CR1, etc), FI cleaves the activation products of C3 (i.e. C3b) and C4 (i.e. C4b) to limit complement activity. In this study, the full length cDNA of factor I (CpFI) is isolated from the liver of the whitespotted bamboo shark (Chiloscyllium plagiosum). The CpFI cDNA is 2326 bp in length, encoding a protein of 671 amino acids, which shares 72-80% identity with FI molecules of other sharks, higher than the teleosts (37-40%) and mammals (44-47%). The sequence alignment and comparative analysis indicates the FI proteins are well conserved, with the typical modular architecture and identical active sites throughout vertebrate evolution, suggesting the conserved function. However, the additional sequence present between the leader peptide (LP) and the factor I membrane attack complex (FIMAC) domain in other fishes is also found in CpFI, which consists of two kind of tandem repeats. Phylogenetic analysis suggests that CpFI belongs to the elasmobranch clade, in parallel with the higher vertebrates, to form a sister taxa to teleosts. Expression analysis revealed that CpFI is ubiquitously distributed in a variety of tissues, with the constitutive expression in liver, which might reflect the species-specific distribution patterns of FI. Together with earlier reports, the presence of FI in various sharks might suggest the existence of a well-developed complement regulation mechanism in cartilaginous fish.


Assuntos
Fator I do Complemento/genética , Proteínas de Peixes/genética , Regulação da Expressão Gênica , Tubarões/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fator I do Complemento/química , Fator I do Complemento/metabolismo , DNA Complementar/genética , Proteínas de Peixes/química , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica , Masculino , Dados de Sequência Molecular , Especificidade de Órgãos , Filogenia , Reação em Cadeia da Polimerase/veterinária , Alinhamento de Sequência/veterinária , Tubarões/metabolismo
19.
Org Lett ; 16(5): 1390-3, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24533828

RESUMO

A novel pyrrolizidine alkaloid, penibruguieramine A (1), characterized by an unprecedented 1-alkenyl-2-methyl-8-hydroxymethylpyrrolizidin-3-one skeleton, was isolated from the endophytic fungus Penicillium sp. GD6, associated with the Chinese mangrove Bruguiera gymnorrhiza. The absolute configuration of penibruguieramine A (1) was established by TDDFT ECD calculations of the vacuum and solution conformers, exploiting the transitions of the lactam chromophore. A plausible pathway for its biosynthesis has been proposed.


Assuntos
Penicillium/química , Alcaloides de Pirrolizidina/isolamento & purificação , Rhizophoraceae/microbiologia , Estrutura Molecular , Alcaloides de Pirrolizidina/química
20.
Huan Jing Ke Xue ; 35(11): 4267-74, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25639105

RESUMO

The extensive use of veterinary tetracycline in the stock husbandry has led to the increasingly serious environmental pollution, the tetracycline resistance genes induced by which could bring more hazardous environmental risk than veterinary tetracycline. This study investigated the effects of environmental factors on the formation of several typical tetracycline resistance genes (tetA, tetC). The results showed that temperature, light and pH could have impacts on the formation of tetracycline resistance genes in soil, the amounts of the tetracycline resistance bacteria and resistance genes induced in different treatments all reached the maximum in the proper environmental condition (25 degrees C, 500 lx, pH7.5), which were all significantly higher than those in other environmental conditions (P < 0.05). In contrast, the adverse condition such as high temperature, strong light and high pH could effectively inhibit the formation of tetracycline resistance genes, probably due to the reduction of tetracycline residues or the direct influence on the formation of tetracycline resistance genes. And the results also showed that environmental factors could affect the growth of tetracycline resistance bacteria. Further analysis proved that the content of tetracycline resistance gene in soil had a positive correlation with the number of tetracycline resistance bacteria in the studied samples, therefore an inferred result was concluded that the growth of tetracycline resistance bacteria played a key role in the formation of the tetracycline resistance genes.


Assuntos
Bactérias/genética , Genes Bacterianos , Microbiologia do Solo , Resistência a Tetraciclina/genética , Bactérias/efeitos dos fármacos , Solo
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